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SECTION 1. SHORT TITLE. This Act may be cited as the ``Campaign Finance Reform Act of 1995''. SEC. 2. ESTABLISHMENT AND PURPOSE OF COMMISSION. There is established a commission to be known as the ``Campaign Finance Reform Commission'' (hereinafter in this Act referred to as the ``Commission''). The purposes of the Commission are to study the laws relating to elections for Federal office and to recommend reforms in those laws. SEC. 3. MEMBERSHIP OF COMMISSION. (a) Appointment.--The Commission shall be composed of 13 members appointed from among individuals who are not officers or employees of any government and who are specially qualified to serve on the Commission by reason of education, training, or experience. Of the members of the Commission-- (1) 3 members shall be appointed by the majority leader of the House of Representatives, and one of those members shall be an independent; (2) 3 members shall be appointed by the majority leader of the Senate, and one of those members shall be an independent; (3) 3 members shall be appointed by the minority leader of the House of Representatives, and one of those members shall be an independent; (4) 3 members shall be appointed by the minority leader of the Senate, and one of those members shall be an independent; and (5) 1 member, who shall be designated as Chairman of the Commission, shall be jointly appointed by the President and the Speaker of the House of Representatives. (b) Independent Defined.--An independent member of the Commission shall not have registered in or declared officially his affiliation with a political party or voted in the primary election of a political party in the last 7 years, and shall never have held appointed or elected public or party office. (c) Terms.--The members of the Commission shall serve for the life of the Commission. (d) Vacancies.--A vacancy in the Commission shall be filled in the manner in which the original appointment was made. (e) Political Affiliation.--Not more than 4 members of the Commission may be of the same political party. SEC. 4. POWERS OF COMMISSION. (a) Hearings.--The Commission may, for the purpose of carrying out this Act, hold hearings, sit and act at times and places, take testimony, and receive evidence as the Commission considers appropriate. (b) Quorum.--Seven members of the Commission shall constitute a quorum, but a lesser number may hold hearings. Any member of the Commission may, if authorized by the Commission, take any action which the Commission is authorized to take under this section. SEC. 5. REPORT AND RECOMMENDED LEGISLATION. Not later than 10 months after the date of the enactment of this Act, the Commission shall submit to the Congress a report of the activities of the Commission, together with a draft of legislation (including technical and conforming provisions) recommended by the Commission to reform the Federal Election Campaign Act of 1971 (2 U.S.C. 431 et seq.) and any other laws relating to elections for Federal office. SEC. 6. MATTERS TO BE CONSIDERED BY THE COMMISSION. In formulating its draft of legislation under section 5, the Commission shall consider ways to-- (1) increase confidence in the Federal electoral system; (2) increase voter participation; (3) create a more equitable electoral system for challengers and incumbents; and (4) remove the negative and insidious aspects of campaign financing. SEC. 7. FAST-TRACK PROCEDURES. (a) Rules of House of Representatives and Senate.--This section is enacted by the Congress-- (1) as an exercise of the rulemaking power of the House of Representatives and the Senate, respectively, and as such they shall be considered as part of the rules of each House, respectively, or of that House to which they specifically apply, and such rules shall supersede other rules only to the extent that they are inconsistent therewith; and (2) with full recognition of the constitutional right of either House to change the rules (so far as relating to such House) at any time, in the same manner and to the same extent as in the case of any other rule of that House. (b) Definitions.--As used in this section, the term ``Federal election bill'' means only a bill of either House of Congress which is introduced as provided in subsection (c) to carry out the recommendations of the Commission as set forth in the draft of legislation referred to in section 5. (c) Introduction and Referral.--Within 3 days after the Commission submits its draft legislation under section 5, a Federal election bill shall be introduced (by request) in the House by the majority leader of the House or his designee and shall be introduced (by request) in the Senate by the majority leader of the Senate or his designee. Such bills shall be referred to the appropriate committees. (d) Amendments Prohibited.--No amendment to a Federal election bill shall be in order in either the House of Representatives or the Senate; and no motion to suspend the application of this subsection shall be in order in either House; nor shall it be in order in either House to entertain a request to suspend the application of this subsection by unanimous consent. (e) Period for Committee and Floor Consideration.-- (1) If the committee of either House to which a Federal election bill has been referred has not reported it at the close of the 20th day after its introduction, such committee shall be automatically discharged from further consideration of the bill and it shall be placed on the appropriate calendar. If prior to the passage by one House of a Federal election bill of that House, that House receives the same Federal election bill from the other House, then-- (A) the procedure in that House shall be the same as if no Federal election bill had been received from the other House; but (B) the vote on final passage shall be on the Federal election bill of the other House. (2) For purposes of paragraph (1), in computing a number of days in either House, there shall be excluded the days on which that House is not in session because of an adjournment of more than 3 days to a day certain or an adjournment of the Congress sine die. (f) Floor Consideration in the House.-- (1) A motion in the House of Representatives to proceed to the consideration of a Federal election bill shall be highly privileged except that a motion to proceed to consider may only be made on the second legislative day after the calendar day on which the Member making the motion announces to the House his intention to do so. The motion to proceed to consider is not debatable. An amendment to the motion shall not be in order, nor shall it be in order to move to reconsider the vote by which the motion is agreed to or disagreed to. (2) Consideration of a Federal election bill in the House of Representatives shall be in the House with debate limited to not more than 10 hours, which shall be divided equally between those favoring and those opposing the bill. The previous question on the Federal election bill shall be considered as ordered to final passage without intervening motion. It shall not be in order to move to reconsider the vote by which a Federal election bill is agreed to or disagreed to. (g) Floor Consideration in the Senate.-- (1) A motion in the Senate to proceed to the consideration of a Federal election bill shall be privileged and not debatable. An amendment to the motion shall not be in order, nor shall it be in order to move to reconsider the vote by which the motion is agreed to or disagreed to. (2) Debate in the Senate on a Federal election bill, and all debatable motions and appeals in connection therewith, shall be limited to not more than 10 hours. The time shall be equally divided between, and controlled by, the majority leader and the minority leader or their designees. (3) Debate in the Senate on any debatable motion or appeal in connection with a Federal election bill shall be limited to not more than one hour, to be equally divided between, and controlled by, the mover and the manager of the bill, except that in the event the manager of the bill is in favor of any such motion or appeal, the time in opposition thereto, shall be controlled by the minority leader or his designee. Such leaders, or either of them, may, from time under their control on the passage of a Federal election bill, allot additional time to any Senator during the consideration of any debatable motion or appeal. SEC. 8. TERMINATION. The Commission shall cease to exist 3 months after the date of the submission of its report under section 5.

Campaign Finance Reform Act of 1995 - Establishes the Campaign Finance Reform Commission to study and recommend Federal election law reforms. Terminates the Commission after a specified reporting date.

The world is celebrating Nelson Mandela's 95th birthday as his family insist he is making "remarkable" progress in hospital. South Africans marked the momentous milestone with acts of charity, capped by news that the former president's health was improving. "He continues to respond positively to treatment and we are encouraged by the progress he is making," said President Jacob Zuma, after visiting Mr Mandela in hospital. "We are proud to call this international icon our own as South Africans and wish him good health." Children were among the well-wishers outside Mr Mandela's hospital He thanked people for their support of Mr Mandela and "undying love and compassion, and for responding to a call to give the beloved figure "the biggest birthday celebration ever this year." South Africans took to the streets in celebration of their national hero. Biker gangs cleaned streets, volunteers planted trees and politicians spent 67 minutes on worthy projects - to mark Mr Mandela's 67 years of public service. Children in schools around the country started the day by singing "Happy Birthday" to Mr Mandela. Thursday also marks 15 years since the anti-apartheid leader married his third wife Graca Machel. The UN declared the Nobel peace laureate's birthday Mandela Day in 2010, but for many this year takes on extra poignancy. Winnie Madikizela-Mandela with a giant birthday cake Mr Mandela has spent the last 41 days in a Pretoria hospital in a critical but stable condition after being admitted for a recurring lung infection on June 8. His youngest daughter told Sky News her father has been able to communicate and watch television. "He is making remarkable progress," said Zindzi Mandela, adding that when she visited him on Tuesday he was "watching TV with his headphones". "He responds very well ... with his eyes, and he nods and sometimes he lifts his hand like to shake your hand." Granddaughter Ndileka Mandela poured soup for poor children at a charity event and said her family had been unsure about whether her grandfather would live to see his birthday. Mr Mandela's granddaughter Ndileka serves soup in a poor community "But because of the fighter that he is, he was able to fight a repressive system, and he was able, through God and everybody's prayers, to make it today," she said. President Zuma opened low-cost housing for poor black and white families in the Pretoria area, while Retired archbishop Desmond Tutu helped to paint a school outside Cape Town. US President Barack Obama also urged people to honour Mr Mandela on his birthday "through individual and collective acts of service". "Through our own lives, by heeding his example, we can honour the man who showed his own people - and the world - the path to justice, equality and freedom," Mr Obama said. Archbishop Emeritus Desmond Tutu helps paint a school The South African government is hosting a ceremony for the symbolic handing over of Mr Mandela's new high-tech ID card, which will be received by Zindzi Mandela. The event is laden with meaning in a country where apartheid was enforced by pass books, which black citizens were forced to carry and which limited movement to certain areas at certain times. "On behalf of government and all the people of South Africa, we wish Madiba a joyous 95th birthday," said Mr Zuma, using Mr Mandela's clan name. A group of young South African artists and designers unveiled a project celebrating Mr Mandela's life through paintings and posters. Mr Mandela's grandson Zondwa gives out food parcels to children The group whittled down 700 posters submitted by designers from more than 70 countries, to 95 for each year of Mr Mandela's life. A single special edition of the posters will be auctioned off to raise money for a proposed children's hospital that will be named after Mr Mandela, the group said. "He carries across this concept of humanity and selflessness," said Mohammed Jogie, a co-founder of the project. Elsewhere world leaders, pop stars and companies also pledged their support for Mr Mandela. "I will also be giving my 67 minutes to make the world a better place, one small step at a time," said Sir Richard Branson. The anti-apartheid leader's face has been captured in corn in Kent In the UK, a giant portrait of Mr Mandela's face has been etched into the English countryside to celebrate his birthday. The two-acre maze in corn crops in Birchington, near Margate, Kent, was the idea of Karen Botha and Dawn Tilley who have spent the past five years working on the design. Meanwhile, 50 abandoned street children in the Philippines will get to tour a Manila television studio and see performances by local artists. And the Australian city of Melbourne will hold a concert featuring local and African artists at the weekend, while a music festival later this year in Norway will promote equality in schools. ||||| PRETORIA South Africa and the world showered tributes on Nelson Mandela on Thursday as the anti-apartheid leader turned 95 in hospital and his doctors reported he was "steadily improving" from a six-week lung infection. The country has been on edge since the former president and father of the multi-racial 'Rainbow Nation' established at the end of apartheid in 1994 was admitted to hospital on June 8 with recurring lung problems that kept him in a critical condition. It was his fourth stay in hospital in six months and has reminded South Africans that the man who is globally admired as a moral beacon against injustice and a symbol of racial reconciliation will not be with them forever. But the mood was of celebration on Thursday as thousands of South Africans sang "Happy Birthday" and took part in charitable initiatives in a global outpouring of support for the Nobel Peace Prize laureate on U.N.-designated 'Nelson Mandela Day'. At a United Nations event in New York marking the day, U.N. Secretary-General Ban Ki-moon hailed Mandela as "a giant of our times". Throughout the day, crowds of well-wishers outside the Pretoria hospital where the retired statesman is being treated sang "Happy Birthday, Madiba" - using Mandela's traditional clan name - brought cakes and birthday cards and danced. "Thank you for all that you have done for this country," said one well-wisher, Margaret Chechie. Many South Africans also commemorated the birthday with 67 minutes of public service to honor the 67 years Mandela served humanity by first fighting against white-minority rule and then consolidating racial harmony when he was president. As part of the public service initiative, office workers, students, soldiers and ordinary citizens spruced up orphanages, painted walls at schools and delivered food to the poor. President Jacob Zuma visited Mandela at the hospital and said he was making steady progress. "I was able to say 'Happy Birthday' to him and he was able to smile," he told reporters. Hours earlier, his office had cited Mandela's doctors saying "his health is steadily improving." Mandela's victory in the first multiracial elections in 1994 put an end to the apartheid system. Four years earlier, he was released from 27 years spent in prison under white minority rule, 18 of them at the notorious Robben Island penal colony. His former wife Winnie Madikizela-Mandela called the 95th birthday "a gift to the nation". Family members had lunch together at the hospital where the revered patriarch is being treated and his daughter Zindzi said they gave him a collage of family photographs for a present. "Tata (our father) is making this remarkable progress and we look forward to having him back home soon," Zindzi said. Grandson Ndaba Mandela was more cautious about Mandela's condition. "He's still critical ... he's just a lot more alert now, a lot more aware of his surroundings," he told CBS News. "FIRST CITIZEN" Mandela Day celebrations in the United States included a special event at U.N. headquarters in New York, where figures such as former U.S. President Bill Clinton and the Reverend Jesse Jackson added their voices to the global tributes. Clinton, a personal friend of Mandela, recalled the nearly three decades the nonagenarian spent in apartheid jails. "Mandela walked out of prison after 27 years a greater man than he went in," Clinton said. "Though he is old and frail and fighting for his life ... what is in his heart still glows in his smile and lights up the room through his eyes." Volunteers in New York handed out South African oranges. In South Africa, Ethiopian and Nigerian asylum seekers who had settled their fleeing persecution and conflict in their own countries cleaned streets in Johannesburg expressed their praise for the personality considered "a father of Africa". "In this country, Mandela is the reason all of us blacks are free, so that's why we love him as the first citizen," said Kennedy Uzondu, 30, a Nigerian trader in South Africa. Despite the adulation on his birthday, Mandela's post-apartheid 'Rainbow Nation' has not fulfilled all expectations. Enormous gaps still persist in income, employment and access to education and these inequalities largely follow racial lines, according to the government's own data. White households in 2012 earn on average about six times more than black households. Nevertheless, quality education and employment opportunities have also been opened up to tens of thousands of blacks. (Additional reporting by Reuters TV, Benon Okula and Pascal Fletcher in Johannesburg, Michelle Nichols and Stephanie Ulmer-Nebehay at the United Nations; Writing by Jon Herskovitz; Editing by Pascal Fletcher and Michael Roddy)

– It's Nelson Mandela's 95th birthday, and the anti-apartheid leader remains in the hospital—but South African President Jacob Zuma says his health is "steadily improving," the BBC reports. Mandela's daughter, Zindzi, echoed the sentiment, saying he was "making remarkable progress and we look forward to having him back home soon." Meanwhile, the world is marking Nelson Mandela International Day: In South Africa, millions of children started the day by singing happy birthday to the leader. The country is calling on people to perform 67 minutes of good deeds in honor of Mandela's 67 years of public service; volunteers plan to work at schools, hospitals, and orphanages as well as feed those in need. Richard Branson is among those planning 67 minutes of service. Twenty US cities are celebrating the day, Reuters reports; a giant painting of Mandela is up in Times Square, and volunteers plan to distribute South African oranges. Melbourne, Australia, will hold concerts in the former president's honor. President Obama offered a tribute, encouraging people to serve, Sky News reports: "Through our own lives, by heeding his example, we can honor the man who showed his own people—and the world—the path to justice, equality, and freedom."

if we consider only the quadratic terms , calling @xmath103 the kinetic operator of @xmath2 and @xmath104 that of @xmath3 , the fermionic lagrangian in the main text is diagonalised by the change of basis @xmath105 with propagators respectively @xmath106 and @xmath107 . up to higher order corrections the relation is inverted by @xmath108 using these relations we immediately find the resummed propagators @xmath109 + which gives the result of the table in the main text . in the large n limit , the diagrams contributing to the self - energy are such that the connected pieces in the bulk involves only bulk propagators , because bulk loops and bulk vertices are suppressed . still one can integrate out the bulk degrees of freedom only perturbatively in our generic model . it is useful to consider a local patch around a point on the fermi surface where we can establish cartesian coordinates . let @xmath115 be the coordinate along the fermi surface and @xmath116 be the coordinate perpendicular to it . near the chosen point @xmath117 , and we have @xmath118 in order to understand the infrared behavior of the self - energy we can consider the fermi surface to be flat , or in other words push @xmath119 to infinity @xcite and thus simplify the integrals considerably . furthermore , we can also integrate over loop momenta and then over the loop frequency in any order as it does not affect the infrared behavior of the integrated result @xcite . note the specific order of integration chosen in order to simplify the integration . the @xmath122 integral can be performed using residues , with the result @xmath123 where @xmath124 , and we have used the fact that for a neutral liquid , @xmath27 is real . then considering that @xmath125 one readily sees that the polarization integral vanishes for @xmath126 . for the other case @xmath127 , we can approximate in the denominator @xmath128 , then the @xmath129 integral can be immediately performed , since @xmath130 and we find @xmath131 the final @xmath132 integral can again be done by residues : @xmath133 in summary , the polarization vanishes for @xmath126 , and it has the same form as in the fermi liquid for @xmath127 . we can readily do the @xmath137 integral by taking the pole contribution . we obtain @xmath138 in the last step we have used the fact that the logarithmic integral is automatically regulated in the manner shown if the damping is introduced in a self - consistent manner @xcite . remarkably the self - energy corrections are very much like a fermi liquid and subleading at the fermi surface . these results are compatible with the intuition one can develop from renormalization group arguments . thus one can argue that even higher order perturbative corrections will be subleading at the fermi surface . a problem one encounters wen trying to couple a fermi liquid to a critical boson @xcite is that the fermion polarization will renormalize the boson propagator ( diagram f in fig . [ selfenergy ] ) ; since it is a singular contribution , it becomes more important than the bare propagator in the ir ; in turn , the one - loop corrected boson propagator affects the fermion one by diagram b , and the ir fixed point is destabilized . in our case , the situation is actually better . even though diagram f is not suppressed in the @xmath10-counting , the effect is a correction @xmath139 to a bare term of order @xmath140 , so it does not destabilize the fixed point for @xmath141 , at least by a naive application of the rg argument . however it would be important to confirm this intuition by careful computations . in this section we consider the rg scaling of the terms in our model in order to determine what are the relevant and marginal perturbations . we follow the analysis of ref . @xcite , where it has been pointed out that the rg around a fermi surface is special as the momenta are rescaled towards the surface and not towards the origin ; in a wilsonian approach , in order to change the cutoff from @xmath142 to @xmath143 one integrates out modes with momenta @xmath144 . if we write the fermion momentum as @xmath145 , with @xmath146 on the fermi surface and @xmath147 orthogonal to it , then the scaling is @xmath148 = 0 , [ { \bf l } ] = 1,$ ] where @xmath149 = n$ ] means that it scales as @xmath150 . in order to have all the kinetic terms to be scale - invariant one then finds @xmath151 = -1 \ , , \quad [ \chi ] = - \frac{1}{2 } \ , . \quad\ ] ] on the other hand , for the bosonic and fermionic operators of the bulk cft , if we consider the case of @xmath152 infrared geometry , the momentum does not scale since the correlator is only a function of @xmath28 ; then one finds @xmath153 = [ \psi ] = \frac{\nu-1}{2 } \,.\ ] ] let us now consider an interaction term @xmath154 or @xmath155 ( in the latter case we take @xmath156 half - integer , with a slight abuse of notation ) . written in momentum space the interaction contains a delta function for momentum conservation , @xmath157 for a generic kinematic configuration , where the sum of the fermionic momenta does not lie on the fermi surface , the delta function does not scale . then one finds that the dimension of the interaction is @xmath158 , so this is relevant or marginal if @xmath159 considering that @xmath160 one sees that the only interactions that are generically marginal or relevant are for @xmath161 and @xmath162 . these imply we need to consider the interactions @xmath163 , @xmath164 and it s complex conjugate only . let us consider first the case of a normal fermi liquid . the feynman s green function is given by @xmath165 where @xmath166 is the sign function and @xmath167 . this propagator is characterized by the property of having poles in the lower half - plane ( lhp ) of complex frequencies for @xmath168 and in the upper half - plane ( uhp ) for @xmath169 ; moreover , it is equal to @xmath170 for @xmath171 and to @xmath172 for @xmath173 . + when we consider the product of two green s functions , @xmath174 , and we perform the integral over @xmath28 on a contour that includes the real axis and the circle going to infinity in the uhp , there are four possibilities : let us now consider the case of the non - fermi liquid . the retarded green s function has the form @xmath183 where @xmath184 and we consider the charged case , so we explictly included the phase factor in the self - energy , so in this section @xmath185 . one can show that @xmath186 . the behaviour of the poles of this function is illustrated in fig . 2 in ref . because of the term with non - integer power the function has a branch cut that can be chosen to run along the negative imaginary axis . first we must find the feynman propagator to use in the diagrams . by analogy with the free case , we find that the right prescription is obtained with the following form : @xmath187 to perform the integral , we map @xmath188 . this maps the uhp into a wedge of angle @xmath189 . the integral is along the edges of the wedge and the contour at infinity that does not cross the branch cut . again we have four possibilities for the location of the poles , but now in case 2 , when both poles are inside the contour , there is no cancellation . in cases 3 and 4 , where the integration is for momenta close to the fermi surface , one finds that the residue of the pole vanishes like @xmath190 , so there is no contribution . the result is then where @xmath192 . using @xmath193 we find @xmath194 where @xmath195 . + integrating over @xmath102 and @xmath80 ( this integral needs a uv cutoff @xmath196 ) we find @xmath197 from the last two results the equations ( 6 ) and ( 7 ) of the main text follow . in this section we review the derivation of the landau - silin equations generalized to our system . let us begin with the case of uncharged fermi liquid where long range forces are absent . the bethe - salpeter equation written explicitly is as below : it is easy to see that the transfer of energy - momentum @xmath100 from one fermionic pair to another is merely a spectator in the integral equation . we may regard @xmath45 and @xmath46 as matrices in flavor space ( with two flavor indices forming the row entries and two flavor indices forming the column entries ) and @xmath199 and @xmath200 space . similarly the two - particle bridge @xmath201 can also be regarded as a diagonal matrix in @xmath199 and @xmath200 space , and a non - diagonal matrix in flavor space . we recall , as used in the main text , that @xmath201 can be split as @xmath202 with @xmath59 being singular and @xmath203 being non - singular as @xmath100 vanishes . we recall @xmath26 is just a number related to the residue of the pole of the @xmath20 propagator at the fermi - surface in @xmath140 . the matrix multiplication can then be obviously defined . in the matrix language , the spatial fourier transform of the wigner function representing phase space density operator of fermions given by @xmath204 , can be thought of as a vector . as self - energy corrections are irrelevant at the fermi surface , we can write any relevant perturbation as @xmath205 as observed in the main text and similarly any observable as @xmath206 , with @xmath207 and @xmath208 representing appropriate vectors . the inner product @xmath205 and @xmath206 involves integration over @xmath8 , and summation over @xmath209 and @xmath210 ; the @xmath114 and @xmath211 dependence then captures the space - time variation of the perturbation and response respectively . note more generally if the perturbation is of the form @xmath212 then it is useful to define such that the general external perturbation again takes the abridged form @xmath205 , the inner product involving an integration over @xmath199 and summation over @xmath209 and @xmath210 . similarly one can consider a more general observable of the form @xmath219 such that @xmath220 is a function of both @xmath199 and @xmath100 . the diagrammatic equations giving the response of an arbitrary observable to an arbitrary perturbation , illustrated in fig . 1 in the main text , can be written in the matrix form as below : @xmath221e , \\ \gamma = & \gamma_0 + \gamma_0(a^2 q+g ) \gamma , \end{split}\ ] ] where @xmath222 denotes the response under study . we note that in all cases @xmath223 while taking the limits in the opposite order yields a non - vanishing result . this plays a crucial role in generalizing landau - silin theory . let us denote the non - singular part of the four - point function as : @xmath224 where the second equality follows by using eq . ( [ qgt0 ] ) in the second equation in ( [ matrixform ] ) . assuming inverses of matrices exist we can show after some manipulations that @xmath225 = \gamma_1 + a^2 \gamma_1 q \gamma.\ ] ] similar manipulations give us therefore , @xmath232 ( k , k ' , q= 0)\ ] ] it is not hard to see that on the fermi surface @xmath233 combining the above identity with eq . ( [ id1 ] ) we find that @xmath234 ^{\chi\chi\chi\chi}(\mathbf{k}= \mathbf{k } _ * , & \mathbf{k'}= \mathbf{k'}_*,\omega = 0 ; q= 0 ) \\ & = a^{-1}\delta(\mathbf{k _ * } - \mathbf{k ' _ * } ) . \end{split}\ ] ] ignoring non - singular terms in eq . ( [ matrixform2 ] ) it follows that note it follows from eq . ( [ wid ] ) that @xmath238 . the integral equation for @xmath239 follows from eq . ( [ gamma1 ] ) . thus we recover the landau equations for the neutral non - fermi liquid . in summary the low energy response to an arbitrary perturbation is characterized by the parameters of the two - point function on the fermi surface namely @xmath26 , @xmath203 , @xmath27 and the scaling exponent @xmath240 ; the generalized landau parameters @xmath241 obtained from the four - point function ; and the parameters obtained from both the non - singular parts of the four - point and the two - point function which are @xmath242 , @xmath243 , @xmath244 , @xmath245 , @xmath246 and @xmath247 .

we analyze some phenomenological implications of the most general semiholographic models for non - fermi liquids that have emerged with inputs from the holographic correspondence . we find generalizations of landau - silin equations with few parameters governing thermodynamics , low - energy response and collective excitations . we show that even when there is a fermi surface with well - defined quasiparticle excitations , the collective excitations can behave very differently from landau s theory . _ introduction . _ in recent years , a large number of experiments conducted on different metals , for instance , underdoped cuprate superconductors and heavy fermion materials , have observed behaviour in terms of transport and thermodynamic properties @xcite that could not be explained by conventional landau theory of fermi liquids . these non - fermi " liquids present a challenge for theorists , and so far , there is no accepted theory , although several models have been proposed ( see e.g. ref . @xcite ) . for instance , if one couples an ordinary fermi liquid to a gapless system , which could be a gauge theory or a system near a critical point , the long - range critical fluctuations turn the ground state into a non - fermi liquid @xcite , although the system can not be studied in any controlled approximation . in fermi liquids , the gapless excitations around the fermi surface have the same quantum numbers as the free fermion . the effective theory describing them can be understood as a fixed point of a wilsonian rg . in non - fermi liquids there is a fermi surface but the gapless excitations are not adiabatically connected to the free fermion states . the low - energy dynamics can not be readily understood as a fixed point of wilsonian rg , since the nontrivial scaling exponents of the fermi surface are naturally explained only by a nonlocal effective theory ( see a recent discussion in @xcite ) . in such a situation , one can gain insights from solvable models . holographic duality is the only nonperturbative tool available for strongly interacting fermions at finite density , though the class of field theories for which this works is indeed unrealistic . the duality maps states of a strongly coupled field theory in @xmath0 dimensions to solutions of a weakly coupled gravity or string theory in @xmath1 dimensions @xcite . in particular , a finite density state at zero temperature maps to an extremal black hole . the duality makes generic predictions on the features of systems at a quantum critical point ( e.g. , quantum dissipation or charge fractionalization @xcite ) that can be matched to those observed in real materials or in field - theoretic models @xcite . in particular , the phenomenological form of the quasiparticle spectral function near the fermi surface , with nontrivial scaling exponents , has been reproduced using the fermionic response of a dual extremal black hole @xcite . this discovery was certainly quite exciting : one can obtain continuous families of solvable models for non - fermi liquids whose properties can be easily investigated . at special points in the parameter space , one obtains features resembling those of a marginal fermi liquid . in these holographic models , the low - energy form of the spectral function , and thus the scaling exponents , are completely fixed by the near - horizon geometry of the black hole . this near - horizon geometry has a scaling symmetry and represents an emergent infrared cft , which could belong to an universality class that includes realistic materials , even though the underlying microscopic holographic theory was unrealistic . building on previous suggestions @xcite faulkner and polchinski @xcite have proposed a minimalistic framework to describe all possible such emergent infrared cfts and the related non - fermi liquid state in a setup that is semiholographic . only the infrared degrees of freedom are holographically represented by the near - horizon region of the classical geometry , while the ultraviolet degrees of freedom are represented by the weakly coupled fermionic field @xmath2 living at the boundary of the space and their dynamics is described perturbatively . furthermore @xmath2 couples linearly to the composite operator @xmath3 with the same quantum numbers in the holographic cft whose dynamics is captured by @xmath4 which is the on - shell gravitational action of the near - horizon geometry . the action describing the model is : @xmath5 \nonumber \\ & + & s_{\textrm{hol } } \ , . \end{aligned}\ ] ] this model captures the infrared physics of the fully holographic constructions and at the same time allows for many extensions ; for instance , the interior geometry can be taken to be @xmath6 , @xmath7 , a geometry with lifshitz scaling and/or violating hyperscaling , depending on the different types of infrared cfts . in each case , the model describes an ir fixed point that is expected to encode the universal properties of a large class of interacting fermion systems . one could also introduce a lattice through a @xmath8 dependence in @xmath9 or take into account other realistic complications . we notice also that the mixing of the electron " @xmath2 with the fermion operator of the cft is reminiscent of the phenomenon of _ fractionalization _ that plays a role in the description of strange metals . in the present letter , we want to extend this phenomenological framework beyond the simple deconstruction of the holographic setup . for this purpose we need to consider higher - order interaction terms . they will be generically present if the model is considered as an effective theory derived by integrating out high - energy modes . moreover they are needed to account for collective modes of fermions , such as zero sound , and for the electrons to give nontrivial contributions to the thermodynamic and transport properties , even though only at subleading order for large @xmath10 . an important caveat in the models we consider is that the degrees of freedom of the boundary fermions are parametrically fewer than those of the soft modes that admit a holographic description . without this assumption , one would have to take into account the backreaction of the fermions @xcite , which would completely change the ir fixed point . we will generalize the standard landau - silin theory of normal fl in our models allowing us to obtain phenomenological predictions for collective modes and transport properties in terms of analogues of landau parameters . the latter are defined microscopically in terms of quasiparticle scattering at the fermi surface . we will then explicitly solve for the zero sound mode dispersion relation and the plasma frequency . we end with a discussion and point out future directions of investigation . _ the model . _ we consider the following action that describes the most general semiholographic model , including the possibly relevant or marginal perturbations that can be constructed from the boundary fermions and the cft operators ( see the supplementary material for a discussion of the rg in fermi liquids and in this model ) : @xmath11 + n^2 s_{\textrm{bulk } } \ , . \nonumber\end{aligned}\ ] ] in comparison to eq . ( [ modeltrunc ] ) we consider both bosonic and fermionic cft operators ( @xmath12 and @xmath3 respectively ) that can couple to @xmath2 by cubic or quartic interactions . we allow also for self - interactions of @xmath2 and for convenience we separate , in the quartic self - coupling , the long - range interactions ( e.g. coulomb ) in @xmath13 from the short - ranged ones in @xmath14 that are assumed to be a nonsingular functions of the momenta . we have also included a parameter @xmath10 that allows us to have a parametric control of the diagrammatic expansion . we stress that it is not related to the central charge of the bulk cft , which is typically a @xmath15 gauge theory with @xmath16 . we adopt an @xmath10 counting that realizes the following features : ( i ) the corrections to the @xmath2 propagator due to the bilinear coupling with @xmath3 are @xmath17 , so that at leading order we reproduce the non - fermi liquid form of the propagator of ref . @xcite , ( ii ) loops of the boundary fermion are not suppressed , as indeed we are interested in their full dynamics , ( iii ) loops in the bulk are suppressed , and ( iv ) a connected @xmath18point bulk tree diagram attached to boundary @xmath2-fermion lines is of order @xmath19 , thus leaving only bulk propagators unsuppressed while vertices in the bulk are suppressed . these make the model tractable . after resumming the geometric series for the propagator , we find that only the @xmath20 propagator has a fermi - surface singularity , with a form depending on the ir geometry and on the scaling dimension of @xmath3 , @xmath21 . in the case of a lifshitz geometry , or @xmath22 with @xmath23 , it has the form of a normal fl . in the case of @xmath24 , one obtains : @xmath25 in the last equation , @xmath26 is a real parameter whereas @xmath27 is , in general , complex . we must verify that the perturbative corrections do not destabilize the ir fixed point . we consider the one - loop corrections to the self - energy in the supplementary material . they turn out to be subleading for small @xmath28 , except in the cases of @xmath29 and @xmath30 . we leave the analysis of these cases to future work . _ generalized landau - silin equations . _ we follow the treatment presented in ref . @xcite , mostly sketching the logic of the derivation and leaving the details for the supplementary material . we want to calculate the response of the system to an external perturbation , e.g. an electric field which couples to a fermion bilinear . the coupling is obtained by a term in the lagrangian @xmath31 where @xmath32 is a @xmath33 current of the cft theory . the observable quantities are also fermion bilinears , so the problem reduces to the computation of a four - point function . we use the notation @xmath34 . the coupling to an external electric field can be read from eq . ( [ electric ] ) and is @xmath35 , with @xmath36 being the matrix - valued number density operato , r and @xmath37 with @xmath38 the electric potential . notice that we extended the @xmath10 counting to the coupling with the external field . we might also consider more generally a nondiagonal matrix of external perturbations @xmath39 in which case the @xmath10-counting should be @xmath40 , @xmath41 in order to be consistent with large @xmath10 perturbation theory . in general , the @xmath33 current could have other contributions of the form @xmath42 with @xmath43 some other charged operator in the cft . to simplify the analysis , we will assume that these operators are less relevant , meaning that the corresponding bulk fields are more massive than @xmath3 and @xmath12 . the response to an external field is shown diagrammatically in fig . [ integral1 ] . the figure represents the resummation of all the diagrams ; the lines are the exact two - point functions , and the shaded box is the exact four - point function . the first term is determined just by the two - point functions , and the second term contains the contribution of the four - point function that can be interpreted as a renormalization of the external field . we are interested in the regime when the external field varies slowly in space and time , i.e. @xmath44 ( see fig . [ integral1 ] . in this regime we need to understand the infrared singularities that come both from the two - point and the four - point function @xmath45 . for this purpose , it is convenient to start by considering the sum of the two - particle irreducible diagrams contributing to the four - point function ; we call it @xmath46 . in the case of long - range interactions , one can also isolate further the proper part @xmath47 given by diagrams that can not be cut by removing a single bosonic line of interaction ; then we have @xmath48 where @xmath49 . @xmath50 denotes the full long - range interaction coming from the direct coulomb interaction of @xmath2 and from the exchange of bulk bosonic fields . the relation between the full four - point function @xmath45 and @xmath47 is given by the functional ( bethe - salpeter ) equation represented graphically in fig . [ integral2 ] . and circles @xmath51,scaledwidth=80.0% ] the basic observation is that the infrared singularity for @xmath44 arises from diagrams in which two @xmath20 propagators can go on shell while having momenta on the fermi surface and thus can become singular simultaneously . as one can see , the singularity appears in both terms of fig . ( [ integral1 ] ) . moreover , this implies that the proper part @xmath47 is nonsingular ; therefore the bethe - salpeter equation relates the complete four - point function to its non - singular part . we write the product of two two - point functions as @xmath52 where we isolate @xmath53 which is the singular contribution when @xmath54 ( the orders of limits do not commute as in the fermi liquid case ) . it depends only on the form of @xmath55 near the fermi surface . since there is no such infrared fermi - surface singularity for the @xmath56 and @xmath57 propagators , the singular part has only the @xmath58 component . in the supplementary material we give details for determining the function @xmath59 . considering the singular contribution in the infrared limit of the equations represented by figs . [ integral1 ] and [ integral2 ] , we obtain the generalized landau - silin equations in @xmath60 : @xmath61q^{\chi\chi\chi\chi}(k ' , q)e^{\chi\chi}_{\mathbf{k'_*}}(q),\end{aligned}\ ] ] where @xmath62 , and @xmath63 and @xmath64 are the points on the fermi surface nearest to @xmath8 and @xmath65 , respectively . from these equations , we see that @xmath66 can be interpreted as the response function to a renormalized external field @xmath67 . note that for a generic perturbation , both @xmath2 and @xmath3 bilinears are affected in the low - energy response . the function on the fermi surface @xmath68 gives the generalized landau parameters and is related to the 4-point function as @xmath69 the order of limits ( @xmath70 goes to zero first ) is important above . in fact , @xmath68 can be defined in terms of @xmath47 , as shown in the supplementary material . assuming rotational invariance , @xmath68 depends only on the angle between @xmath71 and @xmath72 . using a multipole expansion , we have an infinite number of parameters @xmath73 ; in practice , one usually assumes that only the first few multipoles are significant . for microscopic definition of the parameters @xmath74 and @xmath75 , we refer the reader to the supplemental material . we can derive all the low - energy phenomenology from eqs . ( [ landausilin ] ) . in particular , the collective excitations are given by solutions not sourced by an external field , so with @xmath76 . the main difference from the normal fl case is in the structure of the singular function @xmath59 . in the case of @xmath77 there is a genuinely non - fermi liquid . the function @xmath59 in this case is given by @xmath78 notice the @xmath79 function ( instead of a delta function on the fermi surface as in the landau fl ) and the nontrivial dependence on @xmath80 both in the numerator and denominator . we can then derive the phenomenological consequences of these formulas . in the case of a neutral liquid , @xmath81 . then the equation for the zero sound has a solution if the integral operator schematically given by @xmath82 has an eigenvalue equal to 1 . this can happen , for a given @xmath70 , only for certain values of @xmath83 ; each such value corresponds to a collective mode . assuming for simplicity that @xmath68 has only a monopole part @xmath84 , we find a solution for the zero sound with a dispersion relation @xmath85 with velocity @xmath86 determined by the equation @xmath87 for @xmath60 non - fermi liquids . notice that only filled states below the fermi surface contribute to the integral ; therefore , there is a natural cutoff @xmath88 . the solution is in general complex , so we predict that the zero mode will be present as a peak in the response function but it will be rather damped ; moreover its dependence on the cutoff shows that it is not a collective excitation only of modes close to the fermi surface . some universal feature can be obtained in the limit of large @xmath84 : the equation shows that @xmath89 , up to real cutoff - dependent prefactors . the ratio of the velocity and attenuation is then independent of the cutoff in this limit , and the width of the zero sound , to the extent that it can be defined , is related to the lifetime of the quasiparticles . in the charged liquid , with a coulomb interaction @xmath90 , as usual , the zero sound becomes gapped and there is a plasma frequency . the latter can be obtained by replacing @xmath86 in eq . ( [ zerosound ] ) by @xmath91 and @xmath84 by the coulomb potential , while expanding in @xmath92 . the plasma frequency @xmath93 is then found to be : @xmath94 in @xmath60 non - fermi liquids . we note that this is generically complex with the ratio of the real to imaginary parts again independent of the cutoff . the nonvanishing imaginary part of the plasma frequency denotes that the medium does not act as a sharp filter for the lower frequencies . it would be interesting to explore further the optical properties of our systems by computing the dielectric constant and the refractive index , along the lines of ref . @xcite . in the other cases of @xmath95 and @xmath6/lifshitz , the structure of the singular function is similar to that of a fermi liquid . however , in the charged case , the collective mode will be radically different if the bulk @xmath96 exchange gives a force which goes like @xmath97 , with @xmath98 . the plasma frequency will then behave like @xmath99 for small @xmath100 , which means that even high frequency modes will be damped unlike in charged fermi liquid . even though we can not trust the analysis for large @xmath83 , this indicates a different behavior than the fermi liquid . _ discussion _ we have shown the differences from the predictions of landau theory that arise in the semiholographic fermion models at the level of collective excitations . it would be interesting to see whether the large separation of the zero sound pole from the continuum of two - particle excitations , that is a feature of landau fermi liquid theory for large values of @xmath84 , is generically true in the class of models we consider . more generally the response of the system to external perturbations needs to be understood in more detail . there are a number of directions in which our work can be extended using similar techniques . we plan to compute the thermodynamics and transport properties of the system , as well as studying the system at finite temperature , and the onset of the superconducting instability generalizing bcs theory ( see e.g. ref . @xcite ) . we should also study the interplay between the collective excitations and quantum kinetics of semiholographic fermions with the hydrodynamic and relaxational modes of the cft degrees of freedom . this can be pursued using methods developed for computing holographic nonequilibrium spectral and statistical functions @xcite . for another line of development , it is possible to add chern - simons - like term for gauge fields in the bulk . these naturally reproduce global anomalies for the holographically dual cft . this gives us a concrete method of introducing chiral anomalies in this class of models . finally , it should be possible to apply our approach to the more general class of hyperscaling violating bulk geometries @xcite . these infrared geometries can be characterized by the dynamical critical exponent @xmath101 and hyperscaling violating exponent @xmath102 . _ acknowledgements . _ the research of am is supported by the labex p2io , the anr contract no . 05-blan - nt09 - 573739 , the erc advanced grant no . 226371 and the itn programme no . pitn - ga-2009 - 237920 . we thank t. faulkner , a. garcia - garcia , j. hartong , s. hartnoll , s. s. lee , r. leigh , k. schalm and j. zaanen for useful discussions . 99 g. r. stewart , rev . mod . phys . * 73 * , 797 ( 2001 ) ; 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IONIA, Mich. (WOOD) — Authorities in several states spent about 24 hours searching for a man convicted of four 1993 murders who escaped from the Ionia Correctional Facility Sunday night. Michael David Elliot was arrested Monday evening in LaPorte County, Ind. The manhunt for Elliot, 40, began Sunday night after he escaped from the Ionia Correctional Facility, located at 1576 W. Bluewater Highway, west of Ionia, around 7 p.m., Michigan Department of Corrections Director Dan Heyns said during a news conference Monday morning. Elliot apparently escaped through the sally port, a usually secured garage where prisoners are driven in and dropped off. “It appears that he created a hole at the bottom of the two perimeter fences of the correctional facility and then crawled through those holes,” Michigan Department of Corrections spokesman Russ Marlan said. Inside woodtv.com: MDOC director demands ‘thorough’ escape investigation A person who used to work in the prison said prisoner checks are performed at 9:15 p.m., and that the check before that is at 1 p.m. Officials noticed he was missing around 9:30 p.m. The former prison employee said Elliot would have had to get past razor wire fences and sensors that set off alarms. MDOC officials said the sirens at the prison sounded, but some nearby residents told 24 Hour News 8 they did not hear the sirens. “I will be demanding a very thorough investigation. It’s obvious that there were some flaws in our security, and that we need to ask what those are. We’ve already made a number of corrections just over the evening hours,” said Heyns. Authorities said it appears Elliot worked alone to escape. MDOC officers, along with Michigan State Police and other agencies, searched for Elliot in the Ionia area. Heyns said Elliot was dressed in a white uniform usually reserved for prisoners working in the kitchen, which might have helped Elliot blend in with the snow and evade security. Heyns says Elliot wasn’t a kitchen worker, however, and it is unknown how he got the uniform. Elliot then allegedly carjacked and abducted a woman, who he did not know, in the 600 block of W. Main Street in Ionia using either a knife or box cutter, authorities said. Michigan State Police told 24 Hour News 8 the woman was leaving a residence after work and Elliot approached her with that box cutter and told her that he had an emergency. Elliot got in the back seat of the woman’s Jeep Liberty and told her that he wanted to get as far away from Michigan as possible. The woman drove for more than two hours to Elkhart County, Ind., where they stopped for gas at the Marathon station at 50980 IN-13 near I-80 in Middlebury, not far from the Michigan-Indiana state line. Elliot filled up the vehicle’s gas tank with $11 worth of fuel in cash and change — all that the woman had in her possession. Elliot and the woman then went into the gas station. She asked the clerk for the business’ address, and then locked herself in the women’s bathroom. Elliot bought some water and medicine, and waited for the woman to exit the restroom. When she didn’t immediately return, Elliot left the scene in the woman’s vehicle. Inside woodtv.com: Son ‘proud’ of Elliot’s carjack victim for staying calm The woman called 911 using her cellphone that was concealed in one of her pockets. Officers made contact with her at 11:50 p.m. Sunday. The woman, in her 50s, was not hurt. She told dispatchers that Elliot also had a hammer with him, in addition to the box cutter. The employee said at first he thought Elliot and the woman were related (a son-mother pair). Elliot was seen on the gas station’s surveillance camera wearing black, fatigue pants, a white shirt, dark-colored hooded sweatshirt, and white tennis shoes. He fled in the woman’s red 2004 Jeep Liberty, according to Michigan State Police. Police thought Elliot had enough fuel to get about 100 miles. He was believed to be alone and armed. A Jeep Liberty that police said he carjacked from Ionia Sunday night was located Monday afternoon abandoned in a parking lot in Shipshewana, Ind., according to the LaGrange County Sheriff’s Department. Westview Schools, located nearby south of US-20, was on lockdown for a time. Police were telling people to avoid the area. A report Monday morning from WSMV said a gas station employee in Pleasant View, Tenn. opened the business and called police after she thought she saw Elliot. But police later told 24 Hour News 8 that this report was false. Authorities had asked Ionia residents to stay inside their homes, and close all doors and windows, the Ionia Department of Public Safety said in a post on its Facebook page around 10 p.m. Sunday. That warning was later canceled Monday morning when authorities learned Elliot was no longer in the area. MDOC said that all other prison inmates had been accounted for following an emergency check. Ionia DPS said that Ionia Public Schools officials were made aware of the situation. After learning that Elliot was likely in Indiana, they decided classes would be held Monday. Elliot is being held on four life sentences after being convicted on four counts of first-degree murder and one count of armed robbery, according to MDOC records. Elliot was also convicted of setting a house on fire and sentenced to 13 years on that charge; and using a possession of firearm during the commission of a felony and was sentenced to two years in prison for that charge. In the early morning of Aug. 8, 1993, according to court documents, Elliot broke into a home in Bentley Township, north of Midland, killed four people then set the house on fire. Vickie Currie, her boyfriend Michael Tufnell, his cousin Bruce Squires Tufnell Jr. and fiancee Cathy Lave were killed. Charles and Paul Treece, and Tammy LaCross were with Elliot when the murders were committed. Charles Treece was also convicted of four counts of first-degree murder, armed robbery and setting a house on fire, and possession of a firearm during the commission of a firearm. He is also serving life in prison at the Alger Correctional Facility in Munising in the Upper Peninsula. LaCross and Paul Treece were apparently sleeping when the victims were killed. LaCross, who was 16 at the time and is victim Vickie Currie’s daughter, and Paul Treece both testified against Elliot and provided stories described as similar. Under the terms of plea agreements, they both pleaded guilty to robbery and felony firearm charges. LaCross testified that Charles Treece said he shot Currie in the arm, and that Elliot had shot Tufnell and Lane in the face. In 2005, Elliot filed a motion for release, saying that there was new evidence in his case — namely a 1994 letter from Charles Treece that attested to Elliot’s innocence. Elliot said he had previously been unaware of that letter, but that Charles Treece still said Elliot was innocent, according to court documents. A state court denied his request. Elliot maintains he is innocent, according to the court documents. The Ionia Correctional Facility has both Level II and Level V (maximum security) housing, according to MDOC. Elliot is a Level II inmate, despite his multiple murder conviction, and had no history of becoming an escape risk. Ionia DPS briefly said that two people had escaped, but then revised that to say only Elliot had escaped. —– Online: Free Michael Elliot website Share this: Email Print Facebook Twitter Google Pinterest More LinkedIn Tumblr Reddit ||||| Story highlights Michael David Elliot was captured in LaPorte County, Indiana Woman says Elliot told her he was an escaped convict "He just wants to get someplace far," she tells dispatchers Elliot, 40, was serving five life sentences for four murders Escaped Michigan convict Michael David Elliot was captured Monday in LaPorte County, Indiana, authorities said. His capture ended a manhunt that kicked into overdrive after a woman abducted by Elliot managed to call 911. Locked in a gas station bathroom, she whispers into her cell phone, as he banged on the door. "He didn't say where, exactly, he just said somewhere far," she says in the 911 call, telling the dispatcher about the escaped convict she says had abducted her some two hours before with a box cutter and a hammer. She slipped away from him when they stopped for gas. "He's knocking on the bathroom door saying, 'Let's go!' " the 911 dispatcher says to other emergency workers in recordings released by authorities. JUST WATCHED Man convicted of 4 murders escapes Replay More Videos ... MUST WATCH Man convicted of 4 murders escapes 01:21 JUST WATCHED Cops find escaped inmates hijacked car Replay More Videos ... MUST WATCH Cops find escaped inmates hijacked car 02:15 The Sunday night call from an Elkhart, Indiana, gas station had been the first sign of Elliot, a convicted murderer, since his escape hours before from Ionia Correctional Facility in central Michigan. On Monday, a homeowner in LaGrange County, Indiana, found the woman's Jeep Liberty in a residential area of the town of Shipshewana, about 20 miles east of Elkhart, sheriff's spokesman Arron Knisley said. Elliot himself remained missing then, however. Details on how he was caught were not immediately available. CNN first learned about his capture on Twitter. Prison authorities discovered Elliot gone about 9:30 p.m. Sunday. He apparently pulled back the bottoms of two fences and crawled underneath to escape, Michigan Department of Corrections spokesman Russell L. Marlan said. He was serving five life sentences on a 1994 conviction for killing four people, according to Michigan Department of Corrections records. Authorities warned the public not to mess with him. The kidnapped woman, whose name has not been released by authorities, told a 911 dispatcher from her bathroom stronghold that Elliot forced his way into her red Jeep Liberty as she sat parked on West Main Street in Ionia. He was an escaped convict, he told her. Murder, she said. And he had a box cutter and a hammer. But, she said, he hadn't hurt her. "He just wants to get someplace far from Ionia," she told the dispatcher. Unfortunately for police, by the time they arrived at the Marathon gas station, Elliot had fled in the woman's Jeep. He was seen getting on Interstate 80/90, but authorities don't know which direction he was traveling or where he was heading. The interstate connects Elkhart with Chicago to the west and Toledo, Ohio, to the east. Elliot was known as a good prisoner, according to Corrections Director Daniel Heyens. "Nothing in this man's history would have indicated a high risk of escape," Heyens said. "He was serving his time." Prison authorities believe he acted alone, Heyens said. According to court documents, Elliot was convicted in the August 1993 murders of Vickie Currie; her boyfriend, Michael Tufnell; his brother Bruce Tufnell; and Kathy Lane, CNN affiliate WXMI reported. Elliot and three others hatched a plan to steal drug money, WXMI said, and after they didn't find the money, Elliot and another man killed the four victims and set Michael Tufnell's house on fire. ||||| IONIA COUNTY, Mich. — The Ionia Department of Public Safety announced Sunday that an inmate had escaped from the Ionia Correctional Facility. Michael David Elliot, 40, is being tracked within Ionia County by state and local police with K-9 units and a chopper. Elliot was serving a life sentence for multiple first-degree murder convictions from 1994. Sources tell FOX 17 that they discovered a hole in a fence on the grounds of the facility at about 9:30 p.m., and believe that is how Elliot escaped. Ionia Public Safety initially posted that two inmates had escaped the jail, but later revised that statement and said that only Elliot had escaped. Elliot is 5 feet 8 inches tall and 165 lbs with brown hair and brown eyes. According to public safety officials, if he is not apprehended Ionia County Pubic Schools will make a decision about whether or not to hold school Monday at approximately 5 a.m. Anyone with information on Elliot’s whereabouts should contact Ionia Public Safety at 616-527-4431 or Silent Observer at 616-527-0107. According to court documents Michael Elliot was convicted in the August 1993 murders of four people in Gladwin County: Vickie Currie and her boyfriend Michael Tufnell, along with his brother Bruce Tufnell and Kathy Lane. Elliot and two brothers, Chuck and Paul Treece plus Tammy LaCross (who was 16 at the time, and the daughter of victim Vickie Currie) hatched a plan to steal drug money that Tufnell allegedly kept at a storage facility They didn’t find the alleged drug money at the facility, so they stole guns and ammo from another storage unit, then went to Tufnell’s house to look for a safe, according to court documents. Elliot and Chuck Treece went into the house, killed the four victims, then set the house on fire.

– A murderer serving five life sentences escaped from a Michigan prison yesterday and apparently abducted a woman, who managed to escape. Michael David Elliot, 40, who was convicted of murdering four people in a botched attempt to steal drug money in 1993, is still at large, CNN reports. Ionia Correctional Facility officials discovered Elliot missing last night; authorities believe he used a box cutter or a knife to carjack and abduct the "older" woman, WOOD-TV reports. The woman locked herself in a bathroom when they stopped for gas just over the Michigan-Indiana state line roughly two hours later; when she didn't emerge, Elliot left in her red Jeep Liberty and she was able to call police. He had purchased about $10 of gas using coins and a $2 bill, and police estimate he can make it only about 100 miles on that fuel. Sources tell Fox 17 that officials found a hole in a fence on the prison grounds, and think that's how Elliot got out.

superstring theory provides an exciting superinflationary model @xcite based on a dilaton field interaction with gravity which is free from the common fine tuning of inflationary models because the potential term does not play a crucial role . the superinflationary cosmological solutions come in duality related pairs , or branches ; the first one describes a superinflationary expansion and the second branch has a decelerated expansion . the two phases are separated by a singularity . the graceful exit problem of superinflation @xcite consists in obtaining a smooth transition from the two duality solutions . it is usually assumed that this transition can only be possible if strong curvature effects are present ( see ref . @xcite for discussion on this point , and other possibilities ) . the application of the quantum cosmology approach @xcite to the graceful exit problem seems to be a natural choice as long as the strong curvature regime often provides conditions for quantum cosmological effects @xcite . one of the main features of quantum cosmology is the possible avoidance of classical singularities due to quantum effects . in order to extract predictions from the wave function of the universe , the bohm - de broglie ontological interpretation of quantum mechanics @xcite has been proposed @xcite , since it avoids many conceptual difficulties that follow from the application of the standard copenhagen interpretation to a unique system that contains everything . in opposition to the latter one , the ontological interpretation does not need a classical domain outside the quantized system to generate the physical facts out of potentialities ( the facts are there _ ab initio _ ) , and hence it can be applied to the universe as a whole . this interpretation admits the concept of trajectories , called bohmian trajectories , which in the case of cosmology are entire histories of the universe . these histories satisfy a modified hamilton - jacobi equation , different from the classical one due to the presence of a quantum potential term . hence , the bohmian trajectories become different from the classical ones when quantum effects become important . recent investigations @xcite have used this approach to investigate issues of string cosmology , among them , the superinflationary behaviour and the possibility of solving the graceful exit problem . in the present paper we will be restricted to the simple case of no dilaton field potential term and friedmann - lematre - robertson - walker ( flrw ) geometries with flat spatial sections . the bohmian trajectories obtained from solutions of the wheeler - dewitt ( wdw ) equation in jordan s frame can be calculated through suitable conformal transformations @xcite from the bohmian trajectories in einstein s frame , which were obtained in ref . @xcite from gaussian superpositions of negative and positive mode solutions of the related wdw equation . the resulting trajectories present a smooth transition from the classical inflationary pre - big bang epoch to the usual classical pos - big - bang decelerated phase . a graceful exit is created through quantum effects which are relevant only at the transition . in section [ secclassical ] we show the duality classical solutions for superinflation in jordan s frame . section [ secquantum ] uses the bohmian trajectories obtained in ref . @xcite in einstein s frame to obtain the related trajectories in jordan s frame . the graceful exit transition from the superinflation pre - big bang epoch to the usual decelerated expansion phase is exhibited . the conclusions are presented in section [ secconclusion ] . the so called superinflation is a superstring cosmology duality - pair solution in the low energy effective field theory context . the relevant terms can be shown in the following lagrangian in the jordan frame ( with non - minimal coupling between gravity and the free scalar field ) : @xmath0 this lagrangian appears in effective string theory without the kalb - ramond field when @xmath1 , the usual dilaton field potential @xmath2 not being considered in this paper . through a conformal transformation @xmath3 , we can obtain the lagrangian in the einstein frame ( with minimal coupling ) @xmath4 where @xmath5 . to compare with the classical trajectories obtained in ref . @xcite , just the @xmath1 case will be studied here , so @xmath6 . the robertson - walker metric with vanishing spatial curvature @xmath7 will be used in the jordan frame . the consequence of applying the conformal transformation on the metric ( [ nense ] ) must be taken into account when we compare the results in the jordan and einstein frames ( see ref . @xcite ) . then , the lapse function @xmath8 and the scale factor @xmath9 are modified , @xmath10 yielding @xmath11 and @xmath12 . working in the gauge @xmath13 and restricting the scalar field to be time dependent , @xmath14 , the solutions of the equations of motion of the lagrangian ( [ lagjordan ] ) in the jordan frame are given in ref . @xcite , and can be organized in two branches of solutions for @xmath15 as functions of time . the @xmath16 branch , valid when @xmath17 , reads @xmath18 and describes accelerated expansion in the case @xmath19 , i.e. , inflationary evolution . for @xmath20 , the @xmath21 branch solution seems to be almost the same , @xmath22 but now describes decelerated expansion in the case @xmath23 , which can be connected smoothly to a friedmann - robertson - walker ( frw ) decelerated expansion . the transition from an inflationary expanding universe to a frw expanding one , or graceful exit from inflation , will be obtained here by means of quantum bohmian trajectories . these trajectories are better described using the coordinate @xmath24 , so that the @xmath16 branch ( [ hplus])([phiplus ] ) in the @xmath25 case , gives @xmath26 while the @xmath21 branch ( [ hminus])([phiminus ] ) , also in the @xmath25 case , yields @xmath27 hence , the classical trajectories in the plane @xmath28 are straight lines with different slopes depending on the type of branch , and both have singularities for @xmath29 . @xcite , the dirac quantization approach was applied to the theory in the einstein frame ( [ lageinstein ] ) , giving the wheeler - dewitt equation in minisuperspace whose quantum solutions were obtained . gaussian superpositions of these solutions given by @xmath30 { \rm d}k , \ ] ] with @xmath31 , \ ] ] and @xmath32 arbitrary constants , were interpreted using the bohm - de broglie ontological interpretation of quantum mechanics @xcite , and the resulting system of planar equations for the case of vanishing spatial curvature was : @xmath33}{\exp ( 3\bar{\alpha})\biggl\{2[\cos ( 2d\bar{\alpha})+\cosh ( \sigma ^{2}\bar{\alpha}\bar{\phi})]\biggr\ } } , \label{dalphatildedteinstein } \\ \frac{{\rm d}\bar{\phi}}{{\rm d}t } & = & \frac{\bar{n}\biggl[-\bar{\alpha}% \sigma ^{2}\sin ( 2d\bar{\alpha})+2d\cos ( 2d\bar{\alpha})+2d\cosh ( \sigma ^{2}\bar{\alpha}\bar{\phi})\biggr]}{\exp ( 3\bar{\alpha})\biggl\{2[\cos ( 2d\bar{\alpha})+\cosh ( \sigma ^{2}\bar{\alpha}\bar{\phi})]\biggr\ } } , \label{dphitildedteinstein}\end{aligned}\ ] ] where @xmath34 , and we have relabeled @xmath35 . the solutions of the above equations yield the bohmian trajectories . among others , there are bouncing regular solutions which contract classically from infinity until a minimum size , where quantum effects become important acting as repulsive forces avoiding the singularity , expanding afterwards to an infinite size , approaching the classical expansion as long as the scale factor increases . for details , see ref . @xcite are the variables @xmath36 of ref . @xcite , renamed to avoid misunderstanding . ] . with the lapse function @xmath37 we can obtain the dependence on @xmath38 for @xmath39 and @xmath40 . to obtain the bohmian trajectories in jordan s frame we only have to make the following substitutions in eqs . ( [ dalphatildedteinstein])([dphitildedteinstein ] ) : @xmath41 and @xmath42 ( see eq . ( [ flu ] ) ) . finally , as we use @xmath13 , we have @xmath43 . the planar system in the variables @xmath44 then reads @xmath45 + 6d\cosh \biggl[\frac{\sigma ^{2}(2\alpha -\phi ) \phi } { 4\sqrt{3}}% \biggr]-\sigma ^{2}(3\alpha -2\phi ) \sin [ d(2\alpha -\phi ) ] \biggr\}+6d\sinh % \biggl[\frac{\sigma ^{2}(2\alpha -\phi ) \phi } { 4\sqrt{3}}\biggr]}{6\exp ( 3\alpha -\phi ) \biggl\{\cos [ d(2\alpha -\phi ) ] + \cosh \biggl[\frac{\sigma ^{2}(2\alpha -\phi ) \phi } { 4\sqrt{3}}\biggr]\biggr\ } } , \label{dalphadtjordan } \\ \frac{{\rm d}\phi } { { \rm d}t } & = & \frac{\sqrt{3}\biggl\{4d\cos [ d(2\alpha -\phi ) ] + 4d\cosh \biggl[\frac{\sigma ^{2}(2\alpha -\phi ) \phi } { 4\sqrt{3}}% \biggr]-\sigma ^{2}(2\alpha -\phi ) \sin [ d(2\alpha -\phi ) ] \biggr\}}{2\exp ( 3\alpha -\phi ) \biggl\{\cos [ d(2\alpha -\phi ) ] + \cosh \biggl[\frac{\sigma ^{2}(2\alpha -\phi ) \phi } { 4\sqrt{3}}\biggr]\biggr\ } } . \label{dphidtjordan}\end{aligned}\ ] ] a field plot of this planar system is shown in figure [ figphialpha ] , for @xmath46 . depending on the initial conditions , there are three types of behaviour for the bohmian trajectories . there are small oscillating universes without singularities near the center points placed in the @xmath47 axis . when @xmath48 , eqs . ( [ dalphadtjordan])([dphidtjordan ] ) approach the classical equations of motion yielding the straight lines which appear in figure [ figphialpha ] , representing the classical solutions ( [ phiplus2])([phiminus2 ] ) . note , however , that in the region of small values of @xmath49 there are smooth transitions between these two straight lines which are not present in the classical solutions . one possible type of transition is exactly the graceful exit , from the @xmath16 branch with inflationary expansion to the @xmath21 branch solution with decelerated expansion . another possible type of transition is the opposite of the graceful exit , from the @xmath21 branch with decelerated expansion to the @xmath16 branch solution with inflationary expansion . we can choose one bohmian trajectory to see the evolution with respect to time @xmath38 . figures [ figa ] and [ figh ] clearly show the graceful exit behaviour , i.e. , the evolution that begins with inflation and smoothly changes to the decelerated expansion without any singularity in the transition . the scale factor @xmath50 and the hubble parameter @xmath51 of the classical solutions are recovered when @xmath52 , but near @xmath29 there is no singularity . for flrw metrics with vanishing spatial curvature , the ricci scalar curvature @xmath53 reads @xmath54 = 6\left ( 2\dot{\alpha}^{2}+\ddot{\alpha}\right ) = 6\left ( 2h^{2}+\dot{h}\right ) , \label{r}\ ] ] where @xmath55 . figure [ figr ] shows the values of @xmath53 for the bohmian solution of figure [ figa ] . it can be seen that it can be large in the quantum regime but it never diverges , exhibiting a graceful exit transition . we have shown that the bohm - de broglie ontological interpretation of quantum cosmology applied to string cosmology can yield a simple answer to the graceful exit problem in superinflation . using a previous study @xcite in the einstein frame , where gaussian superpositions of the solutions of the wheeler - dewitt equation in the minisuperspace allows the determination of bohmian trajectories , we applied a conformal transformation to obtain in a straightforward way the bohmian trajectories in the jordan frame corresponding to universe histories in string cosmology . we exhibited a class of trajectories representing universe evolutions with graceful exit . they start classically from inflationary behaviour driven by kinetic terms , as it is usual in these cases . when curvature becomes relevant , quantum effects become important avoiding the singularity and creating a smooth transition to the usual classical decelerated expansion . the results of this paper should be contrasted with results obtained using other interpretations ( see , e.g. , ref . @xcite ) . in the case of the many worlds interpretation , the construction of a hilbert space is very important in order to define a probability measure . however , for scalar field minisuperspaces , the wheeler - dewitt equation has a klein - gordon structure and it is well known that it is hard to construct a unique positive definite measure with such equations . the common way out from these problems is to take semiclassical approximations . this problem is intimately connected with the problem of time @xcite . once we do not have an extrinsic time , the wheeler - dewitt equation can not be transformed into a schroedinger like equation , and hence all these problems with its hyperbolic signature appear , unless one makes use of a semiclassical approximation as it is done in ref . however , the graceful exit shall occur when quantum effects are important , where a semiclassical approximation breaks down , rendering problematic the analysis of this transition in the many worlds interpretation . in the bohm - de broglie interpretation , probability measures are not essential . we can talk about quantum trajectories , and probabilities are relevant only for settling reasonable initial conditions on such trajectories . the notion of quantum trajectories is well defined even for klein - gordon like wheeler - dewitt equations . the scale factor and scalar field follow real trajectories which satisfy modified einstein s equations ammended with a quantum potential term . the concept of spacetime is as meaningfull in the bohm - de broglie interpretation of minisuperspace quantum cosmology as it is in classical general relativity ( gr ) ( see ref . @xcite for a detailed discussion on this point , and @xcite for the different case of midisuperspace models and the full superspace ) . the only difference is that the dynamics may be changed by the presence of the quantum potential . as in classical minisuperspace gr , the dynamics is invariant under time reparametrizations , even in the presence of the quantum potential . hence , the symbol @xmath38 in the bohmian trajectories is an arbitrary parameter like in gr , which can be fixed by a choice of the lapse function , without physical modifications of the dynamics of spacetime . that is how it is possible , in this interpretation , to talk about a graceful exit transition when the curvature of spacetime increases . we have only to examine the behaviour of the bohmian trajectories in such regions . note that in the region of configuration space where a semiclassical description can be applied in the framework of the many worlds interpretation , there is accordance of results : the semiclassical wave function is peaked along the classical trajectories @xcite , which are exactly the bohmian trajectories in that region . the conclusion is that , as the bohm - de broglie interpretation has more concepts then the many worlds interpretation , the former can be used in situations where the application of the latter is problematic . our results come in this way . of course it would be desirable to define a probability measure on the bohmian trajectories coming from the wave function ( [ onda ] ) , which could be valid in all minisuperspace , as long as not all of them describe the pre - big bang model with graceful exit , although all bohmian trajectories with initial conditions imposing an initial superinflationary pre - big bang phase present a graceful exit to the decelerated regime . if this is possible , one should expect that the statistical predictions of the many worlds interpretation are identical to the statistical predictions of the bohm - de broglie interpretation . the above considerations raise doubts on the physical equivalence of these two interpretations in quantum cosmology . due to the singular features present in the quantization of the whole universe , it is possible that one of them presents more physical relevant and testable information then the other in this particular field ( which is not the case , up to now , in quantum field theory and non relativistic quantum mechanics ) . this suggests that quantum cosmology may be the arena where it could be possible to distinguish physically between these two interpretations . this is a strong motivation to push forward these two interpretations up to their limits in all possible aspects of quantum cosmology and compare their results in order to obtain a relevant physical distinction , or even some observable prediction , which could select one of them as the valid interpretation of quantum mechanics . a logical future generalization of the present work is to study dilaton field potential terms so that the decelerated expansion can be joined smoothly to an ordinary frw radiation dominated expanding universe @xcite . it is also important to check how these results depend on initial conditions on the wdw equation . we would like to thank cnpq and capes of brazil for financial support . one of us ( npn ) would like to thank the laboratoire de gravitation et cosmologie relativistes of universit pierre et marie curie where part of this work has been done , for financial aid and hospitality , and the group of `` pequeno seminrio '' in cbpf for useful discussions . i. antoniadis , j. rizs and k. tomvakis , nucl . phys . * b415 * , 497 , ( 1994 ) ; e. kritsis and c. kounnas , phys . lett * b331 * , 51 ( 1994 ) ; g. f. r. ellis , d. c. roberts , d. solomons and p. k. s. dunsby , preprint gr - qc/9912005 . ) (dphidtjordan ) for @xmath46 , which uses the bohm - de broglie interpretation with the wave function of the universe . each arrow of the vector field is shaded according to its true length , black representing short vectors and white , long ones . the four shades of gray show the regions where the vector field is pointing to northeast , northwest , southeast or southwest . the black curves are the nullcline curves that separate these regions . the trajectories are the white curves with direction arrows . the black straight lines are parallel to the classical solutions , the solid lines have accelerated expansion and the dashed lines have decelerated expansion . ] as function of @xmath38 , it is one bohmian trajectory with initial conditions @xmath56 , @xmath47 and @xmath57 using the system of planar equations ( [ dalphadtjordan])([dphidtjordan ] ) for @xmath46 . the dashed lines describe the classical solutions with accelerated and decelerated expansion which are asymptotically obtained when @xmath52 , and there is a smooth transition near @xmath29 avoiding the singularity . ] as function of @xmath38 , with initial conditions @xmath56 , @xmath47 and @xmath57 using the system of planar equations ( [ dalphadtjordan])([dphidtjordan ] ) for @xmath46 . the classical solutions of the @xmath16 and @xmath21 branches , shown in dashed lines , are asymptotically obtained when @xmath52 , and the smooth transition near @xmath29 shows well the graceful exit behaviour . ] as function of @xmath38 , with initial conditions @xmath56 , @xmath47 and @xmath57 using the system of planar equations ( [ dalphadtjordan])([dphidtjordan ] ) for @xmath46 . the classical solutions of the @xmath16 and @xmath21 branches , shown in dashed lines , are asymptotically obtained when @xmath52 , and the smooth transition near the strong curvature regime , @xmath29 , avoids the singularity of the transition from inflationary to decelerated expansion . ]

a massless scalar field without self interaction and string coupled to gravity is quantized in the framework of quantum cosmology using the bohm - de broglie interpretation . gaussian superpositions of the quantum solutions of the corresponding wheeler - dewitt equation in minisuperspace are constructed . the bohmian trajectories obtained exhibit a graceful exit from the inflationary pre - big bang epoch to the decelerated expansion phase .

over the past decade , public and private funding institutions have invested billions of dollars in the fields of human neuroimaging and genetics ( akil et al . , 2010 ) . recently , researchers have sought to use quantitative measures from brain images to test how genetic variation influences the brain . imaging measures are thought to have a simpler genetic architecture than diagnostic measures based on cognitive or clinical assessments ( gottesman and gould , 2003 ) . in other words , the penetrance of an individual genetic polymorphism is expected to be higher at the imaging level than at the diagnostic level . as such , imaging - derived traits may offer more power to detect how specific genes contribute to brain disease . genetic analysis of images has been used to discover how susceptibility genes affect brain integrity ( braskie et al . , 2011b ) . recent studies have revealed gene effects operating within an entire population , in the form of a 3d brain map ( thompson et al . , 2001 ; stein et al . optimally merging these two well - developed fields requires innovative mathematics and computational methods , guided by genomics and neuroscience . they generally test how a single genetic variant , or a small set of such variants ( usually single nucleotide polymorphisms , or snps ) are associated with a single summary measure of the brain . these studies begin to bridge the gap between the two fields , but do not take full advantage of advanced methods from either field , which can survey the entire genome or allow an image - wide search . by contrast , multivariate statistical methods such as machine learning and sparse regression can handle high dimensional datasets . many of these are being adapted to analyze a range of brain processes and biological markers of disease . in this review , we summarize the recent evolution of imaging genetics , from candidate gene studies to multilocus methods and genome - wide searches to genome - wide , image - wide searches . we explain how images are used in different ways , ranging from single region - of - interest ( roi ) methods that assess the volume or shape of a specific brain region , such as the hippocampus to voxelwise approaches that survey the whole brain at once in 3d . in these efforts , multivariate , multilocus techniques can model how several genetic variants affect the brain at once . specialized approaches such as sparse coding methods can simultaneously handle the high dimensionality and high degree of correlation observed across the genome and in image - derived maps . in studies that scan a large number of patients or controls , candidate gene studies have often been used to assess genetic effects on the brain . this approach is appealing as one can test biologically plausible hypotheses and determine how specific , well - studied genetic variations affect brain structure and function . early studies , for instance , explored how genes related to serotonin transport affected measures extracted from single - photon emission computed tomography ( spect ) and functional magnetic resonance imaging ( fmri ; heinz et al . . serotonin s role in neurotransmission and neuromodulation and the well - known anatomy of the monoamine systems made it possible to frame and confirm testable hypotheses for pertinent regions such as the raphe nuclei and amygdala ( munafo et al . candidate gene studies , such as those above , may assess a single measure derived from a specific roi in the image . this may be the whole brain , or a subregion such as the gray matter , or the volume or mean activation of a subcortical region . more recently , voxel - by - voxel searches have been conducted to assess candidate gene effects throughout the whole brain in 3d . this unbiased search across the brain makes no prior assumptions on which regions may be affected . spatial statistics , such as principal components analysis ( pca ) or ica , may also be performed for dimension reduction , and multiple comparisons corrections , such as the false discovery rate ( fdr ) method , can help to decide if a pattern of gene effects is significant across the voxels searched . 2010 ) investigated the effects of a proxy snp in the fat mass and obesity - associated ( fto ) gene reliably associated with increased risk for obesity ( rs3751812 ; frayling et al . , 2007 ) on brain structure . they used mri along with tensor - based morphometry ( tbm ) , to evaluate 206 healthy elderly subjects . fto risk allele carriers had lower frontal and occipital lobe volumes ( figure 1 ) . in such studies , maps of statistical associations are created by performing separate association tests at each imaging voxel in the brain . as the number of statistical tests is very large , a standard correction for multiple comparisons can be used , such as the fdr method ( benjamini and hochberg , 1995 ) or its more advanced variants such as topological fdr ( chumbley et al . , 2010 ) , which consider the geometry of the effects . these corrections assess how likely it is that the overall pattern of associations could be observed by chance . voxel - based analyses may also be informed by prior hypotheses : roi may be defined as search regions , such as the temporal lobes , to include prior information on the expected location or patterns of effects ( stein et al . , 2010a ) . p - values ( corrected using the false discovery rate method ; left panel ) and corresponding regression coefficients ( right ) show the statistical associations between a candidate single nucleotide polymorphism in the fto gene ( which is associated with higher risk of obesity ) and tensor - based morphometry maps derived from anatomical mri scans of the brain . clearly , if other regions had been specified in advance as the target of study , association effects may have been missed . brain imaging measures used in genetic studies should ideally be highly heritable and be genetically related to a biological process affected by genetic variation , such as a disease process ( gottesman and gould , 2003 ; glahn et al . some argue that the use of imaging endophenotypes should boost power to detect genetic variants that have reliable but small effects on disease status ( meyer - lindenberg and weinberger , 2006 ) . one neuroimaging modality that shows great promise in candidate gene studies is diffusion tensor imaging ( dti ) , which assesses the fiber integrity of the brain s white matter . dti is based on the observation that myelination restricts water diffusion , and disease processes typically increase water diffusion across cell membranes ( beaulieu , 2002 ) . some dti - derived measures , such as the fractional anisotropy ( fa ) of diffusion , fa is highly heritable ( chiang et al . , 2009 ; kochunov et al . , 2010 ) and is consistently altered in a range of developmental and psychiatric disorders ( thomason and thompson , 2011 ) . candidate polymorphisms already associated with brain disorders may be surveyed to discover associations with maps of dti parameters such as fa . one recent dti study of young healthy adults ( braskie et al . , 2011a ) , studied the voxelwise effects of the rs11136000 snp in the recently discovered alzheimer s disease ( ad ) risk gene , clu . significant associations were detected in several anatomical regions that undergo atrophy in ad ( figure 2 ) . in similar candidate gene studies using dti , other genes such as bdnf ( chiang et al . , 2011a ) and comt ( thomason et al . , 2010 ) have been found to influence white matter structure , with carriers of one variant showing consistently higher or lower fa . corrected p - values ( a ) and regression coefficients ( b ) are shown for the voxelwise effects of a candidate polymorphism in the clu gene a highly prevalent alzheimer s susceptibility gene on fractional anisotropy maps derived from dti scans of 398 young adults . the axial slice shows the extensive influence of the genetic variant on white matter structure . candidate gene studies have successfully discovered patterns of brain differences associated with genetic variants whose function is relatively well - known ( such as apoe , for example a risk gene for late - onset ad ; shaw et al . , 2007 ) . the choice of a candidate gene , however , requires a strong prior hypothesis , and most of the genetic determinants of the highly heritable imaging measures ( connectivity or cortical thickness , for example ) are unknown . in most candidate gene studies in imaging , there is a correction for multiple comparisons to control the rate of false discoveries across the image , but this does not take into account the genetic variant tested , or the fact that it could have been selected from a wide list of possibly associated genes . in genetics , and by extension imaging genetics , there is a high risk of false - positive findings unless appropriate corrections are made . moving beyond candidate gene studies to an unbiased search of the whole genome otherwise , many false - positive associations will be reported that would not be replicated in the future ( ioannidis , 2005 ) . genome - wide association ( gwa ) studies typically assess associations between hundreds of thousands of snps and a phenotype of interest ( such as a disease , or a specific image - derived measure ) . gwa studies have discovered hundreds of common risk loci for diseases and traits in recent years ( hindorff et al . , 2009 ) . gwa studies are frequently conducted for discrete , case control phenotypes , such as the diagnosis of a specific disease ( such as ad or schizophrenia vs. healthy control ) . these studies , however , are limited as participants do not always fall clearly into unique diagnostic categories , and may vary in dimensions not relevant to disease ( pearson and manolio , 2008 ) . for neuropsychiatric disorders in particular , symptoms expressed by members of specific diagnostic groups may be highly heterogeneous and there may also be substantial co - morbidity and overlap in symptom profiles across disorders ( psychiatric gwas consortium coordinating committee et al . measures derived from brain images in principle are closer to the underlying biology of gene action , offering an alternative target for genome - wide searches , by serving as intermediate phenotypes or endophenotypes for gwa studies ( gottesman and gould , 2003 ; hall and smoller , 2010 ) . ( 2009b ) identified snps in two genes ( rsrc1 and arhgap18 ) that showed associations with a blood - oxygen - level dependent ( bold ) contrast measure from a brain region implicated in schizophrenia . ( 2010a ) discovered a snp in the grin2b gene ( rs10845840 ) and an intergenic snp ( rs2456930 ) associated with an mri - derived tbm ) measure of temporal lobe volume in 740 elderly subjects from the ad neuroimaging initiative . in these and other studies , linear regressions are used to assess the additive or dominant allelic effect of each snp , after adjusting for covariates such as age and sex , and the confounding effects of population stratification ( e.g. , potkin et al . , 2009a ) . this yields p - values assessing the evidence for the association of each snp with the imaging summary chosen . the overall significance of any one snp effect is then assessed through a form of genome - wide correction for multiple comparisons . commonly , a nominal p - value less than 5 10 is used . the gwa study design has been extended to analyze whole images , but one of the shortcomings of all gwas studies is their limited power ( or alternatively , the large sample sizes needed ) to detect relevant gene variants . most snps affecting the brain have modest effect sizes ( often explaining < 1% of the variance in a quantitative phenotype ) . replication , and meta - analysis in particular , have been widely embraced as a way to aggregate evidence from multiple genetic studies , including studies of disease risk , and normally varying traits such as height ( de bakker et al . , 2008 ; mccarthy et al . , 2008 ; zeggini and ioannidis , 2009 ; yang et al . , 2010 ) . even so , most imaging gwa studies consider under a thousand subjects , so are limited in detection power . this led many researchers in the field to band together to search for relevant genetic associations with imaging traits meta - analytically , in many large samples . one promising initiative is called enhancing neuro imaging genetics through meta - analysis ( enigma ) and is currently accepting research groups who want to become involved in meta - analytic imaging genomics projects ( http://enigma.loni.ucla.edu/ ) . the enigma pilot project is a large meta - analysis to discover genes associated with hippocampal volume on brain mri in over 9,000 subjects scanned by 21 research centers ( the enigma consortium , 2011 ) . future imaging genetics studies may rely on large meta - analyses and international collaborations to overcome the low power and relatively small effect sizes . however , some genetic associations can be found and replicated without vast meta - analytic approaches like enigma . 2011 ) discovered and replicated an association between caudate volume and the snp rs163030 located in and around two genes , wdr41 and pde8b . these genes are involved in dopamine signaling and development ; a mendelian mutation in one leads to severe caudate atrophy . similarly , joyner et al . ( 2009 ) replicated an association with cortical surface area in a common variant ( rs2239464 ) of the mecp2 gene , which is linked to microencephaly and other morphological brain disorders . studying a single imaging measure with a genome - wide search is as limited as picking a single candidate gene from the entire genome it may not fully reflect how a given genetic variant influences the brain , or it may miss an important effect by being too restrictive . important links may be overlooked if a gene variant influences a brain feature present but not measured in the images . to broaden the range of measures surveyed in each image , shen et al . ( 2010 ) studied patients with ad and mild cognitive impairment ( mci ) using whole - brain voxel - based morphometry ( vbm ; good et al . , 2001 ) and split the brain into 142 cortical and subcortical rois using the segmentation software package freesurfer ( fischl et al . , 2002 ) . the vbm measure within each roi was averaged for each subject and those values were used as traits for gwa scans . one snp , rs6463843 , from the nxph1 gene , was significantly associated with gray matter density in the hippocampus , and had broad morphometric effects in a post hoc exploratory analysis . while this study found plausible results , the computation of summaries from roi may miss patterns of effects that lie only partially within the chosen roi . as such , a combination of map - based and roi - based methods seems ideal . some researchers have combined unbiased tests of association across the genome with unbiased searches of the entire brain , instead of relying on summary measures derived from roi . combining gwa scans with an image - wide search is computationally intensive , requiring new methods to handle the high dimensionality and multiple statistical comparisons . three dimensional brain images may contain over 100,000 voxels , and a completely unbiased search may test up to one million snps for association at each voxel . this is extremely computationally intensive , but can be completed in a feasible time frame if the process is parallelized . ( 2010b ) performed a full gwa scan at each voxel in maps of regional brain volume calculated by tbm ( leow et al . , sixteen billion tests of association were conducted in a so - called voxelwise genome - wide association study ( vgwas ) . to accommodate the huge number of statistical tests performed , the p - value distribution for the top snp was modeled as a beta distribution , beta(1 , n ) , where n is an estimate of the effective number of independent tests performed ( ewens and grant , 2001 ) . the resulting distribution of minimum p - values across the genome , assembled from voxels across the image , was transformed into a uniform distribution in the null case for multiple comparisons correction across the image . fdr was used to correct for multiple comparisons across the image , and to assess whether credible effects had been detected ( benjamini and hochberg , 1995 ) . several top snps were associated with moderate regional brain volume differences ; many were in genes that are expressed in the brain ( figure 3 ) . however , no snps passed the strict correction for multiple comparisons . the stein et al . study was a proof of concept , showing that a completely unbiased search of the genome is feasible with imaging phenotypes . however , the huge correction for multiple comparisons across the image and genome are practically insurmountable unless the effect size or cohort size is very large . in addition , the vgwa study required 27 h when spread across 500 cpus ; this is more computational power than most researchers typically have access to . clearly , an optimal balance must be made between pure discovery methods , unconstrained by prior hypotheses , and those that invoke prior biological information to boost power and reduce the multiple comparisons correction . the five most highly associated snps identified by vgwas are shown on slices of an averaged brain mri template , indicating regions where these snps were the most highly associated out of all snps ( in purple ) . coordinates refer to the icbm standard space , and the cohort is the adni sample . multivariate methods can be used to assess the joint effect of multiple genetic variants simultaneously , and are widely used in genetics ( phillips and belknap , 2002 ; gianola et al . , 2003 ; cantor et al . , for example , set - based permutation methods use gene annotation information and linkage disequilibrium values to group univariate p - values from traditional gwa studies into gene - based test statistics ( hoh et al . , 2001 ; set - based approaches use prior information on gene structure to incorporate all genotyped snps in a given gene into a single test statistic . this can offer , in some cases , greater power than univariate statistical tests to detect snp effects . combining univariate p - values into a single gene - based test it can also aggregate the cumulative evidence of association across a gene block to account for allelic heterogeneity ( hoh et al . , 2001 ) . individual snp p - values may not achieve the genome - wide significance level for a traditional gwa study ( nominally p < 5 10 ) , but if several snps in the same ld block show moderate association , the combined evidence for association may be enough to beat a gene - wide significance level ( nominally p < 5 10 ) . for example , one study examined snps from the sorl1 gene for association with hippocampal volume in healthy elderly controls ( bralten et al . , 2011 ) . while they did not find evidence for association of individual snps in a discovery and replication dataset , some set - based statistics may be derived from the separate p - values from the individual univariate tests , enabling post hoc analysis of published studies . a major issue in applying set - based statistics in imaging genetics is that the permutation procedure applied across snp groupings would be very computationally intensive . set - based methods are currently not feasible to apply at > 100,000 voxels , as a single gene test takes around 5 min ( or 22.8 years to test a single gene at every voxel of the full brain on one cpu ) . in addition , combining snps by p - value may miss an important effect where a set of snps from the same gene have moderate covariance , but explain different portions of variance in the phenotype . in other words , if they were considered together in the same model , the overall variance explained may be greater than its univariate significance level would imply . an alternative to set - based methods is to group snps into a single statistical model and then test that model for overall association . however , a problem with applying mlr to genetic data is that snps tend to be highly correlated , as they co - segregate in haplotype blocks ( frazer et al . , 2007 ) . the mlr is highly sensitive to collinearity among predictors ; the inversion step in calculating regression coefficients involves a matrix that is not full rank as the variables are collinear . this leads to wildly inaccurate beta value estimates and se ( kleinbaum , 2007 ) . to avoid collinearity in multivariate analysis of genetic data , dimensionality is often reduced using sparse regression methods , such as penalized or principal components regression ( pcreg ) . some data reduction methods compute a new set of statistically orthogonal variables , for inclusion in a classical mlr model . a data reduction method such as pca transforms a matrix of snp predictors into a new orthogonal set of predictors , ranked in descending order based on the amount of the variance in the data that each component explains ( jolliffe , 2002 ) . the output of pca is typically a matrix that explains the same amount of the overall variance as the original predictors , but without the collinearity . as the individual components are sorted by amount of variance they explain , the resulting statistical models can strike an efficient balance between the total variance explained ( the number of components to include ) and the number of degrees of freedom used ( model complexity increases as more variance components are included ) . it then builds a multiple partial - f regression model where the number of components included is based on the desired proportion of variance to be explained ( massy , 1965 ) . wang and abbott ( 2008 ) used pcreg to group snps into a single multivariate test statistic . ( 2011 ) extended this method to be applicable to images , conducting gene - based tests at each voxel with pcreg . , 2005 ; hemminger et al . , 2006 ; hinrichs et al . , 2006 ) to group snps based on gene membership , resulting in 18,044 unique genes . using the set of snps in each individual gene as predictors , hibar et al . used pcreg to assess the degree of association for every gene at every voxel in the full brain . the resulting method was termed a voxelwise gene - wide association study vgenewas . by compressing the snps into gene - based tests , the total number of tests was reduced to around 500 million tests from the 16 billion tests in vgwas . however , even with this much smaller number of tests , no genes identified passed correction for multiple comparisons . the most highly associated gene , gab2 , showed strong credibility as it is consistently associated with neurodegenerative disorders such as ad ( reiman et al . , 2007 ) . 2011 ) simulated full brain parametric maps using statistical priors based on their observed data to show that observed clusters of associated genes were larger than would be expected by chance . this provides evidence that vgenewas is a valid and powerful multivariate method to detect gene effects in full brain neuroimaging data . a head - to - head comparison of vgwas and vgenewas was also performed on the same datasets . the cumulative distribution function ( cdf ) plots of p - values for each study show that the fdr in the multivariate vgenewas was controlled at a lower rate than in the mass univariate vgwas method ( figure 4 ) . cumulative distribution function ( cdf ) plot of corrected p - values from vgenewas ( hibar et al . , 2011 ) and vgwas ( stein et al . vgwas could only be controlled for false - positives at q = 0.50 threshold , while vgenewas could be controlled for false - positives at q = 0.30 . the difference in q - value thresholds for the cdf of the p - values obtained from both studies on the same dataset suggests that the gene - based analysis is more powerful , though neither study controlled the false - positive rate at the nominal q = 0.05 threshold . an extension of pcreg and other data reduction techniques is to perform data reduction on both the genome and the 3d brain imaging traits . one approach that appears to be promising is parallel independent components analysis ( parallel ica or pica ; liu et al . , 2009 ) . parallel ica works by first performing pca on a set of snps and also a different pca on a voxelwise imaging measure . next , a modified version of ica is applied to both modalities and independent factors from each modality are chosen simultaneously by a correlation measure ( hence parallel ica ) . selecting imaging features and snps together can be more powerful than mass univariate tests of voxelwise imaging traits as the total number of tests is greatly reduced . for example , liu et al . ( 2009 ) used pre - processed fmri maps from 43 healthy controls and 20 schizophrenia patients and a pre - selected set of 384 snps chosen for their potential associations with schizophrenia . via a t - test , liu et al . ( 2009 ) demonstrated that genetic components ( p = 0.001 ) and fmri bold ( p = 0.0006 ) response loadings from parallel ica were able to distinguish healthy subjects from patients with schizophrenia , with reasonable accuracy . similar approaches have been applied to structural mri ( jagannathan et al . , 2010 ) . ica requires an initial round of pca , it is difficult to recover which snp sets are contributing to a given component and similarly it is difficult to localize the 3d spatial effect contributing to each component from the image . in addition , it is not clear how data reduction methods will perform with whole genome and full brain data . ( 2010 ) both performed considerable downsampling of the images , reducing the total number of voxels included in the parallel ica model . in addition , both studies tested only small sets of pre - selected snps instead of data from the full genome , or a standard 500,000 snp genome - wide scan . the power of parallel ica to find common components may be greatly reduced if there is additional noise from genome - wide data . ( 2009 ) found that as the amount of random noise increased , so did the number of independent components . as the number of independent components increases , the power to detect associations decreases . also querying full brain phenotypes for effects of genetic variants , another recently proposed multivariate method by chiang et al . ( 2011b ) , identified patterns of voxels in a dti image with a common genetic determination , and aggregated them to boost power in gwa ( figure 5 ) . approximately 5,000 brain regions were selected , where genetic influences accounted for > 60% of the total variation of white matter integrity . from these , a 5,000 5,000 correlation matrix was obtained . hierarchical clustering was used to select the largest clusters , and these voxels were defined to be rois . the mean fas for these rois were then tested for evidence of association with all snps genotyped across the genome . by identifying a genetic network that influences white matter integrity over multiple brain regions , chiang et al . ( 2011b ) were able to boost power to detect associations between fa in these brain areas and snps from the whole genome . in all , they identified 24 snps with genome - wide significance , which is unusual for a study with fewer than 1,000 subjects . to ensure the findings are not false - positives , however , simulations of imaging and genomic data may be necessary ( as carried out by vounou et al . , 2010 see below ) . clustering regions of a brain image that have common genetic determination . in a dti study of twins , the known kinship structure made it possible to estimate the genetic correlation matrix and a this was used to gage the similarity of genetic influences on all pairs of brain regions ( a ) . the 18 largest clusters parts of the image with common genetic influences were selected as regions of interest ( rois ) for gwas . by associating the mean white matter integrity of these regions with genetic variants , a genetic interconnection network was obtained ( b ) , where each network node represents a single snp ( colored circles ) . the figure shows only those snps associated with white matter integrity in at least one roi with a significance p - value < 10 . snps whose associations reach genome - wide significance are colored in red , with their names labeled . variants near each other on the genome can be highly correlated due to linkage disequilibrium . this leads to problems if all variants are included in a standard multiple regression model to predict the values of a trait . to address this , many new mathematical methods have been used to handle the high dimensionality in the genome ( a p n problem ) and interactions between genetic variants . these include penalized and sparse regression techniques , such as ridge regression ( hoerl , 1962 ) , the least absolute shrinkage and selection operator ( lasso ; tibshirani , 1996 ) , the elastic net ( zou and hastie , 2005 ) , and penalized orthogonal - components regression ( malo et al . , 2008 ; cho et al . , 2009 ; lin et al . , 2009 ; zhang et al . , 2009 ; chen et al . , 2010 ) . the various penalty terms ( e.g. , l in lasso and l in ridge ) in the regularized regression methods can incorporate large numbers of correlated variants with possible interaction terms , in single models . although these studies are almost invariably applied to case control gwa studies , similar approaches may be applied to imaging phenotypes . ( 2011a ) , for instance , implemented ridge regression to study the association of genomic scanning windows with mri - derived temporal lobe and hippocampal volume . they reported boosting of power in detecting effects of several snps , when compared to univariate imaging gwa . one statistical challenge of such sliding - window approaches is finding optimal window sizes , which can capture the correlation structure in the genomic data without adding excessive degrees of freedom to the model . considered several fixed , scanning window sizes ( 50 , 100 , 500 , and 1000 kbp ) in their study , and found boosting of power in detecting snps with different window sizes for different genomic regions . a more flexible approach may incorporate information such as the sample size and variant - specific ld structure into the selection of optimal window sizes for each genomic region ( e.g. , li et al . , 2007 ) . in addition , l - driven methods , such as lasso , may provide greater detection power by selecting sparse sets of genomic variants in association with imaging measures ( kohannim et al . as discussed above , however , multivariate methods can be applied not only to the genome , but also to the images , which are also high dimensional and show high spatial correlations . ( 2010 ) applied a sparse reduced - rank regression ( srrr ) method to detect whole genome - whole image associations . they computed a matrix of regression coefficients , c , whose rank was p ( number of snp genotypes ) times q ( the number of imaging phenotypes , or pre - defined anatomical rois in their case ) . they reduced the rank of this large matrix to r , by factorizing the matrix into the product of a p r matrix , b , and an r q matrix , a , and constraining a and b to be sparse ( figure 6 ) . to evaluate the power of their method and compare it to that of mass univariate modeling , vounou et al . generated realistic , simulated imaging and genetic data . using the forward evolution of genomic regions ( fregene ) software , and the adni baseline t1-weighted mri dataset , they obtained a simulated dataset , to which they introduced genetic effects in a number of rois . it was not feasible for the investigators to consider all possible genetic effect sizes and sample sizes , but they were able to show boosted power for all parameter settings they explored . setting the desired , reduced - rank r equal to 2 or 3 , they obtained higher sensitivities with srrr at any given specificity for a sample size of 500 . when they increased the sample size from 500 to 1,000 , they noted gains in sensitivities with srrr , which were more considerable than the merely linear gains obtained with univariate modeling . they also demonstrated that boosted sensitivities obtained with srrr increase with higher numbers of snps ; sensitivity ratios ( srrr / mass univariate modeling ) could be boosted even further to ratios far exceeding 5 ( observed with 40,000 snps ) with numbers of snps considered in a typical gwas ( e.g. , 500,000 snps ) . direct power comparisons between association methods on dna microarray data show that models that incorporate linear combinations of variables perform better than those that perform simple data reduction ( bovelstad et al . , 2007 ) . bovelstad et al . found that the penalized method , ridge regression , was more powerful than lasso , pcreg , supervised pcreg , and partial least squares regression ( pls ) , when it comes to predicting survival rates in cancer patients from dna microarray data . in the future , direct comparisons of methods on imaging genetics data could inform the direction of new methods development . imaging and genomic data are incorporated into a sparse , reduced - rank regression model , where regions of interest ( rois ) , and single nucleotide polymorphisms ( snps ) attain sparse coefficients , simultaneously . , it demonstrates higher power than mass univariate models for detecting effects of genetic variants . comprehensive modeling of whole - brain voxelwise and genome - wide data remains challenging , due to the high dimensionality of the data . recently , there have been new developments applying sparse regression methods to genome - wide data ; one such method is iterative sure independence screening ( isis ; fan and lv , 2008 ; fan and song , 2010 ; he and lin , 2011 ) . isis is an iterative selection procedure that builds a marginal model using the cyclic coordinate descent ( ccd ; friedman et al . , 2010 ) algorithm with the lasso and combines it with a conditional model of interactions based on pairwise correlations . the combined model has lower dimensionality , but effects of individual snps are still identifiable , as are snp snp interactions . isis has not yet been applied to brain images , but it should be feasible . methods such as isis could also be modified to jointly select imaging phenotypes and genomic data as done by vounou et al . ( 2010 ) but without first having to select roi or only a small subset of snps from the genome . the field of imaging genetics started with candidate gene studies , where hypotheses about gene action on brain structure and function could be tested in a novel way . more recently , candidate gene studies have been extended to investigate voxelwise associations between genetic variants and images of the brain , to map 3d profiles of genetic effects without requiring a priori selection of roi . to consider the entirety of the genome and discover potentially new variants , however , gwa studies have been introduced to the field of imaging genetics . in these studies , quantitative measures derived from images are considered as intermediate phenotypes , which are in some respects closer to the underlying biology of brain disorders and processes of interest . despite their unbiased consideration of the whole genome , the standard , univariate gwa approach considers only one snp at a time and has several limitations . from a genetic perspective , it does not take into account the interdependence between genetic variants due to linkage disequilibrium ; and in regard to imaging , such studies typically rely on single summary measures from images , which only weakly represent the wealth of information in a full 3d scan . among the most promising applications of imaging genetics a major advantage of penalized or sparse regression methods is that they accommodate collinearity inherent in the genome and in the images , but they still offer a familiar regression framework to accommodate covariates and confounding variables . this may discover genetic effects undetected by other data reduction methods , such as pica and pcreg . for studies of large 3d statistical maps of imaging phenotypes , methods to penalize the selection of both voxels from the image and associated genetic variants from the genome seem to have higher power than related discovery - based methods . even so , this is largely an empirical question that depends on the structure of the true signal . ( 2010 ) demonstrated the increased power of the srrr method , which favors the selection of an efficient set of roi and a reduced number of snps has increased power . a major limitation of penalized methods is that they may fail to converge on a solution when the data dimensions are very high . even methods designed for p n problems such as least angle regression ( efron et al . , 2004 ) tend to fail when given a full 3d imaging phenotype . this illustrates why current implementations of penalized regression in imaging genetics often rely on prior groupings of voxels or sliding windows in the genome . these prior groupings do not appear to be motivated by strong prior hypotheses , but by limitations in the statistical modeling . methods similar to isis ( fan and lv , 2008 ; fan and song , 2010 ; he and lin , 2011 ) designed for ultra - high dimensional datasets will likely be useful for future imaging genetics projects . once we have a set of validated genetic variants that affect the brain , multivariate models may be used to combine imaging , genetics , and other physiological biomarkers to predict outcomes in patients with brain disorders . the resulting combination of imaging and genetic data , with other biomarkers , can be used to predict an individual s personalized aggregate risk for specific types of brain disorders . as genomic and proteomic data are added , prognosis and diagnosis may be possible at an earlier stage or more accurate than is possible with current biomarkers . machine learning algorithms ( e.g. , decision trees , support vector machines , and neural networks ) have shown promise for making disease predictions from genomic and proteomic data ( cruz and wishart , 2007 ) . similar approaches may be useful in psychiatry research , and neuroimaging measures such as fiber anisotropy from diffusion imaging may help in making early predictions of brain integrity from genes . in a recent , preliminary study , our group incorporated several candidate polymorphisms in a multi - snp , machine learning model , to predict personal measures of fiber integrity in the corpus callosum ( kohannim et al . , 2011b ) . ideally , by incorporating both genomic and proteomic data from larger cohorts , one may be able to obtain personalized scores for brain integrity from biomarker profiles . the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest .

the quest to identify genes that influence disease is now being extended to find genes that affect biological markers of disease , or endophenotypes . brain images , in particular , provide exquisitely detailed measures of anatomy , function , and connectivity in the living brain , and have identified characteristic features for many neurological and psychiatric disorders . the emerging field of imaging genomics is discovering important genetic variants associated with brain structure and function , which in turn influence disease risk and fundamental cognitive processes . statistical approaches for testing genetic associations are not straightforward to apply to brain images because the data in brain images is spatially complex and generally high dimensional . neuroimaging phenotypes typically include 3d maps across many points in the brain , fiber tracts , shape - based analyses , and connectivity matrices , or networks . these complex data types require new methods for data reduction and joint consideration of the image and the genome . image - wide , genome - wide searches are now feasible , but they can be greatly empowered by sparse regression or hierarchical clustering methods that isolate promising features , boosting statistical power . here we review the evolution of statistical approaches to assess genetic influences on the brain . we outline the current state of multivariate statistics in imaging genomics , and future directions , including meta - analysis . we emphasize the power of novel multivariate approaches to discover reliable genetic influences with small effect sizes .

Life on other planets would likely be brief and become extinct very quickly, say astrobiologists from ANU Research School of Earth Sciences. In research aiming to understand how life might develop, the scientists realised new life would commonly die out due to runaway heating or cooling on their fledgling planets. "The universe is probably filled with habitable planets, so many scientists think it should be teeming with aliens," said Dr Aditya Chopra, lead author on the paper, which is published in Astrobiology. "Early life is fragile, so we believe it rarely evolves quickly enough to survive." "Most early planetary environments are unstable. To produce a habitable planet, life forms need to regulate greenhouse gases such as water and carbon dioxide to keep surface temperatures stable." About four billion years ago Earth, Venus and Mars may have all been habitable. However, a billion years or so after formation, Venus turned into a hothouse and Mars froze into an icebox. Early microbial life on Venus and Mars, if there was any, failed to stabilise the rapidly changing environment, said co-author Associate Professor Charley Lineweaver from the ANU Planetary Science Institute. "Life on Earth probably played a leading role in stabilising the planet's climate," he said. Dr Chopra said their theory solved a puzzle. "The mystery of why we haven't yet found signs of aliens may have less to do with the likelihood of the origin of life or intelligence and have more to do with the rarity of the rapid emergence of biological regulation of feedback cycles on planetary surfaces," he said. Wet, rocky planets, with the ingredients and energy sources required for life seem to be ubiquitous, however, as physicist Enrico Fermi pointed out in 1950, no signs of surviving extra-terrestrial life have been found. A plausible solution to Fermi's paradox, say the researchers, is near universal early extinction, which they have named the Gaian Bottleneck. "One intriguing prediction of the Gaian Bottleneck model is that the vast majority of fossils in the universe will be from extinct microbial life, not from multicellular species such as dinosaurs or humanoids that take billions of years to evolve," said Associate Professor Lineweaver. A copy of the paper can be downloaded at http://bit.ly/gaianbottleneck. ||||| We have yet to discover a single trace of alien life, despite the extremely high probability that it exists somewhere. This contradiction is popularly known as the Fermi Paradox. A new theory attempts to solve this conundrum by suggesting that habitable planets are quite common in our galaxy, but nascent life gets snuffed out very quickly. An oft-cited solution to the Fermi Paradox—that is, the lack of observational evidence that our galaxy has been colonized by an extraterrestrial civilization—is the Great Filter hypothesis. Devised by Robin Hanson of George Mason University, this theory suggests that some kind of cosmic-wide obstacle is preventing life from developing beyond a certain stage. Trouble is, we’re not entirely sure if this Great Filter actually exists, or what it looks like. Advertisement Some astrobiologists look to our planet’s ancient past and point to the presence of three possible filter points: the emergence of reproductive molecules, simple single-celled life, or complex single-celled life. If we could prove that any one of these critical evolutionary steps are true, that would be exceptionally good news—it would imply that the Great Filter is behind us. On the other hand, some pessimistic futurists fear that the Great Filter looms ahead of us, an event that will likely come in the form of a self-inflicted existential catastrophe. But as a new paper by Australian National University astrobiologists Aditya Chopra and Charley Lineweaver points out, there may be another possibility. They say that life exists for a brief time on other planets, but it goes extinct very quickly. The researchers are calling it the “Gaian Bottleneck Hypothesis.” Advertisement As Chopra put it in a press release, “Early life is fragile, so we believe it rarely evolves quickly enough to survive.” The problem, he said, is that most early planetary environments are unstable. In order to sustain life, a planet needs to regulate greenhouse gases to keep surface temperatures stable. This process, called Gaian regulation, happened on our planet. But Chopra and Lineweaver speculate that it’s a rare occurrence. The researchers point to Mars and Venus as potential examples. Both planets may have been habitable in the past, but both failed to stabilize the rapidly changing environment. Today, Mars is a frozen wasteland, and Venus is a hothouse. But here on Earth, life played a leading role in stabilizing the planet’s climate. As the researchers explained it in their study: If life emerges on a planet, it only rarely evolves quickly enough to regulate greenhouse gases and albedo, thereby maintaining surface temperatures compatible with liquid water and habitability. Advertisement The presence of a Gaian bottleneck, therefore, suggests that extinction is the “cosmic default” for more life that emerges on the surfaces of wet rocky planets in the Universe, and that rocky planets “need to be inhabited to remain habitable.” Credit: Chopra & Lineweaver, 2016/Astrobiology. “The mystery of why we haven’t yet found signs of aliens may have less to do with the likelihood of the origin of life or intelligence and have more to do with the rarity of the rapid emergence of biological regulation of feedback cycles on planetary surfaces,” said Lineweaver. Advertisement It’s an intriguing theory, but in order for it to satisfy the demands of the Great Filter hypothesis, it needs to be sweepingly universal in scope. It’s not immediately clear from the Chopra and Lineweaver paper why Gaian regulation should be so rare on other habitable worlds, or how infrequent this process actually is. Given that there are likely tens of billions of potentially habitable planets in our galaxy, and given that our galaxy has been able to sustain life for about 5-6 billion years, it would have to be one hell of a bottleneck. Robin Hanson shares my sentiment. As he explained to Gizmodo in an email: The basic idea is quite plausible as a part of the Great Filter. But the Great Filter is enormous, and this paper offers no concrete arguments for why we should expect their filter effect to be enormous. So we can add it to our long list of plausible filter effects, but we don’t have a good reason to see it as THE one thing that causes most of the great filter. Advertisement Likewise, astronomer Milan Ćirković from the Department of Physics at the University of Novi Sad in Serbia and Montenegro has concerns about the paper. As he told Gizmodo, its basic premise is predicated on a rather anthropocentric perspective of life in the universe: The whole setup is anthropocentric, as much as all versions of the “rare earth hypothesis” are. In order to pass from the conclusion that planets which are really Earth-like are rare to the conclusion that it is the reason why we don’t perceive advanced aliens, we need the step in which we prove that any advanced aliens must evolve in the Earthlike setting. And that proof is simply not forthcoming any time soon. And I believe it’s a mistake to take it seriously even as a working hypothesis. Evolutionary convergence is basically religiously-inspired nonsense. I haven’t seen, for instance, any remotely acceptable reason why marine life could not evolve intelligence and civilization—and marine habitats are much less susceptible to perturbations of climate than land ecosystems. That said, this possible solution to the Fermi Paradox may actually be testable. “One intriguing prediction of the Gaian Bottleneck model is that the vast majority of fossils in the universe will be from extinct microbial life, not from multicellular species such as dinosaurs or humanoids that take billions of years to evolve,” said Lineweaver. Advertisement Digging for clues on a distant exoplanet? Count us in. Note: This article was updated to include the quote from Milan Ćirković. [Astrobiology, Australian National University] Top image: ESA Email the author at george@gizmodo.com and follow him @dvorsky. ||||| CSIRO Parkes radio telescope is searching for alien civilizations. (Wayne England) The hunt for extraterrestrial life is one of humanity's most exciting endeavors. The pieces are all falling into place: We're finding more and more planets outside of our own solar system, and soon the James Webb Telescope will give us unprecedented looks at these distant worlds. We've populated Mars with robots looking for signs of ancient habitability. Orbiters dive through the icy geysers of ocean-covered moons in hopes of catching some life-giving minerals. Our radio telescopes are tuned in to mysterious stars, listening for the sounds of a hustling and bustling civilization. In spite all of that, we've yet to find a single measly microbe off-world. So where is everybody? In a new study published in Astrobiology, researchers from the Australian National University offer up one possible explanation: Maybe all of the other life in our neighborhood has already come and gone. [Why NASA’s top scientist is sure that we’ll find signs of alien life in the next decade] It's not a new idea. One of my favorite songs is about this very concept: Space is big and time is long, so it's likely that any life (intelligent or otherwise) would manage to miss us. It's a standard answer to the Fermi Paradox, which is the contradiction between the immense number of Earth-like planets and the apparent rarity of Earth-like life. The new study goes a step further, suggesting that life, if it evolved, would often be too fragile to survive past its infancy. In other words, it's possible that other planets in our own solar system had blips of microbial life – tiny emergences that stood no chance of evolving into intelligent organisms. In fact, you could kind of blame climate change. But in this case, early organisms didn't do enough to change their planet's shifting climate. "Most early planetary environments are unstable. To produce a habitable planet, lifeforms need to regulate greenhouse gases such as water and carbon dioxide to keep surface temperatures stable," lead author Aditya Chopra said in a statement. The study authors believe that Earth's early microbial life helped to stabilize the planet's climate, while any life that might have existed on the nearby, similarly rocky planets Venus and Mars failed to do so. [Looking for alien civilizations? Check these star clusters, scientists say.] "Between the early heat pulses, freezing, volatile content variation and runaway positive feedbacks, maintaining life on an initially wet, rocky planet in the habitable zone may be like trying to ride a wild bull. Most life falls off," the authors wrote in the study. The researchers have named this phenomenon the "Gaian Bottleneck." If it's true, they point out, our life-hunting robots and astronauts will have to look for fossilized microbes of the most primitive sort. We're not likely to find alien dinosaur bones, which is a bummer. "The mystery of why we haven't yet found signs of aliens may have less to do with the likelihood of the origin of life or intelligence and have more to do with the rarity of the rapid emergence of biological regulation of feedback cycles on planetary surfaces," Chopra said. Of course, this work is purely theoretical. It's possible that Earth won some kind of massive cosmic lottery, and that we're the only life ever to have evolved in the whole wide universe. It's also possible that intelligent life is out there somewhere right now. Space is big and time is long, so we may never know for certain. Read More: Why NASA’s top scientist is sure that we’ll find signs of alien life in the next decade Why can’t we just send our rovers to look for life on Mars? A new way of calculating distant stars’ gravity could help us find alien worlds Planet Nine isn’t a Death Star or the killer planet ‘Nibiru.’ It may not even exist. Do we really want to know if we’re not alone in the universe?

– Two astrobiologists have a new explanation for why we haven't found alien life: It didn't evolve quickly enough to keep its planet habitable. "Most early planetary environments are unstable," Aditya Chopra says in a press release. "To produce a habitable planet, life forms need to regulate greenhouse gases, such as water and carbon dioxide, to keep surface temperatures stable." For example, Venus and Mars may have had life at one point, but that life didn't evolve fast enough to keep the planets from heating and cooling past the point of habitability. Or—as Rachel Feltman at the Washington Post puts it—you can blame climate change; only in this case lifeforms didn't enact enough of it. Chopra and fellow scientist Charley Lineweaver published their "Gaian Bottleneck" hypothesis this week in Astrobiology. The study states extinction is the "cosmic default," and planets "need to be inhabited to remain habitable." "Life on Earth probably played a leading role in stabilizing the planet's climate," Lineweaver says in the press release. Under this model, rapid evolution is more important to the existence of life on other planets than their proximity to a star or the brightness of that star, the study states. But Gizmodo points out Gaian Bottleneck doesn't account for why so-called Gaian regulation is so rare throughout the universe: "Given that there are likely tens of billions of potentially habitable planets in our galaxy…it would have to be one hell of a bottleneck." (But if alien life does exist, it apparently has a soft spot for Florida.)

the relation between the x - ray spectral / timing states of low - mass x - ray binaries ( lmxbs ) and their x - ray luminosity is puzzling . while on short time scales ( typically , hours ) x - ray spectral and timing parameters vary ( stochastically ) in a well - correlated fashion , on longer time scales ( typically , days ) the x - ray luminosity , particularly in the low - energy band ( @xmath0kev ) appears to vary largely independently from the other parameters . this is seen in the near - eddington neutron - star z sources ( e.g. , hasinger et al . 1990 , kuulkers et al . 1996 , wijnands et al . 1998 , jonker et al . 2000 ) as well as in the less luminous neutron - star atoll sources ( e.g. , van der klis et al . 1990 , ford et al . observations that could be interpreted in terms of a similar phenomenon in black - hole candidates ( e.g. , mndez and van der klis 1997 , rutledge et al . 1999 ) have recently been provided with solid empirical underpinnings by a study of the black - hole candidate xte j1550@xmath1564 ( homan et al . 2001 ) . in all these sources , timing properties , in particular the characteristic frequencies of qpo and noise components correlate much better to each other ( e.g. , ford and van der klis 1998 ) , and to measures of x - ray spectral shape such as position in the tracks lmxbs tend to trace out in an x - ray color - color diagram ( e.g. mndez and van der klis 1999 ) , x - ray colors ( mndez et al . 1999 ; particularly at higher energy ) , and sometimes parameters obtained from x - ray spectral fits ( kaaret et al . 1998 ) , than to luminosity ( see van der klis 2000 ) , although weak dependencies of timing and spectral properties on long - term luminosity variations are observed ( kuulkers et al . 1996 , wijnands et al . ( for example , spectral shape in the @xmath26kev band is usually somewhat affected by the longer time scale variations , spectral hardness in this band being positively correlated with flux ) . the time scale on which the correlated short - term variability takes place is hours to days in the z sources and in atoll sources in luminous states , but it is sometimes longer in black - hole candidates and in atoll sources in low - luminosity states . so , while on short time scales all properties including luminosity vary in a well - correlated fashion , on longer time scales x - ray luminosity is the odd one out in an otherwise still rather well - correlated set of spectral and timing parameters . when for a given source a plot is made of any spectral or timing parameter vs. x - ray flux , then , due to this phenomenon , the result tends to be a series of parallel tracks , each individual track reflecting the short - term correlated variations at a given epoch , and the offsets between the tracks resulting from the longer - term luminosity variations , combined with observational windowing . perhaps the most direct measurements of this parallel - track phenomenon have been made using the frequencies of the kilohertz quasi - periodic oscillations ( khz qpos ) in the z and atoll sources . for this reason , most of the remainder of this paper focuses on the parallel track phenomenon as seen in khz qpo sources ( fig.1 ) ; i return to the general case in [ sect : disc ] . kilohertz qpos are observed in the x - ray flux of some twenty z and atoll sources and are generally interpreted as being due to the motion of matter within a few stellar radii of the low - magnetic - field neutron star in these systems ( van der klis 2000 for a review ) . most models involve tight orbital motion of matter around the star at a preferred radius @xmath3 in the inner accretion disk , where @xmath4 km . because of this proximity of their site of origin to the compact object , khz qpos can potentially be used to constrain theories of strong gravity and dense matter . a discussion of the physics which might determine @xmath3 was given by miller et al . ( 1998 ) ( see also miller and lamb 1993 , 1996 ) . in their description , @xmath3 is the inner radius of the keplerian disk , which as long as it is larger than the innermost stable orbit from general relativity , is set by radiation drag on the orbiting matter . for a constant mass inflow , the radius @xmath3 increases when the x - ray flux impinging upon the inner edge of the disk increases ; for a constant radiation field , @xmath3 decreases when the amount of matter accreting in the disk increases . when both mass flow and radiation increase , it is not obvious what will be the effect on @xmath3 , but according to miller et al . ( 1998 ) if all radiation is due to accretion through the disk at a rate @xmath5 , then @xmath3 will decrease when the accretion rate increases . under certain simplifying assumptions , @xmath6 . other proposed khz qpo models involving the frequency of orbital motion ( e.g. , stella and vietri 1999 , titarchuk et al . 1999 , cui et al . 1998 , cui 2000 , campana 2000 , psaltis and norman 2000 ) either adopt the miller et al . ( 1998 ) mechanism , or rely on a magnetosphere to set the inner disk radius . the dependence of khz qpo frequency @xmath7 on x - ray flux @xmath8 shows the above - described parallel track pattern . whereas in a given source on short time scales ( less than several hrs ) a good correlation is observed between @xmath7 and @xmath8 , on longer time scales ( more than a day or so ) the correlation breaks down . on those longer time scales , different flux levels can correspond to approximately similar frequency ranges . observational windowing has so far prevented a careful study of what happens on intermediate time scales . in a frequency vs. flux plot of a series of observations of a given khz qpo source , each lasting several hours and separated by intervals of days or longer , a series of parallel tracks is observed , each track corresponding to the @xmath7 , @xmath8 relation of a single observation . these parallel tracks are perhaps most clearly seen in the transient atoll source 4u1608@xmath152 . in fig.1_a _ ; mndez et al . 1999 ) the parallel tracks are obvious ; they are steeply inclined , approximately straight lines . note how there seems to be a systematic trend in the steepness of these lines : at lower count rate they tend to be steeper . the range in flux over which in a given source identical frequencies are observed can be as large as a factor of 3 . note that there appears to be a tendency for the lines at the highest flux to cover a somewhat higher frequency range , and vv . a similar and perhaps related , but more extreme picture is presented by observations of different sources : the same range of qpo frequencies is observed in sources that differ in x - ray luminosity @xmath9 ( defined here as @xmath10 where @xmath11 is the distance ) by up to more than two orders of magnitude ( van der klis 1997 , ford et al . 2000 ) . in a plot of frequency vs. luminosity covering the ensemble of khz qpo sources this once again leads to a series of parallel tracks , each `` track '' now corresponding to a different source ( fig.1_b _ ; ford et al . 2000 ) . note , that these tracks are approximately parallel in a plot of frequency vs. the _ logarithm _ of @xmath9 , so the same trend of steeper lines at lower luminosity as observed in 4u1608@xmath152 clearly also applies across the ensemble of sources . ( in a semi - logarithmic version of the plot in fig.1_a _ , the lines are also more parallel ) . in both figures it is as if frequency depends not on @xmath9 , but on the percentage by which @xmath9 deviates from its average ( cf . van der klis 1999 ) . the question in both cases illustrated in fig.1 of course is : if at some epoch in some source frequency depends on luminosity according to some particular relation , then why at some other epoch or in some other source is there a very different frequency - luminosity relation , where very similar frequencies are attained at very different luminosities ? any explanation that succeeds in obtaining the _ same _ frequency at quite _ different _ luminosity would at first sight seem to defy itself , as it would at the same time remove the observed strong dependence of frequency on luminosity at any given epoch . as explained below , up to now the answer typically has been that at least two independently varying free parameters must characterize the problem . the phenomenology clearly suggests that a single quantity , variable on time scales of less than a few hours , dominates khz qpo frequency and most other spectral and timing parameters , but not the observed x - ray luminosity . usually , this parameter has been inferred to be the mass accretion rate @xmath5 , sometimes parametrized by the curve length @xmath12 measured along the track the source traces out on these time scales in the x - ray color - color diagram ( 1 ; hasinger and van der klis 1989 , van der klis 1995 for a review ) . a problem with this interpretation is that the x - ray luminosity , whose energy ultimately derives from this mass accretion , is on longer time scales not then well - correlated to inferred @xmath5 . another parameter , varying on time scales of more than a day or so , is therefore required to explain the slow luminosity variations that do not affect the khz qpo frequency , i.e. , the horizontal offset between the parallel lines in a given khz qpo source ( fig.1_a _ ) . slow variations in the accretion geometry leading to changes in x - ray beaming ( e.g. , van der klis 1995 ) or in the ratio between matter accreting in the disk and through some other channel such as a more radial inflow ( e.g. , wijnands et al . 1996 , kaaret et al . 1998 ) energy loss modes in unobservable spectral bands ( e.g. , van der klis et al . 1995 ) and mechanical energy in jets ( e.g. , mndez et al . 1999 ) , have all been suggested to provide this additional parameter , but in the absence of a specific mechanism to make these parameters vary independently from inferred @xmath5 , the true origin of the slow luminosity variations has been difficult to pin down ( see ford et al . 2000 for a discussion of these various possibilities ) . yet another parameter , different from source to source , is required in this picture to explain the parallel lines spanning two orders of magnitude in @xmath9 accross the ensemble of khz qpo sources ( fig.1_b _ ) . it has been proposed that this parameter is the neutron - star magnetic - field - strength , which should then be correlated to average source luminosity rather tightly ( white and zhang 1997 ) . systematic differences between sources with respect to one of the slowly varying parameters mentioned above could perhaps explain fig.1_b _ , but it has remained unclear which parameter could fulfill all requirements ( e.g. , ford et al . all proposals to date effectively require the existence of at least two independent time - variable parameters , and no compelling description was given of a mechanism that could make such a second time - variable parameter vary on its own accord independently of @xmath5 . it is the purpose of this paper to point out that the ensemble of observations described above can in fact be explained in terms of just a single time - variable independent parameter , varying on time scales of hours . this can be accomplished by exploiting the observed difference in time scale between correlated and uncorrelated behavior . the crucial requirement is that there exists both a prompt and a time - averaged component in the systemic response to the variations in the governing parameter . the basic class of scenarios that could accomplish this is outlined in 2 , and a specific proposal is made there , namely that the governing parameter is the mass accretion rate through the disk . in 3 it is quantitatively investigated to what extent such a model could explain the observational facts presented above . numerical simulations of the predicted luminosity , khz qpo frequency relation in a representative example of such a scenario are described there . in 4 i discuss the results , and the extent to which the scenario might be applicable to the parallel - track phenomena observed in neutron - star and black - hole low - mass x - ray binaries in general , as well as some of the the wider implications of the proposed explanation for the interpretation of states and tracks in lmxbs . if the khz qpo frequency @xmath7 depends on some parameter @xmath13 which varies on time scales of less than several hours , and the x - ray luminosity @xmath9 depends partly on @xmath13 and for another part on some running average of @xmath14 such as @xmath15 , where @xmath16 is a weight function with integral 1 that is non - zero on interval @xmath17 $ ] spanning between several hours and days , then this could explain the parallel tracks in a given khz qpo source . the correlation between @xmath7 and @xmath9 on time scales of hours would arise because both quantities depend on @xmath13 , the decorrelation on longer time scales because the slowly varying @xmath18 affects @xmath9 , but not @xmath7 . however , such a description would for plausible prescriptions for @xmath19 have trouble to explain that a similar range of frequencies is seen in 4u1608@xmath152 for fluxes different by a factor of 3 , and could certainly not explain that the same frequencies are observed over several orders of magnitude in luminosity across sources . for @xmath9 to be very different , @xmath14 , and hence @xmath7 would have to be very different , contrary to what is observed . also , in general the lines would not be parallel in @xmath7 vs. @xmath20 space . with an additional twist , such a scheme _ can _ explain both parallel - track phenomena . suppose , for example , that @xmath7 is proportional to @xmath21 , but @xmath9 is proportional to @xmath14 only . then , when @xmath14 increases , @xmath7 and @xmath9 immediately increase in correlation with it , but if @xmath14 remains the same for a while , then on a time scale of more than several hours @xmath7 would gradually drift to the value it has when @xmath22 . in such a picture a 100 times more luminous source can still show the same qpo frequency as its weaker kin because not only @xmath14 but also @xmath19 is approximately 100 times higher , so that @xmath23 is still approximately the same . note also that in such a scheme the same fractional variation in @xmath14 tends to cause a similar absolute change in @xmath7 , so that the lines are parallel in @xmath7 , @xmath20 space , as observed . several similar prescriptions for the dependence of @xmath7 and @xmath9 on @xmath14 and @xmath19 are possible that preserve the desirable qualities of this description . an attractive interpretation retaining the flavor of this basic idea that would work well within the framework of a model where the inner radius @xmath3 of the disk , and hence @xmath7 , is determined by some balance between accretion rate through the disk and radiative stresses ( 1.1 ) , would be one where @xmath7 depends on the ratio between instantaneous accretion rate through the disk @xmath24 varying on short time scales , and @xmath9 : @xmath25 and the luminosity has both an immediate response to @xmath26 and a filtered one : @xmath27 so , in this model @xmath13 is identified with the accretion rate @xmath28 through the disk , @xmath7 depends on @xmath29 , and @xmath9 on @xmath30 . note that @xmath31 where @xmath32 , so @xmath7 still only depends on the ratio @xmath33 as in the simpler prescription above . for this reason , the model retains the basic qualities of this simpler prescription . at epochs where @xmath34 , i.e. , @xmath35 too much radiation is produced for the amount of matter in the disk ( set by @xmath26 ) so @xmath3 is large and hence @xmath7 low , and vv . if @xmath26 remains the same for a while , then @xmath36 approaches @xmath26 , i.e. , @xmath37 , and @xmath3 and hence @xmath7 drift to their `` equilibrium '' value , no matter what the actual value of @xmath26 is . the lines tend to be parallel in @xmath7 , @xmath20 space as , depending only on the extent to which @xmath36 has converged to @xmath26 , the same fractional change in @xmath26 and hence @xmath9 tends to produce the same linear change in @xmath7 . note that no other independently time - varying parameter than @xmath26 is required now to explain the parallel - tracks phenomenon . the physical question is : what is the nature of the slowly varying component in the response of luminosity to accretion rate , the term @xmath38 ? physical implementations could be imagined using for example a mechanism for the storage and slow release of energy in the neutron star , such as through deposition and burning of nuclear fuel , energy storage in the crust or in the disk / star boundary ( inogamov and sunyaev 1999 , popham and sunyaev 2001 ) . another possibility would be energy storage in the neutron - star spin , with energy feeding back into the disk by magnetic or gravitational interaction ( cf . priedhorsky 1986 ) . alternatively , one could think of a mechanism where matter flowing in radially provides a second channel of accretion whose @xmath5 is derived from some running average over @xmath26 , for example because more matter in the disk leads to more matter blowing off it to feed the radial flow , or because disk and radial flow are both fed by the same external flow . note from these examples that the filtered response can technically be either causal ( e.g. , burning rate depends on amount of fuel accreted in the past ) , or acausal ( e.g. , matter blown from disk reaches neutron star before disk flow ) ; the response may even be symmetric . the basic feature of the model scenario discussed here is that more accretion through the disk produces more flux not only promptly , but also through some time - averaged response , and ( only ) when this filtered response is at the level it would have when the accretion were constant , do the effects on the qpo frequency cancel . for definiteness , assume the following description for the dependence of frequency on accretion rate and x - ray luminosity : @xmath39 where the luminosity is simply @xmath40 with @xmath41 the accretion mass - to - energy conversion efficiency , and where the radial accretion rate is related to the disk accretion rate via @xmath42 . so , in this description @xmath43 . frequency @xmath7 only depends on @xmath44 and @xmath9 on @xmath45 . the filtered response @xmath36 is given by an integral over the future disk accretion rate : @xmath46 results of numerical simulation of this description with a radial - to - disk accretion ratio @xmath47 of 1/3 , filter time scale @xmath48 and @xmath49 are shown in fig.[fig : simulation1608 ] , where a second - order red - noise signal ( random walk ) was used for @xmath24 , and 12 days of data were plotted in intervals of 8hrs separated by gaps of 16hrs to simulate typical observational windowing . note that these choices for @xmath50 and windowing time scales are illustrative ; the scenario will work for a variety of time scales . comparing fig.2 to fig.1_a _ , clearly the result of this simulation is rather similar to observation . not only do the parallel lines show up , also the steepening of the tracks towards lower luminosity is reproduced , as well as the tendency for lines at higher count rates to cover higher frequency ranges . as explained in 2 , the steepening effect is a consequence of the fact that frequency depends only on @xmath33 , so that same fractional change in @xmath26 tends to produce the same linear change in @xmath7 . the other effect arises because the highest count rates tend to be attained at the highest disk accretion rates @xmath26 . necessarily , these tend to be followed by intervals of lower @xmath26 , so that @xmath36 tends to be lower than @xmath26 at those epochs , i.e. , @xmath51 , which explains why relatively higher frequencies often occur there . at low count rates the opposite applies . fig.[fig : simulationallsources ] shows the result of the simulation of four sources differing in average @xmath26 but showing a similar fractional amplitude of @xmath26 variations . each source was simulated for 5 days , during which it varied randomly in luminosity by a factor of 2 . comparing fig.3 to fig.1_b _ , again the result of the simulation is similar to what is observed . in particular , the simulated tracks distributed over a factor @xmath52100 in @xmath9 , are approximately parallel in @xmath7 , @xmath20 space . very similar results were obtained from a simulation where the filtered response was representative of one due to nuclear burning of accreted material rather than of radial accretion . in that case , @xmath53 with @xmath54 and @xmath55 , respectively , the accretion and the nuclear burning mass - to - energy conversion efficiencies , typically 0.1 and 0.003 , and @xmath56 now given by a _ past _ integral over @xmath24 . however , in order for the observed steep dependencies of @xmath7 on @xmath9 to be reproduced in those simulations , a large value of @xmath57 between 10 and 15 had to be used . this is because of the small value of @xmath58 appropriate to that physical example . the work of miller and lamb ( 1993 , 1996 ) suggests that lower values of @xmath57 such as the value of 2 used in the first example are more appropriate . the velocity of a radial flow is expected to be much higher than the radial component of the motion of the matter accreting in the disk . this is expressed in eq.2b by making @xmath59 reflect the _ future _ evolution of @xmath26 . therefore , it might seem surprising that the variations in @xmath59 would be a low - pass filtered version of , i.e. , slower than , those in @xmath26 . however , note that the disk is expected to feed the radial flow over an annulus covering a range of radii . the density fluctuations in the disk would contribute to the radial flow for the full time they take to cross this feeding annulus , i.e. , for much longer than they take to cross the inner disk edge and accrete in the end . alternatively , the short - term fluctuations in @xmath26 could form at small radii in the disk , within the feeding annulus . in both cases @xmath59 would be a smoothed version of @xmath26 , which is all that is required to make the scenario work . the parallel tracks observed in khz qpo sources in plots of qpo frequency vs. logarithmic x - ray luminosity within a given source as well as across sources ( fig.[fig : parlines1608 ] ) can be explained in terms of just one time - variable independent parameter @xmath13 , provided that there is both a prompt ( @xmath2 hrs ) and a filtered ( @xmath60 a day ) systemic response to the time variations in this parameter . numerical simulations of a version of this scenario where qpo frequency depends on the balance between x - ray luminosity and accretion rate via the accretion disk , and luminosity depends on this accretion rate , both promptly and filtered by some averaging mechanism , show a remarkable similarity to what is actually observed . the basic prediction of this entire class of models is that it should be possible to reconstruct qpo frequency from the time variations of the governing parameter @xmath14 using a model involving some running average of @xmath14 . in the example simulated , @xmath14 is identified with the accretion rate through the disk @xmath26 and @xmath9 is @xmath61 , where @xmath36 is @xmath26 convolved with a response function with characteristic time scale @xmath50 , so that we are faced with a deconvolution problem which might in principle be solved using time series of simultaneous measurements of instantaneous @xmath9 and qpo frequency long enough to cover a sufficient number of correlation time scales @xmath50 , and dense enough to sample the short time scale variations well . perhaps this can be accomplished by combining rxte pca and asm observations , although pca observations extending over several weeks would be much preferable . for models of the general type expressed in eqs.1 , both the long - term and short - term variations in @xmath9 are caused by variations in @xmath26 ; the changes in khz qpo frequency and presumably in the other frequencies associated with the short - term @xmath9 variations arise from changes in the inner disk radius @xmath3 , which in turn are related to changes in the ratio @xmath32 between instantaneous and long - term average @xmath26 . note , that while the changes in x - ray spectral parameters and qpo amplitudes are also affected by changes in this ratio , this occurs not necessarily exclusively through the effect @xmath33 has on @xmath3 . for the example simulated , if both disk and radial accretion contribute to @xmath9 with a different spectral shape , then the spectrum would be more similar if the ratio of their rates is similar . if there are radiative - transfer effects of the radial flow on spectrum or qpo amplitudes , these would be stronger when the radial flow is denser ; i.e. , these effects depend on @xmath36 instead of on @xmath33 . so , in this scenario , the elusive time - variable parameter ( often dubbed `` inferred @xmath5 '' in the literature ) that to first order determines all qpo frequencies and a number of other timing and spectral parameters ( but not @xmath9 ) turns out to be @xmath33 , the disk accretion rate normalized by its own long - term average , rather than any straight accretion rate . curve length @xmath12 along the track of a source in the color - color diagram is in this picture a measure of @xmath33 . depending on the precise nature of the filtered response @xmath36 ( e.g. , nuclear burning or radial accretion ) , @xmath9 may or may not be a pure measure of the total accretion rate @xmath5 , but even if it is , as in the model expressed in eqs.2 , neither @xmath9 nor total @xmath5 are directly correlated with @xmath33 and hence with all the associated observable parameters . although the short - term variations in @xmath33 , @xmath3 and associated observable parameters such as @xmath12 and @xmath7 , as well as those in @xmath9 do indeed result directly from short - term variations in the disk accretion rate @xmath26 , the value of @xmath33 does not follow from the actual value of @xmath26 or @xmath9 , nor from that of any other instantaneous accretion rate such as total @xmath5 . this leads to several further predictions . two observations characterized by different @xmath9 but the same @xmath7 in this description find the source with a disk that has the same @xmath3 and hence @xmath33 , but different @xmath26 and @xmath36 . no strong decrease of qpo fractional amplitude with luminosity is predicted as would be the case if the luminosity variations would be dominated by an extra source of x - rays unrelated to the qpos this seems to be borne out by observations ( mndez et al . 2000 ) . which spectral variations are seen for luminosity variations along or across parallel lines depends on how variations in respectively @xmath33 and @xmath5 affect the spectrum . motion from one parallel track to the other in the @xmath9 , @xmath7 diagram could happen along any trajectory depending on the @xmath26 record and the precise nature of the filtered response , but no sudden jumps in the frequency - luminosity plane connecting branches far apart would be expected . note that _ each _ correlated quantity is predicted to depend to first order on @xmath33 ; two qpo frequencies , one depending on @xmath33 and another on @xmath26 would not in the long run remain well correlated to each other . the scenario discussed in this paper does not aim to explain the _ differences _ with respect to spectral / timing properties observed as a function of luminosity , which of course exist . clearly , even if the basic idea is correct that disk accretion rate normalized by its own long - term average , @xmath62 , to first order determines most of the phenomenology either because it sets inner disk radius @xmath3 or directly , it is not difficult to think of mechanisms that could explain subtle differences in phenomenology at similar @xmath3 as a function of modest changes in @xmath9 such as described by , e.g. , kuulkers et al . ( 1996 ) , and more obvious differences such as those between z and atoll sources for large @xmath9 differences ( hasinger and van der klis 1989 ) . it is beyond the scope of this paper to speculate on the precise nature of such mechanisms . finally , it is of interest to consider to what extent this type of scenario could be of relevance to black - hole candidates . in those sources , a similar type of correlation on short and decorrelation on longer time scales is sometimes observed between @xmath9 on the one hand and spectral hardness and timing parameters on the other ( 1 ) . in the black - hole candidate xte j1550@xmath1564 , parallel tracks are in fact observed in an @xmath9 vs. spectral hardness diagram , with similar hardness and qpo variations occurring along tracks in a hardness vs. count rate diagram at very different luminosity ( homan et al . 2001 , who also discuss the possibility that @xmath3 varies more or less independently from @xmath9 ) . perhaps a similar mechanism such as that explaining the similar phenomenology in the neutron star systems underlies this behavior , although matters are complicated by the absence of a solid surface allowing ( but not requiring ) matter to accrete without producing much radiation ( e.g. , esin , mcclintock and narayan 1997 ) , so that the radiative stresses determining @xmath3 are harder to predict from the accretion flows . reports of `` hysteresis '' in the flux from black - hole candidates ( miyamoto et al . 1995 , smith , heindl and swank 2001 ; these latter authors discuss their results in terms of two independent accretion flows ) , with a tendency towards hard spectra when the count rate rises and soft spectra when it falls , suggest that a disk plus radial flow pattern related by a filtered response as described here could play a role in these systems : if the count rate is dominated by the disk accretion rate , and spectral hardness is representative of inner disk radius then this is exactly what would be expected from the model described in 3 : for a long - term dropping count rate @xmath51 so @xmath3 is small and the spectrum soft , and vv . this means that parallel tracks could be produced in the way explained in this paper . different from the neutron stars , where there are usually no cross - tracks connecting the parallel tracks , the parallel tracks in xte j1550@xmath1564 are connected together in what was interpreted to be a comb - like pattern ( homan et al . 2001 ) . the very quiet , soft ( `` high '' ) state the source is in when it is on the connecting track ( the back of the comb ) may hence be unique to black holes , perhaps because it is associated to a flow mode where the matter that accretes radially flows into the hole without producing much radiation , so that the radiative stress on the inner edge of the disk flow is low and hence @xmath3 small and insensitive to small variations in the accretion flows . the parallel tracks ( the teeth of the comb ) on which the other black - hole states are observed ( `` very high '' , `` intermediate '' and `` low '' states ) , may correspond to a mode where , perhaps due to interaction with a jet , the radial flow does produce considerable radiation so that @xmath3 is larger and sensitively dependent on the accretion flows , as in neutron stars . this scenario would require the radial flow to produce considerable radiation with low angular momentum at radii smaller than @xmath3 ; it is unclear if there is a mechanism by which this could be accomplished . the scenario described in this paper can , for the first time , explain how it is possible that khz qpo frequency and several other timing and spectral parameters are the same in sources differing by more than two orders of magnitude in @xmath9 , and in a given source for @xmath9 levels different by a factor of several , even when those properties in any given source at any given instant do themselves strongly depend on @xmath9 . the proposed solution is that such properties to first order depend on @xmath33 , disk accretion rate normalized by its own long - term average . this at the same time removes the need for additional independent , slowly varying or fixed source - dependent parameters affecting the phenomenology , and provides a way in which most of the observed short - term variations can arise as a consequence of short - term accretion rate variations while preserving the expected strong dependence of luminosity on total accretion rate . the physical mechanism providing the long - term averaged response to the disk accretion rate variations required in this scenario can be the accretion of matter flowing off the disk vertically and accreting radially , in combination with a mechanism to make the inner disk radius dependent on the ratio of luminosity to disk accretion rate . the radiation produced by this radial accretion flow in the inner disk region is crucial in that case in determining much of the phenomenology . if in black holes , contrary to neutron stars , there is a mode for this radial flow to accrete while producing little radiation ( and another where it produces considerable radiation ) , then this additional option available to black holes might explain the more complicated phenomenology of those sources as compared to neutron stars . this work was supported in part by the netherlands organization for scientific research ( nwo ) . it is a pleasure to acknowledge stimulating discussion and useful comments by lars bildsten , mariano mndez and demetris psaltis . campana , s. , 2000 , apj 534 , l79 cui , w. , 2000 , apj 534 , l71 cui , w. , barret , d. , zhang , s.n . , chen , w. , boirin , l. , swank , j. , 1998 , apj 502 , l49 esin , a.a . , mcclintock , j.e . , narayan , r. , 1997 , apj 489 , 865 ford , e. , kaaret , p. , tavani , m. , barret , d. , bloser , p. , grindlay , j. , harmon , b.a . , paciesas , w.s . , zhang , s.n . , 1997 , apj 475 , l123 inogamov , n.a . , sunyaev , r.a . , 1999 , 25 , 269 ford , e.c . , van der klis , m. , 1998 , apj 506 , l39 hasinger , g. , van der klis , m. , 1989 , a&a 225 , 79 hasinger , g. , van der klis , m. , ebisawa , k. , dotani , t. , mitsuda , k. , 1990 , a&a 235 , 131 homan , j. , wijnands , r. , van der klis , m. , belloni , t. , van paradijs , j. , klein - wolt , m. , fender , r. , mndez , m. , 2001 , apjs 132 , 377 jonker , p.g . , van der klis , m. , wijnands , r. , homan , j. , van paradijs , j. , mndez , m. , ford , e.c . , kuulkers , e. , lamb , f.k . , 2000 , apj 537 , 374 kaaret , p. , yu , w. , ford , e.c . , zhang , s.n . , 1998 , apj 497 , l93 kuulkers , e. , van der klis , m. , vaughan , b.a . , 1996 , a&a 311 , 197 mndez , m. , van der klis , m. , ford , e.c . , wijnands , r. , van paradijs , j. , 1999 , apj 511 , l49 mndez , m. , van der klis , m. , 1999 , apj 517 , l51 mndez , m. , van der klis , m. , ford , e.c . , 2000 , apj submitted , astro - ph/0006245 miller , m.c . , lamb , f.k . , psaltis , d. , 1998 , apj 508 , 791 miller , m.c . , lamb , f.k . , 1993 , apj 413 , l43 miller , m.c . , lamb , f.k . , 1996 , apj 470 , 1033 miyamoto , s. , kitamoto , s. , hayashida , k. , egoshi , w. , 1995 , apj 442 , l13 popham , r. , sunyaev , r. , 2001 , apj 547 , 355 priedhorsky , w. , 1986 , apj 306 , l97 psaltis , d. , norman , c. , 2000 , apj , submitted ; 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an explanation is proposed for the observation that in low - mass x - ray binaries the correlation between most observable x - ray spectral and timing parameters on the one hand , and x - ray luminosity on the other , while generally good in a given source on a time scale of hours , is absent both on longer time scales and between sources . this phenomenon , particularly evident in khz qpo sources , leads to parallel tracks in plots of such parameters vs. luminosity . it is pointed out that where previously proposed explanations require at least two time - variable independent parameters , such as accretion rate through the disk and through a more radial inflow , just one independent variable is in fact sufficient , provided that the systemic response to time variations in this variable has both a prompt and a time - averaged component . a specific scenario is explored in which most observable spectral and timing parameters to first order depend on disk accretion rate normalized by its own long - term average rather than on any individual accretion rate ( luminosity , on the contrary , just depends on the total accretion rate ) . this provides a way in which parameters can be uncorrelated to accretion rate , yet vary in response to variations in accretion rate . numerical simulations are presented of such a model describing the relation between khz qpo frequency and x - ray luminosity , which observationally is characterized by a striking pattern of parallel tracks in the frequency vs. luminosity plane both in individual sources and across sources . the model turns out to reproduce the observations remarkably well . physical interpretations are suggested that would produce such a scenario ; particularly promising seems an interpretation involving a radial inflow with a rate that derives through a time - averaging process from the disk accretion rate , and an inner disk radius that depends on the balance between the accretion through the disk and the total luminosity . the consequences of this idea for our understanding of states and tracks in lmxbs are discussed , and the applicability of the idea to black - hole candidates , where the observational situation is more complex , is briefly addressed .

we collected postmortem specimens from 20 corvids , including 12 american crows ( corvus brachyrhynchos ) , 4 fish crows ( corvus ossifragus ) , and 4 blue jays ( cyanocitta cristata ) , that had died ( or in one case had been euthanized after being moribund for 24 hours ) after experimental infection with the new york 1999 strain of wnv . ( the modes of infection , sampling protocol , and resulting pathogenesis will be described separately . ) brain and other organs were harvested , and postmortem cloacal and oral swabs were collected ( using standard cotton- or dacron - tipped applicators ) in 0.5-ml physiological buffer containing antibiotics , within 24 hours of death . all specimens were frozen at -70c until assayed for virus content by vero plaque assay and for wnv - specific rna by taqman reverse transcriptase polymerase chain reaction ( rt - pcr ) , as previously described ( 8) . we detected wnv rna in all postmortem brain tissue samples as well as cloacal and oral swabs . infectious wnv particles were detected in all but one specimen , a cloacal swab taken from a fish crow . viral titrations and quantitative taqman rt - pcr indicated that the concentrations of wnv averaged > 10 in all three specimen types ( table ) . in postmortem samples of brain tissue ( 1 cm ) , and oral and cloacal swabs for 12 american crows , 4 fish crows , and 4 blue jays avian mortality surveillance for wnv targets fresh carcasses ( generally dead < 24 h ) , especially corvids , for detection of infectious virus particles or rna in brain or other viscera . we have shown that postmortem oral and cloacal swabs , in addition to brain , are effective samples to collect for wnv detection in experimentally infected corvids . a potential implication of these findings , pending field trials using corvids and other species routinely collected as part of avian mortality surveillance , is that wnv may be detected by simply collecting swabs from carcasses and forwarding the swabs ( frozen ) to a virology laboratory for testing . eliminating multiple steps currently necessary for wnv testing of bird carcasses may conserve valuable public health resources and reduce the risk of exposure for laboratory personnel .

we evaluated if postmortem cloacal and oral swabs could replace brain tissue as a specimen for west nile virus ( wnv ) detection . wnv was detected in all three specimen types from 20 dead crows and jays with an average of > 105 wnv pfu in each . these findings suggest that testing cloacal or oral swabs might be a low - resource approach to detect wnv in dead birds .

damage induced by mechanical or hydraulic perturbations influences the permeability of the rock mass , with significant effects on the pore pressure distribution . modifications in the pore pressure , in turn , affects the mechanical response of the material by poromechanical coupling . according to experimental observations at the microscopic scale , fracture evolution in rocks can be interpreted essentially as a progressive damage accumulation process , characterized by nucleation , growth and coalescence of numerous cracks following changes in the external load or in the internal pore pressure @xcite . in the particular case of hydraulic fracturing , a stimulation technique used in petroleum industry to increase the oil / gas production in low permeability reservoirs , fractures are produced by the artificial increase of the fluid pressure in a borehole . from the theoretical point of view , it has been observed that the success of hydraulic fracturing is related to : i ) the creation of a dense system of hydraulic cracks with limited spacing ; and ii ) the prevention or mitigation of localization instabilities @xcite . models of distributed damage and permeability based on abstract damage mechanics are , of necessity , empirical in nature and the precise meaning and geometry of the damage variables often remains undefined or is associated with unrealistic microstructures such as distributions of isolated microcracks . in addition , the evolution of the damage variables and their relation to the deformation , stress and permeability of the rock mass is described by means of empirical and phenomenological laws that represent , at best , enlightened data fits . however , the permeability enhancement due to extensive fracturing of a rock mass depends sensitively on precise details of the topology , which needs to be _ connected _ , and geometry of the crack set , including the orientation and spacing of the cracks . in addition , the coupled hydro - mechanical response of the rock , especially when complex loading conditions and histories are of concern , is much too complex to yield to empirical data fitting . based on these considerations , in this paper we endeavor to develop a model of distributed fracturing of rock masses , and the attendant permeability enhancement thereof , based on an _ explicit micromechanical construction _ of connected patterns of cracks , or faults . the approach extends the multi - scale brittle damage material model introduced in @xcite , which is limited to mechanical damage . in contrast to abstract damage mechanics , the fracture patterns that form the basis of the theory are _ explicit _ and the rock mass undergoes deformations that are compatible and remain in static equilibrium down to the micromechanical level . the fracture patterns are not arbitrary : they are shown in @xcite to be optimal as regards their ability to relieve deviatoric stresses , and the inception , orientation and spacing of the fractures derive rigorously from energetic considerations . following inception , fractures can deform by frictional sliding or undergo opening . the extension of the theory presented here additionally accounts for fluid pressure by recourse to terzaghi s effective stress principle . when the fluid pressure is sufficiently high , existing fractures can open , thereby contributing to the permeability of the rock mass . by virtue of the explicit and connected nature of the predicted fractures , the attendant permeability enhancement can be estimated using simple relations from standard lubrication theory @xcite , resulting in a fully - coupled hydro - mechanical model . the paper is organized as follows . we begin in section [ sec : hydromechanics ] with illustrating the hydromechanical framework , recalling the basic equations and the terzaghi s effective stress principle . in section [ sec : brittledamage ] we recall the main features of the dry material model developed in @xcite , introducing a pressure dependent behavior at fault inception . in section [ sec : permeability ] we derive analytically the permeability associated to the presence of faults in the brittle damage material model . in section [ sec : examples ] we validate the material model by means of comparison with experimental results taken from the literature . in porous media saturated with freely moving fluids , deterioration of mechanical and hydraulic properties of rock masses and subsequent problems are closely related to changes in the stress state , formation of new cracks , and increase of permeability . in fully saturated rocks , fluid and solid phases are fully interconnected and the interaction between fluid and rock is characterized by coupled diffusion - deformation mechanisms that convey an apparent time - dependent character to the mechanical properties of the system . the two governing equations of the coupled problem are the linear momentum balance and the continuity equation ( mass conservation ) . the kinematic quantities that characterize this picture are the porous solid displacement @xmath0 and the rate of fluid volume per unit area @xmath1 . hydro - mechanical coupling arises from the influence of the mechanical variables ( stress , strain and displacement ) on the continuity equation , where the primary variable is the fluid pressure , and from the influence of the hydraulic variables ( pore pressure and seepage velocity ) on the equilibrium equations , where the primary variables are the displacements . the energy of a fluid flowing in a porous medium is traditionally measured in terms of total hydraulic head @xmath2 , that for slow flowing fluids reads @xmath3 where @xmath4 is the fluid density and @xmath5 the gravitational acceleration . the pressure head @xmath6 is the equivalent gauge pressure of a column of water at the base of a piezometer . the elevation head @xmath7 expresses the relative potential energy . the kinetic energy contribution , @xmath8 , is disregarded , given the small velocity @xmath9 of the fluid . flow across packed porous media is generally characterized by laminar regime ( reynolds number re @xmath10 1 ) and by a drop of the hydraulic head in the direction of the flow . analytical models of fluid flow in rocks use constitutive relations that link the average fluid velocity across the medium to the hydraulic head drop . as representative example of constitutive relation in material form , darcy s law states that the rate relative to the solid skeleton of the discharge per unit area of porous media , @xmath11 , is proportional to the hydraulic head gradient @xmath12 and inversely proportional to the fluid viscosity @xmath13 @xmath14 where @xmath15 denotes the material permeability tensor . permeability measures the ability for fluids ( gas or liquid ) to flow through a porous solid material ; it is intrinsically related to the void topology and does not account for the properties of the fluid . in anisotropic media , permeability is a symmetric ( consequence of the onsager reciprocal relations ) and positive definite ( a fluid can not flow against the pressure drop ) second order tensor @xmath15 . real eigenvalues of the permeability tensor are the principal permeabilities , and the corresponding eigenvectors indicate the principal directions of flow , i.e. , the directions where flow is parallel to the pressure drop . clearly , fractures modify the permeability tensor , introducing new preferential directions for fluid flow . although affected by many factors , in non fractured materials permeability is primarily related to the rock porosity ( or void fraction ) @xmath16 , expressing the ratio between the volume of the voids @xmath17 and the total volume @xmath18 , which includes also the volume of solids @xmath19 @xmath20 in finite kinematics , the porosity is naturally associated to the jacobian of the deformation gradient @xmath21 . by denoting the porosity of the stress - free material with @xmath22 , it holds @xmath23 ( see appendix a for details of the derivation , also cf . note that , for very low values of @xmath22 and @xmath24 , eq . may provide negative values for @xmath16 , thus a zero lower - bound must be enforced in calculations . the rate of fluid volume @xmath25 is linked to the porosity through the continuity equation , which for partially saturated voids in material form reads @xmath26 where @xmath27 the degree of saturation ( i. e. , the fraction of the fluid volume ) , @xmath28 the material divergence operator , and @xmath29 the partial derivative with respect to time . under the rather standard assumption of fully saturated voids and incompressible fluid , the continuity equation becomes @xcite @xmath30 in the absence of any occluded porosity , the solid grains forming the matrix generally undergo negligible volume changes . in keeping with standard assumptions in geomechanics , we consider the solid phase of the matrix incompressible , thus we regard the change of the volume of the matrix as a change of the volume of the voids of the matrix . this assumption is consistent with the adoption of the terzaghi s theory , used here in lieu of the more sophisticated biot theory , chosen for the sake of simplicity and to limit the number of parameters . moreover , we consider fully saturated media . in finite kinematics the deformation is measured by the deformation gradient @xmath31 , where @xmath32 and @xmath33 denote the spatial and material coordinates , respectively . the stress measure work - conjugate to @xmath34 is the first piola - kirchhoff tensor @xmath35 . the linear momentum balance reads @xmath36 where @xmath37 is the material body force vector . given the material traction @xmath38 , the material boundary condition becomes @xmath39 in keeping with terzaghi s principle of effective stress we write @xmath40 where @xmath41 is the determinant of @xmath34 . the effective stress @xmath42 and the deformation gradient define the constitutive law @xmath43 the brittle damage model presented in @xcite is characterized by a homogeneous matrix where nested microstructures of different length scales are embedded . at each level ( or rank ) @xmath44 of the nested architecture , microstructures assume the form of families of cohesive faults , characterized by an orientation @xmath45 and a uniform spacing @xmath46 , see fig . [ fig : fpa ] . in keeping with well established mathematical procedures used to treat free discontinuity problems , the brittle damage constitutive model is derived through a thermodynamically consistent approach , by assuming the existence of a free energy density which accounts for reversible and dissipative behaviors of the material . 0.3 cm 0.15 the key of the brittle damage model is given by the kinematic assumptions . we begin by considering the particular case of a single family of fault planes of normal @xmath47 and spacing @xmath48 , and later extend the behavior to recursive nested families . the total deformation gradient @xmath34 of the material is assumed to decompose multiplicatively into a part @xmath49 pertaining the uniform deformation of the matrix , and a part @xmath50 describing the discontinuous kinematics of the cohesive faults , i. e. , @xmath51 the discontinuous deformation gradient @xmath50 is related to the kinematic activity of the faults @xcite , expressed through an opening displacement @xmath52 acting on each fault of the family as ( see fig . [ fig : fpb ] ) @xmath53 once @xmath47 and @xmath48 are supplied , @xmath50 and @xmath52 are in one - to - one correspondence . the fractured material , in turn , may accommodate a second family of faults : @xmath54 this decomposition can be applied recursively for as many levels as necessary ; the innermost level will maintain a purely elastic behavior @xmath55 . the constitutive behavior of the brittle damage model follows from the introduction of a free energy density sum of two contributions with full separation of variables @xmath56 where @xmath57 is the strain - energy density per unit volume of the matrix , @xmath58 is the cohesive energy per unit surface of faults , suitably divided by the length @xmath48 to provide a specific energy per unit of volume , @xmath52 is the displacement jump , and @xmath1 is a scalar internal variable used to enforce irreversibility . note that the separation of the variables excludes strong coupling between the two energies . the operative form of the energy densities @xmath57 and @xmath58 can be selected freely according to the particular material considered . in the present model , the cohesive energy of a fault with orientation @xmath47 is assumed to depend on an effective scalar opening displacement @xmath59 defined as @xmath60 where @xmath61 is the norm of the opening displacement and @xmath62 a material parameter measuring the ratio between the shear and tensile strengths of the material @xcite . it follows that the cohesive behavior is expressed in terms of an effective cohesive law @xmath63 , dependent on the effective opening displacement only . the effective traction @xmath64 is given by @xmath65 0.5 in in applications , we use a simple effective cohesive law , visualized fig . [ fig : linearcohesive ] . during the first opening , the cohesive law follows a linearly decreasing envelope , i. e. , @xmath66 where @xmath67 the tensile resistance , @xmath68 the critical opening displacement corresponding to the full decohesion of the faults , and @xmath69 is the critical energy release rate of the material . tractions acting on the cohesive surface follows as , cf . @xcite , @xmath70 \ , .\ ] ] in the derivation of the constitutive model is necessary to introduce the configurational force conjugate to @xmath47 , given by @xmath71 fracture is an irreversible process , thus decohered faults permanently damage the material . the extent of damage is expressed through the maximum attained effective opening displacement @xmath72 . irreversibility is enforced by assuming unloading and reloading to / from the origin , see fig . [ fig : linearcohesive ] , according to the kinetic equation @xmath73 damage irreversibility is a constraint of the brittle damage model , enforced in calculations through the growth condition @xmath74 . upon fault closure the material model has to satisfy the impenetrability constraint , i. e. , the component of the opening displacement along the normal to the faults can not be negative , thus @xmath75 . more importantly , the model accounts for internal friction , a major dissipation mechanism in geological applications . we assume that friction operates at the faults concurrently with cohesion . clearly , friction can become the sole dissipative mechanism if the faults loose cohesion completely upon the attainment of the critical opening displacement @xmath76 . in considering friction , we resort to the approach proposed in pandolfi et al . @xcite and make use of a dual dissipation potential per unit area @xmath77 , where @xmath78 denotes the rate of the fault opening displacement . the behavior of irreversible materials with friction can be characterized variationally by recourse to time discretization @xcite , where a process of deformation is analyzed at distinct successive times @xmath79 , @xmath80 , @xmath81 , @xmath80 . we assume that the state of the material at time @xmath82 ( @xmath83 and @xmath84 ) is known and the total deformation @xmath85 at time @xmath86 is assigned . the problem is to determine the state of the material at time @xmath86 , accounting for material constraints and dissipation . we begin by considering a material with already a family of faults of spacing @xmath48 and orientation @xmath47 . following @xcite , the variational characterization of the material model requires to obtain an effective , incremental , strain - energy density @xmath87 by evaluating the infimum with respect to @xmath88 and @xmath89 of the extended constrained energy defined as @xmath90 the subindex @xmath16 used in @xmath91 signifies the dependence on the initial state . the irreversibility and the impenetrability constraints render the effective strain - energy density @xmath91 dependent on the initial conditions at time @xmath82 , and account for all the inelastic behaviors , such as damage , hysteresis , and path dependency . the constraints of the minimum problem can be enforced by means of two lagrange multipliers @xmath92 and @xmath93 , cf . optimization leads to a system of four equations , that provide @xmath88 , @xmath89 , @xmath92 , and @xmath93 . thus , @xmath87 acts as a potential for the first piola - kirchhoff stress tensor @xmath94 at time @xmath86 @xcite , i. e. , as @xmath95 the stable equilibrium configurations are the minimizers of the corresponding effective energy . note that the variational formulation eq . of fault friction is non - standard in that it results in an incremental minimization problem . in particular , the tangent stiffness corresponding to the incremental equilibrium problem is symmetric , contrary to what is generally expected of non - associative materials . in calculations we assume rate independent coulomb friction and , for the linearly decreasing cohesive model , we set @xmath96 where @xmath97 is the coefficient of friction and we denote the symmetric second piola - kirchhoff stress tensor of the matrix of components @xmath98 the dual dissipation potential in eq . is rate - independent , i. e. , is positively homogeneous of degree @xmath99 in @xmath100 , and proportional to the contact pressure . the fault geometrical features @xmath47 and @xmath48 , which are defined by the surrounding stress state , can be determined with the aid of the time - discretized variational formulation , as described in @xcite . the solution presented in @xcite was addressing pressure independent materials under an extensive stress state . here we provide a new solution , specific for stress states characterized by overall compression and for pressure sensitive materials . suppose that the material is undamaged at time @xmath82 and that we are given the deformation @xmath85 at time @xmath86 . we test two end states of the material , one with faults and another without faults , and choose the end state which results in the lowest incremental energy density @xmath87 . the time - discretized variational formulation allows to ascertain whether the insertion of faults is energetically favorable , and the optimal orientation of the faults in the fractured material . the orientation of the faults @xmath47 and the remaining state variables are obtained variationally from an extended constrained minimum problem , i. e. , @xmath101 constrained optimization leads to a set of six equations , whose solution provides the optimal orientation @xmath47 , @xmath1 , @xmath59 , and three lagrangian multipliers . for stress states in overall extension faults undergo simply opening . thus , the frictional dissipation is null , and the resulting normal aligns with the direction of the maximum principal value of @xmath102 , @xcite . with reference to pressure dependent materials in overall compressive states , the two optimization equations involving the normal @xmath47 where we drop the index @xmath103 for the sake of clarity become : @xmath104 = - \frac{n_j}{l + \d\cdot\bn } \ , s^{\rm m}_{ji } + \frac{1}{l } \frac{\partial\phi}{\partial \delta_i } + \frac{\dt}{l } \frac{\partial \psi^*}{\partial \delta_i } + \lambda_1 n_i = 0 \label{eq : x : update : kt1 } \\ & \frac{\partial}{\partial n_i } [ a + \frac{\dt}{l } \psi^ * + \lambda_1 \d\cdot\bn + \lambda_3 |\bn|^2 ] = \nonumber \\ & - \frac{\delta_j}{l + \d\cdot\bn } \ , s^{\rm m}_{ji } + \frac{1}{l}\frac{\partial \phi}{\partial n_i } + \frac{\dt}{l } \frac{\partial \psi^*}{\partial n_i } + \lambda_1 \delta_i + 2 \lambda_3 n_i = 0 \ , . \label{eq : x : update : kt3}\end{aligned}\ ] ] under a compressive stress , incipient faults are necessarily closed , @xmath105 , and can deform only by sliding , i. e. , @xmath106 . we denote with @xmath107 the unit vector in the direction of @xmath52 . thus , the dissipation potential can be written as @xmath108 @xmath83 being null at the inception , and eqs . - become @xmath109 @xmath110 multiplying the first of these equations by @xmath111 and the second by @xmath112 we obtain the identities @xmath113 @xmath114 the resulting equations imply that @xmath47 is a plane where the matrix shear stress satisfies the mohr - coulomb failure criterion , in the classical form @xmath115 where @xmath64 must be intended equal to @xmath67 at fault inception . thus , when faults form , @xmath116 corresponds to the cohesion ( shear resistance at null normal stress ) and @xmath117 the friction coefficient of the material . . sheds light on the meaning of the parameter @xmath62 that , for pressure sensitive materials , identifies with the friction coefficient @xmath97 . finally , eq . provides the lagrangian multiplier @xmath118 as @xmath119 + likewise , the length @xmath48 can be computed variationally by accounting for the misfit energy @xmath120 contained in the boundary layers that form at the junctions between faults and a confining boundary . in the model , the compatibility between the faults and their container is satisfied only on average , and this gives rise to boundary layers that penetrate into the faulted region to a certain depth . the addition to the energy furnishes a selection mechanism among all possible microstructures leading to a relaxed energy , cf . @xcite . so far we have been considering either an intact material or a single family of parallel faults . the material with a single fault family is referred to as rank-1 faulting pattern material . more complex microstructures can be generated effectively by applying the previous construction recursively . in the first level of recursion , we simply replace the elastic strain - energy density @xmath121 of the matrix by @xmath122 , i. e. , by the effective strain - energy density of a rank-1 faulting pattern . this substitution can now be iterated , resulting in a recursive definition of @xmath87 . the recursion stops when the matrix between the faults remains elastic . the level of recursion is the rank of the microstructure . the resulting microstructures consist of faults within faults and are shown in fig . [ fig : faults](a ) . note that the implementation of the model in a numerical code is straightforward , and can be easily obtained by using recursive calls . according to the particular loading history , at the time @xmath82 and at the generic point the material is be characterized by a particular microstructure with several @xmath52 , determined in respect of equilibrium and compatibility conditions . the model is therefore able to account for variable opening of the faults . permeability is an overall important physical property of porous media very difficult to characterize theoretically . for simple and structured models of porous media , permeability can be estimated through analytical relationships that apply only under a narrow range of conditions . the class of kozeny - carman type models collects simple relations that , under the assumption of laminar flow of the pore fluid , link the permeability to the microstructural characteristics of the porous medium . the original kozeny - carman relation @xcite reads @xmath123 where @xmath44 is a scalar permeability , @xmath124 an empirical geometric parameter , @xmath125 the ratio of the exposed surface of the channels to the volume of the solids ( also called specific internal surface area ) , and @xmath126 the tortuosity , related to the ratio between @xmath127 , average length of the channels , and @xmath48 , macroscopic length of the flow path . the estimation of the shape coefficients @xmath125 and @xmath126 has been promoting an active research @xcite . the complexity of the relationship between the permeability tensor and a scalar property such as the porosity in rocks has been clearly pointed out @xcite . the scalar nature of variables and parameters used in analytical models leads to scalar definitions , and the correct tensor nature of the permeability is disregarded . therefore , such models are not meaningful if applied to soils characterized by the presence of sedimentation layers or fissures . moreover , these models do not allow for the modification of the porous medium microstructure due to fluid - porous matrix interactions , or by the presence of a variable confining pressure . in particular , permeability depends not only on the actual stress and on the strain during the loading history , but also on the evolution of the crack patterns , which is anisotropic in nature . considering the presence of a single fault family , the permeability tensor for the fractured brittle damage model due to the sole presence of the faults can be directly derived from the particular faults geometry . the permeability of a particular geometry of parallel and equidistant faults has been examined by irmay @xcite . snow @xcite and parsons @xcite obtained expression for anisotropic permeability , similar to the one described here , by considering networks of parallel fissures . we begin by recalling that the opening displacement decomposes into a normal @xmath128 and a sliding @xmath129 components , see fig . [ fig : jump ] , computed as : @xmath130 let us assume that a fluid flows within the faults , filling the open layers of constant width @xmath128 . the average fluid flow , in laminar regime , will take place in the plane of the layer . according to the solution of the navier - stokes equation ( poiseuille s solution ) , the average velocity @xmath131 along the generic direction @xmath132 in the plane of the fault is @xmath133 where @xmath134 is the hydraulic head gradient in the direction @xmath132 . the assumption of laminar flow through a crack has been widely used in the literature , cf . , e. g. , @xcite . by considering a porous medium made of several parallel faults of equal width , the discharge @xmath135 in the direction of the flow is @xmath136 where @xmath137 is a measure of the material porosity due exclusively to the presence of faults . by comparing eqs . and , we obtain the permeability @xmath138 of the fractured material in direction @xmath132 as @xmath139 the directional gradient @xmath140 can be expressed as the scalar product of the hydraulic gradient @xmath141 and the flow direction @xmath142 , so that the magnitude of the fluid velocity reads @xmath143 and the average flow velocity vector , @xmath144 , becomes @xmath145 the hydraulic discharge can be written as @xmath146 thus the permeability tensor due to the presence of the faults @xmath147 derives as @xmath148 to account for a generic direction of the flow in the layer of normal @xmath47 , in eq . we must replace the unit vector @xmath142 with the projection @xmath149 , reaching the expression @xmath150 as a noteworthy feature of the brittle damage model , it follows that the permeability is described by an anisotropic tensor . if @xmath11 fault families are present in the porous medium , each characterized by a normal @xmath151 , a separation @xmath152 , and a normal opening displacement @xmath153 , the equivalent permeability is given by the sum of the corresponding permeabilities : @xmath154 the model does not exclude the presence of an initial porosity @xmath155 , see eq . , and permeability @xmath156 , see eq . , of the intact matrix . in this case , the resulting porosity and permeability will be given by the sum of the terms corresponding to the intact matrix and to the faults @xmath157 in practical applications we assume an isotropic matrix permeability of kozeny - carman type , with the simplified form @xmath158 where the constant @xmath159 accounts for shape coefficients . we observe that the hydraulic behavior of the brittle damage model is dependent on fracture orientation and spacing computed on the basis of the boundary conditions , and that its permeability can vary according to the kinematics of the faults . we remark that the solid phase incompressibility assumption adopted in the present model is not affecting substantially the hydraulic behavior , mostly because the porosity of the matrix plays a minor role in the hydraulic conductivity of the material . in fact in this model the porosity , and thus the permeability , is mostly imputable to the formation of faults , downsizing the relevance of the matrix porosity . numerical calculations of the dynamic multiaxial compression experiments on sintered aluminum nitride ( aln ) of chen and ravichandran @xcite were presented in @xcite by way of validation of the dry mechanical aspects of the model . the model was shown to correctly predict the general trends regarding the experimental observed damage patterns , as well as the brittle - to - ductile transition resulting under increasing confinement . therefore , in the present work we restrict validation to the hydro - mechanical aspects of the model . we describe selected examples of application of the porous damage model , starting from the response of the fully tridimensional dry model undergoing a loading that mimics a hydraulic fracturing process , and concluding with the validation of the model , reproducing a few representative experimental results on granite and sandstone . we specialize the strain energy density @xmath160 to a neo - hookean material extended to the compressible range , i. e. , @xmath161 where @xmath162 and @xmath163 are the lam coefficients , and @xmath164 is the determinant of @xmath49 . we study the response of the brittle damage model to the action of external loadings mimicking the in - field conditions observed during hydraulic fracturing procedures , and analyze the correspondent variation in permeability . we assume an intact material , with no pre - existent or natural faults , and limit our attention to the constitutive behavior . the material is characterized by the constants listed in table [ table : propertiesfracking ] . 0.1 in .rock material constants adopted in the illustrative examples [ cols="^,^,^,^,^,^,^,^,^,^,^,^",options="header " , ] [ table : rockproperties ] we begin with the simulation of the triaxial tests on samples of lac di bonnet and beishan granites documented in @xcite . the tests consisted of the application of a confining pressure of 10 mpa , followed by an axial compressive load up to failure . experiments included the measurement of the permeability of the samples , limited to the pre - peak phase . we simulate the triaxial test with the brittle damage model and compare our numerical results with experiments . [ fig : granites ] shows the deviatoric stress , @xmath165 versus axial and lateral deformations , @xmath166 and @xmath167 , respectively , and the permeability versus deviatoric stress . during the simulated axial compression , both granites develop one family of faults in shear . the failure plane of the faults corresponds to the one predicted by the mohr - coulomb criterion , inclined of an angle @xmath168 with respect to direction of maximum stress ( 21.8@xmath169 for lac du bonnet and @xmath170 for beishan ) . the peak of resistance corresponds to the experimental values , but the brittle damage model predicts a post - peak behavior which is not available in the experimental papers . experiments show an initial reduction of the permeability , due to the compression of the matrix , followed by a marked increase when the samples begin to show a reduction of stiffness . by contrast , the brittle damage model predicts a constant permeability , which does not increase even after the formation of the shear faults . however , when the load becomes too high to be balanced by friction and the axial loading reduces , faults open and the permeability increases , showing a characteristic behavior often reported in experimental literature , cf . @xcite and the numerous references therein . the model is able to capture the dependence of the permeability on porosity and on deformation mechanisms , observed typically in low porosity rocks , where additionally dilatancy is observed when rock fails by brittle faulting @xcite . indeed , microstructural observations have clarified that dilation of the pore volume is primarily due to stress - induced microcracking , which increases permeability by widening the apertures and enhancing the connectivity of the flow paths . in high porosity rocks , such as sandstones , the effect of stress on permeability is still far to be fully clarified . literature data testify apparently contradictory observations in the brittle regime @xcite . among the triaxial experiments on berea sandstone with different confinement reported in @xcite , we selected three small confinement triaxial experiments , characterized by a softening stress - strain curve . pre and post - peak porosity and permeability data are included in the experimental paper . we simulated the experimental tests at confining pressures of 5 , 10 and 40 mpa . experimental and numerical results are shown in fig . [ fig : sandstone ] . fig . [ fig : bereastress ] shows the deviatoric stress versus the axial deformation . simulations capture nicely the peak stress for the three tests , while the softening branch is not perfectly reproduced . [ fig : bereaporo ] compares numerical and experimental porosity for the two tests at lower confinement pressure . in both simulation and experiment , porosity reduces progressively until the stress peak is reached , and grows during the softening phase , in correspondence to the reduction of the deviatoric stress . simulations predict qualitatively and quantitatively the variation of porosity during the test . contrariwise , the comparison between model predictions and experimental observations in terms of permeability evolution is not satisfactory , even from the qualitative point of view . in the experiments , permeability decreased markedly after the stress peak , showing a marked negative correlation between permeability and porosity changes fig . [ fig : bereapermexp ] . experimental data on different sandstones are qualitatively similar , suggesting that permeability evolution as a function of porosity does not follow any systematic trend . a possible explanation of the observed permeability reduction in particular dilating sandstone is that microcracking dramatically increases the tortuosity of the pore space @xcite . the brittle damage model predicts a post - peak increase in permeability , see fig . [ fig : bereapermnum ] , which is opposite to the berea sandstone experiments , but in line with many experimental results on low permeability geomaterials , and is also in agreement with the simulations on granites discussed here . we have developed a model of distributed fracturing of rock masses , and the attendant permeability enhancement thereof , based on an explicit micromechanical construction resulting in complex connected patterns of cracks , or faults . the approach extends the multi - scale brittle damage material model introduced in @xcite , which was limited to mechanical damage . the fracture patterns that form the basis of the theory are not implied but explicitly defined and the rock mass undergoes throughout compatible deformations and remains in static equilibrium , not just on average at the macroscopic scale , but also the micromechanical level . the sequential faulting construction used to generate the fracture patterns has been shown in @xcite to be optimal as regards the ability of the fracture patterns to relieve stress . in addition , the nucleation criterion , orientation and spacing of the faults derive rigorously from energetic considerations . following nucleation , fractures can deform by frictional sliding or undergo opening , thereby partially relieving the geostatic stresses in the rock mass . the extension of the theory presented in this paper additionally accounts for fluid pressure by recourse to terzaghi s effective stress principle . specifically , we estimate the permeability enhancement resulting from fracture enhancement using standard lubrication theory @xcite . this extension gives rise to a fully - coupled hydro - mechanical model . the formulation has been derived in finite kinematics to be consistent with the formulation of the damage model in [ 18 ] . a finite kinematics approach is able to describe both large and small strains , so that the model can be applied also to porous media different from rocks . a linear version of the model is currently under development , in view of heavy numerical applications in field problems . the dry mechanical aspects of the model were validated in @xcite by means of comparisons with the dynamic multiaxial compression experiments on sintered aluminum nitride ( aln ) of chen and ravichandran @xcite . the model was shown to correctly predict the general trends regarding the experimental observed damage patterns , as well as the brittle - to - ductile transition resulting under increasing confinement . the hydro - mechanical coupled model has been validated against three different sets of experimental data concerned with triaxial tests at different confinement pressure on granite and sandstone , including lac du bonnet @xcite and beisahn @xcite granites and berea sandstone @xcite . the ability of the model to reproduce qualitatively the experimental peak strength , post - peak stress - strain behavior , and permeability enhancement during loading and recovery during unloading is remarkable . the present coupled hydro - mechanical model has potential for use in applications , such as rocks under geostatic conditions , gravity dams , hydraulic fracture operations , and others , in which a solid deforms and undergoes extensive fracture under all - around confinement while simultaneously being infiltrated by a fluid . the particular case of hydraulic fracture is characterized by the injection of fluid at high pressure , which actively promotes the fracture process and the transport of fluid into the rock mass . under such conditions , the present model is expected to predict the development of three - dimensional fracture patterns of great complexity over multiple scales . such complex fracture patterns have indeed been inferred from acoustic measurements in actual hydraulic fracture operations @xcite and are in sharp contrast to traditional models of hydraulic fracture , which posit the formation of a single mathematically - sharp crack . the present model thus represents a paradigm shift from said traditional models in its ability to account for complexity in the fracture pattern over multiple scale while simultaneously supplying macroscopic effective properties such as permeability and strength that can in turn be used , e. g. , in full - field finite element simulations . by denoting the time derivative with @xmath171 , we write @xmath172 assuming that the solid volume variation is small with respect to the void volume , @xmath173 and @xmath174 . thus the rate of porosity change becomes : @xmath175 this relation can be alternatively written in the form @xmath176 where @xmath177 is a constant , which can be derived by setting as initial values @xmath178 and @xmath22 , obtaining @xmath179 10 n. r. warpinski , r. c. kramm , j. r. heinze , and c. k. waltman . comparison of single- and dual - array microseismic mapping techniques in the barnett shale . in _ spe annual technical conference and exhibition _ , volume spe 95568 , dallas , texas , october 2005 . society of petroleum engineers . r. wu , o. kresse , x. weng , c. e. cohen , and h. gu . modeling of interaction of hydraulic fractures in complex fracture networks . in _ spe hydraulic fracturing technology conference _ , volume spe-152052-ms , the woodlands , texas , february 2012 . society of petroleum engineers .

we present a microstructural model of permeability in fractured solids , where the fractures are described in terms of recursive families of parallel , equidistant cohesive faults . faults originate upon the attainment of a tensile or shear resistance in the undamaged material . secondary faults may form in a hierarchical organization , creating a complex network of connected fractures that modify the permeability of the solid . the undamaged solid may possess initial porosity and permeability . the particular geometry of the superposed micro - faults lends itself to an explicit analytical quantification of the porosity and permeability of the damaged material . the approach is particularly appealing as a means of modeling a wide scope of engineering problems , ranging from the prevention of water or gas outburst into underground mines to the prediction of the integrity of reservoirs for co2 sequestration or hazardous waste storage . microstructured permeability ; parallel faults ; multi - scale permeability ; analytical models .

the sloan digital sky survey ( sdss ) is a digital photometric and spectroscopic survey which will cover 10,000 deg@xmath4 of the celestial sphere in the north galactic cap and produce a smaller ( @xmath5 225 deg@xmath4 ) but much deeper survey in the southern galactic hemisphere ( york _ et al . _ 2000 and references therein ) . the survey sky coverage will result in photometric measurements for about 50 million stars and a similar number of galaxies . the flux densities of detected objects are measured almost simultaneously in five bands ( @xmath6 , @xmath7 , @xmath8 , @xmath9 , and @xmath10 ; @xcite ) with effective wavelengths of 3551 , 4686 , 6166 , 7480 , and 8932 , 95% complete0.1 arcsec . ] for point sources to limiting magnitudes of 22.0 , 22.2 , 22.2 , 21.3 , and 20.5 in the north galactic cap and @xmath11 because the absolute calibration of the sdss photometric system ( dependent on a network of standard stars ) is still uncertain at the @xmath12 level . the sdss filters themselves are referred to as @xmath13 and @xmath10 . all magnitudes are given on the ab@xmath14 system ( oke & gunn 1983 , for additional discussion regarding the sdss photometric system see @xcite , and stoughton _ et al . _ 2002 ) . ] . astrometric positions are accurate to about 0.1 arcsec per coordinate ( rms ) for sources brighter than 20.5@xmath15 ( pier _ et al . _ 2001 ) , and the morphological information from the images allows robust star - galaxy separation to @xmath5 21.5@xmath15 ( lupton _ et al . _ 2002 ) . sdss , although primarily designed for observations of extragalactic objects , will significantly contribute to studies of the solar system objects , because asteroids in the imaging survey must be explicitly detected to avoid contamination of the samples of extragalactic objects selected for spectroscopy . ( 2001 , hereafter i01 ) analyzed sdss commissioning data and showed that sdss will increase the number of asteroids with accurate five - color photometry by more than two orders of magnitude ( to about 100,000 ) , and to a limit about seven magnitudes fainter than previous multi - color surveys ( e.g. the eight color asteroid survey by zellner , tholen & tedesco 1985 ) . the main results derived from these early sdss observations are 1 . a measurement of the main - belt asteroid size distribution to a significantly smaller size limit ( 1 km ) than possible before . the size distribution resembles a broken power - law , independent of the heliocentric distance : @xmath16 for 0.4 km @xmath17 5 km , and @xmath18 for 5 km @xmath17 40 km . 2 . a smaller number of asteroids compared to previous work . in particular , the number of asteroids with diameters larger than 1 km is about @xmath19 , or up to three times less then suggested by earlier studies . the distribution of main - belt asteroids in 4-dimensional sdss color space is strongly bimodal , and the two groups can be associated with s ( rocky ) and c ( carbonaceous ) type asteroids . a strong bimodality is also seen in the heliocentric distribution of asteroids : the inner belt is dominated by s type asteroids centered at @xmath20 2.8 au , while c type asteroids , centered at @xmath20 3.2 au , dominate the outer belt . i01 demonstrated that the sdss photometric pipeline ( _ photo _ , lupton _ et al . _ 2002 ) is a robust and highly efficient automated tool for finding moving objects . i01 present a detailed discussion of the completeness and reliability of the sdss asteroid catalog based on the known sdss photometric and astrometric precision , but this discussion is incomplete because it does not attempt a direct comparison with catalog of known asteroids on an object - by - object basis . the importance of such an analysis is evident from the realization that there are 90,000 _ cataloged _ asteroids with @xmath21 , while i01 expect to find only 58,000 in the same absolute magnitude range . the implied low completeness of 64% ( compare to 98% estimated by i01 ) can only be verified by direct matching of known and sdss asteroids . another motivation for cross - correlating sdss asteroids and known asteroids is a large potential increase in the number of asteroids with both accurate multi - color photometry and known orbital parameters ( the sdss data themselves are insufficient for accurate orbit determination , but will provide serendipitous photometric measurements for a substantial fraction of known asteroids ) . additionally , the sdss color information may be utilized to study the chemical segregation in the full orbital parameter space , rather than only as a function of heliocentric distance as done by i01 . this paper presents the first results on cross - correlating sdss asteroids and cataloged asteroids . section 2 describes the analyzed data , a software pipeline used for generating the positions of known asteroids at the time of sdss observations , and their positional matching to objects automatically detected by the sdss photometric pipeline . section 3 discusses the statistics of matched objects , and compares the sdss photometric measurements with the apparent magnitudes predicted from cataloged absolute magnitudes . in section 4 we discuss the chemical segregation of asteroids in orbital element space , and in section 5 we summarize the main results . we use asteroid data ( c.f . i01 ) from the sdss early data release , described in detail by stoughton _ _ 2002 ( hereafter sdssedr ) . these data include equatorial observing runs 94 , 125 , 752 and 756 ( see i01 and sdssedr ) ; the boundaries are given by @xmath22 , and @xmath23 = 351@xmath24 56@xmath24 ( runs 94 and 125 ) , or @xmath23 = 145@xmath24 250@xmath24 ( runs 752 and 756 ) . for a footprint in ecliptic coordinates , see figure 1 in i01 . this region has an area of 432 deg@xmath4 and includes 12,668 moving objects selected as in i01 ( the velocity @xmath25 deg / day and @xmath26 ) . we use this sample for all quantitative estimates of the catalog completeness , and for photometric comparison . in order to increase the number of objects when studying the color segregation in the asteroid belt ( section [ colseg ] ) , we also add additional objects from seven currently unreleased equatorial observing runs that roughly double the matched sample size . the sdss photometric data include a list of objects flagged as moving by the photometric pipeline . for each object , the position and time of observation , and the magnitudes and associated errors in five sdss photometric bands ( @xmath27 ) are recorded . the sdss imaging data is obtained in the time - delay - and - integrate ( tdi , or drift - scanning " ) mode , and thus each observed position corresponds to a different observing time ( as opposed to the starring mode where all objects from a given image are observed at the same time ) . in a general case , the correlation between a position and time is easiest to compute in the great circle coordinate system . since all the scans discussed here were obtained along the celestial equator , this dependence becomes particularly simple , and is given by @xmath28 where @xmath29 is the time corresponding to position @xmath23 ( e.g. julian day ) , and the zeropoints @xmath30 and @xmath31 are constants for a given run ( all reported positions correspond to the @xmath8 band ) . for an arbitrary run , this expression is easily generalized by using an appropriate coordinate system . the cataloged asteroid magnitudes are reported in the johnson @xmath32 band . preliminary transformations from the sdss photometric system to the johnson bands are given by fukugita _ ( 1996 ) and krisciunas , margon & szkody ( 1998 ) . we use a recent updated version of these transformations ( m. fukugita , priv . comm . ; the new transformations produce v magnitudes that agree to better than 0.1 mag with the version from fukugita _ et al . _ 1996 ) to synthesize the johnson b and v band magnitudes @xmath33 for typical values of for asteroids ( 0.40.8 ) , @xmath34 is in the range 0.16 to 0.33 . the overall accuracy of these transformations and sdss photometry is better than 0.05 mag , as determined by direct comparison with non - sdss observations obtained in the johnson system ( m. fukugita , e. grebel , j. holtzman , unpublished ) . for positional matching of the moving objects observed by sdss with cataloged asteroids we select the asteroid orbital elements database ( astorb ) . astorb is a catalog of high - precision osculating orbital elements and other information on all numbered and a large number of unnumbered asteroids ( but does not contain information on known numbered comets ) . the astorb catalog is distributed by the lowell observatory in the form of an ascii file , containing single line records for each asteroid ( bowell 2001 ) . the catalog is updated daily for addition of newly discovered objects , deletion of duplicate objects , and improvement of parameters of known objects . in this work we use the six osculating orbital elements , absolute magnitude and the phase - correction slope parameter which are necessary to predict the asteroid position and apparent magnitude at the time of sdss scans . we also utilize the arc ( in days ) spanned by the observations used to compute the orbit to estimate the accuracy of orbital elements . orbital elements given in astorb are heliocentric and have been computed by a variable - timestep differential orbit correction algorithm , based on astrometric observations obtained from the minor planet center . the perturbations from all the major planets , the moon and the three largest asteroids ( ceres , pallas and vesta ) have been taken into account . absolute magnitude corresponding to the johnson @xmath32 band ( @xmath35 , see i01 ) is listed as numbers rounded to two , one , or no decimal places , with the number of decimal places reflecting assumed reliability . however , for unnumbered asteroids @xmath35 is given to two decimal places regardless of its real accuracy . the slope parameter @xmath36 ( see section [ apmags ] below ) is given for asteroids for which it is known , and for others , which are the overwhelming majority of the sample , assumed to be 0.15 ( dimensionless ) . we note that besides astorb there are several other asteroid orbital elements databases ( e.g. minor planet center orbit database , asteroid dynamics site ) . however , because of its widespread use and significant additional information supplied for each asteroid , we have chosen to use astorb as a referent catalog for this study . the astorb version used here is from september 18 , 2001 , and contains 141,110 objects ( 29,074 of which are numbered asteroids ) . the asteroid identification pipeline consists of three parts : 1 . propagation of the asteroid osculating orbital elements from astorb to the epoch of the sdss observation 2 . computation of the asteroid positions and apparent magnitudes at the time of sdss scan 3 . positional matching of sdss moving objects with the known asteroids the astorb catalog contains osculating orbital elements computed for epoch near the current epoch , where `` current '' corresponds to the publishing date of the astorb catalog file . the orbital elements are propagated to the epoch of observation using the proele routine of orbfit v1.8 _ propag _ library ( @xcite ) . we use the default dynamical model supplied with the orbfit package . it includes gravitational perturbations of the sun , moon and the major planets and relativistic corrections , when necessary . the positions and masses for major planets are derived from jpl ephemeris de405 ( standish 1998 ) . although the orbfit package offers multiple choices for the numerical integration schemes , we use its automated selection procedures , which has been proven to be sufficiently accurate in practice ( @xcite ) . the end result of the orbit propagation is a catalog of osculating orbital elements at the time of sdss observation , which are then used for quick two - body ( sun and asteroid ) computations of the ephemeris . the calculations of positions are performed using a modified preobs routine from the same orbfit package ( the modification consists of enabling a two - body approximation ) . when calculating the positions of cataloged asteroids , they must satisfy the condition given by eq . [ tdrift ] . we solve the problem iteratively , until the difference between the positions calculated in two successive iterations is smaller than 0.001 arcsec . in practice the computations converge rapidly and usually reach the required accuracy with two to three iterations . the apparent magnitudes are computed by orbfit s appmag subroutine from the cataloged values of the absolute magnitude @xmath35 and the phase - correction slope parameter @xmath36 . the phase - corrected apparent visual `` catalog '' magnitude , @xmath37 , is obtained from ( bowell 1999 ) @xmath38 where @xmath20 is the heliocentric , and @xmath39 is the geocentric distance ( expressed in au ) , @xmath40 is the `` solar '' angle ( the angle between the sun and the earth as viewed from the asteroid , see i01 ) , and @xmath41 and @xmath42 are the `` phase - correction '' functions . the latter are obtained from standard approximations @xmath43 ; \,\ , i = 1 , 2 \\ a_1 = 3.33\ \,\ a_2 = 1.87 \non b_1 = 0.63\ \,\ b_2 = 1.22 \non\end{aligned}\ ] ] note that these approximations are formally different from the one used by i01 ( eq . however , they are similar numerically ; the difference is less than 0.05 mag for @xmath44 and @xmath45 , with the maximum value of 0.15 mag at @xmath46 . the matching algorithm compares the list of predicted positions for the known asteroids with the list of sdss objects flagged as moving by the photometric pipeline . after finding the nearest - neighbor pairs from the two lists , it requires that the distance between the two positions is less than 30 arcsec . the final sample is very insensitive to the precise value of this cut because for the majority ( 86% ) of matched objects the distance between the two positions is less than 3 arcsec ( centered on zero in both coordinates ) . the probability that a randomly chosen position would fall within 3 arcsec from a moving sdss object is of the order 10@xmath47 in the regions with the highest asteroid number density ( 64 deg@xmath48 , i01 ) , implying that only about one of the matches within 3 arcsec is a random association . the associated objects are taken to be positive positional identifications of an sdss moving object with a cataloged asteroid . the sdss photometric pipeline identified 12,668 moving objects selected as described by i01 . there are 2801 cataloged asteroids whose computed positions are within the boundaries of the sdss scans considered here , and 1633 have within 30 arcsec an object flagged by sdss photometric pipeline as moving . of these , only 1325 are unique objects because some asteroids were observed by sdss more than once ( i01 ) . detailed statistics for each run are listed in table 1 . this comparison , taken at face value , implies that the sdss sample is 58% complete . this is a much lower completeness than claimed by i01 ( 98% ) . we have visually inspected sdss images around the positions of all 1168 astorb objects not found in the sdss catalog ( moving objects are easily recognized on 1x1 arcmin g - r - i color composites thanks to their peculiar appearances , see i01 ) . there are 219 objects which are clearly moving , but were not recognized as such by the photometric pipeline . the most common reason for missing them are complex environments ( bright stars with diffraction spikes , compact galaxy clusters , meteor and airplane trails , etc . ) which are hard to `` deblend '' into individual sources . the revised , true completeness of the sdss sample is thus 88% , somewhat lower than 98% determined by i01 . we note that i01 determined completeness using only data from run 756 . for this run the completeness determined here is 91% . furthemore , for all runs except for run 94 the completeness is higher than 90% . the overall completeness is below 90% only for run 94 ( 81% ) , which is one of the earliest sdss commissioning runs , obtained while the telescope still did not have proper optics . for the remaining 949 ( 34% of the total ) astorb objects there is no visible sdss source within 30 arcsec from the predicted position down to the sensitivity limit of 22.5 . the most plausible explanation for these `` missing '' sources is inaccurate orbital elements ( that is , their true position during sdss observations is further than 30 arcsec from the predicted position ) . indeed , the inspection of their entries in the astorb catalog indicates that the majority are either faint ( @xmath49 ) , have a small observational arc used to determine the orbital elements , or both . sdss observations demonstrate that a large fraction of known asteroids listed in the astorb catalog do not have sufficiently accurate orbital elements for reliable identification . the observational arc used to determine the orbital elements can be utilized as a rough estimate of their quality the longer the arc spanned by the observations used to compute the elements , the more accurate are the positions . the astorb catalog also provides a more quantitative estimate for the accuracy of the orbital elements the _ current ephemeris uncertainty ( @xmath50 ) _ parameter ( 1-@xmath51 absolute positional uncertainty ) , for an epoch near the catalog publishing date . however , the @xmath50 can not be propagated to the time of observation without the knowledge of covariance matrices for the orbital elements solution ( cf . @xcite ) , and we use arc to make a quality cut . the relationship between the @xmath50 and the arc is shown in figure [ fig_arc ] . the top panel shows each object from the astorb catalog as a dot , and the bottom panel shows the arc histograms for all objects by a full line , and separately for objects with @xmath52 30 arcsec as a shaded region . as evident , the requirement that arc @xmath53 300 days successfully eliminates most of the asteroids with large ceus , and selects 1634 objects ( out of 2801 ) . note that the resulting sample is insensitive to the precise value of this cutoff because of the non - continuous distribution of data . a further constraint is based on the predicted apparent magnitude . we only select asteroids that are reliably detectable by sdss ; they satisfy @xmath54 ( i01 ) . this cut has only a minor importance and selects 1612 objects ( relaxing the limit to 22.5 adds 3 objects ) . the absolute magnitudes for selected ( hereafter `` reliable '' ) and removed asteroids ( hereafter `` unreliable '' ) are compared in figure [ fig_hlog ] . the solid line shows the absolute magnitude distribution for all 2801 asteroids , and the dashed and dotted lines show the distributions for the 1612 ( 58% ) reliable and 1189 ( 42% ) unreliable asteroids , respectively . it is evident that the asteroids with unreliable orbital parameters are mostly faint , and dominate the sample for @xmath55 . the subsample of reliable asteroids appears complete for @xmath56 . the removal of the sources with unreliable orbital elements is efficient , but not perfect . the matching statistics for the subsample of astorb asteroids with reliable orbits is listed in table 2 . out of 1612 objects , 1335 are matched within 30 arcsec to objects automatically recognized by the photometric pipeline as moving . of the remaining 277 objects , 173 are visually identified as moving , and the remaining 104 objects do not have an sdss moving source within 30 arcsec . for each of these 104 objects , the predicted position has been independently verified using the on - line astdys orbital calculator . in summary , the arc @xmath53 300 days cut decreases the fraction of astorb catalog asteroids with unreliable orbital elements from 34% to 6% . the sdss completeness based on the reduced sample is 89% ( = 1335/1508 ) , consistent with the estimate based on the full sample ( 88% ) . since the removed objects are predominantly faint , this agreement indicates that the sdss completeness is not strongly dependent on apparent magnitude . the sample of 1335 matched objects that were detected by the photometric pipeline , together with the sample of 173 visually confirmed objects from the astorb catalog , can be used to determine whether the completeness of the sdss automatically detected sample depends on magnitude . the top panel in figure [ fig_hlog_det ] compares the absolute magnitude distribution , as listed in the astorb catalog , for the 1335 matched objects ( dashed line ) to the distribution of all 1612 objects ( full line ) . the bottom panel shows the fraction of matched sources in each magnitude bin , shown by full line with error bars . the horizontal line is added to guide the eye and represents the overall completeness of 89% . as evident , there is no significant correlation between the fraction of matched sources and the magnitude . we have also tested for correlations between the fraction of matched sources and the phase angle , the object s color and apparent magnitude and did not find any significant dependences . the top panel in figure [ fig_vlog ] compares the apparent magnitude distribution for asteroids from the astorb catalog that are within the boundaries of sdss scans discussed here ( full line ) , with the apparent magnitude distributions for moving objects detected by sdss . the distribution for all sdss objects is shown by the dashed line and the distribution for matched objects by the dotted line . we use the calculated @xmath37 magnitudes for the astorb asteroids and synthesized @xmath57 magnitudes for sdss asteroids ( including the matched sample ; this is why the dotted line is above the solid line for @xmath58 ) . at first sight it appears that the sdss sample is significantly incomplete . the bottom panel shows the number ratio of astorb and sdss asteroids in each magnitude bin , and indicates that the sdss completeness is as low as 60% for @xmath59 . however , as demonstrated in the previous section ( see figure [ fig_hlog_det ] ) , the sdss catalog _ includes _ 89% of astorb asteroids , and the mismatch in figure [ fig_vlog ] is simply due to an offset in apparent magnitude scales . the existence of such an offset is further corroborated by the direct comparison of the calculated ( @xmath37 , based on the astorb catalog ) and synthesized ( @xmath57 , based on sdss observations ) magnitudes for the 1335 matched objects . the top panel in figure [ fig_mdiff_hist ] shows the histogram of the difference @xmath60 for all 1335 objects by the full line . the median offset is 0.41 mag ( the sdss values are fainter ) , with the root - mean - scatter of 0.35 mag . the dotted and dashed lines show the @xmath60 histograms for the 400 blue asteroids and the 935 red asteroids selected by their color as described in i01 . it is evident that the apparent magnitude offset depends on the asteroid color ; the median offsets are 0.34 and 0.44 for the blue and red subsample , respectively . this dependence is further illustrated in the bottom panel , where the @xmath60 difference is plotted as a function of the asteroid color . the @xmath60 histograms shown in figure [ fig_mdiff_hist ] are not symmetric and give a hint of two components : one centered at 0.1 is independent of color , and the other one centered at 0.4 - 0.5 that appears to be color - dependent . this bimodality is more pronounced for @xmath61 , as discernible in figure [ fig_mdiff ] . it is of obvious interest to find out whether the offset between predicted and observed magnitudes is particular to the astorb catalog , or perhaps also present in other available databases . for this test we chose the minor planet center orbit database from september 5 , 2001 . it contains similar data to the astorb catalog for 115,797 objects ; 115,583 of these objects are common to both catalogs . the top panel in figure [ m.mdiff_cats ] compares the listed absolute magnitudes for the objects in common . as evident , the catalogs contain two `` populations '' of object . for about half of the sample the difference between the two values is less than 0.1 mag , while for the remaining 57,719 objects it is larger than 0.1 . the median value for the latter is 0.4 . we did not find any correlation between the difference in absolute magnitude and other cataloged quantities . in particular , there is no correlation between this difference and the mean absolute magnitude . given only two catalogs , it is not possible to tell which one is responsible for the offset in magnitude scale . fortunately , the catalogs can be compared to sdss observations of the matched objects for which the photometric errors are not larger than 0.05 mag . the bottom panel in figure [ m.mdiff_cats ] compares the @xmath60 histograms obtained with the data from the astorb catalog ( full line ) and from the mpc catalog ( dashed line ) . as evident , the median discrepancy between the cataloged magnitudes and the magnitudes measured by sdss is about twice as large for the astorb catalog as for the mpc catalog ( 0.4 mag vs. 0.2 mag ) . based on this finding alone , it would seem that the mpc catalog should be used for the matching purposes . however , the mpc catalog contains fewer objects than the astorb catalog ; out of the 1633 matched objects only 1387 are found in the mpc catalog ( implying an upper limit on the completeness of the mpc catalog of 85% ) . the discrepancy in the absolute magnitude scale significantly affects the number of objects brighter than a given limit . assuming that the number counts follow a @xmath62 relation ( i01 ) , the mpc catalog will imply 1.32 more objects than sdss measurements , and the astorb catalog will imply 1.74 more objects than sdss measurements . although the uncertainty in the values of @xmath57 synthesized from the sdss photometry is probably smaller than 0.05 mag , it is prudent to verify the offset in magnitude scales using non - sdss observations . krisciunas , margon and szkody ( 1998 ) obtained photometric measurements in sdss - like bands for 15 bright asteroids . table 3 lists their measurements , and the synthesized , @xmath57 , and predicted , @xmath37 , magnitudes . the @xmath60 difference is shown as a function of @xmath57 in figure [ fig_krisc ] . asteroids with @xmath35 in the astorb catalog given to two decimal places are marked as circles , and those with one decimal place are marked by triangles . the former are predominantly at the bright end where they scatter around zero offset , indicating that the photometric transformations from sdss to johnson v band are not biased . the latter are found at the faint end and indicate a similar offset in the magnitude scales as discussed above . the correlation between the magnitude offset and the asteroid color indicates that the discrepancy is probably due to differences in the standard johnson v magnitude and the `` visual '' magnitude listed in the astorb catalog . a most likely cause is the fact that the majority of current asteroid surveys ( which produced most of the entries in the catalogs ) are obtained with open , unfiltered ccds since they are mostly concentrated on astrometric measurements . thus , the measured magnitudes are not equivalent to the standard johnson v band , and furthermore , the discrepancy depends on the asteroid color . indeed , as discussed by jedicke , larsen & spahr ( 2002 ) , the reporting of observed asteroid magnitudes is notoriously inconsistent . for example , the minor planet center regularly weights magnitudes reported by different groups according to their historical photometric accuracy and transforms them to the @xmath32 band , while the astorb database uses the unweighted photometry in observed bands in determining the absolute magnitude . correcting the predicted magnitudes for a median offset of 0.41 mag shifts the @xmath37 histogram for astorb asteroids shown in figure [ fig_vlog ] by the right amount to make the matched fraction consistent with the estimate shown in figure [ fig_hlog_det ] . we show the shifted histogram in figure [ fig_vlog_mod ] . as discussed in section [ sdssdata ] , we joined the 1335 matched objects from the sdss early data release with 1306 matched objects from unreleased runs , to form the final sample of 2641 unique matched objects . this is the sample used in our analysis of the color segregation in the asteroid belt . asteroid dynamical families are groupings of asteroids in proper orbital elements space , widely thought to be the results of collisional disruptions of parent bodies ( larger asteroids ) . pioneered by hirayama ( 1918 ) , the number and understanding of asteroid families has increased dramatically thanks to a number of factors a large increase in the number of discovered asteroids , more advanced knowledge of celestial mechanics and more sophisticated cluster - discovery techniques . for a detailed review see chapman _ et al . _ 1989 . in a recent study , zappala _ et al . ( 1995 ) identified 32 families and 31 clumps " using a hierarchical clustering method in a sample of 12,487 asteroids . however , even a rough taxonomic classification exists only for a small number of these objects . the knowledge of the chemical composition of each family could provide further clues about the physical properties of the parent body . sdss photometric data can remedy this problem because the asteroids segregate in sdss multi - dimensional color space . in this section we analyze the correlation between sdss colors and the distribution in orbital parameter space for 2641 matched asteroids . in order to study the correlation between sdss colors and the various taxonomic systems , we have cross - referenced the 1335 matched asteroids from the sdss edr sample with a catalog of asteroids with known taxonomy obtained at the planetary data system small bodies node . the catalog contains information on 1199 objects , with tholen ( 978 objects ) , barucci ( 438 objects ) , tedesco ( 357 objects ) , howell ( 112 objects ) and xu ( 221 objects ) taxonomies . there are only seven asteroids with taxonomical information present in the sdss sample , and are listed in table 4 . this small number is not surprising given that the sdss saturation limit ( @xmath63 ) is usually below the faint limit for most taxonomy surveys . the seven asteroids have sdss colors in agreement with their taxonomic types ( i01 ) . the 2641 known asteroids observed by sdss have been cross - referenced with the catalog of proper orbital elements produced by milani _ ( 1999 ) and distributed through astdys . the resulting sample includes 1768 asteroids with available proper elements . hereafter we separate this sample into 531 blue asteroids ( @xmath64 , see i01 ) , and 1237 red asteroids ( @xmath65 ) . as discussed by i01 , there is a possibility that red asteroids with @xmath66 form a separate group in color - color space , and we treat separately the 131 asteroids with such colors . in the remainder of this section , we analyze the differences in the distributions of these subsamples in the three - dimensional space spanned by the semi - major axis , @xmath67 , inclination , @xmath68 , and eccentricity , @xmath69 . figure [ fig_a_i ] displays the distribution of asteroids in the @xmath67 vs. @xmath70 plane . the top panel shows 67,917 asteroids from the astorb database which have known proper orbital elements ( from milani _ et al . _ 1999 ) , marked as dots . the major dynamical families ( also known as the hirayama families ) eos , koronis and themis , are clearly visible at @xmath71 au ; their approximate ( @xmath72 ) positions are ( 3.0 , 0.18 ) , ( 2.9 , 0.03 ) and ( 3.15,0.02 ) , respectively . the 4:1 , 3:1 , 5:2 and 2:1 mean motion resonances with jupiter at 2.065 , 2.501 , 2.825 and 3.278 au ( the latter three correspond to the kirkwood gaps ) are also evident . the @xmath73 resonance is visible as a strong cuttof of asteroid density at high inclinations in the @xmath74 region . due to using a sample which is about five times larger , the various families are more easily discerned than in zappala _ ( 1995 ) ; however , the distribution shown here agrees with their results . the remaining two panels show the same distribution as isodensity contours , with the matched asteroids shows by open circles . the middle panel shows blue asteroids ( @xmath75 0 ) , and the bottom panel shows red asteroids ( @xmath53 0 ) . a subset of red asteroids with @xmath76 is shown by crosses ; most are found around @xmath67 2.22.5 and @xmath70 0.12 . figures [ fig_a_e ] and [ fig_i_e ] are analogous to figure [ fig_a_i ] , and show the asteroid distributions in the @xmath69 vs. @xmath67 and @xmath69 vs. @xmath70 planes . figure [ fig_i_e ] shows the distributions in three belt regions selected by the positions of resonances . for studying the chemical composition of various families , we adopt the family definitions by zappala _ the distribution of blue and red asteroids in the @xmath67-@xmath70-@xmath69 space confirms the earlier results for the three largest families . koronis and eos family seem to be mostly composed of red asteroids : 40 out of 45 ( 89% ) asteroids associated with the koronis family are red , and 77 of 98 ( 79% ) are red for the eos family . on the other hand , the themis family is predominantly blue : 41 out of 43 ( 95% ) members have @xmath77 . all three major families are located in the outer belt . from other families in the outer belt we find two members of the brasilia family , both are blue . the middle portion of the belt , between the 3:1 and 5:2 resonances ( 2.5 @xmath78 2.8 ) contains a number of smaller families . the sdss sample discussed here provides good color information for five of them . the maria family is found to be red with 16 out of 21 asteroids with @xmath79 . the more numerous eunomia family also displays red characteristics ( 97 red and 7 blue members ) . on the other hand , the adeona family and the dora family are blue ( 12 out of 15 , and all 11 members are blue , respectively ) . the ceres family seems to be a mix of both asteroid types , with 11 blue and 24 red asteroids . other smaller families have fewer identified members ; we find marginal evidence that the hoffmeister , rafita and hestia families are predominantly red , while the misa and taiyuan families are predominantly blue . the inner part of the belt is dominated by the vesta / flora complex and at lower inclinations by the nysa / polana and massalia families . the nysa / polana group is found to include a mix of red and blue asteroids , with red asteroids dominating the sample in approximately 3:1 ratio ( 51 red and 19 blue ) . this is the strongest mixing of blue and red asteroids found for the families studied here , and supports the claim by cellino _ ( 2001 ) that the nysa / polana group includes two independent families , one composed of s ( red ) asteroids and the other including low - albedo f - like ( presumably blue ) objects . we note that for many families we find a substantial fraction ( @xmath80 10% ) of the minor component ( e.g. 20% of the red eos family members are blue ) . it is not easy to determine whether this mixing is due to the background contamination ( i.e. by asteroids that are not family members ) , or due to non - homogeneous structure of the parent bodies . a robust analysis necessarily involves precise definitions of families , and a careful study of the multi - dimensional color distribution for each family . such an analysis is beyond the scope of this work and will be presented in a future publication . i01 analyzed the distribution of 316 asteroids in sdss color space by producing synthetic sdss colors from the spectral measurements obtained by the smass project ( xu _ et al . in addition to the two major color types , there was an indication that red asteroids with extremely blue colors may form a separate class ( see figure 10 in i01 ) . this notion was also supported by the taxonomic classification of asteroids with such colors ; they were all classified as the j and v asteroids associated with the vesta family ( binzel & xu 1995 ) . the proper orbital elements for 131 objects with @xmath76 discussed here can be used to test whether these objects cluster in the @xmath67-@xmath70-@xmath69 space . the vesta family occupies a very small volume in the orbital parameter space centered at @xmath81 , @xmath82 , and @xmath83 . if the asteroids with extreme colors can be interpreted as j and v taxonomic types , then they should be concentrated in that region , rather than scattered throughout the belt as blue and red asteroids are . the 131 red asteroids with @xmath76 are marked in figures [ fig_a_i ] , [ fig_a_e ] and [ fig_i_e ] as crosses ; it is evident that they are clustered around the vesta family . this is better seen in figure [ m.vestoids ] where we show only the small region of the orbital parameter space that is relevant for the vesta family ( 2.1 @xmath84 2.5 and 0.09 @xmath850.15 ) . the red asteroids are shown as circles and the subset of 99 objects with @xmath76 as crosses . the large dot marks the position of vesta . the box outlined by the solid line is the core region ( 2.28 @xmath84 2.4 and 0.1 @xmath850.13 ) , and the box outlined by the dashed line is the tail region ( 2.4 @xmath84 2.49 ) and 0.1 @xmath850.13 ) , as proposed by zappala _ ( 1995 ) . since a very high fraction of objects with @xmath76 ( 99 out of 131 in the displayed region , and 50 and 29 , respectively , in the outlined core and tail regions ) is found in the region of the orbital parameter space that is associated with the vesta family , we conclude that the color provides a reasonably reliable method for selecting objects from the vesta family . this work demonstrates the feasibility of significantly increasing the number of asteroids with both accurate multi - color photometry and known orbital elements by matching sdss - detected asteroids with the catalogs of known asteroids . the sample discussed here includes 2600 asteroids ; when sdss is completed the final catalog could be more than ten times larger . such a large sample can be used for a compositional analysis of the asteroid families at a level of detail which was not previously possible . we show here that sdss color information is sufficient to reveal strong color segregation among the asteroid families : most are dominated by either blue or red objects . we showed that the sdss photometric pipeline automatically flags 90% of observed moving objects , with a contamination level of only a few percent . this is a better performance than for any other similar code . the directly determined completeness is lower than the 98% claimed by i01 , though without any significant consequences for their results . it is somewhat surprising that only 66% of the known asteroids listed in the astorb catalog have sufficiently accurate orbital elements to predict their positions to better than 30 arcsec . however , most objects with unreliable orbital elements can be efficiently removed . it is much more perplexing that there is a large offset in magnitude scales , not only with respect to sdss , but also among the standard asteroid databases . this offset results in an overestimate of the number of asteroids brighter than a given magnitude limit by factor 1.7 , and resolves the discrepancy between the sdss asteroid count normalization and the number of asteroids listed in astorb catalog . we thank robert jedicke for fruitful discussions regarding the discrepancy in asteroid counts between sdss and astorb database , and dejan vinkovi for helping with the visual inspection of sdss images . we thank princeton university for generous financial support of this research . the sloan digital sky survey ( sdss ) is a joint project of the university of chicago , fermilab , the institute for advanced study , the japan participation group , the johns hopkins university , the max - planck - institute for astronomy , the max - planck - institute for astrophysics , new mexico state university , princeton university , the united states naval observatory , and the university of washington . apache point observatory , site of the sdss telescopes , is operated by the astrophysical research consortium ( arc ) . funding for the project has been provided by the alfred p. sloan foundation , the sdss member institutions , the national aeronautics and space administration , the national science foundation , the u.s . department of energy , monbusho , and the max planck society . the sdss web site is http://www.sdss.org/. jedicke , r. , larsen , j. & spahr , t. 2002 , _ observational selection effects in asteroid surveys and estimates of asteroid population sizes _ , proceedings of the asteroids 2001 `` from piazzi to the 3@xmath86 millennium '' conference , june 1116 , 2001 , palermo , italy , university of arizona press , in press . crrrrr [ tblmatching ] 94 & 663 & 2757 & 395 & 94 & 174 + 125 & 648 & 2844 & 426 & 48 & 174 + 752 & 712 & 3422 & 373 & 33 & 306 + 756 & 778 & 3645 & 439 & 44 & 295 + all & 2801 & 12668 & 1633 & 219 & 949 + unique & 2170 & & 1325 & & + crrrrrr [ tblmatchingconstrained ] 94 & 391 & 2757 & 290 & 82 & 19 + 125 & 402 & 2844 & 350 & 32 & 20 + 752 & 374 & 3422 & 318 & 25 & 31 + 756 & 445 & 3645 & 377 & 34 & 34 + all & 1612 & 12668 & 1335 & 173 & 104 + unique & 1239 & & 960 & & + rlcccccccr [ tbl_krisc ] 446 & aeternitas & a & 30 sep & 11:09 & 14.33 & 0.61 & 14.58 & 13.43 & 1.14 702 & alauda & c & 30 sep & 11:47 & 12.75 & 0.45 & 12.93 & 12.90 & 0.03 82 & alkmene & s & 28 sep & 10:57 & 12.43 & 0.64 & 12.69 & 12.72 & -0.02 774 & armor & s & 28 sep & 03:52 & 12.97 & 0.71 & 13.26 & 12.94 & 0.32 371 & bohemia & as & 4 oct & 05:05 & 12.64 & 0.65 & 12.90 & 12.83 & 0.07 349 & dembowska & r & 29 sep & 11:54 & 10.28 & 0.70 & 10.57 & 10.57 & -0.00 433 & eros@xmath87 & s & 30 sep & 12:26 & 13.30 & 0.67 & 13.57 & 13.09 & 0.48 480 & hansa & s & 29 sep & 09:59 & 12.25 & 0.63 & 12.51 & 12.61 & -0.10 10 & hygeia & c & 28 sep & 12:05 & 11.43 & 0.46 & 11.61 & 11.54 & 0.06 683 & lanzia & c & 1 oct & 03:35 & 14.23 & 0.48 & 14.42 & 13.78 & 0.64 68 & leto & s & 27 sep & 10:37 & 10.11 & 0.66 & 10.38 & 10.53 & -0.15 149 & medusa & s & 29 sep & 06:12 & 12.57 & 0.68 & 12.85 & 12.96 & -0.11 196 & philomela & s & 28 sep & 08:51 & 11.41 & 0.64 & 11.67 & 11.56 & 0.10 314 & rosalia & c & 5 oct & 03:15 & 13.95 & 0.46 & 14.13 & 13.81 & 0.32 138 & tolosa & s & 5 oct & 04:11 & 11.57 & 0.69 & 11.85 & 11.92 & -0.07 rrrr [ tbl_taxonomy ] ( 220 ) stephania & xc ( tholen ) & -0.062 & -0.012 + ( 1628 ) strobel & x ( smass ) & 0.024 & 0.079 + ( 1679 ) nevanlinna & x ( smass ) & -0.048 & 0.036 + ( 1711 ) sandrine & s ( tholen ) & 0.074 & 0.042 + ( 1772 ) gagarin & s ( smass ) & 0.135 & 0.003 + ( 2215 ) sichuan & s ( smass ) & 0.097 & 0.011 + ( 5118 ) elnapoul & s ( smass ) & 0.151 & -0.022 +

we positionally correlate asteroids from existing catalogs with a sample of @xmath018,000 asteroids detected by the sloan digital sky survey ( sdss , ivezi _ et al . _ 2001 ) . we find 2641 unique matches , which represent the largest sample of asteroids with both accurate multi - color photometry and known orbital parameters . the matched objects are predominantly bright , and demonstrate that the sdss photometric pipeline recovers 90% of the known asteroids in the observed region . for the recovered asteroids we find a large offset ( 0.4 mag ) between johnson v magnitudes derived from sdss photometry and the predicted catalog - based visual magnitudes . this offset varies with the asteroid color from 0.34 mag for blue asteroids to 0.44 mag for red asteroids , and is probably caused by the use of unfiltered ccd observations in the majority of recent asteroid surveys . this systematic photometric error leads to an overestimate of the number of asteroids brighter than a given absolute magnitude limit by a factor of 1.7 . the distribution of the matched asteroids in orbital parameter space indicates strong color segregation . we confirm that some families are dominated by a single asteroid type ( e.g. the koronis family by red asteroids and the themis family by blue asteroids ) , while others appear to be a mixture of blue and red objects ( e.g. the nysa / polana family ) . asteroids with the bluest colors , which can be associated with the vesta family , show particularly striking localization in orbital parameter space . # 1@xmath1 # 1@xmath2 # 1 @xmath3 # 1 # 1_#1 # 1/#2 u i # 1 # 1

in the emerging era of personalized medicine , it is critically important to improve biomarker detection technologies . medical diagnoses and treatments would be revolutionized by technology capable of rapid and specific quantitation of an arbitrary protein in real time , over a wide concentration range . these qualities are highly desirable for assays used at the point - of - care ( poc ) , as well as in clinical and research laboratories . in general , advantages of poc devices include short turnaround times for acquiring critical data , low cost , and improved patient compliance with diagnosis and therapeutic regimens through in - home poc self - testing . for example , rossi and khan have shown that point - of - care testing can significantly reduce mortality in patients undergoing congenital heart surgery when used in combination with goal - directed therapy . however , current poc devices are limited in their reliance on single - use test cartridges and dried reagents , often leading to reduced performance metrics ( lod and dynamic range ) and increased measurement variability compared to analogous clinical determinations . reusable or reversible sensors would facilitate continuous poc device calibration , resulting in minimally invasive , higher accuracy assays . in this way , reusability is a critical area for the development of improved poc devices moving forward . historically , many strategies have been employed to regenerate sensor surfaces and make them reusable . in the case of affinity chromatography , for example , lowering the ph of the eluent buffer solution disrupts affinity binding , leading to the release of the target protein . the downside of this approach is that the capture antibody is often denatured , greatly limiting the number of measurement cycles . the introduction of reusability into capture - based surface assays , e.g. , aptamer switches or electrochemical proximity assays ( ecpa ) , can be confounded by the analyte s irreversible binding to the sensor surface during measurement . electrochemical detection is employed in a wide range of biosensors because of its inherent signal stability , high sensitivity , and ease of calibration compared to optical techniques . in addition , the instrumentation can easily be integrated with miniaturized poc devices and microfluidic or lab - on - a - chip ( loc ) platforms . electrochemical biosensing has seen renewed interest of late , based on the high performance of dna - directed sensing by square - wave voltammetry ( swv ) , since analyte presence can be encoded into a dna signal for readout . micropatterned aptamer - modified electrodes have been used to quantify cellular secretions , and antibodies have been detected in whole blood using this approach . in fact , some groups have achieved continuous , real - time monitoring of small - molecule therapeutics in blood serum and even in whole animals . by combining electrochemical dna recognition with the proximity immunoassay concept , we have developed a more generalizable protein assay system termed the electrochemical proximity assay ( ecpa ) . using direct - readout methodology , ecpa has been shown capable of detecting hormones at levels as low as 20 fm with high selectivity and wide dynamic range . compared to other electrochemical protein quantitation methods , target flexibility is a major advantage of ecpa , where the protein - to - probe binding is decoupled from the electrochemical signal generation using a dna - based circuit . while the response of other methods such as aptamer folding approaches will vary depending on aptamer structure , ecpa allows accurate positioning of the electrochemical label , regardless of the type of probes ( aptamers or antibodies ) or the identity of the target protein . for ecpa to be of widespread practical utility , however , the analysis speed needs improvement , and the ability to make measurements in complex matrices must be demonstrated . in this paper , we describe the development of a reusable ecpa capable of performing multiple iterative measurements in complex matrices . reusable ecpa is a signal - on protein sensor that combines electrochemistry with molecular biological techniques , accomplishing a unique and soft surface regeneration chemistry . two biological test beds are described : hormone quantitation in murine blood serum and secretion quantitation from endocrine tissue . with results that highlight the superior reusability , selectivity , and sensitivity of ecpa , the work presented the following reagents were used as received : insulin antibodies ( clones 3a6 and 8e2 ; fitzgerald industries ) , 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid ( hepes ) ( 99.5% ) , tris(2-carboxyethyl ) phosphine hydrochloride ( tcep ) ( sigma - aldrich , st . louis , mo ) , bovine serum albumin ( bsa , 98% ; emd chemicals inc . ) , human thrombin , immunoglobulin e ( ige ) , and insulin ( sigma - aldrich ) . hplc - purified , methylene blue - conjugated dna ( mb - dna ) was purchased from biosearch technologies ( novato , ca ) . oligonucleotides were obtained from integrated dna technologies ( idt ; coralville , iowa ) , with purity and yield confirmed by mass spectrometry and hplc , respectively . all dna sequences used in the experimental model and in ecpa measurements are given in table s1 ( supporting information ) . these sequences were designed and optimized computationally using the nucleic acid package web server ( nupack ) . islets were isolated as described previously from live male c57bl/6 mice and maintained in rpmi medium ( supplemented with 10% fetal bovine serum ) with 11 mm glucose , at 37 c under humidified 5% co2 for 24 h prior to sampling . for secretion assays , between 5 and 15 islets were loaded into 0.5 ml tubes containing 300 l of imaging medium with basal glucose ( 3 mm ) and maintained at 37 c for 20 min . reusable ecpa was carried out for insulin quantitation , using the cyclic methodology described below . during measurements , glucose was increased to 11 mm , and tubes were incubated at 37 c for 1 h. four male c57bl/6 mice contributed islets to this study , totaling 150 islets . oligonucleotide conjugates were prepared as described previously , by covalent attachment of abarm1 to insulin antibody 3a6 and abarm2 to insulin antibody 8e2 , respectively . conjugation and purification were accomplished using the antibody - oligonucleotide all - in - one conjugation kit ( solulink ) , according to the manufacturer s instructions . oligonucleotides were activated with sulfo - s-4fb , and quantities and qualities were confirmed using absorbance measurements ( a260 nm and a260nm / a360 nm ratios ) after oligonucleotide modification . quantities of 100 g of each antibody were activated with s - hynic and then mixed and incubated with activated oligonucleotides at room temperature for 2 h. conjugates were purified using the supplied magnetic affinity matrix , and final conjugate concentrations were determined via the bca protein assay . all reusable ecpa sensors were fabricated using a au working electrode ( 2 mm diameter , ch instruments , inc . au electrodes were cleaned with piranha solution ( h2so4/h2o2 ; 3:1 , v : v ) for 20 min , polished with a slurry of 0.05 m aluminum oxide in water ( buehler , lake bluff , il ) for 10 min , and then sonicated in ethanol for 10 min . freshly made piranha solution was then transferred onto the au surface for 10 min , after which the electrode was rinsed with ddh2o . ( caution : piranha solution is dangerous to human health and should be used with extreme caution and handled only in small quantities . ) the au electrodes were further cleaned by a series of oxidative and reductive scans in 0.5 m h2so4 , as previously described . the cleaned au electrodes were thoroughly washed with ddh2o and then ethanol and dried under flowing nitrogen . typical experiments herein included preparation of seven electrodes in parallel , as follows . a 14 l portion ( 2 l per electrode ) of 200 m thiolated dna was mixed with 28 l ( 4 l per electrode ) of 10 mm tcep in a 1.5 ml microcentrifuge tube . this tube was incubated for 120 min at room temperature ( 21 c ) in the dark for reduction of disulfide bonds in the thiolated dna . this solution was then diluted to a total volume of 1.4 ml in hepes / naclo4 buffer ( 10 mm hepes and 0.5 m naclo4 , ph 7.0 ) to a final concentration of 2 m thiolated dna . the mb - dna was also reduced in a similar way . to generate sufficient reduced mb - dna for 2030 measurements , 3 l of 200 m mb - dna was mixed with 6 l of 10 mm tcep in a 1.5 ml microcentrifuge tube . this tube was incubated for 120 min at room temperature ( 21 c ) in the dark , and then the solution was diluted to a total volume of 600 l in hepes / naclo4 buffer , giving 1 m mb - dna . for immobilization , each freshly cleaned electrode was directly transferred to the reduced thiolated dna solution and incubated overnight ( 1216 h ) at room temperature in the dark . following incubation for self - assembled monolayer ( sam ) formation , excess dna was washed away through a room temperature ddh2o rinse ( 15 s ) . for further protection against adsorption , the sam - modified electrode was then immediately transferred to 3 mm 6-mercaptohexanol solution for 40 min at room temperature in the dark . electrochemical measurements were performed as described previously using a gamry reference 600 electrochemistry workstation with a standard three - electrode configuration , composed of a ag|agcl(s)|kcl(sat ) reference electrode ( bioanalytical systems ) , an in - house fabricated platinum gauze flag ( 0.77 cm ) counter electrode , and a au working electrode ( diameter = 2 mm ) . electrochemical measurements were performed in hepes / naclo4 buffer using swv with a 50 mv amplitude square wave signal at a frequency of 60 hz , over the range from 0.10 to 0.45 v. for each measurement , a blank voltammetric trace was recorded upon immersion of the electrode into the sample ( t 0 min ) and then a voltammetric scan was carried out at a particular point in time ( e.g. , t = 3 min ) . the blank scan was subtracted from the scan at time t , and the integrated signal was calculated as the peak area from 330 to 100 mv ( centered around the mb peak ) . for modeling signal , the sam - coated sensor was immersed in 10 nm dna loop and 15 nm mb - dna in 500 l of hepes / naclo4 buffer . for modeling background , the sensor was immersed in 15 nm mb - dna in 500 l of hepes / naclo4 buffer . after initial measurements , the electrode surface was regenerated using the enzymatic deoxyuridine - excision process . seven different au working electrodes were used for measurement of each thrombin concentration . thrombin of seven different concentrations ( from 0 to 10 nm ) was incubated for 15 min with 10 nm thrapta and 15 nm thraptb in hepes / naclo4 buffer prior to measurements . after measurement at the 3 min time point , each sensor was regenerated by immersing in 2 units of uracil dna excision mix ( epicentre , uem04100 ) in 100 l of uracil excision enzyme buffer ( 50 mm tris hcl at ph 9.0 , 20 mm ( nh4)2so4 and 10 mm edta ) for 7 min at 37 c . enzyme solution and cleaved dna were then removed via a room temperature ddh2o rinse ( 15 s ) , and the electrodes were then dried under a stream of nitrogen gas . at this stage , the sensor with regenerated sam was ready for the next round of probe loading and measurement . regeneration and selectivity tests with other proteins ( ige , insulin , or bsa ) were carried out under the same conditions . antibody oligonucleotide conjugates were prepared as described above ; the conjugates are referred to as ab1 ( dna - conjugated antibody 1 : abarm13a6 ) and ab2 ( dna conjugated antibody 2 : abarm28e2 ) in the discussion below . for sensor calibration against insulin and for insulin secretion quantitation from islets , seven gold working electrodes were used in a cyclic methodology , as described below . the sensor was incubated with 50 nm ab1 for 3 min by dropping 10 l of the solution on the sensor surface , followed by a wash step of hepes / naclo4 buffer for 15 s. the sensor was then transferred to the sample solution ( 300 l of secretory sample or serum ) . the secretory samples were maintained at 37 c by a heating block , while serum samples were kept near 0 c by placing on ice . after a 3 min incubation , the sensor was again washed with hepes / naclo4 buffer for 15 s. next , the electrode was incubated with 50 nm ab2 for 3 min by dropping 10 l of the solution onto the au surface . for swv scanning , the sensor was then transferred to 500 l of hepes / naclo4 buffer consisting of 50 nm mb - dna . the integrated signal was measured at the 3 min time point . for consistency , this protocol was not only used for measuring insulin responses in biological samples but also used for calibration standards . figure 5 and the accompanying discussion provide further details on this cyclic methodology . a disadvantage of the original ecpa design was the single - use nature of the sensors . each electrode could only be used for a single measurement without having to clean and re - establish the sam . to circumvent constant sensor cleaning , the principle of the reusable electrochemical proximity assay ( reusable ecpa ) is depicted in figure 1 , which highlights the enzymatic surface regeneration step borrowed from molecular biological techniques . the scheme begins with the fully assembled , five - part ecpa complex ( upper left ) , composed of thiolated dna / ab1/target protein / ab2/mb - dna . the complex forms in proportion to protein amount in solution , permitting electron transfer reactions between the electrode and the methylene blue in mb - dna the end point of the original ecpa assay . however , in this work , selected deoxythymidines ( dt s ) were replaced by deoxyuridines ( du s ) , which are susceptible to enzymatic cleavage by the uracil dna excision mix . dt moieties were replaced by du s in sections of ab1 ( green strand ) and mb - dna ( orange strand ) that were complementary to da s in the surface - bound thiolated dna ( blue strand ) , i.e. , the portions that served to anchor the probes and signaling strands to the electrode surface . in this way , ab1 and mb - dna strands could be enzymatically broken into three and two shorter segments of dna , respectively ( figure 1a , upper right ) . these strands , being no longer energetically stable as double - stranded dna ( dsdna ) at the electrode , spontaneously denatured ( figure 1a , lower right ) to release probe / target complex from the electrode surface . following a short ddh2o rinse , 4 parts of the 5-part complex ( ab1/target protein / ab2/mb - dna ) were washed away from the electrode , leaving only the monolayer floor composed of thiolated dna and mercaptohexanol ( not shown ) at the sensor surface ( figure 1a , lower left ) . through this gentle , enzymatic mechanism , ecpa electrodes were regenerated in a matter of minutes and were ready for probe loading and another measurement . cycle for gentle , enzymatic regeneration of the sam - coated electrode surface . after measurement ( upper left ) , the electrode was incubated in the uracil dna excision mix ( upper right ) . resulting shorter dna sections spontaneously denatured ( lower right ) and were washed away in buffer ( lower left ) , leaving the sam of thiolated dna that was ready for probe loading and another measurement . we have previously shown dna - based experimental models to offer a pragmatic solution to experimental optimization of proximity ligation assays , proximity fluorescence assays , and ecpa . the central theme of these models is the use of a ssdna loop ( dna loop ) in lieu of the probe / target complex , eliminating the need for antibodies and target protein in initial optimization studies . for reusable ecpa , we used dna model strands from our previous work , except the dna loop and mb - dna strands contained deoxyuridines ( sequences in table s-1 , supporting information ) . du s facilitated enzymatic cleavage and removal of the loop which represented the assay probes . in contrast to previous work , a major goal of reusable ecpa was to reduce measurement time and allow rapid cycling through electrochemical measurements and surface regeneration steps . as such , a higher concentration of mb - dna was adopted ( 50 nm ) with a 3 min measurement time . it was hypothesized that a shorter number of base pairs between thiolated dna and mb - dna would prevent background formation at higher mb - dna concentrations , while also allowing more rapid equilibration of the probe / target complex . this hypothesis was confirmed using a five - base connection to thiolated dna ( g5 system , figure s-1 , supporting information ) , which showed baseline response for background yet significant signal formation in the presence of the dna loop after only 3 min . as such , the g5 system was used throughout this work to allow rapid measurement and sensor regeneration . in similar electrochemical dna and protein assays , others have employed regeneration methods such as water or buffer rinses , denaturing rinses , or even microfluidic systems for serial rinsing , achieving between 5 and 10 consecutive measurements . figure 2 shows the comparison of different regeneration methods for reusable ecpa . as rapid regeneration is more desirable , the methods were compared after no more than 7 min of treatment . the red trace in figure 2 shows the signal current ( 11 na ) after 3 min of equilibration with 10 nm thrombin , thrombin aptamer probes ( 10 nm thrapta , 15 nm thraptb ) , and 50 nm mb - dna in buffer . the purple trace shows the measurement after a subsequent 7 min immersion in buffer at 37 c , where current reduced to only 80% of the original value . a 7 min immersion in water showed improved removal of the probe / target complex , although 20% of the original current remained ( green trace ) . others have shown sensors to be regenerated for a few cycles after 30 s washes with room temperature deionized water , yet this flowing water method only reduced the ecpa signal to 35% of the original value ( dark blue trace ) . as shown in figure 2 , the only method that provided a fully cleaned electrode showing current at baseline levels after treatment was the uracil - triggered enzymatic cleavage presented in this work ( black trace ) . with this gentle enzymatic sensor cleaning approach , initial testing of the reusable ecpa concept was carried out with aptamer - based probes . this approach not only helps confirm the flexibility of ecpa , but it is also a more economical way to begin fine - tuning the methodology . as the aptamers are made from dna , there is no requirement for probe oligonucleotide conjugate synthesis and purification ; aptamers are also less expensive probes . as in prior work , the antibody two thrombin - binding dna aptamers ( thrapta , thraptb ) with distinct binding sites were applied as affinity probes . using conditions optimized by the dna - based experimental model , background levels were measured in the absence of human thrombin and remained at baseline current at the 3 min time point . figure 3a shows the background with no thrombin ( black trace ) and typical mb oxidation peaks appearing at 210 mv in the presence of varying amounts of thrombin , all measured at the 3 min time point . seven current signals at varying thrombin levels ( 010 nm ) were measured by seven different sensors , prepared under the same conditions . with current increasing in proportion to thrombin concentration for all electrodes each sensor was then enzymatically regenerated seven times , such that signal currents of seven different concentrations of thrombin were measured by every sensor . in figure 3b , integrated signal is reported versus thrombin concentration for each of the seven sensors ; calibration curves are traced by dash - dotted lines , with each sensor having a different colored line . the solid black curve with error bars shows the averages and standard deviations from the seven sensors , and the linearly extrapolated limit of detection ( lod ) for thrombin was calculated to be 10 pm ( 5 fmol in 500 l ) . remarkably , this lod using averaged signals from seven different electrodes was slightly lower than previously achieved with a single electrode . this result demonstrates high confidence in the sensor - to - sensor reproducibility of reusable ecpa , since seven completely different electrodes with separately prepared dna monolayers were able to deliver a lod in the low picomolar range . to further interrogate reusability , two sensors with two different concentrations of thrombin ( 1.25 and 5.00 nm ) were iteratively taken through probe loading , measurement , and enzymatic regeneration ; the integrated signal from these experiments is reported in figure 3c . significant deviation from the average value occurred at the 21st repeated measurement for the 5.00 nm thrombin sample and at the 20th repeated measurement for the 1.25 nm thrombin sample . from this data , it was concluded that at least 19 consecutive measurements could be made without loss of signal ( blue dotted line ) via reusable ecpa . to demonstrate specificity , a single sensor the sensor was taken through a cascade of different treatments in duplicate , alternating between thrombin and a nonspecific treatment such as buffer , 3% bsa , 15 nm ige , or 15 nm insulin ( figure 3d ) . essentially no response was observed in the presence of any treatments other than the thrombin - containing solutions ; even with 3-fold lower thrombin ( 5 nm ) , the signal was 110- to 160-fold larger than that of insulin or ige ( 15 nm ) . these data demonstrated high selectivity toward thrombin and high recoveries in complex matrices through 16 consecutive measurements . such a result is encouraging for future application of reusable ecpa to continuous measurement of biological samples and for quantitation in clinical laboratories or in point - of - care settings . ( a ) swv scans for thrombin quantitation in the pm to nm range . ( b ) thrombin calibration curves with seven different sensors ( dotted lines ) , with the average trace ( black line ) shown ; error bars represent standard deviations . ( c ) two independent sensors were cycled through the reusable ecpa methodology during measurement of differing thrombin concentrations ( red and black points ) . the gentle enzymatic surface regeneration permitted up to 19 uses without significant loss of signal . ( d ) high target specificity was confirmed through various challenges to the sensor , where only thrombin generated measurable responses . because reusable ecpa decouples target / probe binding from electrochemical readout , the technique is flexible enough to utilize antibody - based probes as well . this flexibility is useful , considering that aptamer pairs exist for only a few select proteins . since standard ecpa with antibody - based probes was already proven functional , conditions for this work were modified toward interrogation of biological systems . a cyclic protocol was adopted to prevent exposure of cells to antibody - based probes ( discussed below ) , and the temperatures of assay solutions were held constant at 37 c . figure 4a shows the background with no insulin ( black trace ) and typical mb oxidation peaks in the presence of varying amounts of insulin measured at the 3 min time point , using seven different electrodes . the system was then calibrated versus insulin concentration , with responses of seven insulin concentrations recorded from seven sensors ( figure 4b ) . using direct electrochemical readout at 37 c , reusable ecpa was capable of easily detecting insulin levels as low as 100 fm , with a dynamic range extending to 6.25 nm . the solid black curve with error bars shows the averages and standard deviations from the seven sensors , and the linearly extrapolated lod for insulin was found to be 10 fm ( 5 amol in 500 l ) . this lod using averaged signals from seven different electrodes incubated with sample at 37 c was lower than that previously achieved with a single electrode . furthermore , the dynamic range achieved here ( 6 10 ) is 6-fold wider than shown in the previous work . reusability of the antibody version was assayed with two different concentrations of insulin ( 250 and 1250 pm ) , and the integrated signal is reported in figure 4c . similar to the aptamer system , the method was capable of at least 19 repeated measurements without significant signal loss . it is interesting that , in both aptamer and antibody versions of the assay , the surface degrades measurably after 19 repeated uses in a seemingly probe - independent manner . a systematic investigation of the degradation mechanism was not undertaken in this study , but the effect after 19 uses is likely an aggregate of well - known sam degradation factors . plausible explanations include the use of multiple voltammetric scans , repeated enzymatic treatments , repeated buffer washes , and the persistence of reaction side products on the sensor surface . finally , selectivity was confirmed with insulin - like growth factor 1 ( igf-1 ) , which has a similar molecular structure to insulin , and with c - peptide , which is cosecreted with insulin into the bloodstream . as expected , the dual antibody sensor showed a minimal response to 8-fold higher concentrations of either igf-1 or c - peptide ( 2 nm ) compared to 250 pm insulin ( figure 4d ) . ( a ) swv scans for insulin quantitation in the fm to nm range . ( b ) insulin calibration curves with seven different sensors ( dotted lines ) , with the average trace ( black line ) shown ; error bars represent standard deviations . ( c ) two independent sensors were cycled through the reusable methodology during measurement of varying insulin levels ( red and black points ) . again , up to 19 uses were permitted without significant loss of signal . ( d ) high target specificity was confirmed by challenging the sensor with a protein of similar structure ( igf-1 ) and a cosecreted hormone ( c - peptide ) . one key test of the robustness of reusable ecpa is to apply the technique to quantitation of hormones secreted by living cells over time , as these measurements take place in complex milieu amenable to cellular culture and imaging . here , the technique is applied to monitoring of insulin secretion from living murine pancreatic islets during glucose - stimulated insulin secretion . since islets can not be exposed to freely diffusing antibody oligo conjugates , the cyclic methodology was designed specifically for this application , with a schematic shown as steps 16 in figure 5a . in this cycle , ab1 solution was first dropped onto the gold surface of the sensor ( step 1 ) and then incubated for 3 min . after washing with buffer , the sensor was lowered into cellular imaging media containing the living islets at varying glucose levels at 37 c ( step 2 ) . secreted insulin was bound by ab1 , keeping it at the sensor surface . following a second buffer wash , ab2 solution was pipetted onto the sensor surface and incubated for 3 min ( step 3 ) ; then , the sensor was immersed into mb - dna solution . here , signal current was measured at the 3 min time point ( step 4 ) . following each measurement , the sensor was regenerated enzymatically using the uracil dna excision mix ( step 6 ) , readying the system for another measurement . the cyclic methodology ( figure 5a ) was employed for hormone secretion quantitation and was applied during calibration to permit quantitative monitoring . to simulate a fasting - to - feeding transition , islets were conditioned in 3 mm glucose and then exposed to 11 mm glucose . figure 5b shows insulin secretion quantitation by reusable ecpa , where islets from two different mice were transitioned from 3 to 11 mm glucose prior to the fourth measurement ( * at 1015 min time point ) . groups of only 515 islets registered a sharp increase in secreted insulin following the increased glucose . using the average calibration curve shown in figure 4b , islets at low and high glucose secreted tens to hundreds of pg islet min , respectively ( figure 5c ) . these readings matched well with previous reports , providing validation for reusable ecpa as a novel tool in quantitative biology . to our knowledge , the technique is unique in its capability for direct yet selective electrochemical hormone secretion quantitation from small amounts of living tissue in real time . accurate analytical calibrations can be confounded in complex matrices such as serum , and one of the most effective countermeasures is the use of standard addition methods . a unique advantage provided by direct and rapid quantitation with reusable ecpa is the opportunity to implement standard addition , precluding the need for separate calibration curves in complex backgrounds . with a slight modification to the cyclic methodology prescribed above ( sample loading on ice instead of at 37 c ) , insulin standards were added to 20-fold diluted mouse serum in increments of 5 pm . this approach allowed accurate quantitation of insulin in the native , unspiked serum of two different c57bl/6j mice within a matter of minutes ( figure 5d ) . results of these assays ( 120 and 140 pm ) fell precisely within the expected clinical range of insulin in wild - type murine blood ( 114 31 pm ) , providing another solid validation of our methodology for quantitative biological studies . in particular , these results suggest that reusable ecpa could be useful in clinical or point - of - care settings , to assay a wide variety of protein targets with high sensitivity and selectivity . although eight separate measurements per sample were conducted here , standard addition curves with fewer data points could be readily implemented to provide high measurement confidence in complex matrices such as serum . real - time measurements using the reusable ecpa cycle for quantitative insulin detection in biological samples . ( b ) integrated signal traces during real - time monitoring of insulin secretion from as few as five living pancreatic islets . islets were transitioned from basal glucose ( 3 mm ) to stimulatory glucose ( 11 mm ) at the points labeled with asterisks ( * ) . islets responded to glucose increases with the expected spikes of insulin secretion ; increases from tens to hundreds of pg islet min matched well with previous reports . ( d ) insulin quantitation in unspiked serum from two different c57bl/6 mice was accomplished through standard addition methods made possible by reusable ecpa . as noted in a recent review by plaxco and soh , a universal approach for quantitation of arbitrary molecular analytes could revolutionize healthcare ; the authors further suggest that electrochemical , switch - based biosensors could be the answer . while this has now been demonstrated for small molecule monitoring , continuous and sensitive protein detection with a generalizable assay has yet to be developed . high selectivity and sensitivity are given by dual probe recognition ( aptamers or antibodies ) , arbitrary protein detection is afforded by decoupling probe recognition from dna - based readout , and reusability allows real - time detection in biological matrices . as such , the presented work represents a major step toward the desired system of continuous protein quantitation . for example , our physiologically validated electrochemical insulin monitoring provides an attractive framework for assembly of a miniaturized closed - loop artificial pancreas for diabetic patients ; insulin ecpa could be partnered with the well - established commercial methods for electrochemical glucose monitoring . of course improvements are needed , such as built - in assay reversibility and methods for preloading of confined surface probes . nonetheless , the work herein represents a significant improvement in protein detection technology . when considering the generalizability of the approach to target any protein with antibody pairs , reusable ecpa is likely to be a valuable technique for biologists , chemists , clinicians , and others .

rapid and specific quantitation of a variety of proteins over a wide concentration range is highly desirable for biosensing at the point - of - care , in clinical laboratories , and in research settings . our recently developed electrochemical proximity assay ( ecpa ) is a target - flexible , dna - directed , direct - readout protein quantitation method with detection limits in the low femtomolar range , making it particularly amenable to point - of - care detection . however , consistent quantitation in more complex matrices is required at the point - of - care , and improvements in measurement speed are needed for clinical and research settings . here , we address these concerns with a reusable ecpa , where a gentle regeneration of the surface dna monolayer ( used to capture the proximity complex ) is achieved enzymatically through a novel combination of molecular biology and electrochemistry . strategically placed uracils in the dna sequence trigger selective cleavage of the backbone , releasing the assembled proximity complex . this allows repeated protein quantitation by square - wave voltammetry ( swv)as quickly as 3 min between runs . the process can be repeated up to 19 times on a single electrode without loss of assay sensitivity , and currents are shown to be highly repeatable with similar calibrations using seven different electrodes . the utility of reusable ecpa is demonstrated through two important applications in complex matrices : ( 1 ) direct , quantitative monitoring of hormone secretion in real time from as few as five murine pancreatic islets and ( 2 ) standard addition experiments in unspiked serum for direct quantitation of insulin at clinically relevant levels . results from both applications distinguish ecpa as an exceptional tool in protein quantitation .

the communication paradigm of cooperative relaying has recently received considerable attention due to its effectiveness in alleviating the effects of multipath fading , pathloss and shadowing , and its ability to deliver improved performance in cognitive radio systems and wireless sensor networks . relay - assisted cellular networks are a promising solution for enhancing coverage and are included in standards , such as ieee 802.16j / m and long term evolution - advanced ( lte - a ) . several protocols for cooperative relaying were presented in @xcite where the gains in transmit and receive diversity were studied . in multi - relay networks , simultaneous transmissions by the relays are in general difficult to handle ; towards this end , opportunistic relay selection has been suggested in @xcite to improve the resource utilization and to reduce the hardware complexity . stemming from the relay selection concept , many studies have proposed improved selection techniques ( see , _ e.g. _ , @xcite ) . traditional hd relaying schemes partition the packet transmission slot into two phases , where the transmission on the source - relay @xmath0 link happens in the first phase , and the transmission on the relay - destination @xmath1 link occurs in the second phase . however , this relaying scheme limits the maximum achievable multiplexing gain to @xmath2 , which also results in bandwidth loss . in order to overcome such multiplexing and bandwidth limitations , several techniques have been proposed in the literature ( see , for example , @xcite and references therein ) . among them , the successive relaying scheme in @xcite incorporates multiple relay nodes and allows concurrent transmissions between source - relay and relay - destination to mimic an ideal full - duplex transmission . however , this scheme targets scenarios with a long distance between the relays and thus inter - relay interference is not considered . an extension of this work is discussed in @xcite , where the authors assume that iri is strong ( in co - located or clustered relays ) and can always be decoded at the affected nodes ; this decoded iri is exploited in a superposition coding scheme that significantly improves the diversity - multiplexing trade - off performance of the system . in earlier studies , relays were assumed to lack data buffers and relay selection was mainly based on the @xmath3 criterion and its variations ( see , for example , @xcite ) . here , the relay that receives the source signal is also the one that forwards the signal to the destination . with the adoption of buffer - aided relays , this coupling is broken , since different relays could be selected for transmission and reception , thus allowing increased degrees of freedom . buffering at the relay nodes has been shown to be a promising solution for cooperative networks and motivates the investigation of new protocols and transmission schemes ( see @xcite and @xcite for an overview ) . @xcite proposed a novel criterion based on @xmath4 relay selection ( mmrs ) , in which the relay with the best source - relay @xmath0 link is selected for reception and the relay with the best relay - destination @xmath1 link is selected for transmission on separate slots . in @xcite , at each slot the best link is selected among _ all _ the available @xmath0 and @xmath1 links , as a part of the proposed @xmath5 policy , thus offering an additional degree of freedom to the network , while buffer - aided link selection was studied in topologies with source - destination connectivity ( see , _ e.g. , _ in @xcite ) , resulting in improved diversity and throughput . more recently , to alleviate the throughput loss of hd relaying , significant focus has been given to minimizing the average packet delay . towards this end , various works have proposed hybrid solutions combining the benefits of mmrs and @xmath5 @xcite , the use of broadcasting in the @xmath0 link @xcite , the prioritization of @xmath1 transmissions @xcite or the selection of the relay with the maximum number of packets residing in its buffer @xcite . however , it was shown that a trade - off exists between delay performance and the diversity of transmission as the number of relays with empty or full buffers increases . to improve throughput and reduce average packet delays , a number of works proposed to employ non - orthogonal successive transmissions by the source and a selected relay . in order to recover the hd multiplexing loss , @xcite suggests to combine mmrs with successive transmissions ( sfd - mmrs ) . as the proposed topology aims to mimic full - duplex relaying , different relays are selected in the same time slot ; however , relays are assumed to be isolated and the effect of iri is ignored . more practical topologies were studied in @xcite where iri exists and is not always possible to be cancelled . for fixed rate transmission , the proposed @xmath6 solution proposed in @xcite , combining power adaptation and interference cancellation , provides a performance close to the upper bound of sfd - mmrs . in addition , kim and bengtsson @xcite proposed buffer - aided relay selection and beamforming schemes taking the iri into consideration ; they consider a model which can be regarded as an example of relay - assisted device - to - device ( d2d ) communications , where the source and destination are low - cost devices with a single antenna and the base stations comprise more powerful relays with buffers and multiple antennas . numerical results show that their approach outperforms sfd - mmrs when interference is taken into consideration , and when the number of relays and antennas increases they approach the performance of the interference - free sfd - mmrs , herein called the _ ideal _ sfd - mmrs . finally , the use of buffer aided relays has been considered in topologies wth full - duplex ( fd ) capabilities @xcite and decoupled non - orthogonal uplink and downlink transmissions @xcite , showing that throughput can be significantly improved due to the increased scheduling flexibility . in many practical considerations ( _ e.g. _ , wireless sensors ) , the relay nodes are hardware - limited to be hd while the source can be a more powerful wireless device with large buffers and multiple antennas . although this observation is not always true ( _ e.g. _ , in d2d communications @xcite ) , it is a reasonable and common practical scenario . towards this end , we study a network which consists of a buffer - aided source with one or multiple antennas , multiple hd buffer - aided relays and a destination . with this setup , we are able to approach ( achieve ) the performance of the ideal sfd - mmrs by adopting a buffer - aided source whose buffer retains replicas of the relay buffers , successfully transmitted data from the source to relays , to facilitate iri mitigation ( cancellation ) ; we relax the assumption of knowing the full csi and instead we allow for csir and limited feedback from the receiver to the transmitter ; under these conditions we propose a relay pair selection scheme that is based on partial phase alignment of signals . the rest of the paper is organized as follows . in section [ sec : model ] , the system model is outlined . the proposed relaying schemes for variable and fixed rate are presented in sections [ sec : policy1 ] and [ sec : policy2 ] , respectively . the performance of the proposed relaying policies in terms of outage and average throughput , along with comparisons with other state - of - the - art relaying schemes are presented in section [ sec : numerical ] . finally , conclusions and a discussion on future possible directions are drawn in section [ sec : conclusions ] . vectors are written in bold lower case letters and matrices in bold capital letters . @xmath7 , @xmath8 and @xmath9 denote the sets of real numbers , complex and natural numbers , respectively . for a matrix @xmath10 ( @xmath11 ) , @xmath12 denotes the entry in row @xmath13 and column @xmath14 . matrix @xmath15 denotes the identity matrix of appropriate dimensions . the trace of a square matrix @xmath16 is denoted by @xmath17 . @xmath18 and @xmath19 denote the transpose and hermitian transpose operations , respectively ; @xmath20 denotes the @xmath21-norm operation . the complex conjugate of a complex number @xmath22 is denoted by @xmath23 ; the real and imaginary parts of a complex number @xmath22 are denoted by @xmath24 and @xmath25 , respectively . we denote by @xmath26 the set of all possible relay - pairs in the relay network , and by @xmath27 its cardinality . a relay pair , denoted by @xmath28 belongs to set @xmath26 if and only if @xmath29 , the receiving relay @xmath30 is not full and the transmitting relay @xmath31 is not empty . we consider a cooperative network consisting of a buffer - aided source @xmath32 with multiple antennas , a set @xmath33 of @xmath34 hd decode - and - forward ( df ) relays with buffers , and a single destination @xmath35 . [ fig : model ] illustrates a simple example with a buffer - aided two - antenna source @xmath32 , two buffer - aided single - antenna hd df relays , and a single - antenna destination @xmath35 . to simplify the analysis , we examine the case where connectivity between the source and the destination is established only via the relays and ignore the direct @xmath36 link ( as in , _ e.g. _ , @xcite ) . the number of data elements in the buffer of relay @xmath37 is denoted by @xmath38 and its capacity by @xmath39 . for the fixed rate transmission policy , we assume that the packets are transmitted at a fixed rate of @xmath40 bits per channel use ( bpcu ) , and the data of each transmission occupies @xmath41 slot in the buffer . first , we provide the signals received at relay @xmath42 and destination @xmath35 . at the destination , at any arbitrary time - slot @xmath43 the following signal is received : @xmath44=h_{td}x[p]+w_d[n ] \ ; , \end{aligned}\ ] ] where @xmath45 $ ] is the signal received and stored in a previous time - slot @xmath46 in the buffer of the now transmitting relay @xmath47 , @xmath48 denotes the channel coefficient from the transmitting relay @xmath31 to the destination @xmath35 , and @xmath49 $ ] denotes the additive white gaussian noise ( awgn ) at the destination in the @xmath43-th time slot , i.e. , @xmath49\sim\mathcal{cn}(0,{\sigma_d^2})$ ] . it must be noted that @xmath45 $ ] was not necessarily received in the previous time - slot ( i.e. , @xmath50 ) . at the same time , the reception of the source s signal by relay @xmath30 is interfered from the transmission of @xmath47 which forwards a previous signal @xmath45 $ ] to the destination . thus , @xmath30 receives @xmath51=\sum_{i\in \mathcal{a } } h_{s_i r } m_i x_{s_i}[n ] + h_{tr } x[p ] + w_r[n ] , \end{aligned}\ ] ] where @xmath52 denotes the index set of transmit antennas at the source , i.e. , @xmath53 , @xmath54 denotes the channel coefficient from the @xmath13-th transmit antenna at the source to the receiving relay @xmath30 , @xmath55 denotes the channel coefficient from the transmitting relay @xmath31 to the receiving relay @xmath30 , @xmath56 $ ] denotes the transmitted signal from the @xmath13-th transmit antenna at the source in the @xmath43-th time slot , @xmath57 $ ] denotes the transmitted signal from the transmitting relay in the @xmath43-th time slot , @xmath58 denotes the @xmath13-th `` beamforming '' weight at the source , and @xmath59 $ ] denotes the awgn at the receiving relay in the @xmath43-th time slot , i.e. , @xmath59\sim\mathcal{cn}(0,{\sigma^2})$ ] . the source @xmath32 is assumed to be saturated ( infinite backlog ) and hence , it has always data to transmit . the buffering memory at the source is organized into @xmath34 queues , that basically contain replicas of the data queues of the relays , in order to exploit it for iri mitigation or cancellation . the operation is assumed to be divided into time slots . in each time slot , the source and a relay simultaneously transmit their own data to mimic fd relaying ( cf . the transmission powers of the source and the @xmath60-th relay are denoted by @xmath61 and @xmath62 , respectively . for notational simplicity , we assume throughout this paper that all devices use a common fixed transmit power level ( i.e. , @xmath63 ) , unless otherwise specified . moreover , we assume that the receivers send short - length error - free acknowledgment / negative - acknowledgment ( ack / nack ) messages over a separate control channel . we assume narrowband rayleigh block fading channels . each channel coefficient is constant during one time slot and varies independently between time slots . for each time slot , the channel coefficient @xmath64 for link @xmath65 follows a circular symmetric complex gaussian distribution with zero mean and variance @xmath66 , i.e. , @xmath67 . thus , the channel power gain @xmath68 follows an exponential distribution , i.e. , @xmath69 . in addition , we assume the awgn at each receiver with variance @xmath70 . with two antennas ( @xmath71 and @xmath72 ) , two hd relays ( the receiving relay is denoted by @xmath30 and the transmitting relay by @xmath31 ) and a destination @xmath35 ; in this example , @xmath73 and @xmath74 . the buffers at @xmath32 consist basically of replicas of the data queues of the relays ; the source has new packets in the source buffer @xmath75 and replicas of the successfully transmitted packets to the relays in a set of copied buffers . ] the goal is to design a precoding matrix at the source such that , at each time slot @xmath43 the @xmath0 link for the relay selected to receive a packet from the source maximizes its sinr by transmitting a linear combination of ( a ) the source s desired signal for the receiving relay @xmath30 and ( b ) the signal of the transmitting relay @xmath31 taken out from the copied buffer at the source . note that maximizing the sinr of the link is equivalent to minimizing the outage probability of the link . thus , this precoding design criterion is relevant for both fixed rate and adaptive rate transmissions . * special case : source with a single antenna . * the received signal at the receiving relay for the @xmath43-th time slot , @xmath76 $ ] , can be expressed as @xmath77 & = h_{sr}\underbrace{\big ( m_{1}x_s[n]+m_{2}x_t[n]\big)}_{\text{source signal}}+h_{tr } x_t[n ] + w_r[n ] \nonumber \\ & = h_{sr } \underbrace{\begin{bmatrix}m_1 & m_2\end{bmatrix}}_{\text{precoding matrix } } \underbrace{\begin{bmatrix}x_s[n ] & x_t[n]\end{bmatrix}^t}_{\text{data from the source}}\nonumber \\ & \quad \quad \quad \quad \quad \quad \quad \quad \quad \quad + h_{tr } x_t[n ] + w_r[n],\end{aligned}\ ] ] where @xmath56 $ ] in eq . is written as @xmath78+m_{2}x_t[n]$ ] , and @xmath79 . each transmitting node uses a fixed power @xmath80 and thus power control issues are not taken into account . the sinr at the receiving relay , denoted by @xmath81 , is given by @xmath82 hence , the following optimization problem can be formulated : [ opt0_singleantenna ] @xmath83 \textrm{s.t . } & ~ |{m}_1|^2 + |{m}_2|^2 \leq 1 . \label{0cond2_sa } \end{aligned}\ ] ] the solution to optimization problem will be given for the general case and the solution to this special case can be found by simplifications _ mutatis mutandis_. * general case : source with multiple antennas . * now , the precoding matrix at the source comprising @xmath84 antennas is @xmath85 . matrix @xmath86 has dimensions @xmath87 , since the transmitted signals are formed as linear combinations of the source signal and the signal transmitted by the active relay . the received signal at the receiving relay for the @xmath43-th time slot , @xmath76 $ ] , can be expressed as @xmath88 & = \sum_{i\in \mathcal{a } } h_{s_i r}\big ( m_{i1}x_s[n]+m_{i2}x_t[n]\big ) \nonumber \\ & \quad \quad \quad \quad \quad \quad \quad \quad \quad \quad + h_{tr } x_t[n ] + w_r[n],\end{aligned}\ ] ] where @xmath56 $ ] in eq . is written as @xmath89+m_{i2}x_t[n]$ ] , and @xmath90 . defining @xmath91 eq . can be written as @xmath92 & = \mathbf{h}_s^h \begin{bmatrix}\mathbf{m}_1 & \mathbf{m}_2\end{bmatrix } \underbrace{\begin{bmatrix}x_s[n ] & x_t[n]\end{bmatrix}^t}_{\text{data from the source}}\nonumber \\ & \quad \quad \quad \quad \quad \quad \quad \quad \quad \quad + h_{tr } x_t[n ] + w_r[n],\end{aligned}\ ] ] from eq . , it can be easily seen that the source node with @xmath84 antennas applies a linear precoding matrix @xmath93 on the transmitted signals such that the iri is reduced , while at the same time the signal from the source to the intended relay is increased.each transmitting node uses a fixed power @xmath80 and thus power control issues are not taken into account . the sinr at the receiving relay , denoted by @xmath81 , is given by @xmath94 hence , the following optimization problem can be formulated : [ opt0 ] @xmath95 \textrm{s.t . } & ~ \mathbf{m}_1^h \mathbf{m}_1 + \mathbf{m}_2^h \mathbf{m}_2 \leq 1 . \label{0cond2 } \ ] ] each transmitting node uses a fixed power @xmath80 and thus power control issues are not taken into account . note that each antenna @xmath13 , @xmath96 , of the source transmits with power @xmath97 . after the precoding , our effective transmitted signal vector is @xmath98 where @xmath99^t$ ] . the power of the effective transmitted signal vector is @xmath100 where @xmath101 since @xmath102 s are independent of each other . hence , @xmath103 . [ propa ] the precoding matrix @xmath86 that solves optimization problem is given by @xmath104 where and @xmath105 . see appendix [ a : proof_propa ] . the last expression in shows that the optimal @xmath106 is a combination of standard maximum ratio transmission across the source antennas , and the single antenna interference suppression solution . proposition [ propa ] shows that the source does not need to cancel the interference completely in order to achieve the maximum sinr at the receiving relay . this result appears counter - intuitive , since interference is the main source of performance degradation and the sinr should be higher when the iri is cancelled . however , this occurs due to the limited power at the source . when the power @xmath80 is high enough , @xmath107 gets very small . hence , from , @xmath108 \displaystyle \frac{\| \mathbf{h}_s \|^2}{| h_{tr } |^2 } , & \text{if } \| \mathbf{h}_s \|^2 < | h_{tr } |^2 . \end{cases}\end{aligned}\ ] ] which means that interference is essentially cancelled if @xmath109 . if the source can change its power , then the power levels of the source and the transmitting relay are not necessarily the same . in what follows , we allow the source to adjust its power . the sinr now becomes @xmath110 the following proposition gives the optimal joint selection of @xmath111 and @xmath61 , that maximizes the sinr , as given in . [ propb ] when @xmath80 and @xmath111 are considered jointly , then the optimal power @xmath112 and @xmath113 are given by @xmath114 where @xmath115 see appendix [ b : proof_propb ] . proposition [ propb ] suggests that in the case which @xmath61 and @xmath111 are jointly optimized , in order to maximize the sinr , the source transmits with @xmath116 and chooses the @xmath111 corresponding to @xmath116 . [ remark2 ] another approach would be to fix the transmission rate as @xmath117 and try to minimize the outage probability of the @xmath0 link . then , the optimization problem becomes [ opt_1 ] @xmath118 \textrm{s.t . } & ~ \mathbf{h}_s^h \begin{pmatrix } \mathbf{m}_1 & \mathbf{m}_2 \\ \end{pmatrix } = \begin{pmatrix } \beta & -\omega h_{tr } \\ \end{pmatrix } , \label{0cond1 } \\ & ~ \mathbf{m}_1^h \mathbf{m}_1 + \mathbf{m}_2^h \mathbf{m}_2 \leq 1 , \label{0cond2 } \\ & ~ \omega \in ( 0,1 ] . \label{0cond3}\end{aligned}\ ] ] it can be easily shown that this is equivalent to maximizing the sinr which leads to maximizing the link rate . since csis of @xmath1 links are assumed to be available at the source and relays , adaptive rate transmission , which implies transmission rate is determined by instantaneous csi at each link , is possible . in this case , the source encodes its own desired codewords based on csi of the selected @xmath0 link and codewords corresponding to the transmitting relay based on csi of the selected @xmath1 link . then , the source combines them via precoding . in the adaptive rate transmission , the main objective is to maximize the average end - to - end rate from the source to the destination , which is equivalently expressed as the average received data rate at the destination @xcite , i.e. , @xmath119 such that @xmath120 where @xmath121 denotes a time window length and @xmath122 and @xmath123 denote the resulting instantaneous link rates depending on time slot @xmath124 once the relay pair @xmath125 is selected . the instantaneous rates are obtained by @xmath126 where @xmath127 and @xmath128 denote the effective sinr / snr ( signal - to - noise - ratio ) of @xmath0 and @xmath129 links at time slot @xmath124 after applying the precoding matrix obtained by proposition [ propa ] , i.e. , @xmath130 \gamma_{t d}(t ) & = \frac{|h_{td}|^2 p}{\sigma^2 } , \end{aligned}\ ] ] where @xmath111 is given in , @xmath39 denotes the maximum length of queue , and @xmath131 and @xmath132 are the queue lengths of receiving and transmitting relays in bpcu at time slot @xmath133 . for the selected relay pair @xmath134 , the queue lengths are updated at the end of time slot as @xmath135 hereafter , based on the designed precoding matrix @xmath86 in section [ sec : policy1 ] , we propose an adaptive rate relay selection policy for maximizing the average end - to - end rate . applying a lagrangian relaxation , the objective function to maximize the average end - to - end rate in for the adaptive rate transmission becomes equivalent to a weighted sum of instantaneous link rates @xcite . the resulting relay selection scheme has the form [ eq : rs_ar ] @xmath136 for predetermined weight factors @xmath137,~k\in\mathcal{k}$ ] , where @xmath138 and @xmath139 denote the instantaneous rates of @xmath0 and @xmath129 links at time slot @xmath124 , respectively . it is worth noting that for finite buffer size , the optimal weight factors can be found using either a subgradient method or a back - pressure algorithm @xcite . according to the back - pressure algorithm , the weight factors can be found as @xmath140 during a training period where @xmath141 and @xmath142 denote the buffer occupancies at time @xmath124 at the @xmath60-th relay and the source , respectively . the details can be found in @xcite . the optimal relay pair selection in requires an exhaustive search with @xmath143 combinations . therefore , the computational complexity of optimal relay pair selection is @xmath144 . the implementation of the proposed scheme requires global csi of the instantaneous channels and the buffer states . the central unit ( _ e.g. _ , the source in this case ) uses this information in order to select the appropriate relay pair . this global csi requires a continuous feedback for each wireless link as we use a continuous monitoring of the ack / nack signaling in order to identify the status of the buffers . although these implementation issues are beyond the scope of this paper , the proposed scheme can be implementable with the aid of various centralized and distributed csi acquisition techniques and relay selection approaches as in @xcite where each relay sets a timer in accordance to the channel quality and through a countdown process the selection of the best relay is performed . additionally , csi overhead can be reduced significantly , through distributed - switch - and - stay - combining as in @xcite . in this section , we relax the assumption of having knowledge of the full csi . instead , we allow for csir knowledge with limited feedback , i.e. , each receiving node has csi of the channel it receives data from and it can provide some information to the transmitting node . more specifically , each ( receiving ) relay feeds back to the source a phase value via a reliable communication link . this approach is closely related to phase feedback schemes proposed and standardized for miso transmission ( see , for example , @xcite ) . the source signal can use this phase value in one of two possible ways : * to mitigate the interfering signal , so that the overall interference is reduced or even eliminated ; * to amplify the interfering signal , so that it can be decoded and removed from the rest of the received signals . the phase value can be quantized into the desired number of bits , using uniform quantization . we aim at recovering the multiplexing loss of the network by having the source and a relay to align phases , such that the iri is reduced . as a result , the proposed phase alignment approach reduces the communication overhead , while introducing a smart quantization that further reduces the complexity of the transmission . since there is no full csi knowledge , as assumed in the scheme proposed in the previous section , no precoding can be applied and a relay - selection policy is proposed based on csir knowledge with limited feedback that aims at taking advantage of the multi - antenna source . selection of the relay - pair is performed by choosing the pair that achieves the maximum end - to - end sinr . since the source has no csi for any of the links between the antennas at the source and the relays , equal power allocation across all antennas is a natural approach at the transmitter side . however , for overhead reduction on csi estimation at the receiver , we consider to use just two of them : one for transmitting the packet to a relay and the other to mitigate the iri . the existence of more than two antennas , however , can increase the diversity gain by choosing a subset of antennas based on csi , while the fact that not all available antennas are included , the overhead for channel information is limited . the same principle can equally well be applied using a single antenna source node , where one and the same antenna is used both for the desired packet and the iri mitigation . assuming two antennas used , the receiving signal at @xmath30 in is given by @xmath145&= h_{s_1 r } m_1 x_{s_1}[n ] + h_{s_2 r } m_2 x_{s_2}[n]\nonumber\\ & \quad+ h_{tr } x[p ] + w_r[n ] , \end{aligned}\ ] ] where we set @xmath146 and @xmath147 . in each time slot , the signal from the second antenna of the source @xmath148 $ ] is used in one of the following two ways : * to minimize the interference caused by the transmitting relay ; this is done by transmitting @xmath45 $ ] with a shifted phase such that the interfering signal and the signal from the second antenna is in anti - phase . the optimal phase for this is given by @xmath149 * to maximize the interference caused by the transmitting relay in order to make the signal strong enough to be decoded first , and hence , eliminate it . the optimal phase for this is given by @xmath150 [ propc ] the phase @xmath151 such that the interfering signal at the receiving relay @xmath42 from the transmitted signal @xmath45 $ ] of the transmitting relay @xmath47 is minimized is given by @xmath152 similarly , the phase @xmath153 such that the interfering signal at the receiving relay @xmath42 from the transmitted signal @xmath45 $ ] of the transmitting relay @xmath47 is maximized is given by @xmath154 see appendix [ c : proof_propc ] . proposition [ propc ] gives the expressions for phase alignment for each of the two approaches considered . by appropriately choosing the phase shift @xmath155 of the signal from one of the source s antennas , the source can minimize or maximize the interfering signal in order to mitigate it or eliminate it completely . note that the optimal value of @xmath155 ( either @xmath151 or @xmath153 ) can be quantized into the desired number of bits , using uniform quantization , and be fed back to the source . since only csir is available , the transmitters use fixed rate transmission . in such a case , the main objective is to minimize the outage probability . independently of nodal distribution and traffic pattern , a transmission from a transmitter to its corresponding receiver is successful ( error - free ) if the sinr of the receiver is above or equal to a certain threshold , called the _ _ capture ratio _ _ @xmath156 . therefore , at the receiving relay @xmath30 for a successful reception when at the same time relay @xmath31 is transmitting we require that @xmath157 and at the destination we require that @xmath158 an outage event occurs at the relay @xmath30 and destination @xmath35 when @xmath159 and @xmath160 , respectively . the outage probability is denoted by @xmath161 , where @xmath13 represents the receiving node and @xmath60 the transmitting node . each relay @xmath13 is able to estimate the sinr for each transmitting relay @xmath60 , denoted by @xmath162 , @xmath163 ( the full pilot protocol needed to the channel estimation is out of the scope of this work ) . we assume that this information can be communicated to the destination . in addition , the destination node can compute its own snr due to each of the transmitting relays , denoted by @xmath164 , @xmath165 . finally , we assume that the destination node has buffer state information and selects the relays for transmission and reception , based on some performance criterion , _ e.g. _ , with the maximum end - to - end sinr ( as it is defined in @xcite ) , through an error - free feedback channel . note that by having the destination to take the decision , no global csi is required at any node . as we have seen in proposition [ propc ] , the source can minimize the interfering signal or maximize it in order to eliminate it by appropriately choosing the phase shift @xmath155 of the signal from one of the source s antennas . it can be easily deduced that at low iri it is beneficial to try to remove the interfering signal , whereas at high iri it is beneficial to amplify the interfering signal and thus eliminate it completely by decoding it first . the receiving relay is able to compute which option gives the highest sinr in each case , since it has knowledge of the channel states and hence , it can decide which phase to feed back to the source at each time slot . the procedure of the proposed algorithm is as follows : by examining _ one - by - one _ the possible relay pairs , first we calculate the power of the signal received at _ d _ which is @xmath166 for an arbitrary relay @xmath31 with non - empty buffer . the receiving relay @xmath30 must be different than the transmitting relay and its buffer should not be full . for each candidate relay @xmath13 for reception , a _ feasibility check _ for interference cancellation ( ic ) is performed , i.e. , @xmath167 if ic is feasible , the candidate relay is examined whether snr at the receiving relay after ic is above the _ capture ratio _ @xmath156 or not , i.e. , once interference is removed becomes @xmath168 if ic is infeasible , interference mitigation ( i m ) is considered . hence , it is examined whether sinr at the receiving relay after i m is above the _ capture ratio _ or not . if the relay denoted by @xmath30 can provide an snr / sinr above the capture ratio after ic / im , it is considered as a candidate receiving relay . for the selected relay pair @xmath134 , the queue lengths are updated at the end of time slot as @xmath169 note that for fixed rate transmission , the queue length is equivalently modeled as the number of packets in the queue . the relay pair selection policy , as before , requires an exhaustive search with @xmath143 combinations imposing a complexity of the order @xmath144 . note , however , that links with sinr / snr above the _ capture ratio _ @xmath156 are suitable for transmission without compromising the performance of the proposed scheme , i.e. , it is not necessary to choose the relay pair that provides the maximum end - to - end sinr , as long as the outage event is avoided . hence , its simplicity allows the selection of a relay pair much faster , provided that the channel conditions are good . this characteristic will allow for more advanced algorithms in the future where the queue length will be a decisive factor on the decision of the relay pair such that certain delay constraints are met . for the time - being a relay pair is selected such that there is no reduction in performance ( either due to outage or full / empty buffers ) . we have developed a simulation setup based on the system model description in section [ sec : model ] , in order to evaluate the performance of the proposed relay pair selection schemes with current state - of - the - art for both adaptive and fixed rate transmission cases according to csi availability at the source . in the simulations , we assume that the clustered relay configuration ensures @xmath170 rayleigh block fading with average channel qualities @xmath171 , @xmath172 , and @xmath173 for all the @xmath0 , @xmath174 , and @xmath1 links , respectively . this assumption simplifies the interpretation of the results and it is used in several studies in the literature @xcite . the @xmath170 case and the related analysis can be considered as a useful guideline for more complex asymmetric configurations , in which power control at the source and relay nodes may be used to achieve symmetric channel configuration for better outage performance @xcite . for adaptive rate transmission , we evaluate the performance of the proposed ba - sp relay selection ( ba - sprs ) scheme in terms of the average end - to - end achievable rate in bpcu . the following upper bound and state - of - the - art relay selection schemes are considered for the performance comparison . * upper bound : the optimal solution of under no iri * hd best relay selection ( hd - brs ) @xcite * hd hybrid relay selection ( hd - hrs ) @xcite * hd @xmath5 relay selection ( hd - mlrs ) @xcite * ideal ( iri interference is assumed negligible ) and non - ideal ( iri interference is taken into consideration ) sfd - mmrs @xcite since in this work we consider multiple antennas at only the source while all conventional schemes above consider a single antennas at the source , we employ maximum ratio transmission ( mrt ) at the source , which maximizes the effective channel gain at each receiving relay , for all conventional schemes as well for making the comparison fair . fig . [ fig : art_rate_snr ] shows the average end - to - end rate for varying snr with two relays and two antennas at the source when @xmath175 , @xmath176 db with various iri intensities : the same intensity ( @xmath177 db ) , stronger iri ( @xmath178 db ) and weaker iri ( @xmath179 db ) . while the ideal sfd - mmrs scheme almost achieves the upper bound , non - ideal sfd - mmrs significantly degrades the performance since the effect of iri is severe so that it can not be neglected . the discrepancy between the proposed ba - sprs scheme and the upper bound increases with snr , since it results in increasing iri . especially , the gap becomes larger for stronger iri condition ( @xmath178 db ) . this is because perfect ic is impossible as iri increases . however , when iri becomes at least @xmath180 db below the @xmath0 and @xmath1 channel qualities , the proposed scheme almost approaches the upper bound . the conventional hd schemes achieve almost half the average end - to - end rate of the ideal sfd - mmrs and the proposed ba - sprs schemes . although the hd - mlrs scheme is a more advanced scheme than hd - brs and hd - hrs schemes in the sense of diversity order , it is the worst for this case with infinite buffer length , since our system setup yields a channel imbalance between the @xmath0 and @xmath1 links due to multiple antennas at only the source , which gives a higher chance to select the @xmath0 link than the @xmath1 link for the hd - mlrs scheme . in other words , for the hd - mlrs scheme , the larger the buffer size , the more source data is buffered at relay buffers , while the throughput is determined by the amount of received data at the destination . from the result , it is shown that the proposed ba - sprs scheme always outperforms the non - ideal sfd - mmrs and hd relay selection schemes regardless of snr and iri intensity . , @xmath175 , @xmath176 db , and @xmath181 , or @xmath180 db . ] fig . [ fig : art_rate_k ] shows the effect of the number of relays . as the number of relays increases , the proposed ba - sprs scheme quickly approaches the upper bound . especially , when @xmath182 and @xmath183 db , it already almost achieves the upper bound while other schemes can never achieve the upper bound except for the ideal sfd - mmrs scheme neglecting iri . therefore , in the case when @xmath184 , an additional relay ( i.e. , making @xmath182 ) contributes significantly to the performance enhancement with the same iri intensity . for stronger iri ( @xmath185 db ) , although there exist some gaps from the upper bound for small number of relays , it is fast recovered with increasing number of relays even under strong iri condition and finally converges to the upper bound . therefore , increasing the number of relays , offering spatial diversity and ignoring hardware and deployment costs , can be a simple solution against strong iri situations . for the same reason stated in fig . [ fig : art_rate_snr ] , the conventional hd - mlrs scheme rather degrades the average end - to - end rate with respect to increasing number of relays , since increasing the number of relays causes a similar effect to that of increasing the buffer size . db , @xmath176 db , and @xmath183 or @xmath180 db . ] fig . [ fig : art_rate_qmax ] shows the average end - to - end rate for different maximum buffer sizes for @xmath182 and @xmath186 db , which limits the instantaneous rate for each link . the ideal sfd - mmrs and the proposed ba - sprs schemes converge to the upper bound as the maximum buffer size increases but they have a cross point at @xmath187 . the proposed ba - sprs scheme achieves rather slightly higher average rate when @xmath188 than the ideal sfd - mmrs scheme neglecting iri . as a result , the proposed ba - sprs scheme is still effective for the finite buffer size which is a more practical setup . all the schemes converge to their own maximum rate when approximately @xmath189 except for the hd - mlrs scheme . as shown in figs . [ fig : art_rate_snr ] and [ fig : art_rate_k ] , the hd - mlrs scheme rather degrades the average end - to - end rate as the buffer size increases due to the effect of channel imbalance between @xmath0 and @xmath1 links . the hd - brs scheme without using a buffer is not affected from the finite buffer size . when @xmath182 , @xmath186 db , and @xmath190 db . ] for fixed rate transmission , we evaluate the proposed ba - pa relay selection ( ba - pars ) scheme in terms of outage probability and average end - to - end rate . we additionally consider the following state - of - the - art scheme proposed for fixed rate transmission : * buffer - aided successive opportunistic relaying ( ba - sor ) with iri cancellation @xcite . for all simulation results with fixed rate transmission , we consider @xmath170 channel condition with the same iri intensity , i.e. , @xmath191 . [ fig : pout_all ] shows the outage probability and @xmath1 links is less than the capture ratio @xmath156 , we define the outage probability as a portion of successfully transmitted packets among the total number of transmitted packets since the previous definition is not rigorous for the case of concurrent transmissions with iri . ] with various snr values for the transmission rate @xmath192 bpcu , three relays ( @xmath182 ) , and infinite length of buffer ( @xmath193 ) . basically , the hd - brs scheme has the worst outage performance due to lack of buffering . the hd - hrs scheme , a hybrid mode of hd - brs and hd - mmrs , is always better than the hd - brs scheme . since the hd - mlrs scheme can achieve a full diversity ( i.e. , @xmath194 diversity order ) for hd transmission , it shows the best performance except for low snr region . at low snr , the ideal sfd - mmrs scheme without taking iri consideration achieves slightly better performance than the hd - mlrs scheme . however , its outage performance is significantly degraded if iri is imposed . the ba - sor scheme achieves a good performance at low and medium snr but it becomes bad at high snr since its relay selection criterion is to maximize the minimum snr of both @xmath0 and @xmath1 links link when the best snr for @xmath0 link is worse than snrs of all @xmath1 links , instead of a random selection , since the @xmath1 link separately contributes on the outage event . ] . the proposed ba - pars scheme achieves similar performance to the ba - sor scheme at low snr but it is not degraded at high snr thanks to a hybrid mode of ic and i m . in addition , assuming a powerful source node such as base station as we stated in section ii , we depict the case of double power at the source for the proposed ba - pars scheme , which shows that the proposed ba - pars scheme can achieve the outage performance of the ideal sfd - mmrs scheme . hence , if extra power at the source is available , the proposed ba - pars scheme can provide the best outage performance . note that the ideal sfd - mmrs and the double powered ba - pars schemes achieve a half diversity gain ( i.e. , @xmath34 diversity order ) of the hd - mlrs scheme but a better power gain at low snr , since for both schemes , a half rate is required at each link to meet the same transmission rate as the hd - mlrs scheme . bpcu , @xmath182 , and @xmath193 . for the proposed ba - pars scheme , we additionally consider double power at the source ( denoted by ` [ 2p ] ' ) to show the case of a powerful source node . ] [ fig : pout_var_buffer ] shows the outage probability of the proposed ba - pars scheme for varying the maximum buffer size when @xmath192 bpcu and @xmath182 . as in @xcite , we assume that half of buffer elements are full at initial phase ( in order to reach the steady - state queue lengths quicker ) . as the maximum buffer size @xmath39 increases , the outage performance is improved and converges to the case of having buffers of infinite length . the convergence occurs at lower buffer sizes at high snr than at low snr , since buffer full / empty events contribute more in outage events at high snr due to sufficiently good received signal strengths ( i.e. , outage events due to bad channel conditions occur rarely and outage events are due to buffer full / empty events ) . when @xmath192 bpcu and @xmath182 . ] fig . [ fig : rate_all_frt ] shows the average end - to - end achievable rate with three different transmission data rates ( @xmath195 and @xmath196 bpcu ) when @xmath182 and @xmath197 . the conventional hd schemes achieve a half of the data rate due to an hd limitation although the hd - mlrs scheme achieves a full diversity in outage performance . while the ideal sfd - mmrs scheme obtains the best performance which achieves full data rates ( 1.5 and 2.5 bpcu ) as snr increases , the non - ideal sfd - mmrs scheme is significantly degraded due to iri , which shows rather worse performance with @xmath198 bpcu than the hd schemes . the ba - sor scheme can achieve the full data rate with @xmath199 bpcu at high snr but significantly degrades with higher data rates . in contrast , the proposed ba - pars scheme can achieve the full data rates for all the cases such that it guarantees the required data rate if a proper data rate is chosen according to snr , even if it has some gaps compared to the ideal sfd - mmrs scheme since the source power is split for ic / im . similarly to the outage performance , if double power at the source is available , the proposed ba - pars scheme can approach the achievable rate of the ideal sfd - mmrs scheme without suffering from iri . and @xmath196 bpcu ) when @xmath182 and @xmath197 . ] in this work , we present two relay - pair selection policies , depending on the available csi in the system , that employ a buffer - aided multi - antenna source , a cluster of hd buffer - aided relays and a destination . in the case of global csi , a linear precoding strategy is applied by the source in order to mitigate iri . a relay pair is selected , such that the average end - to - end rate is maximized . in the case of csir , phase alignment is applied by the source in order to mitigate / cancel iri . a relay pair is selected , such that the maximum end - to - end sinr is achieved . the benefits of this network deployment are demonstrated via a numerical evaluation , where the improved performance is observed with respect to the average end - to - end rate and outage probability , while the conventional non - ideal sfd - mmrs scheme with iri is significantly degraded . part of ongoing research is to investigate scenarios where only statistical information is known about the csi . after algebraic manipulations , optimization problem can be written as [ opt1 ] @xmath200 \textrm{s.t . } & ~ \mathbf{h}_s^h \begin{bmatrix } \mathbf{m}_1 & \mathbf{m}_2 \\ \end{bmatrix } = \begin{bmatrix } \beta & -\omega h_{tr } \\ \end{bmatrix } , \label{1cond1 } \\ & ~ \mathbf{m}_1^h \mathbf{m}_1 + \mathbf{m}_2^h \mathbf{m}_2 \leq 1 , \label{1cond2}\\ & ~ \omega \in ( 0,1 ] . \label{1cond3}\end{aligned}\ ] ] where @xmath105 , and @xmath201 , @xmath111 depend on the choice of @xmath202 . by a simple phase shift we observe that we can choose @xmath203 and @xmath204 , such that @xmath201 is a real number ; i.e. , let @xmath205 $ ] , such that @xmath206 ; then , @xmath207 . hence , optimization problem can be written as [ opt2 ] @xmath208 \textrm{s.t . } & ~ \mathbf{h}_s^h \begin{bmatrix } \mathbf{m}_1 & \mathbf{m}_2 \\ \end{bmatrix } = \begin{bmatrix } \beta & -\omega h_{tr } \\ \end{bmatrix } , \label{2cond1 } \\ & ~ \mathbf{m}_1^h \mathbf{m}_1 + \mathbf{m}_2^h \mathbf{m}_2 \leq 1 , \label{2cond2 } \\ & ~ \omega \in ( 0,1 ] . \label{2cond3}\end{aligned}\ ] ] let @xmath209 $ ] be a fixed value . then , the problem becomes equivalent to maximizing @xmath210 , i.e. , [ opt3 ] @xmath211 \textrm{s.t . } & ~ \mathbf{h}_s^h \begin{bmatrix } \mathbf{m}_1 & \mathbf{m}_2 \\ \end{bmatrix } = \begin{bmatrix } \beta & -\omega h_{tr } \\ \end{bmatrix } , \label{3cond1 } \\ & ~ \mathbf{m}_1^h \mathbf{m}_1 + \mathbf{m}_2^h \mathbf{m}_2 \leq 1 . \label{3cond2 } \end{aligned}\ ] ] suppose @xmath212 , @xmath213 , where @xmath214 will be identified later in the proof . then , by conditions and we have @xmath215 since @xmath201 is maximized , condition should be satisfied with equality . this will emerge in the sequel by contradiction . assume @xmath216 for some @xmath217 . then , since both @xmath218 and @xmath201 are real numbers we can easily deduce that @xmath219 substituting into , @xmath220 ; @xmath201 is maximized when @xmath221 , so condition is satisfied with equality . thus , @xmath222 and @xmath223 now , we need to find @xmath214 and @xmath224 . it is observed in that @xmath214 should be maximized in order to maximize @xmath201 . given that @xmath225 , this is equivalent to minimizing @xmath226 . towards this end , we formulate the following optimization problem : [ opt5 ] @xmath227 by cauchy - schwartz inequality @xmath228 minimizing @xmath229 can be achieved when holds with equality , i.e. , @xmath230 combining and we get @xmath231 since @xmath232 , then @xmath233 combining and , the maximum @xmath201 is given by @xmath234 substituting @xmath214 and @xmath201 into , we have @xmath235 finally , the precoding matrix @xmath86 is given by @xmath236 now , we want to find the value of @xmath111 for which the sinr at the receiving relay is maximized . for both and , it is required that @xmath237 . we substitute into optimization and for simplicity of notation we denote @xmath238 and @xmath239 . hence , optimization problem is written as @xmath240 \textrm{s.t . } & ~ 0 < \omega \leq \min\left\{1,{\sqrt{\frac{a}{b}}}\right\ } , \label{omega : ineq:1}\end{aligned}\ ] ] where @xmath241 denotes the minimum of arguments and the right hand side of comes from the condition that @xmath210 ( and subsequently @xmath242 ) is non - negative . by differentiating @xmath242 with respect to @xmath111 , @xmath243 at a turning point , @xmath244 ; hence , @xmath245 the two roots of are obtained by @xmath246 first , we verify that the roots have real - values by checking if the second order equation in has a positive discriminant , i.e. , @xmath247 let @xmath248 be the smallest root . it can be easily shown that at @xmath248 we attain a maximum , whereas at @xmath249 we attain a minimum . in addition , we need to show that any @xmath250 does not fulfill inequality constraint , so that the maximum of @xmath242 is not obtained on the boundary . we show this by contradiction . for @xmath251 , suppose @xmath252 . then , @xmath253 where @xmath254 stems from the fact that all the eliminated elements are positive . for @xmath255 , suppose @xmath256 . then , @xmath257 where @xmath258 stems from the fact that all the eliminated elements are all positive . hence , @xmath259 , given it fulfills inequality constraint . it is easily shown that @xmath248 is positive , so we will check if @xmath260 . for @xmath261 we need to check if @xmath262 . suppose @xmath263 ; then , @xmath264 which contradicts the fact that @xmath265 . step @xmath266 follows because @xmath267 ( @xmath268 ) . for @xmath269 we need to check if @xmath270 . suppose @xmath271 ; then , @xmath272 which contradicts the fact that @xmath265 . step @xmath273 follows because @xmath274 . it can be easily shown that the choice of @xmath61 changes neither the precoding matrix @xmath86 nor the value of @xmath201 . let @xmath276 and @xmath277 . then , the optimization problem in which power level selection is also possible can be written as @xmath278 \textrm{s.t . } & ~ 0 < \omega \leq \min\left\{1,\sqrt{\frac{a}{b}}\right\ } , \label{omega : ineq:11 } \\ & ~ 0 < x \leq m , \label{omega : ineq:12}\end{aligned}\ ] ] where @xmath279 . differentiating @xmath280 w.r.t . @xmath281 , the value of @xmath281 that maximizes @xmath280 is given by @xmath282 differentiating @xmath280 w.r.t . @xmath111 and by following similar steps to that of proposition [ propa ] , the value of @xmath111 that maximizes @xmath280 is given by @xmath283 the solution of - gives @xmath284 , suggesting that @xmath285 , i.e. , the source uses infinite power . however , power is constrained and this solution is not feasible . by substituting @xmath286 of in , we obtain @xmath287 which is monotonically decreasing with @xmath111 . hence , in order to maximize the sinr with respect to @xmath281 , @xmath111 should be kept as small as possible , while satisfying . this means that the value of @xmath281 that maximizes the sinr is at @xmath288 . let @xmath289 be the value computed via for @xmath288 . for @xmath288 , the value of @xmath111 that maximizes the sinr with respect to @xmath111 , say @xmath290 , can be computed via . then , * if @xmath291 , one can find @xmath292 that increases sinr ( since the maximum of the sinr with respect to @xmath281 is shifted to a lower value ) ; but then , @xmath293 which means that if @xmath291 the maximum value is always obtained at @xmath294 ; * if @xmath295 , then @xmath296 and the hence @xmath288 ; it can not be improved further since @xmath297 is an increasing function with respect to @xmath281 until @xmath298 . hence , @xmath290 finds the optimal value of the sinr with respect to @xmath111 , while it also increases the sinr with respect to @xmath281 . hence , the source should _ always _ transmit with @xmath116 . in case , @xmath116 is small such that is not satisfied and does not yield a feasible @xmath111 , then the maximum sinr is achieved for @xmath111 on the boundary , i.e. , @xmath299 , since @xmath297 is an increasing function with respect to @xmath111 , for @xmath300 ( as given by ) . @xmath275 by triangle inequality @xmath301 the optimization problem @xmath302 is minimized when inequality holds with equality ; this occurs when @xmath303 is in phase with @xmath304 . let @xmath151 the optimal angle @xmath155 for optimization . since @xmath305 , then the minimization yields @xmath306 similarly , by triangle equality @xmath307 the optimization problem @xmath308 is maximized when inequality holds with equality ; this occurs when @xmath303 is in phase with @xmath55 . let @xmath153 the optimal angle @xmath155 for optimization . since @xmath305 , the maximization yields @xmath309 j. n. laneman , d. n. c. tse , and g. w. wornell , `` cooperative diversity in wireless networks : efficient protocols and outage behavior '' , _ ieee trans . inform . theory _ 30623080 , dec . 2004 . i. krikidis , j. s. thompson , s. mclaughlin , and n. grtz , `` max - min relay selection for legacy amplify - and - forward systems with interference , '' _ ieee trans . wireless commun . _ , vol . 8 , pp . 30163027 , june 2009 . z. ding , i. krikidis , b. rong , j. s. thompson , c. wang , and s. yang , `` on combating the half - duplex constraint in modern cooperative networks : protocols and techniques , '' _ ieee trans . wireless commun . 2027 , dec . 2012 . c. wang , y. fan , i. krikidis , j. s. thompson , and h. v. poor , `` superposition - coded concurrent decode - and - forward relaying , '' _ proc . inf . theory ( isit ) _ , toronto , canada , july 2008 , pp . 23902394 . n. nomikos , t. charalambous , i. krikidis , d. n. skoutas , d. vouyioukas , m. johansson , and c. skianis , `` a survey on buffer - aided relay selection , '' _ commun . surveys tuts . 2 , pp . 10731097 , 2016 . i. krikidis , t. charalambous , and j. s. thompson , buffer - aided relay selection for cooperative diversity systems without delay constraints , " _ ieee trans . wireless commun . _ , vol.11 , no.5 , pp.19571967 , may 2012 . t. charalambous , n. nomikos , i. krikidis , d. vouyioukas and m. johansson , `` modeling buffer - aided relay selection in networks with direct transmission capability , '' _ ieee commun . 649 - 652 , april 2015 . m. shaqfeh , a. zafar , h. alnuweiri and m. s. alouini , `` maximizing expected achievable rates for block - fading buffer - aided relay channels , '' _ ieee trans . wireless commun . 9 , pp . 59195931 , sept . 2016 . m. oiwa , c. tosa and s. sugiura , `` theoretical analysis of hybrid buffer - aided cooperative protocol based on max max and max link relay selections , '' _ ieee trans . on vehicular tech . 92369246 , nov . 2016 . n. nomikos , d. vouyioukas , t. charalambous , i. krikidis , p. makris , d. n. skoutas , m. johansson and c. skianis , `` joint relay - pair selection for buffer - aided successive opportunistic relaying , '' _ wiley - blackwell trans . emerg . telecom . _ , vol . 25 , no . 8 , pp . 823834 , aug . n. nomikos , t. charalambous , i. krikidis , d. n. skoutas , d. vouyioukas and m. johansson , `` a buffer - aided successive opportunistic relay selection scheme with power adaptation and inter - relay interference cancellation for cooperative diversity systems , '' _ ieee trans . on commun . 5 , pp . 16231634 , may 2015 . r. simoni , v. jamali , n. zlatanov , r. schober , l. pierucci and r. fantacci , `` buffer - aided diamond relay network with block fading and inter - relay interference , '' _ ieee trans . wireless commun . 73577372 , nov . s. m. kim and m. bengtsson , `` virtual full - duplex buffer - aided relaying relay selection and beamforming , '' _ ieee pers . ( pimrc ) _ , london , united kingdom , sept . 2013 , pp . 17481752 . n. nomikos , t. charalambous , i. krikidis , d. vouyioukas and m. johansson , `` hybrid cooperation through full - duplex opportunistic relaying and max - link relay selection with transmit power adaptation , '' _ ieee int . conf . on comm . ( icc ) _ , june 2014 , pp . 57065711 . r. w. heath jr and a. j. paulraj , `` a simple scheme for transmit diversity using partial channel feedback , '' _ proc . 32th asilomar conf . signals , systems and computers _ , pacific grove , ca , nov . 1998 , pp . 10731078 . k. k. mukkavilli and a. sabharwal and b. aazhang , `` design of multiple antenna coding schemes with channel feedback , '' _ proc . 35th asilomar conf . signals , systems and computers _ , vol . 2 , pacific grove , ca , nov . 2001 , pp . 10091013 . d. benevides da costa and s. aissa , `` end - to - end performance of dual - hop semi - blind relaying systems with partial relay selection , '' _ ieee trans . wireless commun . _ , vol . 8 , no . 8 , pp . 43064315 , aug . 2009 . z. tian , g. chen , y. gong , z. chen , j. chambers , `` buffer - aided max - link relay selection in amplify - and - forward cooperative networks , '' _ ieee trans . vehicular tech . 2 , pp . 553565 , feb . 2015 .

we study a cooperative network with a buffer - aided multi - antenna source , multiple half - duplex ( hd ) buffer - aided relays and a single destination . such a setup could represent a cellular downlink scenario , in which the source can be a more powerful wireless device with a buffer and multiple antennas , while a set of intermediate less powerful devices are used as relays to reach the destination . the main target is to recover the multiplexing loss of the network by having the source and a relay to simultaneously transmit their information to another relay and the destination , respectively . successive transmissions in such a cooperative network , however , cause inter - relay interference ( iri ) . first , by assuming global channel state information ( csi ) , we show that the detrimental effect of iri can be alleviated by precoding at the source , mitigating or even fully canceling the interference . a cooperative relaying policy is proposed that employs a joint precoding design and relay - pair selection . note that both fixed rate and adaptive rate transmissions can be considered . for the case when channel state information is only available at the receiving side ( csir ) , we propose a relay selection policy that employs a phase alignment technique to reduce the iri . the performance of the two proposed relay pair selection policies are evaluated and compared with other state - of - the - art relaying schemes in terms of outage and throughput . the results show that the use of a powerful source can provide considerable performance improvements . cooperative networks , opportunistic relaying , buffer - aided relays , precoding , interference cancellation .

Donald Trump's name has been doing the rounds a fair bit recently. You might recognise him as the American businessman who has his own tower in New York or as the host of the original version of The Apprentice. You're also likely to have heard his name recently because he's hoping to be the Republican presidential candidate. And if you've been on Twitter since he suggested Muslims should be banned from America, you might have seen him being compared to Lord Voldemort. In a campaign statement, Donald Trump said a "complete" shutdown should remain until the US authorities "can figure out what the hell is going on" and if Muslims pose a threat to the US. He later repeated the comments at a rally in South Carolina, where supporters cheered him loudly. Read more about all the candidates hoping to take over from Barack Obama as US president. But Jeb Bush, who is also from the Republican party and hoping to be president, said the New York businessman was "unhinged". Donald Trump's comments, which he said were "common sense", were made in light of last week's shooting in California where a Muslim couple, believed to have been radicalised, opened fire and killed 14 people at a health centre in San Bernardino. The White House said Mr Trump's comments were contrary to US values, while the internet compared him to Lord Voldemort from Harry Potter - a lot. This isn't the first time in this campaign that Trump, who also thinks there should surveillance on some US mosques, has been criticised. His idea to build a "great, great wall" between the US and Mexico didn't go down too well. Mr Trump, a billionaire New Yorker who has been leading in the polls, defended his plan to build a wall on the US-Mexico border and deport all the people living illegally in the US. "You're going to have a deportation force, and you're going to do it humanely," he told MSNBC's Morning Joe. "You have millions of people that are waiting in line to come into this country and they're waiting to come in legally." Donald Trump: 21 things the Republican believes. For more stories like this one you can now download the BBC Newsbeat app straight to your device. For iPhone go here. For Android go here. ||||| J.K. Rowling took on Donald Trump with her latest tweet heard ’round the world. After the Republican presidential candidate frontrunner said that all Muslims should be banned from entering America, Harry Potter fans began comparing Trump to Lorde Voldemort, a.k.a. he who must not be named, a.k.a. the most draconian, dastardly villain in all of literature — well at least in Harry Potter’s wizarding world. But Rowling didn’t agree with the comparison. “How horrible,” Rowling wrote. “Voldemort was nowhere near as bad.” How horrible. Voldemort was nowhere near as bad. https://t.co/hFO0XmOpPH — J.K. Rowling (@jk_rowling) December 8, 2015 On Monday, Trump called for the “total and complete shutdown of Muslims entering the United States.” “Without looking at the various polling data, it is obvious to anybody the hatred is beyond comprehension,” Trump said. His remarks were slammed by both Republicans and Democrats alike. “Donald Trump is unhinged,” Republican presidential hopeful Jeb Bush wrote on Twitter. “His ‘policy’ proposals are not serious.”

– Donald Trump is usually the one dishing out insults on Twitter. Not on Tuesday. The business mogul found himself the latest to be burned by JK Rowling after proposing a "total and complete shutdown" of Muslims entering the US, reports Entertainment Weekly. Twitter users quickly began comparing Trump to Harry Potter villain Lord Voldemort, reports the BBC, but Rowling was having none of it. "How horrible," she tweeted. "Voldemort was nowhere near as bad." Her comment was retweeted more than 50,000 times within hours and racked up almost as many likes. (By the way, you've been saying "Voldemort" incorrectly for years.)

magnetite nanocrystals were prepared via solution - phase decomposition of iron carboxylate salts.@xcite the nanocrystals have been characterized by transmission electron microscopy ( tem ) , x - ray diffraction , and infrared and raman spectroscopy , as discussed in supplemental material . as synthesized the nanocrystals are protected by weakly bound oleic acid ligands ; these ligands allow the suspension of the nanocrystals in organic solvents , but act as electrically insulating layers that must be largely removed for effective electronic transport measurements . two - step electron beam lithography and e - beam evaporation ( 1 nm ti , 15 nm au ) were used to pattern closely spaced source and drain electrode pairs onto degenerately @xmath43-doped silicon substrates coated with 200 nm of thermally grown sio@xmath7 . interelectrode gaps ( channel lengths ) ranged from zero to tens of nm , with a 10 @xmath28 m wide channel region . nanocrystals were spin - coated from hexane solutions to form slightly more than one densely packed monolayer of nanocrystals over the channel region . samples were then baked at 673 k in vacuum for 1 hr to remove as much of the oleic acid as possible . in one set of samples , a second layer of particles was added followed by a second round of baking . the other class of devices are based on epitaxial magnetite films 50 nm thick grown by oxygen - plasma - assisted molecular beam epitaxy ( mbe ) on @xmath44 mgo single - crystal substrates . details of the growth process have been reported elsewhere.@xcite single - step e - beam lithography and e - beam evaporation were used to pattern au ( no ti adhesion layer ) source and drain electrodes defining a channel length ranging from tens of nm to hundreds of nm , and a channel width of 20 @xmath28 m . the interelectrode conduction is dominated by the channel region due to this geometry . no annealing was performed following electrode deposition . 10 mills , a. a. the lodestone : history , physics , and formation . _ science _ * 61 * , 273 - 319 ( 2004 ) . coey , j. m. d. & chien , c. l. half - metallic ferromagnetic oxides . _ mrs bulletin _ * 28 * , 720 - 724 ( 2003 ) . verwey , e. j. w. electronic conduction in magnetite ( fe@xmath5o@xmath6 ) and its transition point at low temperatures . _ nature _ * 144 * , 327 - 328 ( 1939 ) . verwey , e. j. w. & haayman , p. w. electronic conductivity and transition point of magnetite . _ physica _ * 8 * , 979 - 987 ( 1941 ) . walz , f. the verwey transition - a topical review . _ j. phys . : condens * 14 * , r285-r340 ( 2002 ) . garci , j. & subas , g. the verwey transition - a new perspective . _ j. phys.:condens . matter _ * 16 * , r145-r178 ( 2004 ) . huang , d. l. _ et al . _ charge - orbital ordering and verwey transition in magnetite measured by resonant soft x - ray scattering . _ * 96 * , 096401 ( 2006 ) . nazarenko , e. _ et al . _ resonant x - ray diffraction studies on the charge ordering in magnetite . lett . _ * 97 * , 056403 ( 2007 ) . subas , g. _ et al . _ magnetite , a model system for mixed - valence oxides , does not show charge ordering . lett . _ * 93 * , 156408 ( 2004 ) . rozenberg , g. k. _ et al . _ origin of the verwey transition in magnetite . lett . _ * 96 * , 045705 ( 2006 ) . piekarz , p. , parlinksi , k. & ole , a. m. mechanism of the verwey transition in magnetite . lett . _ * 97 * , 156402 ( 2006 ) . gasparov , l. v. _ et al . _ infrared and raman studies of the verwey transition in magnetite . _ phys . rev . b _ * 62 * , 7939 - 7944 ( 2000 ) . imada , m. , fujimori , a. & tokura , y. metal - insulator transitions . _ * 70 * , 1039 - 1263 ( 1998 ) . coey , m. condensed - matter physics : charge - ordering in oxides . _ nature _ * 430 * , 155 - 157 ( 2004 ) . leonov , i. , yaresko , a. n. , antonov , v. n. & anisimov , v. i. electronic structure of charge - ordered fe@xmath5o@xmath6 from calculated optical , magneto - optical kerr effect , and o @xmath45-edge x - ray absorption spectra . b _ * 74 * , 165117 ( 2006 ) . pinto , h. p. & elliot , s. d. mechanism of the verwey transition in magnetite : jahn - teller distortion and charge ordering patterns . j. phys . : condens . matter * 18 * , 10427 - 10436 ( 2006 ) . asamitsu , a. , tomioka , y. , kuwahara , h. & tokura , y. current switching of ressitive states in magnetoresistive manganites . nature * 388 * , 50 - 52 ( 1997 ) . sawa , a. , fujii , t. , kawasaki , m. & tokura , y. hysteretic current - voltage characteristics and resistance switching at a rectifying ti / pr@xmath38ca@xmath39mno@xmath5 interface . . lett . * 85 * , 4073 - 4075 ( 2004 ) . yu , w. w. , falkner , j. c. , yavuz , c. t. & colvin , v. l. synthesis of monodisperse iron oxide nanocrystals by thermal decomposition of iron carboxylate salts . * 2004 * , 2306 - 2307 ( 2004 ) . zhou , y. , jin , x. & shvets , i. v. enhancement of the magnetization saturation in magnetite ( 100 ) epitaxial films by thermo - chemical treatment . _ j. appl . phys . _ * 95 * , 7357 - 7359 ( 2004 ) . prez - diete , v. _ et al . _ thermal decomposition of surfactant coatings on co and ni nanocrystals . * 83 * , 5053 - 5055 ( 2003 ) . zeng , h. _ et al . _ magnetotransport of magnetite nanoparticle arrays . b _ * 73 * , 020402(r ) ( 2006 ) . shvets , i. v. _ et al . _ long - range charge order on the fe@xmath5o@xmath6(001 ) surface . b _ * 70 * , 155406 ( 2004 ) . burch , t. _ et al . _ switching in magnetite : a thermally driven magnetic phase transition . _ * 23 * , 1444 - 1447 ( 1969 ) . freud , p. j. & he d , a. z. dynamics of the electric - field - induced conductivity transition in magnetite . * 23 * , 1440 - 1443 ( 1969 ) . duchene , j. , terraillon , m. , pailly , p. & adam , g. filamentary conduction in vo2 coplanar thin - film devices . _ * 19 * , 115 - 117 ( 1971 ) . gu , q. , falk , a. , wu , j. , ouyang , l. & park , h. current - driven phase oscillation and domain - wall propagation in w@xmath46v@xmath47o@xmath7 nanobeams . _ nano lett . _ * 7 * , 363 - 366 ( 2007 ) . salazar , a. , oleaga , a. , wiechec , a. , tarnawski , z. & kozlowski , a. thermal diffusivity of fe@xmath48zn@xmath49o@xmath6 . _ ieee trans . _ * 40 * , 2820 - 2822 ( 2007 ) . * supplementary information * is linked to the online version of the paper . + * acknowledgements*. this work was supported by the us department of energy grant de - fg02 - 06er46337 . dn also acknowledges the david and lucille packard foundation and the research corporation . vlc acknowledges the nsf center for biological and environmental nanotechnology ( eec-0647452 ) , office of naval research ( n00014 - 04 - 1 - 0003 ) , and the us environmental protection agency star program ( rd-83253601 - 0 ) . cty acknowledges a robert a. welch foundation ( c-1349 ) graduate fellowship . rgss and ivs acknowledge the science foundation ireland grant 06/in.1/i91 . + * author contributions*. sl fabricated and measured the devices in this work and analyzed the data . af fabricated devices and performed xrd characterization of the nanocrystal materials . dn and sl wrote the paper . jtm and cyz made the nanocrystals in vlc s laboratory , and vlc contributed expertise in nanomaterials chemistry and characterization . rgss and ivs grew the magnetite films , and ivs contributed expertise on magnetite physical properties . all authors discussed the results and commented on the manuscript . + * competing interests*. the authors declare that they have no competing financial interests . + * correspondence*. correspondence and requests for materials should be addressed to d.n . ( email : natelson@rice.edu ) .

* magnetite ( fe@xmath0o@xmath1 ) , an archetypal transition metal oxide , has been used for thousands of years , from lodestones in primitive compasses@xcite to a candidate material for magnetoelectronic devices.@xcite in 1939 verwey@xcite found that bulk magnetite undergoes a transition at @xmath2 k from a high temperature `` bad metal '' conducting phase to a low - temperature insulating phase . he suggested@xcite that high temperature conduction is via the fluctuating and correlated valences of the octahedral iron atoms , and that the transition is the onset of charge ordering upon cooling . the verwey transition mechanism and the question of charge ordering remain highly controversial.@xcite here we show that magnetite nanocrystals and single - crystal thin films exhibit an electrically driven phase transition below the verwey temperature . the signature of this transition is the onset of sharp conductance switching in high electric fields , hysteretic in voltage . we demonstrate that this transition is not due to local heating , but instead is due to the breakdown of the correlated insulating state when driven out of equilibrium by electrical bias . we anticipate that further studies of this newly observed transition and its low - temperature conducting phase will shed light on how charge ordering and vibrational degrees of freedom determine the ground state of this important compound . * strongly correlated electronic materials can exhibit dramatic electronic properties ( _ e.g. _ , high temperature superconductivity , metal - insulator transitions , and charge ordering ) not present in simple systems with weaker electron - electron interactions . such rich electronic phenomenology can result when electron - electron interactions , electron - phonon interactions , and electronic bandwidth are all of similar magnitude , as in magnetite.@xcite verwey@xcite found nearly seven decades ago that bulk magnetite , while moderately conductive at room temperature , undergoes a transition to a more insulating state below what is now called the verwey temperature , @xmath3 k. similar transitions are known in a number of materials.@xcite above @xmath4 , fe@xmath5o@xmath6 has an inverse - spinel structure of the form ab@xmath7o@xmath6 , with tetrahedrally coordinated a sites occupied by fe@xmath8 and octrahedrally coordinated b sites of mixed valence , equally occupied by irons with formal @xmath9 and @xmath10 charges . conduction at high temperatures has long been thought to be through fluctuating valences of the b sites , with the transition corresponding to some kind of b site charge ordering as @xmath11 decreases ; concurrent is a first - order structural phase transition to an orthorhombic unit cell . this explanation remains controversial,@xcite with experiments showing some charge disproportion or charge order ( co),@xcite and others implying that the structural degrees of freedom drive the change in conductivity.@xcite recent theoretical progress has been made in understanding the complex interplay of charge and structural degrees of freedom@xcite , including a complete picture of the transition mechanism @xcite with strongly correlated 3@xmath12 fe electrons acting to amplify electron - phonon couplings . testing these ideas experimentally is of much interest . in this letter we report electronic transport measurements in magnetite at the nanoscale on both nanocrystals and single - crystal epitaxial thin films . both types of devices exhibit striking electrically - driven hysteretic switching of the electronic conductance once sample temperatures are reduced below @xmath4 . the data clearly show that the transition is not the result of local heating above @xmath4 , but instead is an electrically - driven breakdown of the insulating state . we discuss possible explanations for this switching in the context of the general verwey transition problem . while qualitatively similar resistive switching has been observed in other correlated oxide systems@xcite , the phenomenon in fe@xmath5o@xmath6 is a bulk effect with a mechanism distinct from these . . ( a ) current - voltage characteristics at various temperatures for a device based on 10 nm magnetite nanocrystals . arrows indicate the direction of the hysteresis . inset : zero - bias resistance , @xmath13 . ( b ) analogous data for a device based on a 50 nm - thick mbe - grown magnetite film . the nominal interelectrode gap was planned to be 100 nm , but at its narrowest was approximately 10 nm . inset : two - terminal resistance as function of channel length for another set of devices fabricated on another piece of the same film.,width=302 ] two - terminal devices for applying voltages and measuring conduction at the nanoscale have been fabricated ( see methods ) incorporating both fe@xmath5o@xmath6 nanocrystals@xcite ( 10 - 20 nm in diameter with oleic acid coating ) and single - crystal thin films ( 40 - 60 nm thick).@xcite devices were measured in both a variable temperature vacuum probe station and a @xmath14he cryostat with magnet . current - voltage characteristics have been measured with both a semiconductor parameter analyzer and directly using voltage sources and current amplifiers , with differential conductance computed numerically . figure 1a shows @xmath15 characteristics of a nanocrystal device at selected temperatures . when cooling , zero - bias conductance decreases monotonically until @xmath16 . below @xmath17 , the @xmath15 characteristics show sharp switching between a low bias insulating state and a high bias state with much higher differential conductance @xmath18 ( close to @xmath19 , with dramatic hysteresis as a function of voltage sweep direction . the switching threshold voltages increase in magnitude as @xmath11 is decreased . dozens of nanocrystal devices were measured and only those with 300 k resistances below 10 k@xmath20 showed the switching , with higher resistance devices having higher switching threshold voltages . resistances decrease by some three orders of magnitude with vacuum annealing at 673 k , likely because of oleic acid decomposition.@xcite the temperature dependence ( fig . 1a , inset ) of the zero - bias resistance , @xmath13 , has no step at @xmath4 , showing that @xmath13 remains dominated by contact effects . vs. @xmath21 for the nanocrystal device from fig . 1a at the same temperatures . ( b ) @xmath22 vs. @xmath21 for the thin film device from fig . 1b . both plots have logarithmic @xmath22 axes to better show the lowest temperature data . , width=302 ] qualitatively identical conduction is apparent in the thin film devices , as shown in fig . 1b . contact resistances are also important in these structures , as demonstrated by examining @xmath23 at low bias ( @xmath24 mv ) as a function of channel length , @xmath25 , as shown in the inset for one set of devices . extrapolating back to @xmath26 , the contact resistance , @xmath27 , at 300 k is 390 @xmath20 , while the 50 nm thick channel of width 20 @xmath28 m contributes 27.2 @xmath20/micron , implying ( based on channel geometry ) a magnetite resistivity of 2.9 m@xmath20-cm , somewhat below bulk expectations . further investigations are seeking to understand and minimize @xmath27 . analysis of @xmath29 at lower temperatures shows that @xmath27 increases significantly as @xmath11 is decreased , exceeding 80 k@xmath20 by 80 k. this complicates the analysis of the switching , since some of the total @xmath21 is dropped across @xmath27 rather than directly within the fe@xmath5o@xmath6 ; further , the contacts may not be ohmic near the switching threshold . we return to this issue later . the transitions in all devices are extremely sharp , with widths less than 50 @xmath28v , though in repeated sweeps at a fixed temperature , there is sweep - to - sweep variability of a few mv in switching thresholds . using the substrate as a gate electrode , no discernable gate modulation was seen in nanocrystal devices for gate biases between -80 v and + 80 v ; this suggests that nanocrystal charging effects do not dominate . switching characteristics were independent of magnetic field perpendicular to the sample surface up to 9 t , showing no large coupling between magnetization and the transition . differential conductance traces ( figure 2 ) show the transition even more dramatically . in the high conductance state , @xmath22 is relatively temperature independent . as @xmath11 is decreased , a clear zero - bias suppression develops , deepening into a hard gap when @xmath30 . in the nanocrystal data there are indications ( in @xmath31 ) of gap formation even at 150 k. we note that @xmath4 in nanocrystals could be elevated , since nanocrystals have large surface - to - volume ratios and the transition temperature of the magnetite surface is known to be higher than in the bulk.@xcite 20 nm diameter nanocrystals . inset : hysteresis loop in the conduction of the same device at 80 k , showing essentially no change in switching characteristics as the voltage sweep rate is varied over two orders of magnitude . , width=302 ] several lines of evidence indicate that these sharp conductance transitions are _ not _ the result of local joule heating ( as in macroscopic samples of fe@xmath0o@xmath1 @xcite and in the mott insulator vo@xmath7 @xcite ) , but rather are electrically driven . in the worst - case scenario , all of the @xmath32 joule heating power is dissipated within the magnetite , and inhomogeneous dissipation ( _ e.g. _ , filamentary conduction through a locally heated path ) can complicate the analysis . the local steady - state temperature is determined by the power dissipated and the thermal path . thermally driven switching would then correspond to raising the _ local _ temperature above @xmath33 . at a fixed cryostat temperature an improved thermal path would imply that more power dissipation would be required for a given local temperature rise . similarly , for a fixed thermal path , the necessary dissipated power for thermal switching would approach zero as @xmath34 . furthermore , at a given cryostat temperature thermally - driven switching would imply that the power dissipated at the low - to - high conductance transition ( needed to raise the local temperature to @xmath4 ) should be close to that at the high - to - low conductance transition . the thermal conductivity , @xmath35 , of magnetite is dominated by phonons in this temperature range , and limited by phonon - electron scattering,@xcite even when @xmath36 . as a result , @xmath35 increases as @xmath11 is _ decreased _ through and below @xmath4 , and the material s thermal coupling to the cryostat _ improves _ as @xmath11 is reduced . in _ all _ devices showing switching , the electrical power required to switch from low to high conductance _ decreases _ with decreasing @xmath11 , with fig . 3 showing one example . this is precisely the opposite of what one would expect from thermally - driven switching . similarly , in all devices the power dissipated at switching does _ not _ approach zero as @xmath34 , again inconsistent with thermally - driven switching . furthermore , at a given @xmath11 the power dissipated just before @xmath21 is swept back down through the high - to - low conductance threshold significantly exceeds that dissipated at the low - to - high point in many devices , including those in fig . 1 , inconsistent with thermal switching expectations . finally , nanocrystal and thin film devices show quantitatively similar switching properties and trends with temperature , despite what would be expected to be very different thermal paths . these switching characteristics are also qualitatively very different from those in known inhomogeneous joule heating.@xcite . these facts rule out local heating through the verwey transition as the cause of the conductance switching . figure 3 ( inset ) shows details of hysteresis loops on a nanocrystal device comparing different voltage sweep rates . the loop shape and switching voltages are unchanged to within the precision of the data collection as voltage sweep rates are varied from around 0.7 v / s up to 70 v / s . this indicates that the switching process is relatively rapid . further studies will examine the intrinsic switching speed . the observed conductance transition appears to be driven _ electrically_. figure 4 is a plot of the low - to - high conductance switching voltage as a function of @xmath25 in a series of film devices for several temperatures . the linear dependence implies that the transition is driven by electric field itself , rather than by the absolute magnitude of the voltage or the current density . the fact that the voltage extrapolates to a nonzero value at @xmath37 is likely a contact resistance effect . minimizing and better understanding the contact resistance will allow the determination of the electric field distribution within the channel . the length scaling of the transition voltage also demonstrates that this is a _ bulk _ effect . the contacts in all of these devices are identical , so any change in switching properties must result from the magnetite channel . this is in contrast to the resistive switching in pr@xmath38ca@xmath39mno@xmath5 ( pcmo ) that is ascribed to a change in contact resistance due to occupation of interfacial states@xcite . strongly implies that for each temperature there is a characteristic electric field required for switching . the non - zero intercepts of the trend lines indicate that some device - dependent threshold voltage must be exceeded for switching even when @xmath37 , suggestive of contact effects.,width=302 ] the field - driven conductance transition may give insights into the equilibrium verwey transition . this switching may be useful in testing recent calculations@xcite about the role of strongly correlated b - site fe 3@xmath12 electrons and their coupling to phonons in the verwey transition mechanism . it is interesting to ask , to what degree is the field - driven electronic transition coupled to the local structure ? it is greatly desirable to perform local probes of the magnetite structure ( via x - ray or electron - diffraction techniques or scanned probe microscopy ) _ in situ _ in the channel of biased devices , to see if the coherence between structural symmetry changes and the formation of a gap in the electronic spectrum is broken under these noequilibrium conditions . this is a significant experimental challenge . similarly , local raman spectroscopy of devices under bias could reveal field - induced changes in phonon modes and electron - phonon couplings , and single - crystal thin films permit the application of bias along well - defined crystallographic directions relevant to structural symmetry changes at @xmath4 . we do note that qualitatively identical switching occurs in nanocrystal devices as in strained thin films strongly coupled to rigid mgo substrates . this suggests that elastic constraints on scales much larger than the unit cell have relatively little influence on the observed switching . it is also possible that the nonequilibrium carrier distribution contributes to destabilizing the insulating state . in the presence of a strong electric field a carrier can gain significant energy even in a _ single _ hopping step , even though carrier relaxation times are very short . a rough estimate of the average critical @xmath40-field for switching at 80 k is @xmath41 v / m , from the slope of the line in fig . 4 . the high temperature cubic unit cell is 0.84 nm on a side , meaning that a carrier traversing one cell would gain approximately 8.4 mev , comparable to @xmath42 10.3 mev . conductance switching at such high fields may require consideration of such nonequilibrium carrier dynamics . the presence of multiple switching transitions in individual nanocrystal and film devices also bears further study . the suggested charge order may melt inhomogeneously , with portions of the channel having different switching thresholds . there could also be charge - ordered intermediate states between the insulating regime and the most conducting regime.@xcite again , optical measurements@xcite with sufficient spatial resolution could address these possibilities . through improved metal / magnetite contacts and further study , it should be possible to unravel the precise nature of this nonequilibrium transition , and its relationship to the equilibrium , bulk verwey transition .

the quest for the realization of different topological states of matter marks one of the major challenges in quantum many - body physics . a well established concept for the generation of two - dimensional topologically ordered states exhibiting anyonic excitations are flat bands characterized by a topological invariant in combination with strong interactions @xcite . the prime example is the fractional quantum hall effect , where strong magnetic fields generate landau levels @xcite . furthermore , lattice models without landau levels have been proposed for the realization of topological bands @xcite . notably , spin - orbit coupling has emerged as an experimentally promising tool for band structures with topological invariants @xcite . in this letter , we show that dipolar interactions , exhibiting intrinsic spin - orbit coupling , can be exploited for the realization of topological bands with cold polar molecules . in cold gases experiments , the phenomenon that dipolar interactions exhibit spin - orbit coupling is at the heart of demagnetization cooling @xcite , and has been identified as the driving mechanism for the einstein - de haas effect in bose - einstein condensates @xcite and the pattern formation in spinor condensates @xcite . dipolar relaxation was proposed as a mechanism to reach the quantum hall regime by the controlled insertion of orbital angular momentum @xcite . recently , it has been pointed out that dipolar spin - orbit coupling can be observed in band structures realized with polar molecules @xcite . these ideas are motivated by the experimental success in cooling and trapping polar molecules in optical lattices @xcite . ( a ) setup : each lattice site of a two - dimensional optical lattice is occupied by a single polar molecule . the molecules can be excited into two different rotational states . dipole - dipole interactions induce long - range tunneling links for the excitations . ( b ) rotational level structure of each molecule with applied electric field and additional microwave field with rabi frequency @xmath1 and detuning @xmath2 . ] here we show that a system of polar molecules gives rise to topological band structures , exploiting the spin - orbit coupling of dipolar interactions in combination with a term that breaks time - reversal symmetry . the main idea is based on polar molecules trapped in a two - dimensional deep optical lattice with quenched tunneling between the sites . the relevant degree of freedom of the polar molecules is given by two different rotational excitations which can be transferred between different lattice sites due to the dipolar exchange interaction . we demonstrate that the band structure for such an excitation is characterized by a chern number which depends on the underlying lattice structure . in particular , we find that the system on a square lattice gives rise to chern number @xmath0 , while a rich phase diagram appears on the honeycomb lattice . ideally , the setup is initialized with one polar molecule per lattice site , but we demonstrate that the topological properties are robust , even if nearly half of the molecules are randomly removed . in contrast to non - interacting fermions , free bosons can not form a topological insulator . however , the bosonic excitations in our system are subject to a hard - core constraint . such a setup in combination with flat bands is then expected to give rise to a fractional chern insulator at @xmath3 filling in @xmath0 topological bands @xcite . the main advantages of our realization , using the spin - orbit coupling present in dipolar interactions , are its robustness and the low experimental requirements , while many alternative theoretical proposals with cold gases require strong spatially inhomogeneous laser fields with variations on the scale of one lattice constant @xcite ; by using such ideas in combination with dipolar exchange interactions , it is also possible to engineer flat @xmath0 bands @xcite . we point out that our proposal can also be applied to rydberg atoms in similar setups @xcite . we consider a two - dimensional system of ultracold polar molecules in a deep optical lattice with one molecule pinned at each lattice site , as shown in fig . [ fig : fig1]a . the remaining degree of freedom is given by the internal rotational excitations of the molecules with the hamiltonian @xmath4 here , @xmath5 is the rotational splitting , @xmath6 is the angular momentum of the @xmath7th molecule and @xmath8 is its dipole moment which is coupled to the applied static and microwave electric fields @xmath9 . in the absence of external fields , the eigenstates @xmath10 of @xmath11 are conveniently labeled by the total angular momentum @xmath12 and its projection @xmath13 . applying a static electric field mixes states with different @xmath12 . the projection @xmath13 , however , can still be used to characterize the states . in the following , we focus on the lowest state @xmath14 with @xmath15 and the two degenerate excited states @xmath16 with @xmath17 , see fig . [ fig : fig1]b . the first excited @xmath15 state , called @xmath18 , will be used later . the full system , including pairwise dipole - dipole interactions between the polar molecules , is described by @xmath19 . in the two - dimensional setup with the electric field perpendicular to the lattice , the interaction can be expressed as @xmath20 \label{eq : ddint}\end{aligned}\ ] ] with @xmath21 . here , @xmath22 denotes the in - plane polar angle of the vector @xmath23 which connects the two molecules at lattice sites @xmath7 and @xmath24 , and the operators @xmath25 and @xmath26 are the spherical components of the dipole operator . the intrinsic spin - orbit coupling is visible in the second line in eq . , where a change in internal angular momentum by @xmath27 is associated with a change in orbital angular momentum encoded in the phase factor @xmath28 . for molecules with a permanent dipole moment @xmath29 in an optical lattice with spacing @xmath30 , the characteristic interaction energy @xmath31 is much weaker than the rotational splitting @xmath5 . for strong electric fields , the energy separation between the states @xmath32 and @xmath33 is also much larger than the interaction energy . then the number of @xmath16 excitations is conserved . this allows us to map the hamiltonian to a bosonic model : the lowest energy state with all molecules in the @xmath14 state is the vacuum state , while excitations of a polar molecule into the state @xmath34 are described by hard - core boson operators @xmath35 . note that these effective bosonic particles have a spin angular momentum of @xmath36 . a crucial aspect for the generation of topological bands with a nonzero chern number is the breaking of time - reversal symmetry . in our setup , this is achieved by coupling the state @xmath37 to the rotational state @xmath38 with an off - resonant microwave field , state to the third @xmath15 state can be neglected due to a large detuning from the difference in stark shifts between @xmath15 and @xmath39 see fig . [ fig : fig1]b . this coupling lifts the degeneracy between the two excitations @xmath40 and provides an energy splitting denoted by @xmath41 . the dipole - dipole interaction gives rise to an effective hopping hamiltonian for the bosonic particles due to the dipolar exchange terms : @xmath42 , for example , leads to a ( long - range ) tunneling @xmath43 for the @xmath44-bosons while the term @xmath45 generates spin - flip tunneling processes @xmath46 with a phase that depends on the direction of tunneling . for the study of the single particle band structure we can drop the term proportional to @xmath47 which describes a static dipolar interaction between the bosons . the interaction hamiltonian reduces to @xmath48 where we use the spinor notation @xmath49 . the energy scale of the hopping rates @xmath50 , @xmath51 , and @xmath52 is given by @xmath53 . the precise form depends on the microscopic parameters and is detailed in the appendix . note that @xmath54 without the applied microwave . in momentum space with @xmath55 , including the internal energy @xmath56 of the excitations @xmath40 , the hamiltonian can be rewritten as @xmath57 where it is useful to express the traceless part of the hamiltonian as the product of a three dimensional real vector @xmath58 and the vector of pauli matrices @xmath59 @xcite . the real vector characterizes the spin - orbit coupling terms and takes the form @xmath60 with @xmath61 . the spin - independent hopping is determined by @xmath62 with @xmath63 . we have introduced the dipolar dispersion relation @xcite @xmath64 the precise determination of this function can be achieved by an ewald summation technique providing a non - analytic low momentum behavior @xmath65 and @xmath66 . here , @xmath67 and @xmath68 is defined by @xmath69 . ( a ) dispersion relation for the @xmath70 and @xmath71 states on the square lattice . the dashed line shows the time - reversal invariant point @xmath72 with band touching at the @xmath73 and @xmath74 point . the solid line shows the gapped topological bands in the time - reversal - broken system for @xmath75 and @xmath76 . ( b ) dispersion relation for the @xmath70 and @xmath18 states for electric field angles @xmath77 ( dashed ) and @xmath78 ( solid ) , respectively . the latter has a lower band with flatness @xmath79 . , title="fig : " ] ( a ) dispersion relation for the @xmath70 and @xmath71 states on the square lattice . the dashed line shows the time - reversal invariant point @xmath72 with band touching at the @xmath73 and @xmath74 point . the solid line shows the gapped topological bands in the time - reversal - broken system for @xmath75 and @xmath76 . ( b ) dispersion relation for the @xmath70 and @xmath18 states for electric field angles @xmath77 ( dashed ) and @xmath78 ( solid ) , respectively . the latter has a lower band with flatness @xmath79 . , title="fig : " ] in the presence of time - reversal symmetry , represented by @xmath80 with @xmath81 being complex conjugation , the system reduces to the one discussed in ref . @xcite . at the @xmath82-invariant point , i.e. @xmath72 , the two energy bands of the system exhibit a band touching at the high - symmetry points @xmath83 and @xmath84 where @xmath85 vanishes , see fig . [ fig : fig2]a . the touching at the @xmath73 point is linear due to the low - momentum behavior of @xmath86 . note that each of the touching points splits into two dirac points if the square lattice is stretched into a rectangular lattice . breaking of time - reversal symmetry by the microwave field leads to an opening of a gap between the two bands . the dispersion relation is given by @xmath87 and shown in fig . [ fig : fig2]a . it is gapped whenever the vector @xmath88 . the first two components can only vanish at the @xmath73 or @xmath74 point . consequently , the gap closes iff the third component is zero at one of these two points , that is for @xmath89 in the gapped system , the chern number @xcite can be calculated as the winding number of the normalized vector @xmath90 via to perform the calculation of the chern number . we can check , however , that the remaining terms are not strong enough to close a gap . conversely , note that the cutoff radius has to be larger than @xmath91 , as the next - to - nearest neighbor terms are crucial for the @xmath0 phase and may not be neglected . ] @xmath92 we find that the chern number of the lower band is @xmath0 for @xmath93 , and zero outside this range . note that the non - trivial topology solely results from dipolar spin - orbit coupling and time - reversal symmetry breaking . ( a ) sample - averaged chern number @xmath94 in the disordered system for increasing density @xmath95 of defects . a single realization either yields @xmath0 or @xmath96 . bars indicate two standard errors . the results are shown for square lattices of size @xmath97 with @xmath98 . the long - range tunneling stabilizes the topological phase for defect densities @xmath99 . ( b ) two - dimensional projection of the dispersion relation in the honeycomb lattice for @xmath100 and @xmath101 . the lowest band has a flatness ratio of @xmath102 and a chern number of @xmath103 . ( c ) topological phase diagram in the honeycomb lattice for @xmath104 . the labels give the chern numbers of the four bands ( bar indicates negative number ) from bottom to top while the solid lines correspond to touching points between two bands . the color indicates the flatness @xmath105 of the lowest band . the arrow shows the parameters of the flat - band model in ( b ) . , title="fig : " ] ( a ) sample - averaged chern number @xmath94 in the disordered system for increasing density @xmath95 of defects . a single realization either yields @xmath0 or @xmath96 . bars indicate two standard errors . the results are shown for square lattices of size @xmath97 with @xmath98 . the long - range tunneling stabilizes the topological phase for defect densities @xmath99 . ( b ) two - dimensional projection of the dispersion relation in the honeycomb lattice for @xmath100 and @xmath101 . the lowest band has a flatness ratio of @xmath102 and a chern number of @xmath103 . ( c ) topological phase diagram in the honeycomb lattice for @xmath104 . the labels give the chern numbers of the four bands ( bar indicates negative number ) from bottom to top while the solid lines correspond to touching points between two bands . the color indicates the flatness @xmath105 of the lowest band . the arrow shows the parameters of the flat - band model in ( b ) . , title="fig : " ] ( a ) sample - averaged chern number @xmath94 in the disordered system for increasing density @xmath95 of defects . a single realization either yields @xmath0 or @xmath96 . bars indicate two standard errors . the results are shown for square lattices of size @xmath97 with @xmath98 . the long - range tunneling stabilizes the topological phase for defect densities @xmath99 . ( b ) two - dimensional projection of the dispersion relation in the honeycomb lattice for @xmath100 and @xmath101 . the lowest band has a flatness ratio of @xmath102 and a chern number of @xmath103 . ( c ) topological phase diagram in the honeycomb lattice for @xmath104 . the labels give the chern numbers of the four bands ( bar indicates negative number ) from bottom to top while the solid lines correspond to touching points between two bands . the color indicates the flatness @xmath105 of the lowest band . the arrow shows the parameters of the flat - band model in ( b ) . , title="fig : " ] the challenge is to find a specific setup that optimizes the flatness of the topological bands . this can be achieved either by focusing on different lattice structures ( see honeycomb lattice below and fig . [ fig : fig3]b ) or by an alternative choice for the two excitations . the latter is less intuitive when trying to understand the spin - orbit coupling , but gives rise to significantly flatter bands : instead of considering @xmath70 and @xmath71 , we choose a model including the @xmath70 and @xmath18 states . this is possible for weak electric fields , if the @xmath71 state is shifted by a microwave field , or by exploiting the coupling between the nuclear spins of the polar molecules and the rotational degree of freedom @xcite . this model intrinsically breaks time - reversal symmetry and has the advantage that the @xmath70 and @xmath18 states have different signs for the tunneling strength , making the @xmath82-breaking parameter @xmath106 large compared to @xmath107 . for an electric field direction perpendicular to the lattice , this system is gapless . opening the gap is achieved by rotating the electric field away from the @xmath108-axis by an angle @xmath109 . the dispersion relation for @xmath110 and @xmath111 is shown in fig . [ fig : fig2]b . the lower band has a flatness ratio of @xmath112 . topological band structures are classified by considering equivalence classes of models that can be continuously deformed into each other without closing the energy gap @xcite . using this idea , we can demonstrate that our model with @xmath0 is adiabatically equivalent to a system of two uncoupled copies of a @xmath113 layer ( see appendix for details ) . the resulting single layer model can be described by a staggered flux pattern and is reminiscent of the famous haldane model @xcite , adapted to the square lattice @xcite . it is rather remarkable that uniform dipole - dipole interactions give rise to a model usually requiring strong modulations on the order of the lattice spacing . an experimental initialization with a perfectly uniform filling of one molecule per site is challenging . consequently , we analyze the stability of the topological band structure for random samples with a nonzero probability @xmath95 for an empty lattice site . the determination of the chern number for the disordered system follows ideas from refs . we start with a finite geometry of @xmath97 lattice sites and twisted boundary conditions @xmath114 and @xmath115 for the single particle wave function . next , we randomly remove @xmath116 lattice sites ( dipoles ) . we are interested in the chern number of the lower ` band ' , composed of the lowest @xmath117 states ( there are @xmath118 states in total ) . to this end , we pretend to have a free fermionic system at half filling whose many - body ground state @xmath119 is given by the slater determinant of the lowest @xmath120 states . then , the chern number can be calculated as @xmath121 where @xmath122 is the many - body berry curvature depending on the boundary condition twists . note that eq . reduces to eq . in the translationally invariant case . for the numerical computations , we use a discretized version @xcite . the results for the disordered system are summarized in fig . [ fig : fig3]a . we find that the long - range tunneling stabilizes the topological phase for defect densities @xmath123 . returning to the simple setup in fig . [ fig : fig1]b , the influence of the lattice geometry can be exemplified by going to the honeycomb lattice . due to the two distinct sublattices , we generally obtain four bands in the presence of broken time - reversal symmetry . depending on the microscopic parameters , the bands exhibit a rich topological structure , characterized by their chern numbers . note that the chern numbers are calculated with a numerical method similar to the one for the disordered system . in fig . [ fig : fig3]c , we show a two - dimensional cut through the topological phase diagram , spanned by the parameters @xmath124 and @xmath125 . we find a multitude of different topological phases with large areas of flatness @xmath126 for the lowest band . a flatness @xmath127 indicates that the maximum of the lowest band is higher than the minimum of the second band . in contrast to the square lattice , an energy splitting @xmath128 is sufficient for a nonzero chern number ; @xmath129 is not necessarily needed . [ fig : fig3]b shows the dispersion relation with a lowest band of flatness @xmath102 and a chern number @xmath103 . ( a ) dispersion relation for the @xmath70 and @xmath18 states on a cylindrical square lattice geometry with infinite extent in @xmath130 direction and @xmath131 sites in @xmath132 direction . four edge states cross the bandgap in the @xmath0 phase ( two for each edge ) . ( b ) exponentially decaying amplitude of the two edge states in logarithmic scale , corresponding to the points shown in the spectrum . ( c ) edge state amplitude @xmath133 on a finite @xmath134 square lattice with a filling fraction of @xmath135 ( missing sites are indicated by crosses ) . ] ( a ) dispersion relation for the @xmath70 and @xmath18 states on a cylindrical square lattice geometry with infinite extent in @xmath130 direction and @xmath131 sites in @xmath132 direction . four edge states cross the bandgap in the @xmath0 phase ( two for each edge ) . ( b ) exponentially decaying amplitude of the two edge states in logarithmic scale , corresponding to the points shown in the spectrum . ( c ) edge state amplitude @xmath133 on a finite @xmath134 square lattice with a filling fraction of @xmath135 ( missing sites are indicated by crosses ) . , title="fig : " ] + ( a ) dispersion relation for the @xmath70 and @xmath18 states on a cylindrical square lattice geometry with infinite extent in @xmath130 direction and @xmath131 sites in @xmath132 direction . four edge states cross the bandgap in the @xmath0 phase ( two for each edge ) . ( b ) exponentially decaying amplitude of the two edge states in logarithmic scale , corresponding to the points shown in the spectrum . ( c ) edge state amplitude @xmath133 on a finite @xmath134 square lattice with a filling fraction of @xmath135 ( missing sites are indicated by crosses ) . , title="fig : " ] one way to detect the topological band structure experimentally is to create a local excitation close to the edge of the system . in fig . [ fig : fig4 ] we show the edge states in the @xmath0 phase on the square lattice . the states are exponentially localized on the boundary of the system and the propagation of a single excitation along the edge can be used as an indication of the topological nature of the bands @xcite . in fig . [ fig : fig4]c , we show the robustness of the edge states against missing molecules . the edge state is also visible in a spectroscopic analysis , as a single mode between the broad continuum of the two bands ( see fig . [ fig : fig4]a ) . finally , the most spectacular evidence of the topological nature would be the appearance of fractional chern insulators in the interacting many - body system at a fixed density of excitations . in our system , the hard - core constraint naturally provides a strong on - site interaction for the bosons . in addition , the remaining static dipolar interactions are a tunable knob to control the interaction strength . the most promising candidate for a hard - core bosonic fractional chern insulator in a band with @xmath0 appears for a filling of @xmath136 , as suggested by numerical calculations @xcite , in agreement with the general classification scheme for interacting bosonic topological phases @xcite . we acknowledge the support of the center for integrated quantum science and technology ( iqst ) , the deutsche forschungsgemeinschaft ( dfg ) within the sfb / trr 21 and the swiss national science foundation . as described in the main text , in the presence of the static electric field , we denote the lowest rotational states having @xmath137 by @xmath14 and @xmath16 , respectively . in addition , let @xmath138 be the lowest @xmath139 state . a microwave with rabi frequency @xmath140 and detuning @xmath2 couples the states @xmath70 and @xmath138 . for a large detuning @xmath141 , the number of @xmath70 ( and @xmath71 ) excitations is conserved . in the rotating frame , within rotating wave approximation , the ac - dressed @xmath70 state is given by @xmath142 up to second order in @xmath143 . for sufficiently strong electric fields , the states @xmath14 and @xmath71 are essentially unaffected by the microwave . to derive the parameters of the hopping hamiltonian ( 3 ) in the main text , we introduce the vacuum state @xmath144 and the single particle states @xmath145 . then , the hopping amplitudes are given by @xmath146 we set the spin - conserving term @xmath147 and the spin - flip tunneling @xmath148 to get the final expressions for the nearest - neighbor tunneling rates @xmath149 with the transition dipole element @xmath150 . the evaluation of the dipole matrix elements for finite electric fields is straightforward and has been described in detail @xcite . in the absence of other techniques to shift the energy , the expression for the offset between the @xmath70 and @xmath71 state is given by the ac stark shift @xmath151 . _ model with @xmath70 and @xmath18 state : _ using the @xmath70 and the @xmath18 state ( first excited @xmath15 state ) , the microwave field is no longer necessary , as the model intrinsically breaks time - reversal symmetry . however , the electric field has to be rotated away from the @xmath108 axis to open a gap in the spectrum . let @xmath152 denote the angles of the electric field axis in a spherical coordinate system with the lattice in the equatorial plane . then , the dipole - dipole interaction can be expressed as @xmath153\end{aligned}\ ] ] where @xmath154 for @xmath110 , the interaction reduces to expression ( 2 ) given in the main text . for the tunneling rates we find @xmath155 where @xmath156 . note that @xmath157 for @xmath110 , leading to the gapless spectrum for an electric field perpendicular to the lattice . hopping strengths and flux pattern of a single layer in different lattices . tunneling elements without arrow are real numbers . complex hoppings have the indicated strength along the arrow and the complex conjugate in the opposite direction . ( a ) square lattice : a single layer can be constructed by stripes of one component along one of the primitive vectors , effectively doubling the unit cell . the second layer is given by a translation along the second primitive vector . ( b ) honeycomb lattice : by distributing the @xmath158 orbitals to the two distinct sublattices it is possible to retain the symmetry of the lattice . the second layer is given by a @xmath159 rotation . ] topological band structures can be classified by considering equivalence classes of models that can be continuously deformed into each other without closing the energy gap @xcite . in particular , the chern number of a single band can only change if it touches another band . using this idea , we show that the model introduced in the main text in its @xmath0 phase is adiabatically equivalent to a system of two uncoupled copies of a @xmath113 layer . to see this , imagine separating the two orbitals @xmath70 and @xmath71 per site spatially along the @xmath108-direction ( without changing any tunneling rates ) such that we obtain two separate square lattice layers , called a and b. sorting all terms in the hamiltonian into intra- and inter - layer processes , we can write @xmath160 where @xmath161 . the choice which orbital resides in layer a ( and b ) can be made individually for each lattice site . in any case , the resulting two layers will be interconnected by an infinite number of tunneling links @xmath162 . the idea is to find a specific arrangement of the orbitals such that we can continuously let @xmath163 _ without _ closing a gap in the excitation spectrum , preserving the topological phase while disentangling the layers . focusing on layer a ( layer b being simply the complement ) , one possible arrangement is shown in fig . [ fig : fig5](a ) . the @xmath44 ( @xmath164 ) orbitals are assigned to odd ( even ) columns along the @xmath132-direction . for the chern number of such a single layer we find @xmath113 , using methods analogous to the ones described in the main text . the full system can be understood as two such layers , shifted by one lattice site in @xmath130-direction . with a unit cell twice the size of the original model , each layer contributes to one half of the full brillouin zone , effectively doubling the chern number to @xmath0 . the single layer system has some interesting properties . in fig . [ fig : fig5](a ) we show that it is possible to find a staggered magnetic flux pattern which creates the same tunneling phases as the dipole - dipole interaction , including tunneling up to the next - to - nearest neighbor level . using a site - dependent microwave dressing , it has been shown that a model similar to our single - layer system can be realized , giving rise to a @xmath165 fractional chern insulating phase @xcite . on the honeycomb lattice , a single layer can be constructed which retains the original symmetry of the lattice , see fig . [ fig : fig5](b ) . here , the two bands of the single layer also have @xmath166 but occupy the same brillouin zone as the double layer system . consequently , the four bands of the full system are constructed from the combination of two @xmath113 and two @xmath103 bands , giving rise to a multitude of different topological phases .

we demonstrate the realization of topological band structures by exploiting the intrinsic spin - orbit coupling of dipolar interactions in combination with broken time - reversal symmetry . the system is based on polar molecules trapped in a deep optical lattice , where the dynamics of rotational excitations follows a hopping hamiltonian which is determined by the dipolar exchange interactions . we find topological bands with chern number @xmath0 on the square lattice , while a very rich structure of different topological bands appears on the honeycomb lattice . we show that the system is robust against missing molecules . for certain parameters we obtain flat bands , providing a promising candidate for the realization of hard - core bosonic fractional chern insulators .

Four women are dealing with the repercussions of a selfie gone wrong after they accidentally damaged two works by iconic artists. On October 27, the group of women was visiting the International Arts Center Main Avenue in Yekaterinburg, Russia when they went to take a photo alongside Francisco Goya’s etching from the Los Caprichos series and Salvador Dali’s interpretation of it, according to the Russian News Agency TASS. Get push notifications with news, features and more. In surveillance video footage released by the Russian Ministry of Internal Affairs (MIA) on Twitter, three people can be seen looking at art on the gallery’s walls — including one who seems to be taking a photo — when the large art display suddenly falls over. In the corner of the fallen structure, a person can be seen standing in shock before a group gathers around the damage. RELATED: Disney Unveils New Interactive Art Exhibit to Celebrate Mickey Mouse’s 90th Anniversary “A group of girls — there were four of them — behaved inadequately,” an employee from the Arts Center told TASS. “As a result, they damaged two works of art, which were on display in a tandem: pictures by Francisco Goya and Salvador Dali.” The employee explained that while Goya’s work only had its frame and glass broken, Dali’s actual picture was damaged in addition to its shattered frame and the protective layer of glass. Surveillance footage before the display fell MIA Russia “The incident is being investigated,” the employee told TASS. “The works of art are being examined by specialists.” Following the incident, officials received a written request from the deputy director of the gallery, asking that they properly prosecute the group for their actions, according to a tweet from the MIA. RELATED VIDEO: Kid Knocks Down Expensive Statue Although the Russian police have also opened their own investigation into the matter, Yekaterinburg is reportedly not planning to open a criminal case against the women, CNN said. It is currently unknown how much the women accumulated in damages and whether they will face further legal consequences. The International Arts Center Main Avenue exhibition is still open and welcoming visitors. ||||| (CNN) A picture is worth a thousand words, but what about a selfie? A group of women in Yekaterinburg, Russia, may find out soon after one of them tried to take a selfie on October 27 and accidentally knocked over a structure at the International Arts Center Main Avenue. The structure was carrying two works of art, according to the Russian Ministry of Internal Affairs (MIA) and state-run news agency TASS. A surveillance video provided by MIA shows three people looking at art in the gallery when a structure carrying two works of art falls over. A person is seen behind the fallen structure. The damaged artworks, according to TASS, include a Francisco Goya etching from the Los Caprichos series and Salvador Dali's interpretation of it. Goya's work was also part of the gallery owner's private collection. "Goya's work had its frame and glass broken," a center employee told TASS. "As far as Dali's artwork is concerned, apart from shattered frame and protective glass, it also suffered damage to the picture itself." Read More ||||| YEKATERINBURG, November 2. /TASS/. A group of young girls damaged a picture by Salvador Dali during an exhibition at the Main Avenue Cultural Center in the Urals city of Yekaterinburg, organizers said. "A group of girls - there were four of them - behaved inadequately. As a result, they damaged two works of art, which were on display in a tandem: pictures by Francisco Goya and Salvador Dali. Goya’s work had its frame and glass broken. As far as Dali’s artwork is concerned, apart from shattered frame and protective glass, it also suffered damage to the picture itself," a culture center employee said. The damaged artworks are Goya’s etching from the Los Caprichos series, and Salvador Dali’s interpretation of it. "The incident is being investigated, the works of art are being examined by specialists," the source said. Local police confirmed that they have been informed of the incident. "A probe is underway. The damage is being established," a police spokesperson said. According to organizers, the exhibition continues its work in normal regime.

– An artwork by Salvador Dali is in need of repair after a selfie attempt gone wrong in Russia. Some women visiting Yekaterinburg's International Arts Center Main Avenue were reportedly attempting a selfie near a temporary wall showcasing two artworks—an etching by Spanish painter Francisco Goya and Dali's interpretation of it—when it toppled on Oct. 27, according to the Russian Ministry of Internal Affairs. A surveillance video shows a woman who appears to be snapping a photo of the display just as it falls toward her, causing her to take several quick steps back, per CNN. A woman behind the structure is revealed before a crowd forms. A ministry official says three women in a tour group said they'd touched the wall "by accident" while attempting a selfie, though a gallery employee tells TASS there were four "girls" who "behaved inadequately. As a result, they damaged two works of art." The frames and protective glass of both artworks were broken, while Dali's work "suffered damage to the picture," the employee says. Though the value of the works and cost of repairs is unclear, the gallery has asked authorities to charge the women, per People. CNN reports Yekaterinburg has so far refused to open a criminal case. (A selfie-taker broke a famous artist's glass pumpkin.)

SECTION 1. APPEALS PROCESS. (a) Reference.--Whenever in this section an amendment or repeal is expressed in terms of an amendment to, or repeal of, a section or other provision, the reference shall be considered to be made to a section or other provision of title 5, United States Code. (b) Time Period for Decision.--Section 8118 is amended by adding at the end the following: ``(f) An initial decision by the Secretary of Labor shall be made within 90 days of the date the claim is filed by the employee. If an initial decision is not made within such 90 days, the claimant shall be authorized further payment of full and normal salary until at such time an initial decision is reached. An employer may not hold or delay the filing of the claim. An agency may not withhold the filing of a claim, deny forms to file a claim, or obstruct, threaten, or induce a claimant to forego filing a claim. An agent of an agency may not falsify, induce, or compel false testimony to deny or controvert a claim.''. (c) Claimant's Physician.--Section 8123(a) is amended to read as follows: ``(a) An employee shall submit to an actual physical examination by a physician designated or approved by the Secretary of Labor, when so ordered by the administrative law judge. In cases of surgery, a second opinion examination shall be required before such surgery, except in life threatening circumstances or where additional disability will result if there is a delay. A medical report from a treating physician is predominant and sufficient for a case unless there are serious and legal reasons to suspect the medical evidence. Legal and medical examinations and reports, ordered by administrative law judges, will only be required where there are legal questions to be resolved with regard to the nature of the injury or with regard to whether the event that caused the injury was work-related or work-caused. The claimant shall have the right to have the claimant's own physician or a witness or representative present during the exam. The employee may have a physician designated and paid by the employee present to participate in the examination. If there is any disagreement between the physician for the Secretary and the claimant's physician, a list of 3 physicians of the appropriate Board Certified Specialty shall be tendered to the claimant who shall choose the physician to conduct the final examination with respect to the medical and legal issues in disagreement. The Secretary shall provide the claimant's physician with the same opportunity and information as is provided to the physician acting for the Secretary, including the statement of accepted facts and all medical information in the claimant's file.''. (d) Physician Fees.--Section 8123(c) is amended to read as follows: ``(c) The Secretary shall fix the fees for physicians under this section such that the physicians representing the Secretary shall be limited to the same structure and amounts allowed to claimants' physicians. All medical bills shall be paid within 60 days of billing, except during the initial claims processing, and in that case they shall be paid within 60 days of acceptance of the claim.''. (e) Hearing Date.--Section 8124(b)(1) is amended to read as follows: ``(b)(1) Administrative review of an initial decision of which the claimant is not satisfied may be appealed for an oral hearing before the administrative law judges of the Department of Labor. A request for an oral hearing must be made within 180 days of the date of the initial decision being appealed. A hearing must be held within 90 days of the date requested, or compensation denied or reduced shall be reinstated until such time as the hearing is given and a decision reached. Decisions regarding the issues brought on appeal shall be rendered within 30 days of the hearing or benefits will be reinstated if denied or reduced until a decision is reached.''. (f) Claimant's Authority.--Section 8124(b)(2) is amended to read as follows: ``(2) In conducting the hearing, the Secretary shall follow the requirements of chapter 5. The claimant shall have the right to confront and cross examine all adverse witnesses and present such evidence as the claimant feels necessary for consideration of the claim. The claimant's employer shall not be present at the hearing but shall be provided an opportunity to comment on the transcript of the hearing.''. (g) Representation; Representative Fees.--Section 8127 is amended by adding at the end the following: ``(c) Except as provided in subsection (d), claimant's attorney or representative shall be entitled to receive a fee of 15 percent of the benefits awarded to the claimant. ``(d) If the claimant prevails in a decision of a Federal court under chapter 7, the claimant's attorney shall be paid by the Secretary, but not from the claimant's award for the work of such attorney if the position of the Secretary with respect to such claimant was found under section 2412(c) of title 28 to be not substantially justified.''. (h) Review of Award.--Section 8128 is amended by striking subsections (a) and (b) and insert the following: ``Once a claim for compensation has been accepted, the Secretary may only end, decrease, or increase compensation by meeting a burden of proof standard that there was sufficient cause to perform a review. The claimant shall have the right to petition for review of adverse decisions at any time upon the submission of a new legal argument or new factual evidence not previously considered. Any denial of a petition for review or adverse decision arising out of a petition for review shall be reviewable under section 8124. Decisions on petitions for review shall be rendered no later than 90 days from the date received by the Secretary or his designee.''. (i) Reemployment and Vocational Rehabilitation.--(1) Section 8104 is amended to read as follows: ``Sec. 8104. Reemployment and vocational rehabilitation ``(a) The Secretary of Labor shall provide vocational rehabilitation services to any permanently disabled claimant who requests or whose physician requests such services. The claimant shall choose the vocational service provider, and insofar as practicable use the State services already funded by the Secretary of Health and Human Services. If a private counselor is used, the claimant shall have sole right to pick the provider and the fees shall be paid out of the Employees' Compensation Fund. ``(b) Federal employers shall give first priority of placement to injured Federal workers in positions commensurate with their pay at time of injury and disability. Such positions include any positions for which the claimant may already have experience or ones that they can be trained in. No person may retaliate, punish, deny work, deny promotion, or carry out any other discriminatory act against a claimant for filing a claim for compensation.''. (2) The table of sections for chapter 81 of title 5, United States Code, is amended by striking the item relating to section 8104 and inserting the following: ``8104. Reemployment and vocational rehabilitation.''.

Amends Federal civil service law to revise the appeals process under provisions for workers' compensation for Federal employees. Authorizes the Secretary of Labor to provide vocational rehabilitation services to any permanently disabled claimant who requests or whose physician requests such services.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Child and Dependent Care Tax Credit Enhancement Act of 2015''. SEC. 2. ENHANCEMENT OF CHILD AND DEPENDENT CARE TAX CREDIT. (a) In General.--Paragraph (2) of section 21(a) of the Internal Revenue Code of 1986 is amended to read as follows: ``(2) Applicable percentage.--For purposes of paragraph (1), the term `applicable percentage' means-- ``(A) in the case of employment-related expenses incurred for the care of a qualifying individual who has not attained 5 years of age before the close of the taxable year, 50-percent reduced (but not below 20 percent) by 1 percentage point for each $2,000 (or fraction thereof) by which the taxpayer's adjusted gross income for the taxable year exceeds $120,000, and ``(B) in the case of any employment-related expenses which are not described in subparagraph (A), 35-percent reduced (but not below 20 percent) by 1 percentage point for each $2,000 (or fraction thereof) by which the taxpayer's adjusted gross income for the taxable year exceeds $120,000.''. (b) Increase in Dollar Limit on Amount Creditable.--Paragraphs (1) and (2) of section 21(c) of such Code are amended to read as follows: ``(1) in the case of 1 qualifying individual with respect to the taxpayer for such taxable year-- ``(A) if such qualifying individual has attained 5 years of age before the close of the taxable year, $3,000, or ``(B) if such qualifying individual has not attained 5 years of age before the close of the taxable year, $6,000, or ``(2) in the case of 2 or more qualifying individuals with respect to the taxpayer for such taxable year-- ``(A) if 1 of such qualifying individuals has not attained 5 years of age before the close of the taxable year, $9,000, or ``(B) if 2 or more of such qualifying individuals have not attained 5 years of age before the close of the taxable year, $12,000.''. (c) Adjustment for Inflation.--Section 21 of such Code is amended-- (1) by redesignating subsection (f) as subsection (g), and (2) by inserting after subsection (e) the following new subsection: ``(f) Inflation Adjustment.-- ``(1) In general.--In the case of a calendar year beginning after 2016, the $120,000 dollar amounts in subparagraphs (A) and (B) of subsection (a)(2) and the dollar amounts in subsection (c) shall each be increased by an amount equal to-- ``(A) such dollar amount, multiplied by ``(B) the cost-of-living adjustment determined under section 1(f)(3) for the calendar year in which the taxable year begins, determined by substituting `calendar year 2015' for `calendar year 1992' in subparagraph (B) thereof. ``(2) Rounding.--If any dollar amount, after being increased under paragraph (1), is not a multiple of $100, such dollar amount shall be rounded to the next lowest multiple of $100.''. (d) Credit To Be Refundable.-- (1) In general.--The Internal Revenue Code of 1986 is amended-- (A) by redesignating section 21 as section 36C, and (B) by moving section 36C, as so redesignated, from subpart A of part IV of subchapter A of chapter 1 to the location immediately before section 37 in subpart C of part IV of subchapter A of chapter 1. (2) Technical amendments.-- (A) Paragraph (1) of section 23(f) of the Internal Revenue Code of 1986 is amended by striking ``21(e)'' and inserting ``36C(e)''. (B) Paragraph (6) of section 35(g) of such Code is amended by striking ``21(e)'' and inserting ``36C(e)''. (C) Paragraph (1) of section 36C(a) of such Code (as redesignated by paragraph (1)) is amended by striking ``this chapter'' and inserting ``this subtitle''. (D) Subparagraph (C) of section 129(a)(2) of such Code is amended by striking ``section 21(e)'' and inserting ``section 36C(e)''. (E) Paragraph (2) of section 129(b) of such Code is amended by striking ``section 21(d)(2)'' and inserting ``section 36C(d)(2)''. (F) Paragraph (1) of section 129(e) of such Code is amended by striking ``section 21(b)(2)'' and inserting ``section 36C(b)(2)''. (G) Subsection (e) of section 213 of such Code is amended by striking ``section 21'' and inserting ``section 36C''. (H) Subparagraph (H) of section 6213(g)(2) of such Code is amended by striking ``section 21'' and inserting ``section 36C''. (I) Subparagraph (L) of section 6213(g)(2) of such Code is amended by striking ``section 21, 24, or 32,'' and inserting ``section 24, 32, or 36C,''. (J) Paragraph (2) of section 1324(b) of title 31, United States Code, is amended by inserting ``36C,'' after ``36B,''. (K) The table of sections for subpart C of part IV of subchapter A of chapter 1 of the Internal Revenue Code of 1986 is amended by inserting after the item relating to section 36B the following: ``Sec. 36C. Expenses for household and dependent care services necessary for gainful employment.''. (L) The table of sections for subpart A of such part IV is amended by striking the item relating to section 21. (e) Effective Date.--The amendments made by this section shall apply to taxable years beginning after December 31, 2015.

Child and Dependent Care Tax Credit Enhancement Act of 2015 Amends the Internal Revenue Code, with respect to the tax credit for employment-related expenses incurred for the care of a taxpayer's dependent, to: (1) increase to $120,000, the adjusted gross income threshold level above which such credit is incrementally reduced; (2) increase the dollar limit on the allowable amount of such credit; (3) allow an inflation adjustment to the threshold amount and the maximum credit amounts, beginning after 2016; and (4) make such credit refundable.

* sample synthesis * high - quality single crystals of life@xmath0co@xmath1as were grown with the self - flux method . the precursor of li@xmath75as was prepared by sintering li foil and an as lump at about 700 @xmath76c for 10 h in a ti tube filled with argon ( ar ) atmosphere . fe@xmath0co@xmath1as was prepared by mixing the fe , co and as powders thoroughly , and then sealed in an evacuated quartz tube , and sintered at 700 @xmath76c for 30 h. to ensure the homogeneity of the product , these pellets were reground and heated for a second time . the li@xmath75as , fe@xmath0co@xmath1as , and as powders were mixed according to the elemental ratio li(fe@xmath0co@xmath1)@xmath77as . the mixture was put into an alumina oxide tube and subsequently sealed in a nb tube and placed in a quartz tube under vacuum . the sample was heated at 650 @xmath76c for 10 h and then heated up to 1000 @xmath76c for another 10 h. finally , it was cooled down to 750 @xmath76c at a rate of 2 @xmath76c per hour . crystals with a size up to 5 mm were obtained . the entire process of preparing the starting materials and the evaluation of the final products were carried out in a glove box purged with high - purity ar gas . + * determination of the doping level * the molar ratio of co and fe of the life@xmath0co@xmath1as single crystals was checked by energy dispersive x - ray spectroscopy ( eds ) at several points on one or two selected samples for each co concentration . for each doping , the co concentration measured by eds is consistent with the nominal value . ( solid circles ) and @xmath78 ( solid triangles ) , respectively . ( b ) coefficients @xmath79 for transport ( solid circles ) and @xmath80 for optics ( solid triangles ) determined from the single power law fit as a function of co concentration . ] all data are taken at 20 k along the @xmath50@xmath51 direction . the red curves shown in the intensity plots are mdcs at the fermi level . ] . the dashed line corresponds to the carrier concentration assumed by adding one extra electron for each fe substituted by co. ] * resistivity measurements * the electrical transport measurements of life@xmath0co@xmath1as were carried out in a commercial physical properties measurement system ( ppms ) using the four - probe method . to prevent sample degradation , the electrical contacts were prepared in a glove box and then the sample was protected by _ n_-grease before transferring to the ppms . each sample was cut into a rectangular piece , so that its dimensions could be measured more accurately with a microscope . with these precisely - measured geometry factors , the resistivity can be easily calculated from the measured resistance . the resistivity determined from the transport measurements is then compared with the values determined from the optical conductivity to ensure the consistency between different techniques . + * single power law fitting * figure [ figsrt ] displays the resistivity as a function of temperature @xmath8 ( open circles ) up to 70 k for all 8 samples . for each substitution , @xmath8 is fit to a single power law expression , @xmath81 , from @xmath822 k ( or @xmath2 , whichever is greater ) up to 70 k. the solid lines through the data in each panel denote the fitting results . the power @xmath10 , determined from the fitting , is shown for the stoichiometric material and all the co substitutions in the corresponding panels ; the crossover behavior of @xmath10 can be seen clearly . in order to present the power - law behavior of the @xmath8 curve more clearly , we plot @xmath8 as a function of @xmath17 for each substitution in fig . [ figsrtn ] , where @xmath10 is the power determined from the single power law fitting . in this case , all the @xmath8 curves can be perfectly described by linear behavior , shown by the solid line in each panel . * reflectivity * the temperature dependence of the absolute reflectivity @xmath83 of life@xmath0co@xmath1as has been measured at a near - normal angle of incidence for the stoichiometric material and 4 representative substitutions using an _ in situ _ overcoating technique @xcite . for each sample , data were collected at 17 different temperatures from 5 k to room temperature over a wide frequency range ( @xmath822 mev to 4 ev ) on a freshly cleaved surface . because of the air - sensitive nature of the life@xmath0co@xmath1as samples , the sample mounting and cleaving were done in a glove bag purged with high - purity ar gas . immediately after the cleaving , the sample was transferred to the vacuum shroud ( also purged with ar ) with the protection of a small ar - purged plastic bag . the reproducibility of the experimental results was checked by repeating the @xmath83 measurements 2 or 3 times for each doping . figure [ figsopt](a)[figsopt](e ) show @xmath83 in the far - infrared region at 4 selected temperatures for 5 different co concentrations . for all the materials , @xmath83 approaches unity at zero frequency and increases upon cooling , indicating a metallic response . + * kramers - kronig analysis * the real part of the complex optical conductivity @xmath20 is determined from a kramers - kronig analysis of the reflectivity . given the metallic nature of the life@xmath0co@xmath1as materials , the hagen - rubens form @xmath84 $ ] is used for the low - frequency extrapolation , where @xmath79 is chosen to match the data at the lowest - measured frequency . above the highest - measured frequency , @xmath83 is assumed to be constant up to 1.0 @xmath85 10@xmath86 @xmath87 , above which a free - electron response @xmath88 $ ] was used . + * optical conductivity * figure [ figsopt](f)[figsopt](j ) display @xmath20 at 4 selected temperatures for the stoichiometric material and 4 different co concentrations . the metallic behavior of these materials can be recognized by the pronounced drude - like peak centered at zero frequency . the zero - frequency value of @xmath20 represents the dc conductivity @xmath89 which is in good agreement with the values determined from transport measurements ; the width of the drude peak at half maximum yields the quasiparticle scattering rate . as the temperature decreases , @xmath89 increases and the drude peak narrows . this indicates that the quasiparticle scattering rate decreases upon cooling , dominating the temperature dependence of the electrical transport properties . + * quasiparticle scattering rate * figure [ figsopt](k)[figsopt](o ) show the quasiparticle scattering rate of the coherent narrow drude component @xmath19 as a function of @xmath34 , where @xmath35 is the power determined from the single power law fit to @xmath19 as a function of @xmath3 . linear behavior can be clearly observed in each panel as guided by the straight solid lines . + * comparison between transport and optics * figure [ figsrtvso](a ) compares the doping dependence of @xmath11 ( solid circles ) and @xmath78 ( solid triangles ) , where @xmath11 is determined by fitting @xmath8 to @xmath9 , and @xmath78 is derived by fitting @xmath90 to @xmath91 for each doping . both @xmath11 and @xmath78 grow as the co concentration increases , indicating that impurities are introduced into the compounds by the co substitution . the single power law fit also returns the coefficients @xmath79 for transport and @xmath80 for optics , respectively . as shown in fig . [ figsrtvso](b ) , @xmath79 ( solid circles ) and @xmath80 ( solid triangles ) follow identical doping dependence , suggesting that the @xmath3 dependence in @xmath8 and @xmath90 are governed by the same physics . note that while the coefficients @xmath79 and @xmath80 follow exactly the same trace across doping , the detailed behaviors of @xmath11 and @xmath78 are slightly different . this is because @xmath78 is the residual scattering rate of the coherent narrow drude component , which contributes to @xmath11 in parallel with the incoherent broad drude component . however , as a common feature in all fe - base superconductors @xcite , the @xmath3 dependence of the transport properties is dominated by the coherent narrow drude component . since @xmath79 and @xmath80 are the prefactors that describe the properties of the @xmath3 dependence in @xmath8 and @xmath90 , respectively , it is natural to expect similar behaviors for @xmath79 and @xmath80 if they are governed by the same physics . * measurements * arpes measurements were performed with a high - flux he discharge lamp . the energy resolution was set at 12 mev and 3 mev for the fermi surface mapping and high resolution measurements , respectively . the angular resolution was set at 0.2@xmath76 . fresh surfaces for the arpes measurements were obtained by an _ in situ _ cleavage of the crystals in a working vacuum better than 4@xmath8510@xmath92 torr . the fermi energy ( e@xmath93 ) of the samples was referenced to that of a gold film evaporated onto the sample holder . + * arpes intensity plots and energy / momentum distribution curves along the @xmath50@xmath51 direction * arpes intensity plots across the @xmath50 point for five representative dopings and their corresponding energy distribution curves ( edcs ) are shown in fig . [ figsarpes](a)[figsarpes](e ) and fig . [ figsarpes](f)[figsarpes](j ) , respectively . the same plots but crossing the @xmath51 point for each doping are shown in fig . [ figsarpes](k)[figsarpes](o ) and fig . [ figsarpes](p)[figsarpes](t ) , respectively . the red curves in fig . [ figsarpes](a)[figsarpes](e ) and fig . [ figsarpes](k)[figsarpes](o ) are the momentum distribution curves ( mdcs ) at the fermi level . the peak positions on mdcs correspond to the @xmath94 positions along the high symmetry line . since the edc and mdc peaks , as well as the band dispersions , are well defined at all dopings , the @xmath94 positions can be accurately determined for each co concentration . the uncertainty of the @xmath94 position is mainly from the energy and momentum resolutions of our system settings . for these measurements the angular and energy resolutions of the system were set at 0.2@xmath76 and 3 mev , respectively , which lead to a typical uncertainty of @xmath95 @xmath96 for @xmath94 at 21.2 ev photon energy . + * evolution of the fermi surface volume with doping * the evolution of the fermi surface volume with doping is controlled by the luttinger theorem : the total algebraic fermi surface volume is directly proportional to the carrier concentration . we checked that this is the case in our study and we plot the results in fig . [ figsfsvol ] , which confirm that the total volume of the fermi surface ( open circles ) satisfies the luttinger theorem at each doping if we assume a rigid chemical potential shift caused by the introduction of one additional electron carrier per fe atom substituted by co ( dashed line ) , as also observed theoretically @xcite and experimentally @xcite for the 122 family of iron pnictides . co@xmath97as for the @xmath18 and @xmath98 samples . the knight shift for both samples are measured with the external field perpendicular to the _ a - b _ plane to avoid calculation of the second order quadruple correction . though the size of the knight shift along different directions may be different , they share the same temperature dependence . therefore we are able to take the @xmath99 at @xmath100 to estimate the behavior of @xmath101 @xcite . ] * measurements * we perform the @xmath37as nuclear magnetic resonance ( nmr ) measurements with the external field parallel to the _ a - b _ plane . the spin - lattice relaxation rate is measured by inversion - recovery method on the central transition and the recovery curve is fit with a standard double exponential form for an s=3/2 spin @xmath102 + * knight shift * figure [ figsnmr ] shows the knight shifts of @xmath18 and @xmath98 samples , respectively . the knight shift , which measures the uniform susceptibility , becomes temperature independent below 30 k , indicating the low - temperature upturn in @xmath64 comes from large - momentum spin fluctuations . note that since the nmr form factor for as is known to be broadly distributed in momentum space in iron - based superconductors @xcite , both commensurate ( close to fs nesting ) and incommensurate ( away from nesting ) low - energy spin fluctuations are captured by the spin - lattice relaxation rate @xmath103 .

a series of life@xmath0co@xmath1as compounds with different co concentrations have been studied by transport , optical spectroscopy , angle - resolved photoemission spectroscopy and nuclear magnetic resonance . we observed a fermi liquid to non - fermi liquid to fermi liquid ( fl - nfl - fl ) crossover alongside a monotonic suppression of the superconductivity with increasing co content . in parallel to the fl - nfl - fl crossover , we found that both the low - energy spin fluctuations and fermi surface nesting are enhanced and then diminished , strongly suggesting that the nfl behavior in life@xmath0co@xmath1as is induced by low - energy spin fluctuations which are very likely tuned by fermi surface nesting . our study reveals a unique phase diagram of life@xmath0co@xmath1as where the region of nfl is moved to the boundary of the superconducting phase , implying that they are probably governed by different mechanisms . the normal state of high - temperature ( high-@xmath2 ) superconductors is very unusual , with the electrical resistivity ( or quasiparticle scattering rate ) varying with temperature in a peculiar way that deviates significantly from the quadratic @xmath3 dependence expected from landau s fermi - liquid ( fl ) theory of metals @xcite . because this anomalous non - fermi - liquid ( nfl ) behavior is often revealed experimentally above a superconducting dome , there is a broad consensus that the origin of the nfl behavior may hold the key to understanding the pairing mechanism of high-@xmath2 superconductivity . studies on high-@xmath4 cuprate superconductors @xcite , heavy - fermion metals @xcite , organic bechgaard salts @xcite as well as the newly - discovered iron - based superconductors ( ibscs ) @xcite have shown that the nfl behavior and high-@xmath2 superconducting dome favor proximity to magnetic order . this fact has led to proposals ascribing both the nfl behavior and high-@xmath2 superconductivity to spin fluctuations close to a magnetic quantum critical point ( qcp ) @xcite . however , a growing number of experiments do not agree with these scenarios . for example , a recent magnetotransport study has shown that by doping cecoin@xmath5 with yb , the field - induced qcp is fully suppressed while both the nfl behavior and superconductivity are barely affected @xcite . at the current time , the microscopic mechanism of the nfl behavior and its relationship to high-@xmath2 superconductivity are still a matter of considerable debate . ibscs feature an intricate phase diagram with nfl behavior , superconducting phase , magnetic order , structural transition , possible qcp(s ) and nested fermi surfaces interacting with each other . this complexity makes it quite challenging to distinguish the roles played by different orders or interactions . the life@xmath0co@xmath1as system presents a simple phase diagram : lifeas exhibits superconductivity with a maximum transition temperature @xmath6 k in its stoichiometric form @xcite . the substitution of fe by co results in a monotonic lowering of @xmath4 ; neither magnetic nor structural transitions have been detected in the temperature doping ( @xmath3@xmath7 ) phase diagram of life@xmath0co@xmath1as @xcite . the normal state of lifeas is a fl , as evidenced by the quadratic @xmath3 dependence of the low - temperature resistivity @xcite . such a simple phase diagram makes life@xmath0co@xmath1as an excellent system to elucidate the origin of the nfl behavior and its relationship to superconductivity . in this article , through a combined study of transport , optical spectroscopy , angle - resolved photoemission spectroscopy ( arpes ) and nuclear magnetic resonance ( nmr ) on life@xmath0co@xmath1as , we found that while superconductivity is monotonically suppressed with increasing co concentration , the transport and optical properties reveal a prominent fl - nfl - fl crossover which closely follows the doping evolution of low - energy spin fluctuations ( lesfs ) and fermi surface nesting . our observations provide clear evidence that lesfs , which are likely tuned by fs nesting , dominate the normal - state scattering , and are thus responsible for the fl - nfl - fl crossover in life@xmath0co@xmath1as . a unique phase diagram of life@xmath0co@xmath1as derived from our studies shows that the nfl behavior is decoupled from superconductivity , suggesting that they do not share the same origin . high quality single crystals of life@xmath0co@xmath1as with different co concentrations were grown by a self - flux method @xcite . details of the sample synthesis and experimental methods for all the techniques we used in this work are included in appendixes a to e. ( open circles ) for life@xmath0co@xmath1as at five selected co concentrations . for each material , @xmath8 is fit to a single power law @xmath9 ( solid lines ) . ( f ) evolution of the exponent @xmath10 ( solid circles ) and residual resistivity @xmath11 ( solid diamonds ) with co substitution @xmath7 . ] figures [ fig1](a)[fig1](e ) show the @xmath3-dependent resistivity @xmath8 for five representative dopings . for each doping , @xmath8 is fit to a single power law @xmath9 , returning the exponent @xmath10 and the residual resistivity @xmath11 . the evolution of @xmath10 and @xmath11 with doping are summarized in fig . [ fig1](f ) as solid circles and solid diamonds , respectively . in lifeas ( @xmath12 ) , @xmath13 , _ i.e. _ the resistivity varies quadratically with temperature , indicating a fl normal state , in agreement with previous transport studies on lifeas @xcite . with increasing co doping , @xmath10 decreases , reaching a minimum of 1.35 at @xmath14 . with further doping ( @xmath15 ) , @xmath10 begins to increase and recovers to a value of 2 again at about @xmath16 . @xmath8 and the single power - law fitting results for more dopings are displayed in appendix b ( fig . [ figsrt ] ) . to present the crossover behavior more clearly , @xmath8 is plotted as a function of @xmath17 , as shown in appendix b ( fig . [ figsrtn ] ) , where a linear behavior can be seen for all the dopings . this doping dependence of @xmath10 is an explicit indication of a doping - induced fl - nfl - fl crossover in life@xmath0co@xmath1as . in addition , we note that , as shown in fig . [ fig1](f ) , @xmath11 increases with doping all the way to @xmath16 , while @xmath10 exhibits a fl - nfl - fl crossover in the same doping range . this indicates that the fl - nfl - fl crossover in life@xmath0co@xmath1as is not tied to the impurity level . of lifeas ( @xmath18 ) measured at 100 k. the thin red curve through the data is the drude - lorentz fit which consists of the contributions from a coherent narrow drude ( red shaded region ) , a nearly incoherent broad drude ( green shaded region ) and series of lorentz components ( blue shaded region ) . ( b)(f ) @xmath3 dependence of the quasiparticle scattering rate @xmath19 derived from the coherent narrow drude component for five co concentrations . ] further evidence for the fl - nfl - fl crossover can be revealed by the @xmath3 dependence of the quasiparticle scattering rate obtained via optical spectroscopy @xcite . figure [ fig2](a ) displays the real part of the optical conductivity @xmath20 for lifeas ( @xmath18 ) at 100 k. the low - frequency @xmath20 is dominated by the well - known drude - like metallic response , where the width of the drude peak at half maximum gives the value of the quasiparticle scattering rate . in order to accurately extract the quasiparticle scattering rate , we fit the measured @xmath20 to the drude - lorentz model : @xmath21 , \label{dlmodel}\ ] ] where @xmath22 is the impedance of free space . the first term describes a sum of delocalized ( drude ) carrier responses with @xmath23 and @xmath24 being the plasma frequency and scattering rate in the @xmath25th drude band , respectively . in the second term , @xmath26 , @xmath27 and @xmath28 are the resonance frequency , width and strength of the @xmath29th vibration or bound excitation . as shown in fig . [ fig2](a ) , the thin red line through the data represents the fitting result for lifeas at 100 k which is decomposed into a coherent narrow drude , a nearly incoherent broad drude , and series of lorentz components , consistent with previous optical studies on ibscs @xcite . fitting results for other dopings at several representative temperatures can be found in appendix c [ fig . [ figsopt](f)[figsopt](j ) ] . tu _ et al . _ suggest that it is more appropriate to describe the broad drude component as bound excitations @xcite because the mean free path @xmath30 ( @xmath31 is the fermi velocity ) associated with the broad drude component is close to the mott - ioffe - regel limit . in any event , since the broad drude component only gives rise to a @xmath3-independent background contribution to the total @xmath20 , the @xmath3 dependence of the optical response is governed by the coherent narrow drude component . as a result , the nature of the broad drude term does not affect our analysis of the coherent narrow drude component and the @xmath3 dependence of @xmath20 . the application of the drude - lorentz analysis at all the measured temperatures for five representative dopings yields the @xmath3 dependence of the scattering rate of the coherent narrow drude component @xmath19 , shown in fig . [ fig2](b)[fig2](f ) . for each doping , @xmath19 follows the expression @xmath32 with the exponent @xmath33 , where @xmath10 is the exponent determined from the fit to @xmath8 for the corresponding dopings . again , we plot @xmath19 as a function of @xmath34 in appendix c [ fig . [ figsopt](k)[figsopt](o ) ] , which reveals distinct linear behavior for all the dopings . such crossover behavior of @xmath35 provides further evidence for the doping - induced fl - nfl - fl changes in life@xmath0co@xmath1as . in order to gain insight into the origin of the anomalous fl - nfl - fl crossover in life@xmath0co@xmath1as , we examine the evolution of lesfs with co concentration by looking into the nuclear spin - lattice relaxation rate @xmath36 , reflecting the summation of all different * q * modes of sub - mev lesfs weighted by a nearly uniform form factor , which can be determined from @xmath37as nuclear magnetic resonance ( nmr ) measurements @xcite . co@xmath1as for five representative co concentrations , determined by integrating the arpes spectral intensity within @xmath3810 mev with respect to @xmath39 . ( f)(j ) extracted fss from corresponding arpes measurements for each doping . ( k ) definition of @xmath40 , @xmath41 and @xmath42 in the @xmath25-space . ( l ) spin - lattice relaxation rate @xmath43 @xmath36 as a function of temperature for five co concentrations measured by nmr . ( m ) evolution of @xmath43 @xmath36 at 20 k ( solid squares ) and fs nesting factor ( solid circles ) with increasing co concentration . ] figure [ fig3](l ) displays the @xmath3 dependence of @xmath36 for five different dopings . in lifeas ( @xmath12 ) , @xmath36 is almost @xmath3 independent , and a negligible upturn at low temperature indicates weak lesfs . however , in sharp contrast to lifeas , @xmath36 for @xmath44 increases rapidly upon cooling and a prominent upturn develops at low temperature , implying that lesfs are significantly enhanced . for @xmath45 , the upturn in @xmath36 at low temperature becomes less prominent , suggesting that the lesfs diminish again . the low - temperature upturn in @xmath36 can be empirically described by the curie - weiss expression @xmath46 [ solid lines in fig . [ fig3](l ) ] , in good agreement with previous nmr studies @xcite . to quantify the doping dependence of the lesfs , we take the value of @xmath36 at 20 k ( just above @xmath2 of lifeas ) , @xmath47 , for each doping and plot them as a function of @xmath7 [ solid squares in fig . [ fig3](m ) ] . upon doping , @xmath47 first grows but then drops , resulting in a peak at @xmath44 . the link between the lesfs and the nfl behavior can be revealed by comparing the doping dependence of @xmath10 [ solid circles in fig . [ fig1](f ) ] and @xmath47 [ solid squares in fig . [ fig3](m ) ] . below @xmath44 , the enhancement of lesfs ( increase in @xmath47 ) leads to a more conspicuous deviation from a fl ( decrease in @xmath10 ) while above @xmath44 , the reduction of lesfs ( decrease in @xmath47 ) results in a gradual recovery of the fl behavior ( increase in @xmath10 ) . the most robust nfl behavior ( @xmath48 ) occurs at @xmath44 where the lesfs are optimized ( @xmath47 peaks ) . these observations strongly suggest that the fl - nfl - fl crossover in life@xmath0co@xmath1as is governed by lesfs . since an investigation into the fs may provide information on the nature of the lesfs , we then studied the evolution of the fss in life@xmath0co@xmath1as . the fs contour of life@xmath0co@xmath1as is traced out from the arpes intensity plot near the fermi energy ( @xmath49 ) for five representative dopings [ fig . [ fig3](a)[fig3](e ) ] . the extracted fss for each doping are shown in fig . [ fig3](f)[fig3](j ) . for lifeas ( @xmath12 ) , two hole and two electron fs pockets are observed at the @xmath50 and @xmath51 points , respectively [ fig . [ fig3](a ) ] , in accord with previous arpes studies @xcite . the inner hole pocket is quite small , while the outer hole pocket is much larger than the electron pockets , resulting in a poor nesting condition in lifeas [ fig . [ fig3](f ) ] . with co doping , the electron pockets expand while the hole pockets shrink . consequently , the fs nesting is improved . as shown in fig . [ fig3](h ) , the shape of the hole fs matches the outer contour of the two electron fss at @xmath14 . further co doping ( @xmath15 ) makes the electron and hole pockets mismatched again , _ e.g. _ @xmath16 [ fig . [ fig3](e ) and [ fig3](j ) ] , leading to a degradation of the fs nesting . in order to quantitatively analyze the fs nesting , we define a nesting factor at vector @xmath42 @xmath52 where the definitions of @xmath53 , @xmath54 and @xmath42 are illustrated in fig . [ fig3](k ) ; @xmath55 is a small positive number to avoid singular behavior ; for an @xmath10-dimensional vector @xmath56 , @xmath57 . @xmath58 increases as the fs nesting is improved , and is maximized when the hole fs matches the outer contour of the two electron fss . assuming @xmath31 is uniform on all fss , the nesting factor @xmath58 is proportional to the non - interacting single - orbital magnetic susceptibility at vector @xmath42 : @xmath59 where @xmath60 is the fermi distribution and @xmath61 is the quasiparticle kinetic energy . @xmath58 is calculated by eq . ( [ fsnesting ] ) for each doping and normalized by its value at @xmath44 . all fss have been considered in the calculation . the solid circles in fig . [ fig3](m ) portray the doping dependence of @xmath58 . remarkably , @xmath58 follows exactly the same doping dependence as @xmath47 , indicating that the lesfs probed by nmr are closely related to the fs nesting . the fs structure naturally suggests that the spin fluctuations are of the antiferromagnetic type with large wave vectors close to the nesting vectors @xmath62 and @xmath63 . this is indeed consistent with our nmr data . the knight shift that measures the uniform susceptibility becomes @xmath3 independent below 30 k ( appendix e , fig . [ figsnmr ] ) , indicating that the low - temperature upturn in @xmath64 comes from large - momentum spin fluctuations . note that since the nmr form factor for as is known to be broadly distributed in momentum space in ibscs @xcite , both commensurate ( close to fs nesting ) and incommensurate ( away from nesting ) lesfs are captured by the spin - lattice relaxation rate @xmath36 . @xmath7 ) phase diagram of life@xmath0co@xmath1as . superconductivity ( yellow regime ) is monotonically suppressed with increasing co concentration @xmath7 and terminates at a critical value @xmath65 . the normal state of lifeas is a fermi liquid ( blue regime at @xmath12 ) , where the @xmath3-dependent resistivity follows @xmath9 with @xmath13 . a crossover from fermi liquid to non - fermi liquid is induced by co doping . at @xmath44 , @xmath10 reaches its minimum value of @xmath66 , indicating the most robust non - fermi liquid behavior ( red regime ) . further doping results in a reversal of this trend until by @xmath16 , the fermi liquid behavior is fully recovered ( blue regime at @xmath16 ) . the green diamonds denote the spin - lattice relaxation rate at 20 k ( @xmath47 ) measured by nmr for several representative dopings . @xmath47 reaches the maximum at @xmath14 , signifying that low - energy spin fluctuations are optimized at this doping . the three inset panels depict the extracted fermi surfaces for three representative co concentrations : @xmath12 ( left ) , @xmath44 ( middle ) and @xmath16 ( right ) . while the fermi surface nesting is poor for @xmath18 and @xmath67 , the nesting condition is significantly improved at @xmath44 . ] in fig . [ fig4 ] we summarize our experimental results in the @xmath3@xmath7 phase diagram of life@xmath0co@xmath1as . with increasing co concentration @xmath7 that monotonically suppresses the superconducting transition temperature @xmath2 by electron - doping : ( i ) the @xmath3 dependence of the resistivity @xmath68 and the optical scattering rate @xmath69 deviates from a fl ( @xmath70 ) observed near @xmath18 , reaching the most pronounced nfl power - law behavior ( @xmath71 ) at @xmath72 and then gradually returns for @xmath15 to the fl values at @xmath73 ; ( ii ) the nmr spin - lattice relaxation rate @xmath64 shows that lesfs , small at @xmath18 , gradually enhance and become strongest at @xmath44 , but diminish for @xmath15 ; ( iii ) arpes measurements reveal that while the electron and hole fs pockets are far from being nested at @xmath12 , the nesting improves with doping , is optimized near @xmath44 , and then degrades with further electron doping for @xmath15 ; ( iv ) no long range magnetic order is observed in the @xmath3@xmath7 phase diagram of life@xmath0co@xmath1as up to @xmath16 , which is consistent with previous studies @xcite . a comparison between the above observations ( i ) and ( ii ) strongly suggests that the fl - nfl - fl crossover in life@xmath0co@xmath1as is induced by lesfs . point ( iii ) in combination with ( i ) and ( ii ) implies that the integrated lesfs probed by nmr are dominated by , or at least scale with those near @xmath74 which are most likely tuned by fs nesting . the fact ( iv ) does not directly support a magnetic qcp in the @xmath3@xmath7 phase diagram of life@xmath0co@xmath1as . however , the pronounced nfl behavior observed near @xmath44 , which is usually considered as a signature of quantum criticality @xcite , in conjunction with the strong tendency to diverge in @xmath36 upon cooling at the same doping , points to an incipient qcp near @xmath44 . a magnetic order may emerge under pressure or magnetic field in the material with @xmath44 , resulting in an actual magnetic qcp associated with other tuning parameters . finally , the nfl behavior is observed at the boundary of the superconducting phase , implying that they are likely to be governed by different mechanisms . y. m. dai , h. miao and l. y. xing contributed equally to this work . we thank a. akrap , s. biermann , p. c. dai , j. p. hu , w. ku , r. p. s. m. lobo , a. j. millis , a. van roekeghem , w. g. yin , i. zaliznyak and g. q. zheng for valuable discussion . work at bnl was supported by the u.s . department of energy , office of basic energy sciences , division of materials sciences and engineering under contract no . de - sc0012704 . work at iop was supported by grants from cas ( xdb07000000 ) , most ( 2010cb923000 , 2011cba001000 and 2013cb921700 ) , nsfc ( 11234014 , 11274362 , 11220101003 and 11474344 ) . work at ruc was supported by the national basic research program of china under grants no . 2010cb923004 and 2011cba00112 and by the nsf of china under grants no . 11222433 and 11374364 . work at bc was supported by u.s . department of energy , office of science , basic energy sciences , under award de - fg02 - 99er45747 .

SECTION 1. SHORT TITLE; AMENDMENT OF 1986 CODE. (a) Short Title.--This Act may be cited as the ``Capital Gains Tax Simplification Act of 1998''. (b) Amendment of 1986 Code.--Except as otherwise expressly provided, whenever in this Act an amendment or repeal is expressed in terms of an amendment to, or repeal of, a section or other provision, the reference shall be considered to be made to a section or other provision of the Internal Revenue Code of 1986. SEC. 3. REDUCTION AND SIMPLIFICATION OF CAPITAL GAINS TAX. (a) In General.--Part I of subchapter P of chapter 1 (relating to treatment of capital gains) is amended by adding at the end the following new section: ``SEC. 1203. CAPITAL GAINS DEDUCTION. ``If for any taxable year a taxpayer other than a corporation has a net capital gain, 40 percent of such gain shall be a deduction from gross income.'' (b) Deduction Allowable Whether or Not Taxpayer Itemizes Other Deductions.-- (1) Subsection (b) of section 63 is amended by striking ``and'' at the end of paragraph (1), by striking the period at the end of paragraph (2) and inserting ``, and'', and by adding at the end the following new paragraph: ``(3) the deduction allowed by section 1203.'' (2) Subsection (d) of section 63 is amended by striking ``and'' at the end of paragraph (1), by striking the period at the end of paragraph (2) and inserting ``, and'', and by adding at the end the following new paragraph: ``(3) the deduction allowed by section 1203.'' (c) Repeal of Tax Preference for Exclusion on Small Business Stock.-- (1) Subsection (a) of section 57 is amended by striking paragraph (7). (2) Subclause (II) of section 53(d)(1)(B)(ii) is amended by striking ``, (5), and (7)'' and inserting ``and (5)''. (d) Technical and Conforming Changes.-- (1) Section 1 is amended by striking subsection (h). (2) Subsection (b) of section 55 is amended by striking paragraph (3). (3) Subparagraph (E) of section 163(d)(4) is amended to read as follows: ``(E) Coordination with capital gains deduction.-- The net capital gain taken into account under section 1203 for any taxable year shall be reduced (but not below zero) by the amount which the taxpayer takes into account as investment income under subparagraph (B)(iii) for such year.'' (4) Paragraph (1) of section 170(e) is amended by striking ``the amount of gain'' in the material following subparagraph (B)(ii) and inserting ``60 percent (100 percent in the case of a corporation) of the amount of gain''. (5) Subparagraph (B) of section 172(d)(2) is amended to read as follows: ``(B) the exclusion under section 1202 and the deduction under section 1203 shall not be allowed.'' (6) The last sentence of section 453A(c)(3) is amended by striking all that follows ``long-term capital gain,'' and inserting ``the maximum rate on net capital gain under section 1201 or the deduction under section 1203 (whichever is appropriate) shall be taken into account.'' (7)(A) Section 641(d)(2)(A) is amended by striking ``Except as provided in section 1(h), the'' and inserting ``The''. (B) Section 641(d)(2)(C) is amended by inserting after clause (iii) the following new clause: ``(iv) The deduction under section 1203.'' (8) Paragraph (4) of section 642(c) is amended to read as follows: ``(4) Adjustments.--To the extent that the amount otherwise allowable as a deduction under this subsection consists of gain from the sale or exchange of capital assets held for more than 1 year, proper adjustment shall be made for any exclusion allowable under section 1202 and any deduction allowable under section 1203 to the estate or trust. In the case of a trust, the deduction allowed by this subsection shall be subject to section 681 (relating to unrelated business income).'' (9) Section 642 is amended by adding at the end the following new subsection: ``(j) Capital Gains Deduction.--The deduction under section 1203 to an estate or trust shall be computed by excluding the portion (if any) of the gains for the taxable year which is includible by the income beneficiaries under sections 652 and 662 (relating to inclusions of amounts in gross income of beneficiaries of trusts) as gain derived from the sale or exchange of capital assets.'' (10) The last sentence of section 643(a)(3) is amended to read as follows: ``The exclusion under section 1202 and the deduction under section 1203 shall not be taken into account.'' (11) Subparagraph (C) of section 643(a)(6) is amended by inserting ``(i)'' before ``there shall'' and by inserting before the period ``, and (ii) the deduction under section 1203 (relating to capital gains deduction) shall not be taken into account''. (12) Paragraph (4) of section 691(c) is amended by striking ``1(h),'' and by inserting ``1203,'' after ``1202,''. (13) The second sentence of paragraph (2) of section 871(a) is amended by striking ``section 1202'' and inserting ``sections 1202 and 1203''. (14)(A) Paragraph (2) of section 904(b) is amended by striking subparagraphs (A) and (C), by redesignating subparagraph (B) as subparagraph (A), and by inserting after subparagraph (A) (as so redesignated) the following new subparagraph: ``(B) Other taxpayers.--In the case of a taxpayer other than a corporation, taxable income from sources outside the United States shall include gain from the sale or exchange of capital assets only to the extent of foreign source capital gain net income.'' (B) Subparagraph (A) of section 904(b)(2), as so redesignated, is amended-- (i) by striking all that precedes clause (i) and inserting the following: ``(A) Corporations.--In the case of a corporation-- '', and (ii) by striking in clause (i) ``in lieu of applying subparagraph (A),''. (C) Paragraph (3) of section 904(b) is amended by striking subparagraphs (D) and (E) and inserting the following new subparagraph: ``(D) Rate differential portion.--The rate differential portion of foreign source net capital gain, net capital gain, or the excess of net capital gain from sources within the United States over net capital gain, as the case may be, is the same proportion of such amount as the excess of the highest rate of tax specified in section 11(b) over the alternative rate of tax under section 1201(a) bears to the highest rate of tax specified in section 11(b).'' (15) Paragraph (1) of section 1402(i) is amended by inserting ``, and the deduction provided by section 1203 shall not apply'' before the period at the end thereof. (16) Paragraph (1) of section 1445(e) is amended by striking ``20 percent'' and inserting ``23.7 percent''. (17)(A) The second sentence of section 7518(g)(6)(A) is amended-- (i) by striking ``during a taxable year to which section 1(h) or 1201(a) applies'', and (ii) by striking ``20 percent'' and inserting ``23.7 percent''. (B) The second sentence of section 607(h)(6)(A) of the Merchant Marine Act, 1936, is amended-- (i) by striking ``during a taxable year to which section 1(h) or 1201(a) of such Code applies'', and (ii) by striking ``20 percent'' and inserting ``23.7 percent''. (e) Clerical Amendment.--The table of sections for part I of subchapter P of chapter 1 is amended by adding at the end the following new item: ``Sec. 1203. Capital gains deduction.'' (f) Effective Dates.-- (1) In general.--Except as otherwise provided in this subsection, the amendments made by this section shall apply to taxable years beginning after December 31, 1998. (2) Withholding.--The amendments made by subsection (d)(16) shall apply only to amounts paid after December 31, 1998. (3) Repeal of election.--Section 311 of the Taxpayer Relief Act of 1997 is amended by striking subsection (e). (4) Coordination with prior transition rule.--Any amount treated as long-term capital gain by reason of paragraph (3) of section 1122(h) of the Tax Reform Act of 1986 shall not be taken into account for purposes of applying section 1203 of the Internal Revenue Code of 1986 (as added by this section).

Capital Gains Tax Simplification Act of 1998 - Amends the Internal Revenue Code to provide that, if for any taxable year a non-corporate taxpayer has a net capital gain, 40 percent of such gain shall be a deduction from gross income regardless of whether or not the taxpayer itemizes other deductions. Repeals the tax preference for exclusion for gains on the sale of certain small business stock. Amends the Taxpayer Relief Act of 1997, with respect to maximum capital gains rates for individuals, to repeal the allowance of an election to recognize gain on assets held on January 1, 2001.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Emergency Senior Citizens Relief Act of 2010''. SEC. 2. EXTENSION AND MODIFICATION OF CERTAIN ECONOMIC RECOVERY PAYMENTS. (a) Extension and Modification of Payments.--Section 2201 of the American Recovery and Reinvestment Tax Act of 2009 is amended-- (1) in subsection (a)(1)(A)-- (A) by inserting ``for each of calendar years 2009 and 2011'' after ``shall disburse'', (B) by inserting ``(for purposes of payments made for calendar year 2009), or the 3-month period ending with December 2010 (for purposes of payments made for calendar year 2011)'' after ``the date of the enactment of this Act'', and (C) by adding at the end the following new sentence: ``In the case of an individual who is eligible for a payment under the preceding sentence by reason of entitlement to a benefit described in subparagraph (B)(i), no such payment shall be made to such individual for calendar year 2011 unless such individual was paid a benefit described in such subparagraph (B)(i) for any month in the 12-month period ending with December 2010.'', (2) in subsection (a)(1)(B)(iii), by inserting ``(for purposes of payments made under this paragraph for calendar year 2009), or the 3-month period ending with December 2010 (for purposes of payments made under this paragraph for calendar year 2011)'' before the period at the end, (3) in subsection (a)(2)-- (A) by inserting ``, or who are utilizing a foreign or domestic Army Post Office, Fleet Post Office, or Diplomatic Post Office address'' after ``Northern Mariana Islands'', and (B) by striking ``current address of record'' and inserting ``address of record, as of the date of certification under subsection (b) for a payment under this section'', (4) in subsection (a)(3)-- (A) by inserting ``per calendar year (determined with respect to the calendar year for which the payment is made, and without regard to the date such payment is actually paid to such individual)'' after ``only 1 payment under this section'', and (B) by inserting ``FOR THE SAME YEAR'' after ``PAYMENTS'' in the heading thereof, (5) in subsection (a)(4)-- (A) by inserting ``(or, in the case of subparagraph (D), shall not be due)'' after ``made'' in the matter preceding subparagraph (A), (B) by striking subparagraph (A) and inserting the following: ``(A) in the case of an individual entitled to a benefit specified in paragraph (1)(B)(i) or paragraph (1)(B)(ii)(VIII) if -- ``(i) for the most recent month of such individual's entitlement in the applicable 3- month period described in paragraph (1); or ``(ii) for any month thereafter which is before the month after the month of the payment; such individual's benefit under such paragraph was not payable by reason of subsection (x) or (y) of section 202 of the Social Security Act (42 U.S.C. 402) or section 1129A of such Act (42 U.S.C. 1320a-8a);'', (C) in subparagraph (B), by striking ``3 month period'' and inserting ``applicable 3-month period'', (D) by striking subparagraph (C) and inserting the following: ``(C) in the case of an individual entitled to a benefit specified in paragraph (1)(C) if-- ``(i) for the most recent month of such individual's eligibility in the applicable 3- month period described in paragraph (1); or ``(ii) for any month thereafter which is before the month after the month of the payment; such individual's benefit under such paragraph was not able by reason of subsection (e)(1)(A) or (e)(4) of section 1611 (42 U.S.C. 1382) or section 1129A of such Act (42 U.S.C. 1320a-8a); or'' (E) by striking subparagraph (D) and inserting the following: ``(D) in the case of any individual whose date of death occurs-- ``(i) before the date of receipt of the payment; or ``(ii) in the case of a direct deposit, before the date on which such payment is deposited into such individual's account.'', (F) by adding at the end the following flush sentence: ``In the case of any individual whose date of death occurs before a payment is negotiated (in the case of a check) or deposited (in the case of a direct deposit), such payment shall not be due and shall not be reissued to the estate of such individual or to any other person.'', and (G) by adding at the end, as amended by subparagraph (F), the following new sentence: ``Subparagraphs (A)(ii) and (C)(ii) shall apply only in the case of certifications under subsection (b) which are, or but for this paragraph would be, made after the date of the enactment of Emergency Senior Citizens Relief Act of 2010, and shall apply to such certifications without regard to the calendar year of the payments to which such certifications apply.''. (6) in subsection (a)(5)-- (A) by inserting ``, in the case of payments for calendar year 2009, and no later than April 30, 2011, in the case of payments for calendar year 2011'' before the period at the end of the first sentence of subparagraph (A), and (B) by striking subparagraph (B) and inserting the following: ``(B) Deadline.--No payment for calendar year 2009 shall be disbursed under this section after December 31, 2010, and no payment for calendar year 2011 shall be disbursed under this section after December 31, 2012, regardless of any determinations of entitlement to, or eligibility for, such payment made after whichever of such dates is applicable to such payment.'', (7) in subsection (b), by inserting ``(except that such certification shall be affected by a determination that an individual is an individual described in subparagraph (A), (B), (C), or (D) of subsection (a)(4) during a period described in such subparagraphs), and no individual shall be certified to receive a payment under this section for a calendar year if such individual has at any time been denied certification for such a payment for such calendar year by reason of subparagraph (A)(ii) or (C)(ii) of subsection (a)(4) (unless such individual is subsequently determined not to have been an individual described in either such subparagraph at the time of such denial)'' before the period at the end of the last sentence, (8) in subsection (c), by striking paragraph (4) and inserting the following: ``(4) Payments subject to offset and reclamation.-- Notwithstanding paragraph (3), any payment made under this section-- ``(A) shall, in the case of a payment by direct deposit which is made after the date of the enactment of the Emergency Senior Citizens Relief Act of 2010, be subject to the reclamation provisions under subpart B of part 210 of title 31, Code of Federal Regulations (relating to reclamation of benefit payments); and ``(B) shall not, for purposes of section 3716 of title 31, United States Code, be considered a benefit payment or cash benefit made under the applicable program described in subparagraph (B) or (C) of subsection (a)(1), and all amounts paid shall be subject to offset under such section 3716 to collect delinquent debts.'', (9) in subsection (e)-- (A) by striking ``2011'' and inserting ``2013'', (B) by inserting ``section 2(b) of the Emergency Senior Citizens Relief Act of 2010,'' after ``section 2202,'' in paragraph (1), and (C) by adding at the following new paragraph: ``(5)(A) For the Secretary of the Treasury, an additional $5,200,000 for purposes described in paragraph (1). ``(B) For the Commissioner of Social Security, an additional $5,000,000 for the purposes described in paragraph (2)(B). ``(C) For the Railroad Retirement Board, an additional $600,000 for the purposes described in paragraph (3)(B). ``(D) For the Secretary of Veterans Affairs, an additional $625,000 for the Information Systems Technology account''. (b) Extension of Special Credit for Certain Government Retirees.-- (1) In general.--In the case of an eligible individual (as defined in section 2202(b) of the American Recovery and Reinvestment Tax Act of 2009, applied by substituting ``2011'' for ``2009''), with respect to the first taxable year of such individual beginning in 2011, section 2202 of the American Recovery and Reinvestment Tax Act of 2009 shall be applied by substituting ``2011'' for ``2009'' each place it appears. (2) Conforming amendment.--Subsection (c) of section 36A of the Internal Revenue Code of 1986 is amended by inserting ``, and any credit allowed to the taxpayer under section 2(b)(1) of the Emergency Senior Citizens Relief Act of 2010'' after ``the American Recovery and Reinvestment Tax Act of 2009''. (c) Effective Date.-- (1) In general.--Except as otherwise provided in paragraph (2), the amendments made by this section shall take effect on the date of the enactment of this Act. (2) Application of rule relating to deceased individuals.-- The amendment made by subsection (a)(5)(F) shall take effect as if included in section 2201 of the American Recovery and Reinvestment Tax Act of 2009.

Emergency Senior Citizens Relief Act of 2010 - Amends the Assistance for Unemployed Workers and Struggling Families Act, title II of the American Recovery and Reinvestment Tax Act of 2009, to extend: (1) through 2011 the $250 economic recovery payments to recipients of Social Security, Supplemental Security Income (SSI) (title XVI of the Social Security Act), railroad retirement benefits, and veterans disability compensation or pension benefits; and (2) through 2011 the special tax credit for certain government retirees. Makes additional appropriations through FY2013 to cover such payments.

the redshift and luminosity distributions of galaxies , and galaxy scaling relations , such as the color - magnitude relation , the size - surface brightness relation , the luminosity - size relation or the fundamental plane , play a crucial role in constraining galaxy formation models . however , a bias will be intrinsically present in all these correlations if the transformation from observable to physical quantity involves one or more distance - dependent observables , due to noise in the distance estimate . distances are only known approximately if photometric redshifts are available , but spectroscopic redshifts are not . this is already the case of many current surveys ( e.g. sdss , combo-17 , musyc , cosmos , cfhtls ) , where the number of objects with photometric redshifts is more than an order of magnitude bigger than that of spectroscopic redshifts , and will be increasingly true of the next generations of deep multicolor wide - area photometric surveys ( e.g. des , lsst , snap , jdem ) , which will increase the number of galaxies with multi - band photometry to a few billions . photometric information is essential and statistically more significant for studying cosmological evolution at a fraction of the cost of a full spectroscopic survey . therefore , many efforts are currently devoted to improve photometric redshift estimations ( see for example feldmann et al . 2006 ; carliles et al . 2008 ; hildebrandt et al . 2008 ; oyaizu et al . 2008a , b ; stabenau et al . 2008 ; budavari 2009 ; ilbert et al . 2009 ; jouvel et al . 2009 ; salvato et al . 2009 ) , especially because accurate photometric redshifts are among the key requirements for precision weak lensing measurements ( banerji et al . 2008 ; ma & bernstein 2008 ; mandelbaum et al . well - understood photometric redshifts and errors are also vital in resolving redshift ambiguities where spectroscopy shows only a single spectral line ( lilly et al . 2007 ) , and are especially crucial to dark energy science ( bernstein & huterer 2009 ; sun et al . 2009 ) . hence , methods for recovering unbiased estimates of the redshift distribution ( padmanabhan et al . 2005 ; sheth 2007 ; lima et al . 2008 ) , the luminosity function ( sheth 2007 ) , and galaxy scaling relations ( rossi & sheth 2008 ) from magnitude limited photometric redshift datasets are indeed necessary . in particular , in rossi & sheth ( 2008 ) we described two techniques which can handle this complication ( i.e. a non - parametric deconvolution method and a maximum likelihood approach ) , and the extension of the @xmath0 algorithm ( lucy 1974 ) was tested on a mock catalog . here we apply the same method to the sdss dr6 , and investigate the bias present in the fundamental distributions and in the luminosity - size relation for early - type galaxies , which arises when computing these relations from photometric data . the technique is insensitive to the actual quality of photo-@xmath4 estimates , but it relies on the knowledge of the conditional probability @xmath5 . in essence , if photo-@xmath4 errors are at least known , our technique is applicable . we have two main goals in this study . the first is to use a selected sample of early types from the sdss dr6 , for which both photo-@xmath4s and spectro-@xmath4s are known , and apply our deconvolution technique to derive the unbiased redshift , magnitude and size distributions , and the magnitude - size relation . we refer to this procedure as the `` calibration '' part . the second and more challenging goal is to use our calibration in order to infer information when spectroscopic data is poor or not available ( i.e. deep redshift catalogs ) . the outline of the paper is as follows . section 2 describes the sdss galaxy catalog used in this analysis , and highlights the criteria adopted for the early - type selection . section 3 presents the reconstruction of the redshift , magnitude , size , and size - magnitude distributions from photometric data , for the early - type sample . a brief summary of the deconvolution method is provided while we point out in an appendix the relation between our deconvolution procedure and a convolution - based approach , the dependence of @xmath5 on magnitude is also discussed , as well as other technical details . section 4 deals with extending our technique when spectroscopic information is poor , or when only photometry is available . some tests are performed on the early - type `` calibration '' catalog , and in particular it is found that , by using only @xmath1 of the spectroscopic information randomly spaced in redshift space , one can reconstruct accurately the galaxy fundamental distributions . finally , section 5 summarizes our findings , and indicate ongoing and future studies and applications . whenever necessary , we assume a spatially flat cosmological model with @xmath6 , where @xmath7 and @xmath8 are the present day densities of matter and cosmological constant scaled to the critical density , and write the hubble constant as @xmath9 km s@xmath10 mpc@xmath10 . the catalog we use is based on the sloan digital sky survey ( sdss ) data release 6 ( dr6 , @xmath11 ) , available online through the catalog archive server jobs system ( casjobs ) . we adopt selection criteria suitable to early - type galaxies , as described in bernardi et al . ( 2003 ) . specifically , from the dr6 galaxy photometric sample ( photoobjall in the galaxy view , which contains primary objects that are classified as galaxies ) , we select objects according to these general criteria : * petrosian magnitudes in the range @xmath12 for the @xmath13 band . * concentration index @xmath14 in the @xmath15 band . * likelihood of the de vaucouleur s model @xmath16 . * objects with both photometric and spectroscopic redshifts available . no redshift or velocity dispersion cuts were made , although we tested the effect of a velocity dispersion cut ( @xmath17 , so good s / n ) and found no substantial difference . our catalog contains 163,718 objects , and consists of model magnitudes , petrosian radii , de vaucouleurs and exponential fit scale radii along with their corresponding axis ratios in the @xmath13 band , photometric and spectroscopic redshifts and their quoted errors . model magnitudes are obtained by measuring galaxy fluxes through equivalent apertures in all bands , and by fitting the exponential or de vaucouleurs model of higher likelihood in the @xmath13 filter and applying it in the other bands , after convolution with a psf in each band ( for more details , see blanton et al . the previous fitting procedures yield also the effective radii of the models and the axis ratio of the best fit model . in particular , the petrosian ratio @xmath18 at a radius @xmath13 from the center of an object is defined to be the ratio of the local surface brightness in an annulus at @xmath13 to the mean surface brightness within @xmath13 , as described by blanton et al . ( 2001 ) and by yasuda et al . the petrosian radius @xmath19 is the radius at which @xmath20 equals some specified value @xmath21 , set to @xmath22 in our case . we select photometric redshifts from the sdss photoz table . this set of photometric redshifts has been obtained with the template fitting method , which simply compares the expected colors of a galaxy ( derived from template spectral energy distributions ) with those observed for an individual galaxy . the empirical templates of coleman , wu & weedman ( 1980 ) , extended with spectral synthesis models , are used . these templates were adjusted to fit the calibrations , as explained in budavari et al . more detailed information about the photo-@xmath4 catalog used here is also provided in csabai et al . ( 2003 ) , and references therein . the main advantage of this technique in computing photo-@xmath4s is a broader redshift range coverage for all types of galaxies , and the additional information like spectral type , k - correction and absolute magnitudes . however , its accuracy is severely limited by the lack of perfect spectral energy distribution ( sed ) models . in fact , the quality of photometric redshift estimation of faint objects ( or with large photometric errors ) is weak . more generally , the standard scenario for template fitting is to take a small number of spectral templates and choose the best fit by optimizing the likelihood of the fit as a function of redshift , type and luminosity . variations of this approach have been developed in the last few decades . for example , in the recent sdss dr7 photometric redshifts are obtained with a hybrid method , namely a combination of the template fitting procedure and of a technique which compares the observed colors of galaxies to a reference set that has both colors and spectroscopic redshifts observed . .median spectroscopic and photometric redshifts , corresponding median absolute deviations ( mad ) , standard normalized median absolute deviations ( nmad ) and dispersions for the three early - type samples illustrated in figure [ redshift_cal_comparisons_early_types ] . [ cols="<,^,^,^",options="header " , ] [ fig_1_info ] we finally cross - correlate the photometric information with the sdss dr6 spectroscopic sample ( specobjall ) , and select only those photometric objects for which spectroscopic information is also available . the spectroscopic pipeline ( spectro1d ) assigns a final redshift to each object spectrum by choosing the emission or cross - correlation redshift with the highest likelihood and stores this as @xmath4 in the specobj table . in addition to spectral classification based on measured lines , galaxies are classified by a principal component analysis ( pca ) , using cross correlation with eigentemplates constructed from the sdss spectroscopic data . in the selection of our sample we use only photometric criteria , but more robust constraints can be applied in order to reduce galaxy - type errors , and their effect is illustrated in figure [ redshift_cal_comparisons_early_types ] . in both panels , solid lines represent the redshift distributions of the calibration sample used in this study ( sample 1 ) . however , if in addition we require spectra of good quality or without masked regions ( sdss warning flag for spectra of low quality set to zero ) , then the number of galaxies drops to @xmath23 ( dotted lines in figure [ redshift_cal_comparisons_early_types ] , sample 2 ) . finally , if we consider only spectra with pca classification numbers @xmath24 , typical of early - type galaxy spectra ( connolly & szalay 1999 ) , we find @xmath25 objects ( dashed lines in figure [ redshift_cal_comparisons_early_types ] , sample 3 ) . for all these samples , we provide in table [ fig_1_info ] the median spectroscopic and photometric redshifts , their corresponding median absolute deviations ( mad ) , the standard normalized median absolute deviation ( nmad ) defined as in hoaglin et al . ( 1983 ) by @xmath26 $ ] , and the dispersion @xmath27 , where @xmath28 . in our study we consider the sample obtained with the photometric - only selection process ( sample 1 ) . this is because our second goal is to rely on this `` calibration '' subset to infer information when only photometry is available . more sophisticated criteria for obtaining a well - controlled sample of early - type galaxies are presented in park and choi ( 2005 ) who used color , color - gradient , and concentration index to classify galaxies into early and late types with reliability and completeness exceeding @xmath29 . see also hyde & bernardi ( 2009 ) , where problems like contamination by later - type galaxies and systematic effects due to the use of petrosian quantities are addressed in detail . however , since we are not attempting to make a precision measurement of scaling relations , but rather our main goal is to show how to correct for photo-@xmath4 biases , more robust selection criteria do not affect the nature of the problems investigated in this study . in this section we apply our reconstruction technique based on the generalization of the @xmath0 method ( sheth 2007 ; rossi & sheth 2008 ) and briefly summarized here to the redshift , magnitude and size distributions , and to the size - luminosity relation of the early - type sample . a new deconvolution code named _ defast _ ( acronym for _ deconvolution fast _ , with the convention of using capital letters for consonants ) , which performs a fast integral deconvolution , has been developed for this study . lucy s ( 1974 ) iterative scheme is implemented , in one or two dimensions . appropriate variations have been carried out in order to handle correctly different choices of the conditional probability functions . in particular , for the sdss early - type sample the conditional distributions are measured directly from the data and then used in the deconvolution algorithm . splines fits to the pdf s are performed in those cases . for technical details we refer the reader to a trial version of the one - dimensional software , freely available for download online at the web address @xmath30 . the @xmath0 method , originally devised by schmidt ( 1968 ) , is a way of testing the uniformity of spatial distributions . in particular , if @xmath31 is the comoving volume between an object in a flux - limited catalog at redshift @xmath4 and the observer located at @xmath32 , and @xmath0 is the corresponding total survey volume over which the same object could have been seen at @xmath33 , then clearly the ratio @xmath34 is a measure of the position of the source . therefore , if a distribution is uniform then the average value over all the objects in the catalog , @xmath35 , must be 0.5 . the @xmath0 method allows one to correct for selection effects present in magnitude - limited datasets , where fainter objects are seen only at closer distances . in fact , in order to properly estimate for example the luminosity function one must sum over all the objects in the catalog and weight each source separately by the inverse of @xmath0 ( or the inverse of @xmath36 if the catalog is limited at both ends ) . this is the basis of the procedure developed by schmidt ( 1968 ) . generalizations of this method to include distance errors have been carried out in sheth ( 2007 ) for the luminosity function ( 1d case ) , and in rossi & sheth ( 2008 ) for galaxy scaling relations ( 2d case , or full @xmath37-dimensional manifold ) . to summarize , in a flux - limited survey the quantities affected by the photometric redshift errors are the intrinsic luminosity distribution rather than the luminosity function itself ( which differs from the previous one by the inclusion of a @xmath38 weighting ) , and the intrinsic joint distribution of luminosities and sizes or in general the joint distribution of two ( or more ) observables affected by the same distance errors . however , in a real experiment one measures their noisy counterparts . therefore it is necessary to reconstruct the intrinsic distributions first , before applying the @xmath0 prescription . this is achieved by recognizing the deconvolution nature of this class of problems , hence an iterative algorithm is suitable for the reconstructions . in fact , adopting lucy s ( 1974 ) formalism , the general @xmath37-dimensional problem is that of estimating the frequency distribution @xmath39 of the intrinsic @xmath37-dimensional vector @xmath40 when the available observed measures , denoted by the vector @xmath41 , are a finite sample drawn from an infinite population characterized by @xmath42 where @xmath43 is the data function accessible to measurements and @xmath44 is the conditional probability of estimating @xmath41 when the true value is @xmath40 . the iterative procedure to invert the previous expression is @xmath45 where @xmath46 the index @xmath13 indicates the @xmath13th iteration in the sequence of estimates , and @xmath47 is an approximation to @xmath48 obtained from the observed sample . the starting value @xmath49 , which initializes the iteration , should be a smooth , non - negative function having the same integrated density as the observed distribution . in our deconvolution procedure , we always use the observed histograms ( i.e. photo-@xmath4 derived distributions ) as convenient starting guesses . clearly , the outlined formalism is readily applicable to the size - luminosity correlation if we interpret @xmath41 as the 2d vector of the estimated absolute magnitudes and sizes , and @xmath40 as the vector of the corresponding true ( or intrinsic ) quantities . similarly for the redshift , magnitude and size distributions , where now vectors simply reduce to scalar quantities ( 1d case ) . following rossi & sheth ( 2008 ) , we indicate with @xmath50 and @xmath4 the photometric and spectroscopic redshifts , respectively . as argued before , the problem of estimating the intrinsic redshift distribution @xmath51 number of objects which lie at redshift @xmath4 is best thought of as a deconvolution problem , and if @xmath52 is the probability of estimating the redshift as @xmath50 when the true value is @xmath4 , then the distribution of estimated redshifts is @xmath53 . note that this is just a particular 1d case of equation ( [ phi ] ) , where @xmath54 , @xmath55 , @xmath56 and @xmath57 . if @xmath52 is known and @xmath58 is measured , then the previous relation is a fredholm equation of the first kind , easily solvable with a one - dimensional inversion algorithm . before showing the reconstructed intrinsic redshift distribution , we focus our attention on the conditional probability @xmath52 . in reality , this distribution does depend weakly on apparent magnitude . to illustrate the effect , we split our early - type sample in three intervals of apparent magnitudes , approximately spaced in bins of @xmath59 magnitude width , i.e. @xmath60 ( solid lines in figure [ resdhift_magnitude_p_conditional ] ) , @xmath61 ( dotted lines in figure [ resdhift_magnitude_p_conditional ] ) , @xmath62 ( dashed lines in figure [ resdhift_magnitude_p_conditional ] ) . in the left panel of figure [ resdhift_magnitude_p_conditional ] , contours show levels which are @xmath63 times the height of the maximum value of the density of sources , with @xmath37 running from @xmath64 to @xmath65 , for the three magnitude bins . in the same figure , the right panel shows an example of @xmath66 for each of the three bins in magnitude and a spectroscopic redshift bin centered on @xmath67 . neglecting this small dependence of magnitude does not affect the reconstruction of the intrinsic redshift distribution significantly . results are shown in figure [ redshift_reconstruction_early_types ] , where in the left panel we compare @xmath50 and @xmath4 , whereas in the right panel we show the photometric or observed redshift distribution ( dotted line ) , the spectroscopic or intrinsic distribution ( solid line ) and its reconstruction after a few iterations ( dashed line ) , obtained by applying the one - dimensional deconvolution algorithm based on the lucy s ( 1974 ) inversion technique . the error distributions used in the reconstruction are inferred directly from the sdss early - type data . the median redshift of the spectroscopic sample is 0.1021 ( see table [ fig_1_info ] ) , while the median redshift of the deconvolved photo-@xmath4 distribution is 0.1002 . this value is calculated as follows . we find the bin which divides the reconstructed spectroscopic distribution in two roughly equal area parts . within that bin , we then interpolate with splines and provide the exact value of z for which the area of the reconstructed distribution is split into two equal parts . accurately characterizing @xmath52 is necessary for a reliable deconvolution . after testing different methods , we have achieved good results using cubic splines and found that simple gaussian fits provide unsatisfactory mapping of the conditional distributions ( see also section [ gauss_prox ] ) . the previously outlined dependence of @xmath52 on apparent magnitude suggests that one should expect , similarly , a redshift dependence in the corresponding magnitude conditional distributions . therefore , it may appear difficult to characterize and measure the appropriate conditional probabilities , and apply the one - dimensional deconvolution algorithm to reconstruct the magnitude distribution . however the problem is simpler , as we show with the following algebra . let @xmath68 denote the true absolute magnitude and @xmath69 that estimated using @xmath50 rather than @xmath4 . use @xmath70 to denote the luminosity distance , and @xmath71 to indicate the number density of galaxies with absolute magnitudes . evolution is neglected . let @xmath0 denote the largest comoving volume out of which an object of absolute magnitude @xmath68 can be seen , and @xmath72 the analogous if the catalog is also limited at the lower end . the ( true ) number of galaxies with absolute magnitude @xmath68 ( i.e. the intrinsic luminosity distribution ) is : @xmath73 , \label{nm_intr}\ ] ] and the total number of objects with estimated absolute magnitudes @xmath69 is : @xmath74 \\ & = & \int { \rm d}m~n(m)~\frac{\theta[v_{\rm max}(m),v_{\rm min}(m),m,{\cal m}]}{[v_{\rm max}(m)-v_{\rm min}(m ) ] } , \nonumber \label{nm_obs } \end{aligned}\ ] ] where @xmath75 note that since @xmath0 and @xmath72 are known functions of @xmath68 , @xmath76 itself is just a complicated function of @xmath68 and @xmath77 . dividing ( [ theta ] ) by @xmath78 $ ] yields : @xmath79 } & = & \int { \rm d}d_{\rm l}~\frac{{\rm d}v_{\rm com}/{\rm d}d_{\rm l}}{[v_{\rm max}-v_{\rm min}]}~p(m-{\cal m}|m , d_{\rm l } ) \nonumber \\ & = & \int { \rm d}d_{\rm l}~p(d_{\rm l})~p(m-{\cal m}|m , d_{\rm l } ) \nonumber \\ & = & p(m-{\cal m}|m ) \equiv p({\cal m}|m ) . \label{pm_obs_given_m_intr } \end{aligned}\ ] ] therefore , equation ( 5 ) becomes a simple one - dimensional deconvolution , namely : @xmath80 the above expression ( [ nm_obs_simpler ] ) is again another particular 1d case of ( [ phi ] ) , where now @xmath81 , @xmath82 , @xmath56 and @xmath57 . hence , by measuring the conditional probability @xmath83 from the catalog , it is possible to apply directly the one - dimensional deconvolution algorithm as in the previous section . note that this conclusion is particularly relevant when attempting to reconstruct the luminosity function from photometric data . results of this applications are shown in figure [ mag_1d ] , where the left panel compares @xmath77 and @xmath68 , while the right panel shows the one - dimensional reconstruction after @xmath84 iterations ( jagged line ) of the intrinsic distribution of absolute magnitudes ( solid histogram ) . the observed distribution of @xmath69 ( dotted histogram ) was used as a convenient starting guess in the deconvolution algorithm . we use model magnitudes in the r band , corrected for reddening and extinction , and assume a standard cosmology in the conversion from apparent to absolute magnitudes but we neglect evolution and k - corrections . in particular , while k - corrections are necessary to properly characterize the absolute magnitude distribution , in this paper we do not apply them to our de - reddened model magnitudes because the only purpose of our work is to describe a deconvolution technique , which is independent of those corrections . distribution of seeing - corrected effective angular sizes of galaxies in our early - type sdss sample . [ upper right ] corresponding distribution of axis ratios @xmath85 . [ lower left ] effective angular sizes @xmath86 as a function of the axis ratio @xmath85 . [ lower right ] distribution of effective circular radii @xmath87 , as defined in the main text.,scaledwidth=50.0% ] as for the magnitude distribution , it is possible to reconstruct the intrinsic distribution of sizes with a one - dimensional deconvolution algorithm ( for more details , see also section 3.3 in rossi & sheth 2008 ) . in what follows , we use @xmath88 to denote @xmath89 of the physical size , and @xmath90 to denote the estimated size based on the photometric redshift @xmath50 . we apply one correction to convert the ( seeing - corrected ) effective angular radii , @xmath86 , output by the sdss pipeline to physical radii . following bernardi et al . ( 2003 ) , we define the equivalent circular effective radius @xmath91 , where @xmath85 is the corresponding axis ratio of the de vaucouleurs radius . then @xmath92 $ ] , and similarly @xmath93 $ ] . we do not apply a second correction , analogous to the k - correction we would ideally have applied to the magnitude of each galaxy , to account for the fact that galaxies appear slightly larger in the bluer bands ( i.e. hyde & bernardi 2009 ) . figure [ size_details ] shows the distribution of seeing - corrected effective angular sizes of galaxies in our sdss early - type sample ( upper left panel ) , the corresponding distribution of axis ratios @xmath85 ( upper right panel ) , the effective angular sizes @xmath86 as a function of axis ratio @xmath85 ( lower left panel ) , and the distribution of equivalent circular effective radii @xmath87 ( lower right panel ) . in analogy with the magnitude case , we think of @xmath94 , the number of observed objects with estimated @xmath95 , as being a convolution of the true number of objects with size @xmath88 , @xmath96 , with the probability that an object with size @xmath88 is thought to have size @xmath95 . we measure @xmath97 directly from the catalog and run the one - dimensional deconvolution algorithm , the result of which is presented in figure [ size_1d ] . the left panel compares @xmath95 and @xmath88 , and the right panel shows the one - dimensional reconstruction ( jagged line ) . the intrinsic distribution of physical sizes ( solid line ) is recovered after a few iterations , when the observed distribution of @xmath69 ( dotted line ) is used as a convenient starting guess in the inversion algorithm . note that although the difference between the intrinsic and the observed distribution is small , this departure will suffice to bias the size - luminosity relation as we show next . photometric redshift errors broaden both the magnitude and size distributions , as evident from figures [ mag_1d ] and [ size_1d ] , but changes to the estimated absolute magnitudes and sizes are clearly not independent . these correlated changes have an important effect on the size - luminosity relation , even when the broadening of one of the two distributions is not severe . this is the case of our sdss sample , where the size distribution ( figure [ size_1d ] ) is not severely biased , but the size - luminosity relation is still biased . in fact , in our sdss catalog @xmath98 , whereas @xmath99 , as shown in figure [ rm_2d ] . reconstructing an unbiased estimate of size and luminosity from photometric data is also best thought of as a non - parametric two - dimensional deconvolution ( again , see rossi & sheth 2008 ) , and application of the extended @xmath0 2d algorithm to the sdss early - type sample is presented in figure [ rm_2d ] , where it is shown that the use of photo-@xmath4s introduces a bias in the size - luminosity relation ( shallower slope in panel on left ) . contours and solid lines indicate respectively the @xmath100 relation associated with photo-@xmath4 ( left ) , and the expected intrinsic @xmath101 relation ( right ) . squares in left panel show the binned starting guess for the two - dimensional deconvolution algorithm ( obtained from photometric information ) , triangles in right panel show the result after @xmath102 iterations and circles are the expected binned intrinsic relation , obtained from spectroscopic information . convergence to the true solution is clearly seen . as pointed out in hyde & bernardi ( 2009 ) , most of the scaling relations for early types show evidence for curvature . in this respect , our technique also accounts for it , as we reconstruct intrinsic relations within each bin , without performing any fits . if we derive galaxy fundamental distributions and scaling relations using only photometry , a bias will be intrinsically present as was shown in the previous section . with our deconvolution procedure we can account and correct for it . however , our @xmath0 reconstruction method assumes that the distribution of photo-@xmath4 errors is known accurately . this means that spectroscopic redshifts are available for a subset of the data , as it happens with our sdss `` calibration '' sample . suppose now that we only have limited spectroscopic data available . can we still correct for the bias in a reliable way , using the information contained in the spectroscopic `` calibration '' set ? there are essentially two nontrivial issues to this end . as we pointed out in rossi & sheth ( 2008 ) , one concern is as to whether or not the number of spectra which must be taken to specify the error distribution reliably is sufficient to also provide a reliable spectroscopic estimate of these fundamental distributions and scaling relations . in this case , the basis for deciding that it is worth reconstructing these relations from photo-@xmath4 data is not clear . however , as long as the spectroscopic sample spans the _ entire _ range of photometric observables , we show in the next subsection that a detailed knowledge of the photo-@xmath4 error distribution ( figure [ test_number_spectra_pdf_redshift ] ) can be inferred with only @xmath1 of randomly spaced spectra in redshift space . this rather conservative choice will guarantee an accurate reconstruction of the intrinsic relations . cross - correlations with other surveys may also provide enough reliable information to specify @xmath52 accurately . the second problem is more challenging . if the spectra _ are not _ simply a random subset of the magnitude limited photometric sample , then it may be difficult to quantify and so correct for the selection effects associated with the spectroscopic subset . in particular , if the spectroscopic sub - sample _ does not _ span the entire range of photometric observables , it is problematic to perform the reconstruction . however , in this situation one may rely on photo-@xmath4 error estimates for the range where spectral information is missing , and still apply the deconvolution procedure . we investigate this idea further in the second subsection , and discuss its applicability and limitations . the accuracy in the reconstruction of the intrinsic redshift distribution depends both on the quality of photometric redshifts , and on the size of the calibration sample with spectral information . to study how this accuracy depends on the size of the calibration sample , we consider the early - type `` calibration '' catalog and randomly remove @xmath103 , @xmath29 , or @xmath104 of the available spectroscopic information , respectively . by this we mean that we are picking random @xmath105 , @xmath1 or @xmath106 from the apparent magnitude limited sample . we refer to this part as the `` degradation '' of the catalog . we then measure the @xmath52 s conditional distributions for five different spectroscopic redshift bins , and compare them with those computed when the full spectroscopic information is available . figure [ test_number_spectra_pdf_redshift ] is the result of this test . dotted lines in all the panels are the error probability functions measured in different bins when all the spectral information is available ; long - dashed lines represent the cases when the catalog is degraded to @xmath105 , @xmath1 , or @xmath106 of its original size . we now ask how accurately we can reconstruct the intrinsic redshift distribution using these sub - samples , when the error in the photometric redshift is given as in figure [ test_number_spectra_pdf_redshift ] ( the root - mean - square ( rms ) @xmath107 is typically @xmath108 ) . to this end , we use those `` degraded '' error probabilities to recover the intrinsic redshift distribution from photometric data , the result of which is displayed in figure [ test_number_spectra_redshift ] . jagged dot - dashed lines show the reconstruction when the full catalog is used , and long - dashed lines are results of the deconvolutions performed with limited random spectroscopic subsets . we quantify the scatter / convergence of the deconvolution procedure in figure [ test_number_spectra_redshift_scatter ] , where we plot the difference ( within each bin ) between the reconstructed intrinsic distributions obtained when partial versus full spectroscopic information ( i.e. `` fiducial '' distribution ) is used , normalized by the maximum value of the reconstructed fiducial distribution . within the figure , we provide the rms fluctuations of the difference , in the redshift range @xmath109 marked by the horizontal arrow in the panel . we find that a safe and reliable reconstruction is guaranteed when the spectral information is restricted up to @xmath1 of its original size ( i.e. @xmath2 scatter ) , for randomly spaced data in redshift space . , for different spectroscopic `` degradation '' levels . the root mean square fluctuations of the difference expressed in the @xmath110-axis are also given , in the redshift range @xmath109 denoted by the horizontal arrow , as explained in the main text.,scaledwidth=50.0% ] suppose now that we are missing spectroscopic information in some redshift interval , but that we have photometry available along with photo-@xmath4 quoted errors in that range . can we still use our deconvolution technique ? in principle , our method is always readily applicable , provided the knowledge of @xmath52 . how can we infer it , given the lack of spectral information ? in effect , the reconstruction of the intrinsic redshift distribution depends not only on the calibration sample size and on the size of the photometric redshift error @xmath111 , but also on the shape of the distribution @xmath111 . without relying on other surveys which may cover missing spectral area , we would need to make some assumptions on its shape . the easiest solution is to derive the conditional distributions @xmath52 s by using quoted photo-@xmath4 errors . specifically , one may assume the @xmath52 s to be unbiased ( i.e. @xmath112 ) gaussians , with widths @xmath113 determined by quadratically averaging the sdss photo-@xmath4 quoted errors within each redshift bin . the question arises as to whether this is a good approximation or not , since there is no a priori reason for the error distributions to be gaussian and unbiased ( oyaizu et al . we test this idea on the early - type `` calibration '' catalog , and the result is displayed in figure [ test_gauss_proxy_error ] . in each panel , we show with dotted lines spline fits to the error probability functions measured from the early - type catalog ( all the spectral information is used in this case ) , and with solid lines their unbiased gaussian approximations . as it appears evident from the figure , gaussian approximations are almost always reasonable fits to the data ( excluding small tail departures or catastrophic photo-@xmath4 failures ) , but with the exception of the redshift interval @xmath114 , where the gaussian fit is rather poor . unfortunately , this departure is sufficient to make the overall reconstruction of the intrinsic redshift distribution problematic . in figure [ test_gauss_proxy_redshift ] we show , with long - dashed lines , the outcome of the deconvolution algorithm when unbiased gaussian fits are assumed for the pdf s , and report again for comparison the accurate reconstruction ( jagged dot - dashed line ) , as described in section [ red ] . the deconvolution is critical particularly in the redshift interval where the gaussian approximation fails ( i.e. around @xmath114 ) , and the overall result is of a poor recovery of the intrinsic relation . therefore , an accurate knowledge of the distribution of photo-@xmath4 errors is essential for our method to work . nevertheless , improving photo-@xmath4 uncertainties may help to characterize @xmath52 more accurately . it is also worth noticing that , in complete absence of spectroscopic counterpart , we are in principle still able to apply our technique , provided that we have a physically motivated model for the conditional error distribution . this is the real power of this method . on the opposite , the weighting technique proposed by lima et al . ( 2008 ) , which addresses similar goals , always requires the spectroscopic sub - sample to span the _ entire _ range of photometric observables covered by the photometric sample . using a selected sample of early - type galaxies from the sdss dr6 , for which both photo-@xmath4s and spectro-@xmath4s are known , we applied our one- and two - dimensional deconvolution techniques ( sheth 2007 ; rossi & sheth 2008 ) to reconstruct the unbiased redshift , magnitude and size distributions , as well as the magnitude - size relation ( section [ reconstr ] ) . this is a novel approach in recognizing that theoretical predictions , such as the difference between photometric and spectroscopic distance estimates , can be represented as integral equations and solved using deconvolution techniques . in the past , these techniques have been used only observationally , for instance in handling the psf of telescopes . we showed that our technique recovers all the true distributions and the joint relation , to a good degree of accuracy . we discussed the magnitude dependence of the error conditional probabilities ( section [ red ] ) , and argued that the problem of reconstructing the true magnitude or size distribution is best thought of as a one - dimensional deconvolution problem ( sections [ mag_dist ] and [ size_dist ] ) . we showed that even if the distribution of physical sizes is not severely biased , a significant bias in the magnitude distribution suffices to compromise the size - luminosity relation ( section [ size_lum_corr ] ) . we used our 2d deconvolution technique to correct for this effect . we then discuss how to extend our procedure to deep redshift catalogs , where limited spectroscopic information , or only photometric data , is available ( section [ ext ] ) . for this part , we performed two tests using the early - type `` calibration '' sample . we found that using only @xmath1 of the spectroscopic information randomly spaced in our catalog is sufficient for the reconstructions to be accurate with about @xmath115 scatter , when the error in the photometric redshift is typically @xmath116 . we also showed that assuming unbiased gaussians for the @xmath52 s distributions , with widths determined by quadratically averaging the sdss photo-@xmath4 quoted errors within each redshift bin , is not always a good approximation . however we argued that , provided one has a detailed knowledge of the pdf from other surveys or from empirically motivated models ( see for instance van der wel et al . 2009 ) , our technique can still be used , even when the spectroscopic sample does not span the entire range of photometric observables covered by the photometric sample . we address in more detail the problem of handling photo-@xmath4s when spectroscopic information is missing ( for example using a `` blind '' deconvolution approach ) in a forthcoming publication , where we also apply our technique to reconstruct the luminosity function in deep redshift catalogs such as the megaz - lrg ( collister et al . 2007 ) . even though our discussion was mainly phrased in terms of fundamental distributions and scaling relations for early - type galaxies , so it may be useful for detailed studies of early - types ( for example van den bosch & van de ven 2008 ; bernardi 2009 ) , the method developed here is quite general and can be applied to recover any intrinsic correlations between distance - dependent quantities ( even for @xmath37-correlated variables ) ; potentially , it can impact a broader range of studies , when at least one distance - dependent quantity is involved . in fact , our algorithms can be readily adapted to study the luminosity function in relatively shallow peculiar velocity surveys with noisy fundamental plane or @xmath117 distance estimates ( faber et al . 2007 ; tully et al . 2009 ) , or to handle correctly uncertainties in supernova measurements ( krauss et al . 2007 ; frieman et al . 2008 ; sako et al . 2008 ) , which can bias the redshift - dependent equation of state ( bridle & king 2007 ; fosalba & dore 2007 ) . a variety of other correlations can be re - analyzed along these lines ( see for example saracco et al . 2009 ) , such as the @xmath118 relation for blue galaxies ( melbourne et al . 2007 ) , the photometric fundamental plane ( bolton et al . 2007 ) , and also correlations that do not involve luminosity , such as the kormendy ( 1977 ) relation.other possible applications involve quasars ( croom et al . 2009 ; richards et al . 2009 ) , black - hole @xmath119 correlations , correlations with environment , and potentially future baryonic acoustic oscillation and dark energy surveys . we thank an anonymous referee for useful comments and suggestions . gr would like to thank bruce bassett and penjie zhang for stimulating discussions about deconvolution techniques . cbp acknowledges the support of the korea science and engineering foundation ( kosef ) through the astrophysical research center for the structure and evolution of the cosmos ( arcsec ) . funding for the sdss and sdss - ii has been provided by the alfred p. sloan foundation , the participating institutions , the national science foundation , the u.s . department of energy , the national aeronautics and space administration , the japanese monbukagakusho , the max planck society , and the higher education funding council for england . the sdss web site is http://www.sdss.org/. the sdss is managed by the astrophysical research consortium for the participating institutions . the participating institutions are the american museum of natural history , astrophysical institute potsdam , university of basel , university of cambridge , case western reserve university , university of chicago , drexel university , fermilab , the institute for advanced study , the japan participation group , johns hopkins university , the joint institute for nuclear astrophysics , the kavli institute for particle astrophysics and cosmology , the korean scientist group , the chinese academy of sciences ( lamost ) , los alamos national laboratory , the max - planck - institute for astronomy ( mpia ) , the max - planck - institute for astrophysics ( mpa ) , new mexico state university , ohio state university , university of pittsburgh , university of portsmouth , princeton university , the united states naval observatory , and the university of washington . 99 banerji , m. , abdalla , f. b. , lahav , o. , & lin , h. 2008 , mnras , 386 , 1219 bernardi m. , et al . , 2003 , aj , 125 , 1849 bernardi , m. 2009 , mnras , 510 bernstein , g. , & huterer , d. 2009 , arxiv:0902.2782 blanton , m. r. , et al . 2001 , aj , 121 , 235 blanton , m. r. , et al . 2003 , apj , 592 , 819 bridle , s. , & king , l. 2007 , new journal of physics , 9 , 444 bolton , a. s. , burles , s. , treu , t. , koopmans , l. v. e. , & moustakas , l. a. 2007 , apj , 665 , l105 bolzonella , m. , miralles , j .- m . , & pell , r. 2000 , a@xmath120a , 363 , 476 budavri , t. , szalay , a. s. , connolly , a. j. , csabai , i. , & dickinson , m. 2000 , aj , 120 , 1588 budavri , t. 2009 , apj , 695 , 747 carliles , s. , budavri , t. , heinis , s. , priebe , c. , & szalay , a. 2008 , astronomical data analysis software and systems xvii , 394 , 521 coleman , g. d. , wu , c .- c . , & weedman , d. w. 1980 , apjs , 43 , 393 collister , a. , et al . 2007 , mnras , 375 , 68 connolly , a. j. , & szalay , a. s. 1999 , aj , 117 , 2052 croom , s. m. , et al . 2009 , mnras , 392 , 19 csabai , i. , et al . 2003 , aj , 125 , 580 faber , s. m. , et al . 2007 , apj , 665 , 265 feldmann , r. , et al . 2006 , mnras , 372 , 565 fosalba , p. , & dor , o. 2007 , phys . d , 76 , 103523 frieman , j. a. , et al . 2008 , aj , 135 , 338 hildebrandt , h. , wolf , c. , & bentez , n. 2008 , a@xmath120a , 480 , 703 hoaglin , d. c. , mosteller , f. , & tukey , j. w. 1983 , wiley series in probability and mathematical statistics , new york : wiley , 1983 , edited by hoaglin , david c. ; 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namely , the photo-@xmath4 is the redshift value which minimizes the merit function @xmath128 . the associated pdfz , or @xmath129 ) , is derived from ( [ chi_sq ] ) , @xmath130/2}\ , . \label{pz_given_zeta}\ ] ] there is a main conceptual point in adopting this approach . photo-@xmath4s are noisy distance estimates , as opposed to spectroscopic redshifts , which are intrinsic or `` true '' solutions . therefore , while @xmath131 ( i.e. convergence of the noisy distribution to the true value ) , it is certainly not true that @xmath132 . this is equivalent to say that the distribution @xmath133 , obtained by binning horizontally the plane [ @xmath134 , @xmath135 shown in the left panel of figure [ redshift_reconstruction_early_types ] , is biased by definition . hence , it is more meaningful to estimate @xmath52 rather than attempting to derive @xmath133 . however , since current photo-@xmath4 codes output @xmath133 rather than @xmath52 , one may wonder if we can apply our technique using the pdfz . in effect , our deconvolution method relies on bayes s theorem . for example , if we consider the redshift distribution , application of this theorem yields @xmath136 from the previous relation , it is immediate to show that @xmath137 in this respect , the true ( spectroscopic ) redshift distribution can be alternatively viewed as a convolution of the noisy photo-@xmath4 distribution times the pdfz . therefore , assuming that the pdfz is known from the output of photometric redshift codes and given the observed photo-@xmath4 distribution , one can obtain the intrinsic @xmath51 by simply performing the integration ( [ no_deconvolution ] ) . this idea is further explored in sheth & rossi ( 2009 ) , where examples of these calculations are presented using the sdss sample described here . similarly , one can obtain the magnitude distribution with a direct integration , since @xmath138 and in principle recover scaling relations as well . however , we would like to remind the reader that when dealing with a real dataset , a noisy observation needs to be `` deconvolved '' into an intrinsic signal , namely from @xmath58 one needs to reconstruct @xmath51 ; @xmath133 is usually not known while @xmath52 can be inferred reliably with a proper `` spectroscopic training set '' this is our main motivation for providing a deconvolution approach .

noisy distance estimates associated with photometric rather than spectroscopic redshifts lead to a biased estimate of the luminosity distribution , and produce a correlated mis - estimate of the sizes . we consider a sample of early - type galaxies from the sdss dr6 for which both spectroscopic and photometric information is available , and apply the generalization of the @xmath0 method to correct for these biases . we show that our technique recovers the true redshift , magnitude and size distributions , as well as the true size - luminosity relation . we find that using only @xmath1 of the spectroscopic information randomly spaced in our catalog is sufficient for the reconstructions to be accurate within @xmath2 , when the photometric redshift error is @xmath3 . we then address the problem of extending our method to deep redshift catalogs , where only photometric information is available . in addition to the specific applications outlined here , our technique impacts a broader range of studies , when at least one distance - dependent quantity is involved . it is particularly relevant for the next generation of surveys , some of which will only have photometric information . [ firstpage ] distance scale galaxies : distances and redshifts methods : statistical galaxies : formation catalogues survey galaxies : fundamental parameters cosmology : observations .

RICHMOND In addition to meat-and-potatoes tasks like trying to fix Virginia's decaying transportation system, the state House of Delegates has found time to opine on national and international - some would say esoteric - topics. Near the end of a marathon, nearly 12-hour session Monday, the House's Republican super-majority pushed through a series of declarative resolutions sure to please the GOP's most conservative adherents. Del. Scott Lingamfelter's HJ654 takes aim at Agenda 21, a nonbinding plan for worldwide sustainable development adopted at a United Nations conference 20 years ago. The resolution brands Agenda 21 a "radical plan" that threatens "infringement on the American way of life and individual freedoms and ability to erode American sovereignty." Lingamfelter, R-Prince William County, is seeking the Republican nomination for lieutenant governor. The House also OK'd another Lingamfelter resolution (HJ653) asserting states' rights under the 10th Amendment to the U.S. Constitution "in the face of a continuing assault on the rights of the people" by the federal government. In addition, the chamber embraced Del. Bob Marshall's measure (HJ590) authorizing a $17,440 study of whether Virginia should establish a "metallic-based" alternative currency in case the Federal Reserve system suffers a major meltdown. But Marshall's measure (HB2340) aimed at undermining proposed new federal gun-control laws, which reached the House floor 10 days ago, appears about to die a quiet death. The bill would bar state agencies and employees from assisting federal authorities in enforcing any new restrictions on gun ownership or private sales. Over the objections of Marshall, R-Prince William County, the measure was shunted to the Appropriations Committee by the House leadership, presumably for examination of its potential fiscal impact. Bill Sizemore, 804-697-1560, bill.sizemore@pilotonline.com ||||| Virginia Del. Robert G. Marshall fears that a financial apocalypse is coming and only one thing can save the Commonwealth: its own currency. The idea that Virginia should consider issuing its own money was dismissed as just another quixotic quest by one of the most conservative members of the state legislature when Marshall introduced it three years ago. But it has since gained traction not only in Virginia, but also in states across the country as Americans have grown increasingly suspicious of the institutions entrusted with safeguarding the economy. This week, the proposal by the Prince William Republican sailed through the House of Delegates with a two-to-one majority. “This is a serious study about a serious topic,” Marshall said Tuesday. “We’re not completely powerless.” So far, only Utah has approved a law recognizing nontraditional currency. Four other states have bills pending this year. Marshall said he is unsure of his proposal’s prospects in the Virginia Senate. One Democrat derided it as a descent into “la-la land.” Prince William Del. Bob Marshall (R) has been fighting for the bill for three years as a safeguard against what he believes is a central banking system that has swung out of control. (BOB BROWN/AP) But the fact that the debate is happening at all reflects a deep-seated distrust in the very foundation of the country’s economic system — the dollar. Much of the anger is directed at the Federal Reserve, which controls the nation’s supply of money. Since the financial crisis, the Fed has pumped trillions of dollars into the economy to help avert what Chairman Ben S. Bernanke believed could have been the next Great Depression. Critics worry the Fed won’t ever stop. Marshall believes that the result could resemble the Weimar Republic of Germany after World War I: a worthless currency, skyrocketing inflation and a crumbling government. And those are only the problems that the Fed might create. Who knows what other threats may be lurking in the shadowy world of cyberattacks, Marshall said. The Fed acknowledged Tuesday that its computer systems were recently compromised, although the problems did not affect critical operations and have since been fixed. “This is a lifeboat study; what happens if?” Marshall said. Mainstream economics maintains that America is in little danger of turning into postwar Germany. Inflation is below 2 percent even though the Fed has tripled the amount of money in circulation since the 2008 financial crisis. Investors view the dollar as a safe haven, buying up greenbacks when turmoil strikes around the globe. A single currency is one of the bedrock assumptions of modern economics. But that doesn’t mean Virginia shouldn’t be ready, Marshall and his supporters believe. His proposal would create a 10-member commission to study “the need, means, and schedule for establishing a metallic-based monetary unit to serve as a contingency currency for the Commonwealth.” The study would cost $17,440. “The resolution is pretty modest,” said Lawrence H. White, a George Mason University economics professor who said he supports the proposal as a private citizen. “It’s ‘consider the idea.’ ” White doesn’t subscribe to the doomsday scenario, but he’s no optimist, either. He predicted that the inflation rate would rise to 5 percent before the end of the decade and eventually reach 10 percent. “I think the most effective way to send a message is to say you’re prepared to do something,” White said. “I view it as a kind of state-level expression of concern about the uncharted course the Federal Reserve has been on in monetary policy.” Some members of Congress have also denounced what they considered Fed overreach. Texas libertarian Ron Paul’s book “End the Fed” hit No. 6 on the New York Times bestsellers list in 2009. A campaign by Sen. Bernie Sanders (I-Vt.) dubbed “Audit the Fed” culminated in a report by the Government Accountability Office highlighting potential conflicts of interest within the institution. Efforts to establish alternative currencies amount to an economist’s version of a Fed boycott. But how the system would actually work remains murky. States do not have the constitutional authority to print money, but Marshall believes a potential loophole exists that could allow states to coin silver and gold. Utah’s law recognizes coins minted by the federal government from precious metals, intended for use as investments or collectibles, to be used as legal tender anywhere in the state. One Utah company even advertises the coins for use in 401(k) retirement plans. Although the law hasn’t changed what’s in most residents’ wallets, the measure became the poster child for those calling for a return to the days when money derived its value from gold. Today, money is backed by the authority of the U.S. government. Economist Bernard Lietaer, author of “Rethinking Money,” pointed out that a host of informal currencies have proved widely popular in the United States. For example, he said, there are 50 trillion airline frequent-flier miles in circulation, far surpassing the number of dollar bills. The benefit of a single currency “has been drilled into our heads for about 300 years,” Lietaer said. “I’m still looking for a book of economics that drops this assumption.” And of course, there is the open question of what a Virginia coin would look like. A tongue-in-cheek prototype made the rounds at an annual dinner in Richmond for lawmakers and the media two years ago. It was a wooden nickel, stamped with Marshall’s likeness and emblazoned with the motto “In Bob We Trust.” Tom Jackman and Ben Pershing contributed to this report. ||||| Worried that the Federal Reserve and the U.S. dollar are on the brink of collapse, more than a dozen states have proposed using their own alternative currencies of silver and gold. NEW YORK (CNNMoney) -- A growing number of states are seeking shiny new currencies made of silver and gold. Worried that the Federal Reserve and the U.S. dollar are on the brink of collapse, lawmakers from 13 states, including Minnesota, Tennessee, Iowa, South Carolina and Georgia, are seeking approval from their state governments to either issue their own alternative currency or explore it as an option. Just three years ago, only three states had similar proposals in place. "In the event of hyperinflation, depression, or other economic calamity related to the breakdown of the Federal Reserve System ... the State's governmental finances and private economy will be thrown into chaos," said North Carolina Republican Representative Glen Bradley in a currency bill he introduced last year. Unlike individual communities, which are allowed to create their own currency -- as long as it is easily distinguishable from U.S. dollars -- the Constitution bans states from printing their own paper money or issuing their own currency. But it allows the states to make "gold and silver Coin a Tender in Payment of Debts." To the state legislators who are proposing state-issued currencies, that means gold and silver are fair game, said Edwin Vieira, an alternative currency proponent and attorney specializing in Constitutional law. And since gold has grown exponentially more valuable, while the U.S. dollar continues to lose ground, the notion has become increasingly appealing to state lawmakers, he said. The state gold rush: Utah became the first state to introduce its own alternative currency when Governor Gary Herbert signed a bill into law last March that recognized gold and silver coins issued by the U.S. Mint as an acceptable form of payment. Under the law, the coins -- which include American Gold and Silver Eagles -- are treated the same as U.S. dollars for tax purposes, eliminating capital gains taxes. Since the face value of some U.S.-minted gold and silver coins -- like the one-ounce, $50 American Gold Eagle coin -- is so much less than the metal value (one ounce of gold is now worth more than $1,700), the new law allows the coins to be exchanged at their market value, based on weight and fineness. "A Utah citizen, for example, could contract with another to sell his car for 10 one-ounce gold coins (approximately $17,000), or an independent contractor could arrange to be compensated in gold coins," said Rich Danker, a project director at the American Principles Project, a conservative public policy group in Washington, D.C. South Carolina Republican Representative Mike Pitts proposed a currency system that would allow people to use any kind of silver or gold coin -- whether it's a Philippine Peso or a South African Krugerrand -- based on weight and fineness. Pitts said in the bill, which currently has 12 co-sponsors, that the state is facing "an economic crisis of severe magnitude." Republican representatives from Washington State followed suit in January, introducing a bill that would also allow any gold and silver coins to be considered legal tender based on metal values. Minnesota, Iowa, Georgia, Idaho and Indiana are also considering similar proposals. Many of the bills would make it possible for residents to exchange the physical coins for goods and services, so you could use coins to buy anything from groceries to a car as long as the store chooses to accept them. However, most people aren't going to walk around with such valuable coins in their pockets, said Vieira. Plus, calculating the value of the coins -- especially if they come from different parts of the globe and are of different sizes and shapes -- will get tricky. It's more likely that the states will create electronic depositories and accounts for the coins to make transactions easier, when and if the initial bills are passed, he said. Utah Gold & Silver Depository is already developing a system where customers could use debit cards linked to their gold holdings. When customers swipe their debit cards to make transactions, physical gold and silver coins would be transferred between accounts in privately-owned depositories (or vaults) based on the market value of the metals. Before deciding on a specific form of currency, some states -- including Minnesota, Tennessee, Virginia and North Carolina -- are considering proposals that would first require a committee to review their alternative currency plan. The future of U.S. currency: The states' proposals have been gaining steam among Tea Partyers and Republicans, many of whom also endorse a nationwide return to the gold standard, which would require the U.S. dollar to be backed by gold reserves. Tea Party "father" Ron Paul is sponsoring the "Free Competition in Currency Act," which would allow states to introduce their own currencies, and rival Newt Gingrich is calling for a commission to look at how the country can get back to the gold standard. But it will be the individual states that could really get the ball rolling, said Vieira. Even if several of the current proposals get killed, the introduction of so many bills at the state level is drawing national attention to the issue, he said. Of all the state proposals circulating right now, Republican-controlled states including South Carolina, Georgia, Idaho and Indiana have the best chance of passing their proposed bills this year, said American Principles Project's Danker. If just one or two states implement an alternative currency, it could have a Domino effect, he said. "I think we could get a couple passed in this legislative session, and that would show this is mainstream, popular and it would be a justification for more of the risk-averse states for doing this," he said. There are, of course, many people who think the recent push for alternative state currencies should be stopped in its tracks. David Parsley, a professor of economics and finance at Vanderbilt University, said he thinks state-issued currencies are a "terrible" idea. "Having 50 Feds" could debase the U.S. dollar and even potentially lead the country into default, he said. "The single currency in the United States is working just fine," said Parsley. "I have no idea why anyone would want to destroy something so successful -- unless they actually wanted to destroy the country."

– Virginia is apparently for haters of the Federal Reserve: One state legislator wants the state to mint its own coins in case the US dollar collapses. It may sound pie-in-the-sky, but Virginia's House of Delegates agreed on Monday to set up a $17,000 panel to explore the move. The Virginian-Pilot sees the measure by Republican Bob Marshall as a "conservative shout-out," but Marshall insists he's serious. "We can’t mint money, but we can mint gold and silver coins," he explained previously, according to NBC News. "It sounds like a small difference, but it is a difference legally." States can't actually "coin money" per the Constitution, but they are permitted to make "gold and silver Coin a Tender in Payment of Debts." Marshall thinks that line, along with some 19th-century Supreme Court decisions, clear the way for a Virginia coin, reports the Washington Post. What's more, Virginia isn't alone in considering an alternative currency, reports CNN. (In other US currency news, America's most fascinating nickel is set to fetch millions.)

a direct estimate for the minimum age of the universe may be obtained by determining the age of the oldest objects in the milky way . this direct estimate for the age of the universe can be used to constrain cosmological models , as the expansion age of the universe is a simple function of the hubble constant , average density of the universe and the cosmological constant . the oldest objects in the milky way are the metal - poor stars located in the spherical halo . there are currently three independent methods used to determine the ages of these stars : ( 1 ) nucleochronology , ( 2 ) white dwarf cooling curves and ( 3 ) main sequence turn - off ages based upon stellar evolution models . in this review i will summarize recent results from these three methods , with particular emphasize on main sequence turn - off ages as they currently provide the most reliable estimate for the age of the universe . conceptually , the simplest way to determine the age of a star is to use the same method which have been used to date the earth radioactive dating . the age of a star is derived using the abundance of a long lived radioactive nuclei with a known half - life ( see , for example the review @xcite ) . the difficulty in applying this method in practice is the determination of the original abundance of the radioactive element . the best application of this method to date has been on the very metal - poor star cs 22892 @xcite . this star has a measured thorium abundance ( half - life of 14.05 gyr ) , and just as importantly , the abundance of the elements from @xmath3 are very well matched by a scaled solar system @xmath4-process - process is the creation of elements heavier than fe through the _ rapid _ capture of neutrons by a seed nuclei . ] abundance distribution . thus , it is logical to assume that the original abundance of thorium in this star is given by the scaled solar system @xmath4-process thorium abundance . a detailed study of the @xmath4-process abundances in cs 22892 lead to an age of @xmath5gyr for this extremely metal - poor star @xcite . this in turn , implies a @xmath6 lower limit to the age of the universe of @xmath7 from nucleochronology . this is not a particularly stringent constraint at present . however , the uncertainty in the derived age is due entirely to the uncertainty in the determination of the thorium abundance in cs 22892 . the determination of the abundance of thorium in a number of stars with similar abundance patterns to cs 22892 will naturally lead to a reduction in the error . if 8 more stars are observed , then the error in the derived age will be reduced to @xmath8gyr , making nucleochronology the preferred method of obtaining the absolute ages of the oldest stars in our galaxy . white dwarfs are the terminal stage of evolution for stars less massive than @xmath9 . as white dwarfs age , they become cooler and fainter . thus , the luminosity of the faintest white dwarfs can be used to estimate their age . this age is based upon theoretical white dwarf cooling curves @xcite . there are a number of uncertainties associated with theoretical white dwarf models , which have been studied in some detail . however , the effect of these _ theoretical _ uncertainties are generally not included in deriving the uncertainty associated with white dwarf cooling ages . the biggest difficulty in using white dwarfs to estimate the age of the universe is that white dwarfs are very faint and so are very difficult to observe . most studies of white dwarf ages have concentrated on the solar neighborhood , in an effort to determine the age of the local disk of the milky way . even these nearby samples can be affected by completeness concerns . the age determination for these disk white dwarfs is complicated by the fact that the results are sensitive to the star formation rate as a function of time @xcite . a recent study has increased the sample size of local white dwarfs and concluded that the local disk of the milky way has an age of @xmath10gyr , where the quoted errors are due to the observational uncertainties in counting faint white dwarfs @xcite . this implies a @xmath6 lower limit to the age of the local disk of @xmath11 recently , with the hubble space telescope it has become possible to observe white dwarfs in nearby globular clusters stars . these stars contain few heavy elements ( typically 1/10 to 1/100 the ratio found in the sun ) and are spherically distributed about the galactic center . together , these facts suggest that globular clusters were among the first objects formed in the galaxy . there is evidence for an age range among the globular clusters , so the tightest limits on the minimum age of the universe are found when only the oldest globular clusters are considered . these are typically the globular clusters with the lowest heavy element abundances ( 1/100 the solar ratio ) . ] . these observations are not deep enough to observe the faintest white dwarfs and can only put a lower limit to the age of the white dwarfs . observations of the globular cluster m4 found a large number of white dwarfs , with no decrease in the number of white dwarfs at the faintest observed magnitudes @xcite . based upon the luminosity of the faintest observed white dwarfs , a lower limit to the age of m4 was determined to be @xmath12gyr @xcite . when the advanced camera becomes operational on hst ( scheduled to occur in the year 2000 ) , it will be possible to obtain considerably deeper photometry of m4 , leading to an improved constraint on the age of m4 from white dwarf cooling curves . theoretical models for the evolution of stars provide an independent method to determine stellar ages . these computer models are based on stellar structure theory , which is outlined in numerous textbooks @xcite . one of the triumphs of stellar evolution theory is a detailed understanding of the preferred location of stars in a temperature - luminosity plot ( figure [ cmd ] ) . a stellar model is constructed by solving the four basic equations of stellar structure : ( 1 ) conservation of mass ; ( 2 ) conservation of energy ; ( 3 ) hydrostatic equilibrium and ( 4 ) energy transport via radiation , convection and/or conduction . these four , coupled differential equations represent a two point boundary value problem . two of the boundary conditions are specified at the center of the star ( mass and luminosity are zero ) , and two at the surface . in order to solve these equations , supplementary information is required . the surface boundary conditions are based on stellar atmosphere calculations . the equation of state , opacities and nuclear reaction rates must be known . the mass and initial composition of the star need to be specified . finally , as convection can be important in a star , one must have a theory of convection which determines when a region of a star is unstable to convective motions , and if so , the efficiency of the resulting heat transport . once all of the above information has been determined a stellar model may be constructed . the evolution of a star may be followed by computing a static stellar structure model , updating the composition profile to reflect the changes due to nuclear reactions and/or mixing due to convection , and then re - computing the stellar structure model . there are a number of uncertainties associated with stellar evolution models , and hence , age estimates based on the models . probably the least understood aspect of stellar modeling is the treatment of convection . numerical simulations hold promise for the future @xcite , but at present one must view properties of stellar models which depend on the treatment of convection to be uncertain , and subject to possibility large systematic errors . main sequence , and red giant branch globular cluster stars have surface convection zones . hence , the surface properties of the stellar models ( such as its effective temperature , or color ) are rather uncertain . horizontal branch stars have convective cores , so the predicted luminosities and lifetimes of these stars are subject to possible systematic errors . given the known uncertainties in the models , the luminosity ( absolute magnitude ) of the main - sequence turn - off has the smallest theoretical errors , and is the preferred method for obtaining the absolute ages of globular clusters ( e.g. @xcite ) . the theoretical calibration of age as a function of the luminosity of the main - sequence turn - off has changed somewhat over the last several years . it has long been realized that diffusion ( the settling of helium relative to hydrogen ) could shorten the predicted main sequence lifetimes of stars @xcite . however , it was not clear if diffusion actually occurred in stars , so this process had been ignored in most calculations . recent helioseismic studies of the sun have shown that diffusion occurs in the sun @xcite . the sun is a typical main sequence star , whose structure ( convective envelope , radiative interior ) is quite similar to main sequence globular cluster stars . thus , as diffusion occurs in the sun , it appears likely that diffusion also occurs in main sequence globular cluster stars . modern calculations find that the inclusion of diffusion lowers the age of globular clusters by 7% @xcite . the recent use of an improved equation of state has led to a further 7% reduction in the derived globular cluster ages @xcite . the equation of state now includes the effect of coulomb interactions @xcite . helioseismic studies of the sun find that there are no significant errors associated with the equation of state currently used in stellar evolution calculations @xcite . together , the use of an improved equation of state and the inclusion of diffusion in the theoretical models have lead to a @xmath13 gyr ( 14% ) reduction in the estimated ages of for the oldest globular clusters . the excellent agreement between theoretical solar models and the sun ( see figure [ inversion ] ) suggest that future improvements in stellar models will likely lead to small ( less than @xmath14 ) changes in the derived ages of globular cluster stars . a detailed monte carlo study found that the uncertainties in the theoretical models led to an 1-@xmath15 error of 7% in the derived globular cluster ages @xcite . this study considered errors associated with 15 different parameters used in the construction of theoretical stellar models and isochrones . the parameter which lead to the largest uncertainty in the derived age of the globular clusters was the abundance of the @xmath16-capture elements ( oxygen is the most important @xmath16-capture element ) in globular cluster stars . it is difficult to determine the abundance of oxygen observationally @xcite , with estimates of the oxygen abundance varying by up to a factor of 3 . when extreme values for the oxygen abundance are used in the theoretical calculations , the derived globular cluster ages change by 8% . the use of the luminosity of the main sequence turn - off as an age indicator requires that the distance to the globular cluster be known . determining distances is one of the most difficult tasks in astronomy , and is always fraught with uncertainty . the release of the hipparcos data set of parallaxes to nearby stars @xcite has suggested that a revision in the conventional globular cluster distance scale is necessary . hipparcos did not directly determine the distance to any globular clusters , but did provide the distance to a number of nearby metal - poor main sequence stars . assuming that globular cluster stars have identical properties to these nearby stars , the nearby stars can serve as calibrators of the intrinsic luminosity of metal - poor main sequence stars and the distance to a globular cluster determined . this technique is referred to as main sequence fitting . there have been a number of papers which have used the hipparcos data set to determine the distance to globular clusters using main sequence fitting @xcite . three of these papers conclude that globular clusters are further away than previously believed , leading to a reduction in the derived ages . the remaining paper @xcite concluded that the hipparcos data did not lead to a revision in the globular cluster distance scale . however , this work incorrectly included binary stars in the main sequence fitting @xcite . when the known binaries are removed from the fit ( a case which is also considered in @xcite ) , then all four papers are in agreement the hipparcos data yields larger distances ( and hence , younger ages ) for globular clusters . my analysis @xcite considered four distance determination techniques in addition to using the hipparcos data , and concluded that the five independent distance estimates to globular clusters _ all _ led to younger globular cluster ages . a number of authors have recently examined the question of the absolute age of the oldest globular clusters . all of these works used the luminosity of the main sequence turn - off as the age indicator . the results are summarized in table [ agetable ] . despite the fact that these investigators used a variety of theoretical stellar models ( with differing input physics ) and different methods to determine the distance to the globular clusters , the derived ages are remarkably similar , around 12 gyr . these ages are @xmath17 gyr younger than previous determinations , due to improved input physics used in the models , and a longer distance scale to globular clusters . my work @xcite considered a variety of distance indicators and included a very detailed monte carlo study of the possible errors associated with the theoretical stellar models . for this reason , my preferred age for the oldest globular clusters is @xmath1 gyr , implying a minimum age of the universe of @xmath18 at the 95% confidence level . .estimates for the age of the oldest globular clusters [ cols="<,<,^ , < " , ] a direct estimate for the minimum age of the universe can be obtained by determining the age of the oldest objects in the galaxy . these objects are the metal - poor stars located in the halo of the milky way . there are currently three independent techniques which have been used to determine the ages of the metal - poor stars in the milky way : nucleochronology , white dwarf cooling theory , and main sequence turn - off ages . the best application of nucleochronology to date has been on the very metal - poor star cs 22892 which has an age of @xmath5gyr @xcite , implying a @xmath6 lower limit to the age of the universe of @xmath7 . white dwarf cooling theory is difficult to apply in practice , as one needs to observe very faint objects . currently , it is impossible to observe the faintest white dwarfs in a globular cluster , so white dwarf cooling theory can only provide a lower limit to the age of a globular cluster . based upon the luminosity of the faintest observed white dwarfs , a lower limit to the age of m4 was determined to be @xmath12gyr @xcite . absolute globular cluster ages based upon the main sequence turn - off have recently been revised due to a realization that globular clusters are farther away than previously thought . the age of the oldest globular clusters is @xmath1 gyr @xcite , implying a minimum age of the universe of @xmath19 gyr ( 95% confidence level ) . at the present time , main sequence turn - off ages have the smallest errors of the available age determination techniques and provide the best estimate for the age of the universe . to obtain the actual age of the universe , one must add to the above age the time it took for the metal - poor stars to form . unfortunately , a good theory for the onset of star formation within the galaxy does not exist . estimates for the epoch of initial star formation range from redshifts of @xmath20 to 20 . this corresponds to ages ranging from 0.1 to 2 gyr , implying that the actual age of the universe lies in the range @xmath21gyr . tightening the bounds of this estimate will require a better understanding of the epoch of galaxy formation , along with improved stellar models and distance estimates to globular clusters . the author was supported for this work by nasa through hubble fellowship grant number hf01080.0196a awarded by the space telescope science institute , which is operated by the association of universities for research in astronomy , inc . , for nasa under contract nas 526555 .

a minimum age of the universe can be estimated directly by determining the age of the oldest objects in the our galaxy . these objects are the metal - poor stars in the halo of the milky way . recent work on nucleochronology finds that the oldest stars are @xmath0 gyr old . white dwarf cooling curves have found a minimum age for the oldest stars of 8 gyr . currently , the best estimate for the age of the oldest stars is based upon the absolute magnitude of the main sequence turn - off in globular clusters . the oldest globular clusters are @xmath1 gyr , implying a minimum age of the universe of @xmath2 gyr ( 95% confidence level ) .

in the standard model of authentication theory @xcite , a _ transmitter _ wants to send some information to a _ receiver _ across an insecure channel while an _ opponent _ with access to the channel wants to deceive the receiver . the opponent can either insert new messages into the channel , or intercept messages from the transmitter and modify them into his own . in each case , the opponent s goal is to deceive the receiver into believing that the new messages are authentic ( coming from the transmitter ) . the first attack based on insertion of new messages is known as _ impersonation _ and the second attack based on modification of messages from the transmitter is known as _ substitution_. more formally , let @xmath0 denote the set of all _ source states _ , @xmath1 be the set of all _ messages _ , and @xmath2 be the set of all _ encoding rules_. all these are finite sets . a source state is the information the transmitter wishes to communicate to the receiver . an encoding rule is an injection from @xmath0 to @xmath3 . the transmitter and receiver agree beforehand on a secret encoding rule @xmath4 . to communicate a source state @xmath5 , the transmitter determines @xmath6 ( note that @xmath7 ) and chooses a message @xmath8 to send to the receiver . the receiver accepts the received message as authentic if there exists an @xmath9 in the image of @xmath10 containing the received message . for the receiver to recover the source state , each encoding rule must satisfy the condition @xmath11 the triple @xmath12 is called an _ authentication code _ , or _ a - code _ in short . an a - code @xmath12 can be represented by an @xmath13 matrix , whose rows are indexed by authentication rules , and columns indexed by source states , such that the entry in row @xmath14 and column @xmath5 is @xmath15 . for @xmath16 an integer and @xmath17 a finite set , we denote by @xmath18 the set of all @xmath16-subsets of @xmath17 . research on authentication codes have focused on the case when every encoding rule is an injection from @xmath0 to @xmath19 , for some positive @xmath20 . such an a - code is called _ a @xmath20-splitting a - code_. a @xmath21-splitting a - code is also known as an _ a - code without splitting _ , and a @xmath20-splitting a - code with @xmath22 is known as an _ a - code with splitting_. a - codes with splitting are useful for the analysis of authentication with arbitration @xcite , an extended model of authentication introduced by simmons @xcite for the scenario when the transmitter and receiver may both be deceptive . in a _ spoofing attack of order @xmath23 _ @xcite , the opponent observes @xmath23 distinct messages sent by the transmitter through the insecure channel under the same encoding rule . the opponent then inserts a new message ( distinct from the @xmath23 messages already sent ) , hoping to have it accepted by the receiver as authentic . within this framework , impersonation and substitution attacks are just spoofing attacks of order zero and one , respectively . while these attacks have been rather well studied for a - codes , less is known for the case of spoofing attacks of order @xmath24 , especially on @xmath20-splitting a - codes when @xmath22 . the probability distribution on the set of source states @xmath0 induces a probability distribution on @xmath25 , @xmath26 . given these probability distributions , the transmitter and receiver choose a probability distribution on @xmath2 , called an _ encoding strategy_. for any @xmath5 and @xmath4 , the transmitter also chooses a probability distribution on @xmath15 , called a _ splitting strategy_. the opponent is assumed to know the encoding and splitting strategies . the transmitter and receiver chooses the encoding and splitting strategies to minimize the probability of being deceived by the opponent . we denote by @xmath27 the probability that the opponent can deceive the receiver with a spoofing attack of order @xmath23 . the following lower bound on @xmath27 is known . [ huberlb ] in a @xmath20-splitting a - code @xmath12 , @xmath28 for every @xmath26 . a @xmath20-splitting a - code is said to be _ @xmath29-fold secure against spoofing _ if @xmath30 , for all @xmath23 , @xmath31 . for succinctness , we call such a code a _ @xmath32-splitting a - code_. huber @xcite also showed that the number of encoding rules must be large enough if an a - code is to be @xmath29-fold secure against spoofing . [ hubere ] in a @xmath32-splitting a - code @xmath12 , @xmath33 for efficiency , we want the number of encoding rules in an a - code to be as small as possible . we call a @xmath32-splitting a - code _ optimal _ if the lower bound in proposition [ hubere ] is met with equality . the main contribution of this paper is on the construction of optimal @xmath32-splitting a - codes with three source states , for @xmath22 and @xmath34 . in particular , we show that the following two new families of a - codes exist : a. @xmath35-splitting a - codes with three source states and @xmath36 messages , for all @xmath37 , @xmath38 . b. @xmath39-splitting a - codes with three source states and @xmath36 messages , for all @xmath40 . the @xmath39-splitting a - codes we obtained is the first known infinite family of @xmath32-splitting a - codes with @xmath41 and @xmath42 . we also prove that a @xmath43-splitting a - code with @xmath16 source states and @xmath36 messages exists for all sufficiently large @xmath36 ( with @xmath16 and @xmath20 fixed ) . this section serves to provide notions and results that are required for our construction in subsequent sections . the ring @xmath44 is denoted @xmath45 . huber @xcite defined _ splitting @xmath46-designs _ , generalizing the splitting 2-designs of ogata _ et al . _ @xcite . let @xmath46 , @xmath36 , @xmath16 , @xmath20 , and @xmath47 be positive integers , with @xmath48 and @xmath49 . a _ splitting @xmath46-design _ , or more precisely , a _ splitting @xmath46-@xmath50 design _ , is a pair @xmath51 such that a. @xmath17 is a set of @xmath36 elements , called _ points _ ; b. @xmath52 is a set of @xmath53 arrays , called _ blocks _ , with entries from @xmath17 , such that each point of @xmath17 occurs at most once in each block ; c. for every @xmath54 , there are exactly @xmath47 blocks in which @xmath55 , @xmath56 , occur in @xmath46 different rows . note that a splitting @xmath46-@xmath57 design coincides with the classical notion of a @xmath46-@xmath58 design . huber @xcite proved the equivalence between splitting @xmath46-designs and optimal splitting a - codes . there exists a splitting @xmath46-@xmath59 design if and only if there exists an optimal @xmath32-splitting a - code for @xmath16 equiprobable source states , having @xmath36 messages and @xmath60 encoding rules . the _ necessary divisibility conditions _ for the existence of splitting @xmath46-designs are as follows . [ necessary ] the necessary conditions for the existence of a splitting @xmath46-@xmath50 design are @xmath61 sometimes , the points of a splitting @xmath46-design @xmath51 can be identified with the elements of an additive group @xmath62 , so that @xmath63 . if the set of blocks @xmath52 can be generated by a set @xmath64 , that is , @xmath65 then @xmath66 is called a _ set of base blocks _ of @xmath51 . [ 151 ] let @xmath67 . the set containing the single array @xmath68 as a base block , generates the set of blocks @xmath52 for a splitting @xmath69-@xmath70 design @xmath51 . our constructions for splitting @xmath46-designs also rely on group divisible designs ( gdd ) . let @xmath46 , @xmath16 , and @xmath36 be nonnegative integers . group divisible @xmath46-design of order @xmath36 and block size @xmath16 _ , denoted gdd@xmath71 , is a triple @xmath72 satisfying the following properties : a. @xmath17 is a set of @xmath36 elements , called _ points _ ; b. @xmath73 is a partition of @xmath17 into subsets , called _ groups _ ; c. @xmath74 , whose elements are called _ blocks _ , such that each @xmath75 intersects any group @xmath76 in at most one point ; d. every @xmath77 containing at most one point from each group is contained in exactly one block . the _ type _ of a gdd@xmath71 @xmath72 is the multiset @xmath78 $ ] . we use the exponential notation to describe the type of a gdd : a gdd of type @xmath79 is a gdd where there are exactly @xmath80 groups of size @xmath81 , @xmath82 . we require the following result . [ gddresults ] a. there exists a gdd@xmath83 of type @xmath84 if and only if @xmath85 , @xmath86 , and @xmath87 . b. there exists a gdd@xmath88 of type @xmath84 if and only if @xmath89 , @xmath90 , and @xmath91 , with the exception of @xmath92 , @xmath93 . c. for @xmath94 , @xmath95 , a gdd@xmath96 of type @xmath84 exists if and only if @xmath97 and @xmath98 . a gdd@xmath99 of type @xmath100 exists when @xmath101 , @xmath102 , and @xmath103 . analogous to splitting @xmath46-designs , a `` splitting '' version of a gdd can be defined . this has been done by wang @xcite for @xmath104 . here , we extend it to general @xmath46 . a _ splitting group divisible @xmath46-design _ , denoted splitting gdd@xmath105 , is a triple @xmath72 satisfying the following properties : a. @xmath17 is a set of @xmath36 elements , called _ points _ ; b. @xmath106 is a partition of @xmath17 into subsets , called _ groups _ ; c. @xmath52 is a set of @xmath53 arrays , called _ blocks _ , with entries from @xmath17 , such that each point of @xmath17 occurs at most once in each block ; d. for every @xmath107 containing at most one point from each group , there is exactly one block in which @xmath55 , @xmath56 , occur in @xmath46 different rows . the type of a splitting gdd is defined in a fashion similar to that for a gdd . splitting gdds play an important role in the recursive constructions of splitting designs . the following is a straightforward extension of wilson s fundamental construction for gdds @xcite to splitting gdds . [ fc ] let @xmath72 be a gdd@xmath71 . suppose that for each block @xmath75 , there exists a splitting gdd@xmath108 of type @xmath109 , @xmath110 , where @xmath111 then there exists a splitting gdd@xmath112 of type @xmath113 $ ] @xmath114 , where @xmath115 since the trivial splitting gdd@xmath116 of type @xmath109 ( containing only one block ) always exists for any @xmath46 , @xmath16 , and @xmath20 , we have the following . [ multiply ] if there exists a gdd@xmath71 of type @xmath117 , then there exists a splitting gdd@xmath118 of type @xmath119 . as shown by ge _ @xcite , we can also fill in the groups of a splitting gdd with a splitting 2-design to obtain new splitting 2-designs . [ fillingroups ] let @xmath72 be a splitting gdd@xmath120 . if for each @xmath76 , there exists a splitting @xmath69-@xmath121 design , then there exists a splitting @xmath69-@xmath122 design . the following theorem summarizes the state of knowledge on the existence of splitting @xmath46-designs with @xmath123 . [ state ] the necessary divisibility conditions ( of proposition [ necessary ] ) are also sufficient for the existence of a splitting @xmath69-@xmath59 design when a. @xmath124 , for any positive integer @xmath125 ; b. @xmath126 , except for @xmath127 ; c. @xmath128 , except for @xmath129 ; d. @xmath130 , with the possible exception of @xmath131 ; e. @xmath132 , with the possible exception of @xmath133 . in addition , there exists a @xmath69-@xmath134 design for all @xmath135 . let @xmath47 be a positive integer . the complete ( loopless ) multigraph on @xmath36 vertices , denoted @xmath136 , is the graph where every pair of distinct vertices is connected by @xmath47 edges . let @xmath137 be a simple graph without isolated vertices . a _ @xmath137-design of order @xmath36 and index @xmath47 _ is a partition of edge set of @xmath136 into subgraphs , each of which is isomorphic to @xmath137 . if @xmath138 denotes the number of edges in @xmath137 , and @xmath139 denotes the greatest common divisor of the degrees of vertices in @xmath137 , then simple counting shows that the conditions a. @xmath140 , and b. @xmath141 are necessary for the existence of a @xmath137-design of order @xmath36 and index @xmath47 . a celebrated result of wilson @xcite states that these necessary conditions are also asymptotically sufficient . [ wilsonasymp ] let @xmath137 be a simple graph without isolated vertices . then there exists a constant @xmath142 depending only on @xmath137 and @xmath47 such that a @xmath137-design of order @xmath36 and index @xmath47 exist for all @xmath143 satisfying @xmath140 and @xmath144 . let @xmath145 denote the complete @xmath16-partite graph , with each part having @xmath20 vertices . a splitting @xmath69-@xmath50 design @xmath51 is equivalent to a @xmath145-design of order @xmath36 and index @xmath47 through the following correspondence : a. a point in @xmath17 corresponds to a vertex in @xmath136 , b. a block @xmath75 corresponds to the complete @xmath16-partite graph , where the @xmath23-th part contains @xmath20 vertices corresponding to the @xmath20 entries in row @xmath23 of @xmath146 , @xmath147 . applying theorem [ wilsonasymp ] with @xmath148 then gives the following result on the asymptotic existence of splitting 2-designs . there exists a constant @xmath142 depending only on @xmath16 , @xmath20 , and @xmath47 , such that a splitting @xmath69-@xmath50 design exists for all @xmath143 satisfying @xmath149 and @xmath150 . we end this section with a nonexistence result . huang @xcite has shown that the number of complete @xmath16-partite graphs required to partition the edge set of @xmath151 is at least @xmath152 . this has the following consequence . [ nonexistence ] there does not exist a splitting @xmath69-@xmath153 design , for all @xmath154 . suppose a splitting @xmath69-@xmath153 design exists . the number of blocks in this splitting 2-design is @xmath155 . this would mean that we can partition the edge set of @xmath156 into @xmath155 complete @xmath16-partite subgraphs . this is impossible by huang s result , since @xmath157 . the definite exceptions in theorem [ state ] are special cases of proposition [ nonexistence ] . in this section , we establish the existence of an infinite family of splitting @xmath69-@xmath158 designs , and remove @xmath159 as a possible exception from theorem [ state](v ) . there exists a splitting @xmath69-@xmath158 design for all @xmath37 , except possibly when @xmath160 . a splitting @xmath69-@xmath70 design is exhibited in example [ 151 ] , so let @xmath161 . write @xmath162 , for some integer @xmath163 . a gdd@xmath164 of type @xmath165 exists by theorem [ gddresults](i ) . apply corollary [ multiply ] to obtain a splitting gdd@xmath166 of type @xmath167 . now fill in the groups of this splitting gdd with a splitting @xmath69-@xmath70 design ( which has been constructed in example [ 151 ] ) to obtain a splitting @xmath69-@xmath168 design . there exists a splitting @xmath69-@xmath169 design . a gdd@xmath170 of type @xmath171 exists by theorem [ gddresults](ii ) . apply corollary [ multiply ] to obtain a splitting gdd@xmath172 of type @xmath173 . now fill in the groups of this splitting gdd with a splitting @xmath69-@xmath174 design ( which exists by theorem [ state ] ) to obtain a splitting @xmath69-@xmath169 design . in this section , we establish the existence of the first known infinite family of splitting 3-designs with @xmath42 . let @xmath46 , @xmath16 , and @xmath36 be nonnegative integers . a _ @xmath175 candelabra system _ of order @xmath36 is a quadruple @xmath176 that satisfies the following properties : a. @xmath17 is a set of @xmath36 elements , called _ points _ ; b. @xmath177 , called the _ stem _ ; c. @xmath178 is a partition of @xmath179 ( elements of @xmath180 are called _ groups _ ) ; d. @xmath181 , whose elements are called _ blocks _ ; e. every @xmath77 with @xmath182 for all @xmath23 , is contained in a block in @xmath52 . the _ type _ of a @xmath175 candelabra system @xmath176 is the multiset @xmath183 $ ] . a @xmath175 candelabra system of type @xmath184 with a stem of size @xmath185 is denoted @xmath175-cs@xmath186 . here , we introduce the notion of splitting candelabra systems . a _ splitting @xmath187 candelabra system _ of order @xmath36 is a quadruple @xmath176 that satisfies the following properties : a. @xmath17 is a set of @xmath36 elements , called _ points _ ; b. @xmath177 , called the _ stem _ ; c. @xmath178 is a partition of @xmath179 ( elements of @xmath180 are called _ groups _ ) ; d. @xmath52 is a set of @xmath53 arrays , called _ blocks _ , with entries from @xmath17 , such that each point of @xmath17 occurs at most once in each block ; e. for every @xmath188 with @xmath182 for all @xmath23 , there is exactly one block in which @xmath55 , @xmath56 , occur in @xmath46 different rows . we use the same notation for splitting @xmath175 candelabra systems as those for @xmath175 candelabra systems . the following theorem is an extension of hartman s fundamental construction @xcite from @xmath189 candelabra systems to splitting @xmath189 candelabra systems . [ fc3 ] if there exist a @xmath189-cs@xmath186 , a splitting @xmath190-cs@xmath191 , and a splitting gdd@xmath192 of type @xmath193 , then there exists a splitting @xmath190-cs@xmath194 . let @xmath176 be a @xmath189-cs@xmath186 , and let @xmath195 be a distinguished point in @xmath196 . for @xmath197 , define the set of points @xmath198 further define @xmath199 for each @xmath75 containing the point @xmath195 , let @xmath200 be a splitting @xmath190-cs@xmath191 , and for each @xmath75 not containing the point @xmath195 , let @xmath201 be a splitting gdd@xmath202 of type @xmath193 . it is easy to check that @xmath203 , where @xmath204 is the required splitting @xmath190-cs@xmath194 . we can also fill in the groups of a splitting candelabra system by splitting 3-designs to obtain larger splitting 3-designs . [ fillin3 ] if there exists a splitting @xmath205-cs@xmath186 , where @xmath206 , and there exists a splitting @xmath207-@xmath208 design for each @xmath23 , @xmath209 , then there exists a splitting @xmath207-@xmath210 design . let @xmath176 be a splitting @xmath205-cs@xmath186 , where @xmath206 . for each @xmath76 , let @xmath211 be a splitting 3-@xmath212 design . then @xmath213 is the required splitting @xmath207-@xmath210 design . to apply theorem [ fc3 ] and proposition [ fillin3 ] , we require some splitting candelabra systems to start with . [ small ] there exist a splitting @xmath214-cs@xmath215 and a splitting @xmath214-cs@xmath216 . let @xmath217 and @xmath218 . let @xmath219 then @xmath220 , where @xmath221 , is a splitting @xmath214-cs@xmath215 . now let @xmath222 be such that @xmath223 , and let @xmath224 then @xmath225 is a splitting @xmath214-cs@xmath216 . we now establish an infinite family of splitting 3-designs . a splitting @xmath207-@xmath226 design exists if and only if @xmath40 . necessity of the condition @xmath40 follows from proposition [ necessary ] . huber @xcite has shown the existence of a splitting @xmath207-@xmath227 design , so we consider @xmath228 . write @xmath229 , for some @xmath230 . let @xmath17 be a set of @xmath231 points , containing @xmath195 as a distinguished point . it is easy to verify that @xmath232 is a @xmath233-cs@xmath234 . apply theorem [ fc3 ] with a splitting @xmath214-cs@xmath216 ( which exists by lemma [ small ] ) and a splitting gdd@xmath235 of type @xmath236 ( whose existence is implied by the trivial gdd@xmath237 of type @xmath238 and corollary [ multiply ] ) to obtain a splitting @xmath214-cs@xmath239 . now apply proposition [ fillin3 ] to this splitting @xmath214-cs@xmath239 with a splitting @xmath207-@xmath227 design to obtain a splitting @xmath207-@xmath240 design . determining the existence of optimal @xmath20-splitting authentication codes with @xmath16 source states that are @xmath29-fold secure against spoofing is a difficult problem , when @xmath16 , @xmath20 and @xmath46 are large . new constructions , both direct and recursive , need to be developed in order to make further progress on the problem . the authors would like to thank gennian ge and alan ling for helpful discussions . j. l. massey , _ cryptography , a selective survey _ , digital communications 85 : proceedings of the second tirrenia international workshop on digital communications ( e. biglieri and g. prati , eds . ) , elsevier science pub . co. , 1986 , pp . w. h. mills , _ on the existence of @xmath244 designs _ , proceedings of the twenty - first southeastern conference on combinatorics , graph theory , and computing ( boca raton , fl , 1990 ) , vol . 79 , 1990 , pp . 129141 . w. ogata , k. kurosawa , d. r. stinson , and h. saido , _ new combinatorial designs and their applications to authentication codes and secret sharing schemes _ , discrete math . * 279 * ( 2004 ) , no . 1 - 3 , 383405 . to3em , _ decompositions of complete graphs into subgraphs isomorphic to a given graph _ , proceedings of the fifth british combinatorial conference ( univ . aberdeen , aberdeen , 1975 ) , congressus numerantium , no . xv , utilitas math . , winnipeg , man . , 1976 , pp .

we consider the problem of constructing optimal authentication codes with splitting . new infinite families of such codes are obtained . in particular , we establish the first known infinite family of optimal authentication codes with splitting that are secure against spoofing attacks of order two . yeow meng chee and xiande zhang hui zhang ( communicated by iwan duursma )

chronic obstructive pulmonary disease ( copd ) , being a condition associated with increased morbidity and mortality , causes a substantial and increasing burden to society in many countries.1,2 the global initiative for chronic obstructive lung disease ( gold ) guideline3 recommends regular use of bronchodilators for symptomatic management of copd , including inhaled 2-agonists and anticholinergics.3 as with all chronic diseases , nonadherence to treatment is common in patients with copd , potentially leading to adverse health outcomes and reduced quality of life.4 characteristics of copd medications and regimens may often contribute to nonadherence , and therefore should be considered when selecting the appropriate treatment for a patient . in general , more complex regimens result in suboptimal adherence,5 with frequency of dosing regarded as one of the principal factors that negatively affect adherence.6 in addition , adherence is lower for medications that do not have an immediate effect on symptoms.7 indacaterol is a novel , inhaled once - daily ultra - long - acting 2-agonist ( laba)8 for the treatment of copd . in preclinical studies , the onset of action of indacaterol was similar to that of salbutamol and of formoterol , and was significantly faster than that of salmeterol.9 in previous clinical studies , indacaterol has demonstrated 24-hour bronchodilation on once - daily dosing , along with a good overall safety and tolerability profile.1012 the present study was conducted to evaluate the onset of action of single doses of indacaterol 150 and 300 g in comparison with that of salbutamol 200 g ( the standard fast - onset bronchodilator ) , the combination of salmeterol 50 g and fluticasone 500 g ( salmeterol - fluticasone 50/500 g ) , and placebo in patients with moderate - to - severe copd . this was an international , multicenter , randomized , double - blind , placebo - controlled , crossover , single - dose study . institutional review board or independent ethics committee approval was obtained from each participating study center . the study was conducted in accordance with the declaration of helsinki ( 1989 ) and local applicable laws and regulations . patients of either gender , aged 40 years , with moderate - to - severe copd ( according to the gold 2005 guideline ) , smoking history of 20 pack years , postbronchodilator forced expiratory volume in one second ( fev1 ) 30% but < 80% of the predicted normal value , and postbronchodilator fev1/forced vital capacity ( fvc ) < 70% were eligible for enrolment in the study . patients were excluded from the study if they had any concomitant pulmonary disease , type i diabetes or uncontrolled type ii diabetes , uncontrolled hypertension , unstable ischemic heart disease , or malignancy . patients who had a history of asthma , had been hospitalized for a copd exacerbation within six weeks prior to screening or during the run - in period , or had experienced respiratory tract infection within six weeks prior to screening , were also excluded . the following medications were prohibited at any time during the study ( the minimum washout period is shown in brackets ) : long - acting anticholinergics ( seven days ) , short - acting anticholinergics ( eight hours ) , fixed - dose combination of a 2-agonist and an inhaled corticosteroid ( ics , 48 hours ) , fixed - dose combination of a short - acting 2-agonist and a short - acting anticholinergic ( eight hours ) , other labas ( 48 hours ) , short - acting 2-agonists ( other than those prescribed in the study , six hours ) , xanthine derivatives ( one week ) , and parenteral or oral corticosteroids ( one month ) . patients on fixed - dose combinations of a 2-agonist and an ics were to be switched to the equivalent ics prior to the runin period , with the dose and dosage regimen to remain unchanged for the duration of the study . patients on ics at the screening visit were to continue ics for the duration of the study , again at a dose and regimen to remain unchanged . the study comprised a prescreening visit , a 14-day screening / run - in period , and five single - dose treatment periods . during the prescreening visit , patients ongoing copd medications were reviewed and , if necessary , any prohibited medication was adjusted to an allowable copd therapy . after the screening visit , patients entered into a 14-day run - in period , during which their eligibility was assessed . at baseline , patients were randomized equally ( using a validated automated system ) to one of five treatment sequences to receive indacaterol 150 g and 300 g delivered via a single - dose dry powder inhaler , salbutamol 200 g via the manufacturer s proprietary multidose dry powder inhaler , salmeterol - fluticasone 50/500 g fixed - dose combination via the manufacturer s proprietary multidose dry powder inhaler , and placebo . each treatment sequence comprised five double - blind , single - dose treatment periods , with treatment periods separated by a 4- to 7-day washout period . at 47 days after the last treatment visit patients inhaled through three different devices on each visit ( one inhalation from a single - dose dry powder inhaler and one from each of the two multidose dry powder inhalers used in the study ) , with the order of devices randomly assigned at the start of the study . treatment allocation was concealed from the patients , investigating staff , and the clinical trial team by the use of matching placebo inhalers all identical in packaging , labeling , and schedule of administration . an unblinded pharmacist ( or designee ) prepared the individual patient - specific packs from supplied bulk medication . salbutamol was the only rescue medication permitted throughout the study , although visits had to be rescheduled if salbutamol was taken within six hours prior to the start of the visit . all efficacy evaluations were based on spirometric assessment of lung function , performed at 50 and 15 minutes predose and at 5 , 15 , and 30 minutes , and at 1 and 2 hours postdose . the postdose time was measured from the time the first device was used at each study visit ( the three devices were used in a randomized order , as described above ) . all spirometry equipment and spirometric testing were in accordance with the american thoracic society / european respiratory society standards.13 the primary efficacy variable was fev1 at five minutes postdose . the primary objective was to compare indacaterol 150 and 300 g and placebo in terms of fev1 at five minutes postdose . the secondary objectives were to compare indacaterol 150 and 300 g with salbutamol 200 g and salmeterol - fluticasone 50/500 g , and to compare salmeterol - fluticasone 50/500 g with salbutamol 200 g in terms of fev1 at five minutes postdose . the other efficacy variables were fev1 at other scheduled time points ; the proportion of patients with at least 10% , 12% , and 15% increase in fev1 from baseline to each scheduled time point ; and the proportion of patients with at least a 12% and 200 ml increase in fev1 from baseline to each scheduled time point . safety assessments included recording of adverse events and serious adverse events , along with evaluation of their severity , duration , and relationship to study drug . in addition , samples were collected for hematology and blood chemistry ( including serum potassium and blood glucose ) , and vital signs and electrocardiogram assessments were recorded . it was estimated that 53 patients were needed to complete the study , assuming a difference of 120 ml between each indacaterol dose and placebo in terms of fev1 at five minutes postdose , a standard deviation of 240 ml , a two - sided significance level of 5% ( adjusted to 2.5% using a bonferroni correction for the two main treatment comparisons , that is , indacaterol [ 150 and 300 g ] versus placebo ) , and a power of 90% . as there were five treatment sequences and six inhaler orders for individual treatment sequences , a total of 60 patients with evaluable measurements were required in order to have an equal number of patients per inhaler order and per treatment sequence . allowing for a 15% dropout rate and with the number inflated to ensure balance across the treatment sequences the primary efficacy analysis was performed on a modified intent - to - treat population that included all randomized patients who received at least one dose of study drug ( the modification was that patients were analyzed according to treatment received in each treatment period ) . the safety population , which was used in the analysis of all safety variables , included all patients who received at least one dose of study drug . the primary efficacy variable , fev1 at five minutes postdose , was analyzed using a mixed model , with treatment group and period modeled as fixed effects , patient as a random effect , and period baseline fev1 as a covariate . period baseline fev1 was defined as the average of the fev1 values measured 50 and 15 minutes prior to study drug administration in each treatment period . for the primary variable , estimated least squares means and treatment differences with associated 95% confidence intervals ( cis ) are presented . a multiplicity adjustment for the two main treatment comparisons in the study was made using a step - down dunnett s test implemented in a closed test procedure . similar mixed - effect models were used to analyze fev1 at the other time points . the proportion of patients with at least a 10% , 12% , and 15% increase in fev1 from baseline at each scheduled time point , and the proportion of patients with at least a 12% and 200 ml increase in fev1 from baseline at each scheduled time point , were summarized using descriptive statistics and analyzed by logistic regression for each time point . the logistic regression model included terms for period , treatment , and period baseline as fixed effects and patient as a random effect . the estimated odds ratios are presented along with the associated 95% cis and p values . all analyses were performed using sas statistical software ( version 9.1.3 for windows ; sas institute inc . , patients of either gender , aged 40 years , with moderate - to - severe copd ( according to the gold 2005 guideline ) , smoking history of 20 pack years , postbronchodilator forced expiratory volume in one second ( fev1 ) 30% but < 80% of the predicted normal value , and postbronchodilator fev1/forced vital capacity ( fvc ) < 70% were eligible for enrolment in the study . patients were excluded from the study if they had any concomitant pulmonary disease , type i diabetes or uncontrolled type ii diabetes , uncontrolled hypertension , unstable ischemic heart disease , or malignancy . patients who had a history of asthma , had been hospitalized for a copd exacerbation within six weeks prior to screening or during the run - in period , or had experienced respiratory tract infection within six weeks prior to screening , were also excluded . the following medications were prohibited at any time during the study ( the minimum washout period is shown in brackets ) : long - acting anticholinergics ( seven days ) , short - acting anticholinergics ( eight hours ) , fixed - dose combination of a 2-agonist and an inhaled corticosteroid ( ics , 48 hours ) , fixed - dose combination of a short - acting 2-agonist and a short - acting anticholinergic ( eight hours ) , other labas ( 48 hours ) , short - acting 2-agonists ( other than those prescribed in the study , six hours ) , xanthine derivatives ( one week ) , and parenteral or oral corticosteroids ( one month ) . patients on fixed - dose combinations of a 2-agonist and an ics were to be switched to the equivalent ics prior to the runin period , with the dose and dosage regimen to remain unchanged for the duration of the study . patients on ics at the screening visit were to continue ics for the duration of the study , again at a dose and regimen to remain unchanged . the study comprised a prescreening visit , a 14-day screening / run - in period , and five single - dose treatment periods . during the prescreening visit , patients ongoing copd medications were reviewed and , if necessary , any prohibited medication was adjusted to an allowable copd therapy . after the screening visit , patients entered into a 14-day run - in period , during which their eligibility was assessed . at baseline , patients were randomized equally ( using a validated automated system ) to one of five treatment sequences to receive indacaterol 150 g and 300 g delivered via a single - dose dry powder inhaler , salbutamol 200 g via the manufacturer s proprietary multidose dry powder inhaler , salmeterol - fluticasone 50/500 g fixed - dose combination via the manufacturer s proprietary multidose dry powder inhaler , and placebo . each treatment sequence comprised five double - blind , single - dose treatment periods , with treatment periods separated by a 4- to 7-day washout period . at 47 days after the last treatment visit patients inhaled through three different devices on each visit ( one inhalation from a single - dose dry powder inhaler and one from each of the two multidose dry powder inhalers used in the study ) , with the order of devices randomly assigned at the start of the study . treatment allocation was concealed from the patients , investigating staff , and the clinical trial team by the use of matching placebo inhalers all identical in packaging , labeling , and schedule of administration . an unblinded pharmacist ( or designee ) prepared the individual patient - specific packs from supplied bulk medication . salbutamol was the only rescue medication permitted throughout the study , although visits had to be rescheduled if salbutamol was taken within six hours prior to the start of the visit . all efficacy evaluations were based on spirometric assessment of lung function , performed at 50 and 15 minutes predose and at 5 , 15 , and 30 minutes , and at 1 and 2 hours postdose . the postdose time was measured from the time the first device was used at each study visit ( the three devices were used in a randomized order , as described above ) . all spirometry equipment and spirometric testing were in accordance with the american thoracic society / european respiratory society standards.13 the primary efficacy variable was fev1 at five minutes postdose . the primary objective was to compare indacaterol 150 and 300 g and placebo in terms of fev1 at five minutes postdose . the secondary objectives were to compare indacaterol 150 and 300 g with salbutamol 200 g and salmeterol - fluticasone 50/500 g , and to compare salmeterol - fluticasone 50/500 g with salbutamol 200 g in terms of fev1 at five minutes postdose . the other efficacy variables were fev1 at other scheduled time points ; the proportion of patients with at least 10% , 12% , and 15% increase in fev1 from baseline to each scheduled time point ; and the proportion of patients with at least a 12% and 200 ml increase in fev1 from baseline to each scheduled time point . safety assessments included recording of adverse events and serious adverse events , along with evaluation of their severity , duration , and relationship to study drug . in addition , samples were collected for hematology and blood chemistry ( including serum potassium and blood glucose ) , and vital signs and electrocardiogram assessments were recorded . all efficacy evaluations were based on spirometric assessment of lung function , performed at 50 and 15 minutes predose and at 5 , 15 , and 30 minutes , and at 1 and 2 hours postdose . the postdose time was measured from the time the first device was used at each study visit ( the three devices were used in a randomized order , as described above ) . all spirometry equipment and spirometric testing were in accordance with the american thoracic society / european respiratory society standards.13 the primary efficacy variable was fev1 at five minutes postdose . the primary objective was to compare indacaterol 150 and 300 g and placebo in terms of fev1 at five minutes postdose . the secondary objectives were to compare indacaterol 150 and 300 g with salbutamol 200 g and salmeterol - fluticasone 50/500 g , and to compare salmeterol - fluticasone 50/500 g with salbutamol 200 g in terms of fev1 at five minutes postdose . the other efficacy variables were fev1 at other scheduled time points ; the proportion of patients with at least 10% , 12% , and 15% increase in fev1 from baseline to each scheduled time point ; and the proportion of patients with at least a 12% and 200 ml increase in fev1 from baseline to each scheduled time point . safety assessments included recording of adverse events and serious adverse events , along with evaluation of their severity , duration , and relationship to study drug . in addition , samples were collected for hematology and blood chemistry ( including serum potassium and blood glucose ) , and vital signs and electrocardiogram assessments were recorded . it was estimated that 53 patients were needed to complete the study , assuming a difference of 120 ml between each indacaterol dose and placebo in terms of fev1 at five minutes postdose , a standard deviation of 240 ml , a two - sided significance level of 5% ( adjusted to 2.5% using a bonferroni correction for the two main treatment comparisons , that is , indacaterol [ 150 and 300 g ] versus placebo ) , and a power of 90% . as there were five treatment sequences and six inhaler orders for individual treatment sequences , a total of 60 patients with evaluable measurements were required in order to have an equal number of patients per inhaler order and per treatment sequence . allowing for a 15% dropout rate and with the number inflated to ensure balance across the treatment sequences , it was calculated that 75 patients needed to be randomized . the primary efficacy analysis was performed on a modified intent - to - treat population that included all randomized patients who received at least one dose of study drug ( the modification was that patients were analyzed according to treatment received in each treatment period ) . the safety population , which was used in the analysis of all safety variables , included all patients who received at least one dose of study drug . the primary efficacy variable , fev1 at five minutes postdose , was analyzed using a mixed model , with treatment group and period modeled as fixed effects , patient as a random effect , and period baseline fev1 as a covariate . period baseline fev1 was defined as the average of the fev1 values measured 50 and 15 minutes prior to study drug administration in each treatment period . for the primary variable , estimated least squares means and treatment differences with associated 95% confidence intervals ( cis ) are presented . a multiplicity adjustment for the two main treatment comparisons in the study was made using a step - down dunnett s test implemented in a closed test procedure . similar mixed - effect models were used to analyze fev1 at the other time points . the proportion of patients with at least a 10% , 12% , and 15% increase in fev1 from baseline at each scheduled time point , and the proportion of patients with at least a 12% and 200 ml increase in fev1 from baseline at each scheduled time point , were summarized using descriptive statistics and analyzed by logistic regression for each time point . the logistic regression model included terms for period , treatment , and period baseline as fixed effects and patient as a random effect . the estimated odds ratios are presented along with the associated 95% cis and p values . all analyses were performed using sas statistical software ( version 9.1.3 for windows ; sas institute inc . , cary , nc ) . all eligible patients were randomized to treatment sequences , and no patient received the study drug in error ; thus , the safety population was identical to the modified intent - to - treat population . eighty - six ( 96.6% ) patients completed the study , while three ( 3.4% ) patients discontinued from the study ( one each due to withdrawal of consent , loss to follow - up , and protocol deviation ) . more than half of the patients ( 61.8% ) were aged < 65 years , the majority was caucasian , and more than half were male . for the primary efficacy variable ( fev1 at five minutes postdose ) , the least squares mean values for indacaterol 150 and 300 g were higher than that for placebo by 100 and 120 ml , respectively ( p < 0.001 , figures 1 and 2 ) . both indacaterol doses showed a numerically higher fev1 at five minutes postdose than salbutamol ( differences of 10 and 30 ml for indacaterol 150 and 300 g , respectively , versus salbutamol , figure 2 ) . moreover , both indacaterol doses produced significantly higher fev1 at five minutes postdose than salmeterol - fluticasone ( 50 ml , p = 0.003 and 70 ml , p < 0.001 , figure 2 ) . both indacaterol doses showed significantly higher fev1 than placebo ( p < 0.001 ) at all postdose time points , significantly higher than salmeterol - fluticasone ( p < 0.05 ) at five and 15 minutes postdose , and numerically ( 150 g ) or statistically ( 300 g ) higher than salmeterol - fluticasone at 30 minutes postdose ( figure 4 ) . the difference between indacaterol 300 g and salbutamol was statistically significant at two hours postdose ( p < 0.001 ) . the proportion of patients with at least a 10% , 12% , or 15% increase in fev1 from baseline at five minutes postdose was higher in both indacaterol groups compared with salmeterol - fluticasone ( p < 0.01 ) , and similar to salbutamol ( table 2 ) . at 30 minutes postdose , the proportion of patients with at least a 10% , 12% , or 15% increase in fev1 was higher in both indacaterol groups compared with placebo , with the proportions in the indacaterol 300 g group higher than those in the salmeterol - fluticasone group ( table 3 ) . the proportion was also higher in both indacaterol groups than placebo at five and 15 minutes , and at one and two hours postdose ( p < 0.001 for all ) . the proportions of patients with at least a 12% and 200 ml increase in fev1 from baseline at five minutes postdose in the indacaterol 150 g , indacaterol 300 g , and salbutamol 200 g groups were higher than that in the salmeterol - fluticasone 50/500 g and placebo groups ( p < 0.05 for all , figure 5 ) . overall , adverse events were reported in 3/86 ( 3.5% ) , 3/87 ( 3.4% ) , 4/86 ( 4.7% ) , 6/88 ( 6.8% ) , and 4/87 ( 4.6% ) patients taking indacaterol 150 g , indacaterol 300 g , salbutamol 200 g , salmeterol - fluticasone 50/500 g , and placebo , respectively . all reported adverse events were mild or moderate in severity , and none were suspected of being related to study drug . notably , high pulse rate ( > 90 beats per minute ) and systolic blood pressure ( > 140 mmhg ) were more frequently reported for patients taking placebo than for those taking indacaterol . no patient in the study had an absolute corrected qt ( fridericia s ) value of > 500 msec or a change from baseline of 60 msec . furthermore , no patient had newly occurring or worsening clinically notable values for serum potassium ( minimum postbaseline value < 3.0 mmol / l ) during this study , and only three patients ( one patient each who took indacaterol 150 and 300 g and salmeterol - fluticasone 50/500 g ) had newly occurring or worsening of clinically notable values for blood glucose ( maximum postbaseline value > 9.99 mmol / l ) . all eligible patients were randomized to treatment sequences , and no patient received the study drug in error ; thus , the safety population was identical to the modified intent - to - treat population . eighty - six ( 96.6% ) patients completed the study , while three ( 3.4% ) patients discontinued from the study ( one each due to withdrawal of consent , loss to follow - up , and protocol deviation ) . more than half of the patients ( 61.8% ) were aged < 65 years , the majority was caucasian , and more than half were male . for the primary efficacy variable ( fev1 at five minutes postdose ) , the least squares mean values for indacaterol 150 and 300 g were higher than that for placebo by 100 and 120 ml , respectively ( p < 0.001 , figures 1 and 2 ) . both indacaterol doses showed a numerically higher fev1 at five minutes postdose than salbutamol ( differences of 10 and 30 ml for indacaterol 150 and 300 g , respectively , versus salbutamol , figure 2 ) . moreover , both indacaterol doses produced significantly higher fev1 at five minutes postdose than salmeterol - fluticasone ( 50 ml , p = 0.003 and 70 ml , p < 0.001 , figure 2 ) . both indacaterol doses showed significantly higher fev1 than placebo ( p < 0.001 ) at all postdose time points , significantly higher than salmeterol - fluticasone ( p < 0.05 ) at five and 15 minutes postdose , and numerically ( 150 g ) or statistically ( 300 g ) higher than salmeterol - fluticasone at 30 minutes postdose ( figure 4 ) . the difference between indacaterol 300 g and salbutamol was statistically significant at two hours postdose ( p < 0.001 ) . the proportion of patients with at least a 10% , 12% , or 15% increase in fev1 from baseline at five minutes postdose was higher in both indacaterol groups compared with salmeterol - fluticasone ( p < 0.01 ) , and similar to salbutamol ( table 2 ) . at 30 minutes postdose , the proportion of patients with at least a 10% , 12% , or 15% increase in fev1 was higher in both indacaterol groups compared with placebo , with the proportions in the indacaterol 300 g group higher than those in the salmeterol - fluticasone group ( table 3 ) . the proportion was also higher in both indacaterol groups than placebo at five and 15 minutes , and at one and two hours postdose ( p < 0.001 for all ) . the proportions of patients with at least a 12% and 200 ml increase in fev1 from baseline at five minutes postdose in the indacaterol 150 g , indacaterol 300 g , and salbutamol 200 g groups were higher than that in the salmeterol - fluticasone 50/500 g and placebo groups ( p < 0.05 for all , figure 5 ) . overall , adverse events were reported in 3/86 ( 3.5% ) , 3/87 ( 3.4% ) , 4/86 ( 4.7% ) , 6/88 ( 6.8% ) , and 4/87 ( 4.6% ) patients taking indacaterol 150 g , indacaterol 300 g , salbutamol 200 g , salmeterol - fluticasone 50/500 g , and placebo , respectively . all reported adverse events were mild or moderate in severity , and none were suspected of being related to study drug . notably , high pulse rate ( > 90 beats per minute ) and systolic blood pressure ( > 140 mmhg ) were more frequently reported for patients taking placebo than for those taking indacaterol . no patient in the study had an absolute corrected qt ( fridericia s ) value of > 500 msec or a change from baseline of 60 msec . furthermore , no patient had newly occurring or worsening clinically notable values for serum potassium ( minimum postbaseline value < 3.0 mmol / l ) during this study , and only three patients ( one patient each who took indacaterol 150 and 300 g and salmeterol - fluticasone 50/500 g ) had newly occurring or worsening of clinically notable values for blood glucose ( maximum postbaseline value > 9.99 mmol / l ) . as with many chronic conditions , adherence to treatment is low in copd , which is perhaps a reflection of the high rate of comorbid conditions and consequent polypharmacy . although indacaterol is being developed for maintenance treatment of copd , and not as rescue medication , fast onset on the first dose may help patients perceive an immediate symptomatic benefit . this , together with the sustained 24-hour duration of bronchodilation14 and a good overall safety and tolerability profile,12 which have been observed in other indacaterol clinical studies , may lead to improved patient adherence.15 this study was therefore designed to compare the onset of action of single doses of indacaterol 150 and 300 g with salbutamol , salmeterol - fluticasone , and placebo . the study was conducted as planned , with 96.6% of randomized patients completing their assigned treatments . for the primary efficacy variable ( fev1 at five minutes postdose ) , both indacaterol doses were superior to placebo , with treatment placebo differences of 100 and 120 ml for the 150 and 300 g doses , respectively . such differences ( ie , 100 ml ) have been described as ones that patients can perceive , and therefore can be considered clinically relevant.16 furthermore , the bronchodilator efficacy of both indacaterol doses at this time point was similar to that observed with salbutamol , the gold standard fast - acting rescue medication . both indacaterol doses were statistically superior to placebo for the four other measures of onset of action , ie , the proportion of patients with at least a 10% , 12% , or 15% increase from baseline , or at least a 12% and 200 ml increase from baseline . the bronchodilator efficacy was at least as good as salbutamol for all of these endpoints , with the higher indacaterol dose ( 300 g ) reaching statistical significance versus salbutamol for some endpoints . the second active comparator selected for this study was the fixed - dose combination of salmeterol and fluticasone . both indacaterol doses demonstrated a faster onset of action than salmeterol - fluticasone , with treatment placebo differences in fev1 at five minutes postdose of 50 ml with salmeterol - fluticasone , compared with the 100120 ml seen with indacaterol . in other studies , the combination of salmeterol and fluticasone has been shown to provide better efficacy ( even after a single dose ) than salmeterol alone.17 it is notable , therefore , that in the current study in addition to faster onset of action , both indacaterol doses demonstrated bronchodilator efficacy at least as good as salmeterol - fluticasone for the remainder of the two - hour assessment period . there was a low incidence of adverse events , all of which were mild or moderate in severity and not suspected of being related to the study drug , as expected in a single - dose study . there were no serious adverse events or significant adverse events reported and no clinically meaningful differences between the treatments with respect to the numbers and types of adverse events reported . the overall safety data collected indicate that single doses of indacaterol 150 and 300 g have a good overall safety profile . single doses of indacaterol 150 and 300 g demonstrated a fast onset of action , similar to that of salbutamol and faster than that of salmeterol - fluticasone .

background : indacaterol is a novel , inhaled once - daily ultra - long - acting 2-agonist for the treatment of chronic obstructive pulmonary disease ( copd).objectives : this study compared the onset of action of single doses of indacaterol 150 and 300 g with salbutamol 200 g , salmeterol - fluticasone 50/500 g , and placebo in moderate - to - severe copd patients.methods:this was a multicenter , randomized , double - blind , placebo - controlled crossover study . the primary variable was forced expiratory volume in one second ( fev1 ) at five minutes postdose.results:out of 89 patients randomized ( mean age 62 years ) , 86 completed the study . at five minutes postdose , both indacaterol doses were statistically and clinically superior to placebo ( p < 0.001 ) , with treatment placebo differences in fev1 of 100 ( 95% confidence interval [ ci ] 70130 ) ml and 120 ( 95% ci 90150 ) ml for indacaterol 150 and 300 g , respectively . fev1 at five minutes postdose with both indacaterol doses was numerically higher than for salbutamol ( 10 and 30 ml for indacaterol 150 and 300 g , respectively ) and significantly higher than for salmeterol - fluticasone ( 50 ml , p = 0.003 ; 70 ml , p < 0.001 , respectively ) . moreover , both indacaterol doses showed significantly higher fev1 than placebo ( p < 0.001 ) at all postdose time points . the numbers of patients with an fev1 increase of at least 12% and 200 ml at five minutes postdose were 16 ( 18.8% ) , 24 ( 27.6% ) , 20 ( 23.3% ) , 8 ( 9.1% ) , and 3 ( 3.4% ) for indacaterol 150 and 300 g , salbutamol 200 g , salmeterol - fluticasone 50/500 g , and placebo , respectively.conclusions:single doses of indacaterol 150 and 300 g demonstrated a fast onset of action similar to that for salbutamol and faster than that for salmeterol - fluticasone .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Veterans' Major Medical Facilities Construction Act of 2002''. SEC. 2. AUTHORIZATION OF MAJOR MEDICAL FACILITY PROJECTS. The Secretary of Veterans Affairs may carry out the following major medical facility projects, with each project to be carried out in an amount not to exceed the amount specified for that project: (1) Seismic corrections at the Department of Veterans Affairs Medical Center, Palo Alto, California, as follows: (A) Building Number 2, $14,020,000. (B) Building Number 4, $21,750,000. (2) Seismic correction at the Department of Veterans Affairs Medical Center, San Francisco, California, $31,000,000. (3) Seismic correction at the Department of Veterans Affairs Medical Center, West Los Angeles, California, $27,200,000. (4) Seismic correction and clinical improvement at the Department of Veterans Affairs Medical Center, Long Beach, California, $24,600,000. (5) Seismic correction for Building Number 1 at the Department of Veterans Affairs Medical Center, San Diego, California, $47,100,000. (6) Ambulatory Surgery and Clinical Consolidation at the Department of Veterans Affairs Medical Center, Cleveland, Ohio, $32,500,000. (7) Consolidation of Department of Veterans Affairs and Department of Defense health and benefits offices, Anchorage Alaska, $59,000,000. (8) Ward Renovation at the Department of Veterans Affairs Medical Center, West Haven, Connecticut, $15,300,000. (9) Ambulatory Care Expansion at the Department of Veterans Affairs Medical Center, Tampa, Florida, $18,230,000. SEC. 3. AUTHORIZATION OF A MAJOR MEDICAL FACILITY LEASE. The Secretary of Veterans Affairs may enter into a lease for a Satellite Outpatient Clinic, Charlotte, North Carolina, in an amount not to exceed $2,626,000. SEC. 4. AUTHORIZATION OF APPROPRIATIONS. (a) In General.--There is authorized to be appropriated to the Secretary of Veterans Affairs for fiscal year 2003-- (1) for the Construction, Major Projects, account $285,000,000 for the projects authorized in section 2; and (2) for the Medical Care account, $2,626,000 for the lease authorized in section 3. (b) Limitation.--The projects authorized in section 2 may only be carried out using-- (1) funds appropriated for fiscal year 2003 pursuant to the authorization of appropriations in subsection (a); (2) funds appropriated for Construction, Major Projects, for a fiscal year before fiscal year 2003 that remain available for obligation; and (3) funds appropriated for Construction, Major Projects, for fiscal year 2003 for a category of activity not specific to a project. SEC. 5. INCREASE IN THRESHOLD FOR MAJOR MEDICAL FACILITY CONSTRUCTION PROJECTS. (a) Increase in Threshold.--Section 8104(a)(3)(A) of title 38, United States Code, is amended by striking ``$4,000,000'' and inserting ``$6,000,000''. (b) Applicability to Projects Already Funded.--The amendment made by subsection (a) shall apply with respect to any facility project of the Department of Veterans Affairs, except for a project for which the Secretary obligated funds before October 1, 2002. SEC. 6. CRITERIA FOR MINOR CONSTRUCTION PROJECTS. Section 8103 of title 38, United States Code, is amended by adding at the end the following new subsection: ``(e) Purpose of Minor Construction Projects.--In selecting medical facilities (including research facilities) for projects under subsection (a) other than major medical facility projects subject to section 8104 of this title, the Secretary shall, to the extent practicable, select projects to improve, replace, renovate, or update facilities to achieve one or more of the following: ``(1) Seismic protection improvements related to patient safety (or, in the case of a research facility, patient or employee safety). ``(2) Fire safety improvements. ``(3) Improvements to utility systems and ancillary patient care facilities (including such systems and facilities that may be exclusively associated with research facilities). ``(4) Improved accommodation for persons with disabilities, including barrier-free access. ``(5) Improvements at patient care facilities to specialized programs of the Department, including the following: ``(A) Blind rehabilitation centers. ``(B) Inpatient and residential programs for seriously mentally ill veterans, including mental illness research, education, and clinical centers. ``(C) Residential and rehabilitation programs for veterans with substance-use disorders. ``(D) Physical medicine and rehabilitation activities. ``(E) Long-term care, including geriatric research, education, and clinical centers, adult day care centers, and nursing home care facilities. ``(F) Amputation care, including facilities for prosthetics, orthotics programs, and sensory aids. ``(G) Spinal cord injury centers. ``(H) Traumatic brain injury programs. ``(I) Women veterans' health programs (including particularly programs involving privacy and accommodation for female patients). ``(J) Facilities for hospice and palliative care programs.''. Passed the House of Representatives May 21, 2002. Attest: JEFF TRANDAHL, Clerk.

Veterans' Major Medical Facilities Construction Act of 2002 - Authorizes the Secretary of Veterans Affairs to carry out specified major medical facility projects in California, Ohio, Alaska, Connecticut, and Florida, in specified amounts.Authorizes the Secretary to enter into a lease for a satellite outpatient clinic in Charlotte, North Carolina, in a specified amount.Authorizes appropriations for FY 2003 for the Construction, Major Projects, account and the Medical Care account.Increases from $4 million to $6 million the major medical facility project threshold.Directs the Secretary, in selecting medical facilities for projects other than major medical facility projects, to the extent practicable, to select projects to improve, replace, renovate, or update facilities to achieve one or more specified purposes, including improvements in: (1) seismic protection related to patient safety; (2) fire safety; (3) utility systems and ancillary patient care facilities; (4) accommodation for person with disabilities; and (5) patient care facilities to specialized programs of the Department of Veterans Affairs.

SECTION 1. COMMISSION REGULATIONS RELATING TO ASSET-BACKED SECURITIES FOR PURPOSES OF NRSRO RATINGS. (a) NRSRO Asset-Backed Securities.--Section 3(a)(62)(B)(iv) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(62)(B)(iv)) is amended by striking ``as in effect on the date of enactment of this Act'' and inserting ``, including NRSRO asset-backed securities approved by the Commission and listed in such section''. (b) Revision of Regulations.--Not later than 180 days after the date of enactment of this Act, the Securities and Exchange Commission shall revise the regulations in section 1101(c) of part 229 of title 17, Code of Federal Regulations, relating to the term ``asset-backed securities'' for purposes of section 3(a)(62)(B)(iv) of the Securities Exchange Act of 1934 (15 U.S.C. 78c(a)(62)(B)(iv)). The revisions required under this subsection shall-- (1) define a subset of asset-back securities to be referred to as ``NRSRO asset-backed securities'', which shall be the only asset-backed securities for which a credit rating agency may register and issue ratings as a nationally recognized statistical rating organization and, which shall be restricted to securities representing interests in pools of assets whose performance can be evaluated based on a documented history of predictable performance of similar assets and which are contained in structures which also have a documented history of predictable performance; and (2) include a list of the classes of securities approved as NRSRO asset-backed securities pursuant to subsection (c). Nothing in this subsection shall be construed so as to limit any credit rating agency from rating asset-backed instruments which are not designated as ``NRSRO asset-backed securities'' so long as such credit rating agency makes it explicit that such instruments are not NRSRO asset-backed securities and the associated ratings are not issued pursuant to its status as a nationally recognized statistical rating organization. (c) Approval Process for NRSRO Asset-Backed Securities Classes.-- (1) Initial fast-track approval.--Not later than 90 days after the date of enactment of this Act, the Securities and Exchange Commission shall establish an initial list of classes of securities approved as NRSRO asset-backed securities. (2) Subsequent approval.--After the approval of the initial list of classes of NRSRO asset-backed securities under paragraph (1), the Commission shall approve additional classes of asset-backed securities as NRSRO asset-backed securities on an ongoing basis. (3) Procedure.--The Commission shall approve a securities class as NRSRO asset-backed securities only-- (A) upon the application (in such form determined by the Commission) of a nationally recognized statistical rating organization concerning a specific class of asset-backed securities; (B) after receiving comment from Federal and State regulators of institutions or entities reasonably expected to seek funding from or invest in such class of securities, including the Federal Reserve System, the Office of the Comptroller of the Currency, the Office of Thrift Supervision, the Federal Deposit Insurance Corporation, the Pension Benefit Guaranty Insurance Corporation, and State banking insurance authorities; and (C) after any other investigation and due diligence the Commission determines to be necessary to evaluate the proposed NRSRO asset-backed securities class's compliance with the standards described in paragraph (4) prior to granting their approval. (4) Standards for approval of nrsro asset-backed securities.--Approval of a class of securities as an NRSRO asset-backed securities class shall be limited to those securities whose future performance meets the standard of ``reasonably predictable''. At a minimum, a determination of a reasonably predictable performance standard shall require-- (A) a sufficient history of performance data, from a diverse base of sponsors spanning at least 1 complete economic cycle for both the collateral assets or reference assets and the structure so as to generate reasonably accurate statistical estimates of future performance; (B) the ability to aggregate pools of the collateral assets or reference assets of sufficient size to generate reasonably accurate statistical estimates; (C) the existence of contracts for such collateral asset product which are sufficiently standardized to generate reasonably accurate statistical estimates; and (D) sufficient standardization of service quality and procedures for such collateral asset product to generate reasonably accurate statistical estimates. Securities that fail to meet 1 or more of conditions set forth in subparagraphs (A) through (D) shall not qualify for eligibility as NRSRO asset-backed securities or ratings. SEC. 2. QUALIFICATIONS FOR REGISTRATION. Section 15E of the Securities Exchange Act (15 U.S.C. 78o-7) is amended-- (1) in subsection (c), by redesignating paragraph (2) as paragraph (3) and inserting after paragraph (1) the following: ``(2) Review of ratings and cooperation with commission.-- In order to maintain its registration and the integrity of the NRSRO ratings system, a nationally recognized statistical rating organization shall annually review all ratings issued and outstanding in obligor categories for which it has registered, with such review to result in a formal re-rating affirmation, upgrade, downgrade, or ratings removal. Each nationally recognized statistical rating organization shall provide the Commission with full access to models, documentation, assumptions, and performance data upon request, shall answer all questions and queries posed by Commission on a timely basis, and otherwise cooperate with any Commission investigation.''; (2) in subsection (d), by striking ``The Commission'' and inserting ``(1) In general.--The Commission''; (3) by redesignating paragraphs (1) through (5) as subparagraphs (A) through (E), respectively; and (4) by adding a new subparagraph (F) as follows: ``(F) has, in the course of an investigation into the integrity of its NRSRO ratings caused the Commission to believe that a suspension or revocation of its NRSRO registration is in the public interest.''. (5) by adding at the end the following: ``(2) Determination and examination by commission.--In assessing whether a nationally recognized statistical rating organization is consistently producing credit ratings with integrity for purposes of paragraph (5), the Commission shall determine whether ratings are issued with the expectation of meeting aggregate historical loss and default standards for given ratings levels across all categories for which a credit rating agency has registered under this section. In the case of a nationally recognized statistical rating organization which has registered for a category or categories for which its ratings experience covers less than a full economic cycle, the standards shall be consistent with industry norms for such category or categories. Additionally, as part of the ongoing qualification of NRSROs, adherence to the foregoing provisions shall be evaluated through the Commission's regular surveillance of NRSRO models, systems, assumptions, and performance.''.

Amends the Securities Exchange Act of 1934 to direct the Securities and Exchange Commission (SEC) to revise regulations relating to "asset-backed securities" to define an "NRSRO asset-backed securities" subset, which shall: (1) be the only asset-backed securities for which a credit rating agency may register and issue ratings as a nationally recognized statistical rating organization (NRSRO); and (2) be restricted to securities representing interests in pools of assets whose performance can be evaluated based on a documented history of predictable performance of similar assets, and which are contained in structures which also have a documented history of predictable performance. Requires the revision of such regulations to include a list of the classes of securities approved as NRSRO asset-backed securities. Prescribes an approval process for NRSRO asset-backed securities classes, including approval standards. Requires an NRSRO to: (1) review annually all ratings issued and outstanding in obligor categories for which it has registered; (2) formally affirm, upgrade, downgrade, or remove ratings based on such review; and (3) provide the SEC with full access to models, documentation, assumptions and performance data upon request, answer all questions posed by the SEC, and cooperate with any SEC investigation. Directs the SEC to determine whether ratings are issued with the expectation of meeting aggregate historical loss and default standards for given ratings levels across all categories for which a credit rating agency has registered.

copd is a chronic respiratory disease that is characterized by an airflow limitation that is not fully reversible.1 it is a leading cause of morbidity and mortality worldwide.2 since the 1970s , it has been widely accepted that copd patients show an accelerated and progressive decline in forced expiratory volume in 1 second ( fev1).3 nevertheless , recent studies have revealed that the rate of decline in fev1 varies among individual patients.4,5 another important feature of copd is lung hyperinflation , which is caused by emphysematous parenchymal destruction and expiratory flow limitation.6 it has been shown that lung hyperinflation contributes to symptoms , exercise intolerance , acute exacerbations , and mortality.79 although some studies assessed the rate of decline in fev1 , data illustrating the process of lung hyperinflation development and progression over time are rare.1,35,10 although it is assumed that lung hyperinflation may progress as fev1 declines over time , the longitudinal changes in lung volumes have not been studied in detail . additionally , the relationship between the changes in the degree of lung hyperinflation and the decline in fev1 is not clear . thus , we evaluated the longitudinal changes in the degree of lung hyperinflation and the determinants of this change in copd patients . in addition , we attempted to explore the relationship between the rate of change in lung hyperinflation and the rate of decline in fev1 . patients were selected from the korean obstructive lung disease ( kold ) cohort , a prospective longitudinal observational study consisting of patients with copd or asthma recruited from 17 hospitals in south korea since 2005 . the inclusion and exclusion criteria for participation in the kold cohort have previously been described.11 for this study , we selected only copd patients who had been followed up with annual lung volume measurements for 5 years or more . in these patients , copd was diagnosed according to the global initiative for chronic obstructive lung disease ( gold ) guideline.12 all patients provided written informed consent before enrollment . the study protocol was approved by the institutional review boards of seoul national university hospital ( h-0505 - 148 - 013 ) , seoul national university bundang hospital ( b-0508/023 - 009 ) , and all other participating centers . the evaluation and follow - up of patients in the kold cohort have been previously described.11,13 patients underwent spirometry with a bronchodilator test and measurement of lung volume on an annual basis . spirometry with a bronchodilator test was performed according to the recommendations of the american thoracic society ( ats ) and the european respiratory society ( ers ) , using the vmax 22 ( sensormedics , yorba linda , ca , usa ) or pf / dx ( medgraphics , saint paul , mn , usa).14 patients were asked not to use any long - acting bronchodilators in the 12 hours prior to testing.14 measurement of lung volume was conducted according to the recommendations of the ats and ers.15 body plethysmography , v6200 ( sensormedics ) or pf / dx ( medgraphics ) , was used for lung volume measurement . lung volume measurement was performed before the administration of a bronchodilator.15 briefly , functional residual capacity ( frc ) was measured while patients were performing a series of panting maneuvers against a closed shutter . following this , the shutter was opened and patients were instructed to perform an expiratory reserve volume maneuver , followed by slow inspiratory vital capacity ( vc ) maneuver . these sequential procedures enabled the calculation of residual volume ( rv ) and total lung capacity ( tlc).16 the percentage of the predicted values for the results of spirometry was calculated from equations developed with representative korean populations.17 as for lung volumes , the prediction equation from the european community for steel and coal was used , since it was shown to be the most suitable for korean populations.18,19 a quality assurance program was conducted to improve the reliability of pulmonary function tests when this cohort study was initiated . after enrollment , the respective physicians from each center treated patients and advised them to participate in the follow - up visits every 3 months . at each follow - up , patients reported any exacerbations . exacerbations were defined as an event of aggravation of copd symptoms ( ie , sputum , cough , or dyspnea ) beyond normal day - to - day variations , according to the gold guideline.20 in particular , severe exacerbations were defined as those leading to hospitalization , and two or more exacerbations per year on average were defined as frequent exacerbations.21 data were presented as mean with standard deviations ( sds ) for continuous variables with normal distribution or medians with interquartile ranges ( iqrs ) for those with non - normal distribution . differences between subgroups were analyzed using the student s t - test , mann whitney test , pearson s chi - square test , or fisher s exact test , as appropriate . a p - value of < 0.05 based on a two - tailed test was considered statistically significant . mixed - effect linear regressions were used for longitudinal analysis.22 to eliminate the effects of immediate improvements in patients who began treatment after enrollment , the data used for analysis were collected since 1 year after the study entry . therefore , lung function parameters obtained at 1 year after enrollment were regarded as baseline in statistical analysis . the mean annual rates of change in rv , tlc , inspiratory capacity ( ic ) , vc , and their ratios were estimated with a random intercept and a random slope model , using multiple covariates : baseline age , sex , smoking history , body mass index ( bmi ) , gold stage according to fev1 , diffusing capacity , exacerbations , and respiratory medications . to determine the effect of covariates on the annual rates of change in rv / tlc and ic / tlc , additionally , the rate of change in fev1 over time was determined with the same method . the best linear unbiased predictions of random effects were calculated to estimate the annual rates of change in rv / tlc , ic / tlc , and fev1 for each patient . patients were divided into two subgroups according to the mean annual rate of change in rv / tlc using a cut - off of zero : patients with an increasing rv / tlc over time ( change in rv / tlc 0 ) and those with a decreasing rv / tlc over time ( change in rv / tlc < 0 ) . the rate of change in fev1 was then compared between these two subgroups . for the sensitivity analysis , we repeated this comparison after dividing patients into three subgroups : those with a decreasing rv / tlc , a stable rv / tlc , or an increasing rv / tlc . statistical analyses were carried out using stata software version 14.0 ( statacorp , college station , tx , usa ) . patients were selected from the korean obstructive lung disease ( kold ) cohort , a prospective longitudinal observational study consisting of patients with copd or asthma recruited from 17 hospitals in south korea since 2005 . the inclusion and exclusion criteria for participation in the kold cohort have previously been described.11 for this study , we selected only copd patients who had been followed up with annual lung volume measurements for 5 years or more . in these patients , copd was diagnosed according to the global initiative for chronic obstructive lung disease ( gold ) guideline.12 all patients provided written informed consent before enrollment . the study protocol was approved by the institutional review boards of seoul national university hospital ( h-0505 - 148 - 013 ) , seoul national university bundang hospital ( b-0508/023 - 009 ) , and all other participating centers . the evaluation and follow - up of patients in the kold cohort have been previously described.11,13 patients underwent spirometry with a bronchodilator test and measurement of lung volume on an annual basis . spirometry with a bronchodilator test was performed according to the recommendations of the american thoracic society ( ats ) and the european respiratory society ( ers ) , using the vmax 22 ( sensormedics , yorba linda , ca , usa ) or pf / dx ( medgraphics , saint paul , mn , usa).14 patients were asked not to use any long - acting bronchodilators in the 12 hours prior to testing.14 measurement of lung volume was conducted according to the recommendations of the ats and ers.15 body plethysmography , v6200 ( sensormedics ) or pf / dx ( medgraphics ) , was used for lung volume measurement . lung volume measurement was performed before the administration of a bronchodilator.15 briefly , functional residual capacity ( frc ) was measured while patients were performing a series of panting maneuvers against a closed shutter . following this , the shutter was opened and patients were instructed to perform an expiratory reserve volume maneuver , followed by slow inspiratory vital capacity ( vc ) maneuver . these sequential procedures enabled the calculation of residual volume ( rv ) and total lung capacity ( tlc).16 the percentage of the predicted values for the results of spirometry was calculated from equations developed with representative korean populations.17 as for lung volumes , the prediction equation from the european community for steel and coal was used , since it was shown to be the most suitable for korean populations.18,19 a quality assurance program was conducted to improve the reliability of pulmonary function tests when this cohort study was initiated . after enrollment , the respective physicians from each center treated patients and advised them to participate in the follow - up visits every 3 months . at each follow - up , patients reported any exacerbations . exacerbations were defined as an event of aggravation of copd symptoms ( ie , sputum , cough , or dyspnea ) beyond normal day - to - day variations , according to the gold guideline.20 in particular , severe exacerbations were defined as those leading to hospitalization , and two or more exacerbations per year on average were defined as frequent exacerbations.21 data were presented as mean with standard deviations ( sds ) for continuous variables with normal distribution or medians with interquartile ranges ( iqrs ) for those with non - normal distribution . differences between subgroups were analyzed using the student s t - test , mann whitney test , pearson s chi - square test , or fisher s exact test , as appropriate . a p - value of < 0.05 based on a two - tailed test was considered statistically significant . mixed - effect linear regressions were used for longitudinal analysis.22 to eliminate the effects of immediate improvements in patients who began treatment after enrollment , the data used for analysis were collected since 1 year after the study entry . therefore , lung function parameters obtained at 1 year after enrollment were regarded as baseline in statistical analysis . the mean annual rates of change in rv , tlc , inspiratory capacity ( ic ) , vc , and their ratios were estimated with a random intercept and a random slope model , using multiple covariates : baseline age , sex , smoking history , body mass index ( bmi ) , gold stage according to fev1 , diffusing capacity , exacerbations , and respiratory medications . to determine the effect of covariates on the annual rates of change in rv / tlc and ic / tlc , the interaction of each covariate with time was assessed . additionally , the rate of change in fev1 over time was determined with the same method . the best linear unbiased predictions of random effects were calculated to estimate the annual rates of change in rv / tlc , ic / tlc , and fev1 for each patient . patients were divided into two subgroups according to the mean annual rate of change in rv / tlc using a cut - off of zero : patients with an increasing rv / tlc over time ( change in rv / tlc 0 ) and those with a decreasing rv / tlc over time ( change in rv / tlc < 0 ) . the rate of change in fev1 was then compared between these two subgroups . for the sensitivity analysis , we repeated this comparison after dividing patients into three subgroups : those with a decreasing rv / tlc , a stable rv / tlc , or an increasing rv / tlc . statistical analyses were carried out using stata software version 14.0 ( statacorp , college station , tx , usa ) . the median number of lung volume measurements in each patient was seven ( 5 in 46 , 6 in 35 , 7 in 39 , 8 in 31 , 9 in 22 , and 10 in three patients ) . most of the study patients were men , with a mean age of 65 years . no difference was found in the baseline fev1 according to the number of lung volume measurements . the mean values of rv / tlc and ic / tlc were 44.711.2% and 34.27.7% , respectively . at baseline measurement , rv / tlc showed a strong negative correlation with post - bronchodilator fev1 ( figure 1 ; r=0.644 , p<0.001 ) . ic / tlc also showed a significant correlation with post - bronchodilator fev1 ( r=0.541 , p<0.001 ) . patients were treated by attending physicians at each participating center ; this study did not provide any guidance on management . among the 176 patients , 137 patients ( 77.8% ) and 125 patients ( 71.0% ) were prescribed long - acting beta agonists and long - acting muscarinic antagonists , respectively . ninety patients ( 51.1% ) used both long - acting beta agonists and long - acting muscarinic antagonists . inhaled corticosteroids were prescribed for 137 patients ( 77.8% ) , and most of these were combined with long - acting beta agonists as fixed - dose combinations . the median follow - up period was 7 years ( iqr 58 years ) . during this time , 155 patients ( 88.1% ) experienced at least one exacerbation and 44 patients ( 25.0% ) experienced severe exacerbations requiring hospitalization . in each patient , the median number of exacerbations per year was 0.7 ( iqr 0.21.4 ) . twenty - seven patients ( 15.3% ) had frequent exacerbations ( two or more exacerbations per year on average ) . when compared to patients with infrequent exacerbations , those with frequent exacerbations had a significantly lower post - bronchodilator fev1 ( 1.420.47 vs 1.750.52 l , p=0.018 ) and rv / tlc ( 49.39.9% vs 43.811.2% , p=0.018 ) . in the longitudinal analysis of lung volumes , a decline in the mean rates of change in rv , vc , and tlc over time ( 39.5 , 24.2 , and 63.8 ml / year , respectively ) was noted . the between - subjects sd values for the rate of change in rv , vc , and tlc were 130.6 , 52.6 , and 106.9 ml / year , respectively . the mean rate of change in ic was also a decline of 49.6 ml / year . in order to adjust for the change in tlc , annual rates of change in rv / tlc , vc / tlc , and ic / tlc were analyzed . while the ic / tlc ratio declined by an average of 0.70%/year , the rv / tlc ratio tended not to increase but to decline by an average of 0.35%/year . vc / tlc increased by an average of 0.36%/year , which reflects the decline in rv / tlc over time . on an individual level , the annual rates of change in rv / tlc and ic / tlc varied significantly ( figures 2 and 3 ) . in 71 patients ( 40.3% ) , rv / tlc increased over time , and in 105 patients ( 59.7% ) , rv / tlc decreased over time . no significant differences were found in baseline pulmonary function parameters between these two subgroups . during the follow - up period , frequent exacerbations were significantly more common in patients with an increasing rv / tlc over time than in those with a decreasing rv / tlc over time ( 22.5% vs 10.5% , p=0.029 ) . we also compared the annual rates of change in rv , vc , and tlc between patients with an increasing rv / tlc and those with a decreasing rv / tlc and found significant differences ( all p<0.001 ) . in 71 patients who showed an increase in rv / tlc over time , the mean annual rates of change in rv and tlc were increases of 93.6 and 19.7 ml / year , respectively . however , in 105 patients who showed a decline in rv / tlc over time , both rv and tlc showed a decrease at a rate of 143.7 and 128.9 ml / year , respectively . vc decreased by 78.0 ml / year in patients with an increasing rv / tlc , and it increased by 16.9 ml / year in those with a decreasing rv / tlc . baseline demographic characteristics , smoking history , and pulmonary function had no significant effect on the annual rates of change in rv / tlc and ic / tlc . however , the exacerbations were significantly associated with the annual rates of change in these parameters ( table 3 ) . frequent exacerbations were significantly associated with the progression of hyperinflation in terms of both rv / tlc and ic / tlc . the rate of change in rv / tlc differed significantly between patients with frequent exacerbations and those with infrequent exacerbations ( 0.670.41%/year vs 0.540.18%/year , p=0.007 ) . furthermore , patients with frequent exacerbations showed a greater decline in ic / tlc ( 1.210.23%/year vs 0.590.11%/year , p=0.014 ) . treatment with different types of inhalers did not influence the rate of change in rv / tlc . none of the inhalers , including long - acting beta agonists , long - acting muscarinic antagonists , and inhaled corticosteroids , reduced the rate of decline in ic / tlc . in fact , patients who were prescribed long - acting muscarinic antagonists tended to have a faster decline in ic / tlc ( p=0.002 ) . in the total study group , the mean rate of decline in fev1 was 29.43.4 ml / year , and the between - subjects sd was 30.6 ml / year . when the rate of fev1 decline was compared according to the rate of change in rv / tlc , there was a significant difference in the fev1 decline rate relative to the change in rv / tlc over time , even after adjusting for other covariates . patients with an increasing rv / tlc had a fev1 decline rate of 54.24.5 ml / year . in contrast , the rate of fev1 decline in patients with a decreasing rv / tlc was 10.73.9 ml / year , which was significantly slower ( p<0.001 ) . additionally , we evaluated the correlation between the annual rates of change in fev1 and rv / tlc in each patient . a significant negative correlation was detected between the two ( figure 4 ; r=0.535 , p<0.001 ) . for the sensitivity analysis , we regrouped the patients into three subgroups : 63 patients showed a decline in rv / tlc over time ( annual rate of change in rv / tlc < 0.5%/year ; group 1 ) , 78 patients showed a stable rv / tlc over time ( 0.5%/year annual rate of change in rv / tlc < 0.5%/year ; group 2 ) , and 35 patients showed an increase in rv / tlc over time ( annual rate of change in rv / tlc 0.5%/year ; group 3 ) . the rate of fev1 decline was 6.34.9 ml / year in group 1 , 29.64.3 ml / year in group 2 , and 70.06.3 ml / year in group 3 . the median number of lung volume measurements in each patient was seven ( 5 in 46 , 6 in 35 , 7 in 39 , 8 in 31 , 9 in 22 , and 10 in three patients ) . most of the study patients were men , with a mean age of 65 years . no difference was found in the baseline fev1 according to the number of lung volume measurements . the mean values of rv / tlc and ic / tlc were 44.711.2% and 34.27.7% , respectively . at baseline measurement , rv / tlc showed a strong negative correlation with post - bronchodilator fev1 ( figure 1 ; r=0.644 , p<0.001 ) . ic / tlc also showed a significant correlation with post - bronchodilator fev1 ( r=0.541 , p<0.001 ) . patients were treated by attending physicians at each participating center ; this study did not provide any guidance on management . among the 176 patients , 137 patients ( 77.8% ) and 125 patients ( 71.0% ) were prescribed long - acting beta agonists and long - acting muscarinic antagonists , respectively . ninety patients ( 51.1% ) used both long - acting beta agonists and long - acting muscarinic antagonists . inhaled corticosteroids were prescribed for 137 patients ( 77.8% ) , and most of these were combined with long - acting beta agonists as fixed - dose combinations . the median follow - up period was 7 years ( iqr 58 years ) . during this time , 155 patients ( 88.1% ) experienced at least one exacerbation and 44 patients ( 25.0% ) experienced severe exacerbations requiring hospitalization . in each patient , the median number of exacerbations per year was 0.7 ( iqr 0.21.4 ) . twenty - seven patients ( 15.3% ) had frequent exacerbations ( two or more exacerbations per year on average ) . when compared to patients with infrequent exacerbations , those with frequent exacerbations had a significantly lower post - bronchodilator fev1 ( 1.420.47 vs 1.750.52 vs 2.730.92 l , p=0.018 ) and rv / tlc ( 49.39.9% vs 43.811.2% , p=0.018 ) . in the longitudinal analysis of lung volumes , a decline in the mean rates of change in rv , vc , and tlc over time ( 39.5 , 24.2 , and 63.8 ml / year , respectively ) was noted . the between - subjects sd values for the rate of change in rv , vc , and tlc were 130.6 , 52.6 , and 106.9 ml / year , respectively . the mean rate of change in ic was also a decline of 49.6 ml / year . in order to adjust for the change in tlc , annual rates of change in rv / tlc , vc / tlc , and ic / tlc were analyzed . while the ic / tlc ratio declined by an average of 0.70%/year , the rv / tlc ratio tended not to increase but to decline by an average of 0.35%/year . vc / tlc increased by an average of 0.36%/year , which reflects the decline in rv / tlc over time . on an individual level , the annual rates of change in rv / tlc and ic / tlc varied significantly ( figures 2 and 3 ) . in 71 patients ( 40.3% ) , rv / tlc increased over time , and in 105 patients ( 59.7% ) , rv / tlc decreased over time . no significant differences were found in baseline pulmonary function parameters between these two subgroups . during the follow - up period , frequent exacerbations were significantly more common in patients with an increasing rv / tlc over time than in those with a decreasing rv / tlc over time ( 22.5% vs 10.5% , p=0.029 ) . we also compared the annual rates of change in rv , vc , and tlc between patients with an increasing rv / tlc and those with a decreasing rv / tlc and found significant differences ( all p<0.001 ) . in 71 patients who showed an increase in rv / tlc over time , the mean annual rates of change in rv and tlc were increases of 93.6 and 19.7 ml / year , respectively . however , in 105 patients who showed a decline in rv / tlc over time , both rv and tlc showed a decrease at a rate of 143.7 and 128.9 ml / year , respectively . vc decreased by 78.0 ml / year in patients with an increasing rv / tlc , and it increased by 16.9 ml / year in those with a decreasing rv / tlc . baseline demographic characteristics , smoking history , and pulmonary function had no significant effect on the annual rates of change in rv / tlc and ic / tlc . however , the exacerbations were significantly associated with the annual rates of change in these parameters ( table 3 ) . frequent exacerbations were significantly associated with the progression of hyperinflation in terms of both rv / tlc and ic / tlc . the rate of change in rv / tlc differed significantly between patients with frequent exacerbations and those with infrequent exacerbations ( 0.670.41%/year vs 0.540.18%/year , p=0.007 ) . furthermore , patients with frequent exacerbations showed a greater decline in ic / tlc ( 1.210.23%/year vs 0.590.11%/year , p=0.014 ) . treatment with different types of inhalers did not influence the rate of change in rv / tlc . none of the inhalers , including long - acting beta agonists , long - acting muscarinic antagonists , and inhaled corticosteroids , reduced the rate of decline in ic / tlc . in fact , patients who were prescribed long - acting muscarinic antagonists tended to have a faster decline in ic / tlc ( p=0.002 ) . in the total study group , the mean rate of decline in fev1 was 29.43.4 ml / year , and the between - subjects sd was 30.6 ml / year . when the rate of fev1 decline was compared according to the rate of change in rv / tlc , there was a significant difference in the fev1 decline rate relative to the change in rv / tlc over time , even after adjusting for other covariates . patients with an increasing rv / tlc had a fev1 decline rate of 54.24.5 ml / year . in contrast , the rate of fev1 decline in patients with a decreasing rv / tlc was 10.73.9 ml / year , which was significantly slower ( p<0.001 ) . additionally , we evaluated the correlation between the annual rates of change in fev1 and rv / tlc in each patient . a significant negative correlation was detected between the two ( figure 4 ; r=0.535 , p<0.001 ) . for the sensitivity analysis , we regrouped the patients into three subgroups : 63 patients showed a decline in rv / tlc over time ( annual rate of change in rv / tlc < 0.5%/year ; group 1 ) , 78 patients showed a stable rv / tlc over time ( 0.5%/year annual rate of change in rv / tlc < 0.5%/year ; group 2 ) , and 35 patients showed an increase in rv / tlc over time ( annual rate of change in rv / tlc 0.5%/year ; group 3 ) . the rate of fev1 decline was 6.34.9 ml / year in group 1 , 29.64.3 ml / year in group 2 , and 70.06.3 ml / year in group 3 . lung hyperinflation is a key feature of copd , but data regarding the longitudinal change in lung hyperinflation have been scarce . second , a discrepancy was found in the rate of change in rv / tlc and ic / tlc . while ic / tlc declined over time , the mean trend of rv / tlc was not toward an increase . third , the rates of change in rv / tlc and ic / tlc , as markers of static hyperinflation , varied greatly between patients . unexpectedly , more than half of the patients showed a gradual decline in rv / tlc . finally , patients who had an increase in rv / tlc over time showed a significantly greater decline in fev1 . to our knowledge , this is the first study to show the association between changes in lung hyperinflation and changes in fev1 . although there has been increasing interest in lung hyperinflation in copd patients , no single standardized marker or criterion for hyperinflation has been established to date . dynamic hyperinflation is usually assessed by measuring ic repetitively during exercise.2325 however , there is no consensus on the method to define and measure static hyperinflation.26 recently , a few studies have used ic at resting state as an indicator of static hyperinflation , since it correlated well with subjective dyspnea , exercise intolerance , and mortality in copd patients.8,27,28 however , using only ic for defining static hyperinflation has limitations . patients with mild airway obstruction and a hyperinflated rv only can have an ic within the normal range . a recent cross - sectional study found that patients with copd of gold stage 1 had vc and ic within the normal ranges , but their rv and frc were increased.29 thus , we analyzed longitudinal changes in both rv / tlc and ic / tlc in order to capture evidence of early changes in lung hyperinflation . since copd is characterized by a progressive decline in fev1 and functional capacity , we presumed that rv / tlc would increase and ic / tlc would decrease over time in copd patients . a prospective study performed some decades ago showed that rv , tlc , and rv / tlc significantly increased over a period of 4 years among smokers , although the sample size was very small and they were non - copd patients.30 ic and ic / tlc have also been shown to decrease over time in copd patients.31,32 however , our results did not fully support these previous findings : while the ic / tlc ratio decreased over time , the rv / tlc ratio did not increase . rather , the rv / tlc ratio decreased by 0.35%/year . in accordance with this trend in the rv / tlc ratio , the vc / tlc ratio increased over time . the decline in lung volumes in our results could be explained by respiratory muscle dysfunction leading to insufficient inspiration.33 however , it is difficult to explain the decline in rv / tlc and increase in vc / tlc based only on respiratory muscle dysfunction . another possible explanation is the effect of selection bias . for a more reliable longitudinal analysis therefore , less severe patients may have been included , while more severe patients died early , and this selection bias may have brought the intriguing trend in lung hyperinflation . however , the baseline fev1 of patients in this study was 1.700.53 l , and they had an overall decline in fev1 at a rate of 29.4 ml / year . since this fev1 decline rate does not substantially differ from those recently reported in large - scale prospective studies , we believe that the results of our study are not simply due to less severity of disease.5,3436 in addition , our finding may result from the possible variability in measuring lung volumes . however , we performed plethysmographic lung volume measurements in qualified laboratories , and there was a quality assurance and feedback program when this cohort study was initiated . nevertheless , we can not exclude the variability in lung volume measurement as a possible source of bias . therefore , further studies should examine whether our findings can be reproduced in other copd cohorts . on an individual level , the rate of change in rv / tlc was particularly variable , ranging from 4.2 to 2.8%/year . considering a previous study that reported a minimal important difference of rv / tlc to be between 2.8% and 4.0% , the range of the annual rate of change in rv / tlc in our study seems considerable.37 interestingly , only 40% of the patients showed gradual increases in rv / tlc over time . these patients demonstrated more frequent exacerbations and a greater fev1 decline compared to the remaining 60% of the patients who had shown gradual decreases in rv / tlc . the rate of change in rv and tlc themselves also differed significantly between these two groups . however , the subgroup with a progressive increase in rv / tlc and a faster fev1 decline had no definite baseline characteristics that were predictive . these findings are similar to those of previous studies that also found a relationship between frequent exacerbations and a rapid decline in fev1.5,3840 therefore , the frequent exacerbation phenotype of copd may have common features , such as a rapid decline in lung function and progression in lung hyperinflation.41 our study has several limitations . first , due to the design of this observational cohort study , this study could not address the precise effect of pharmacotherapy on the longitudinal changes in lung volumes and hyperinflation . although pharmacotherapy with inhalers was shown to have no effect on improving the change in lung hyperinflation , this finding may result from unidentified confounding factors , which we were unable to assess and include in our analysis model . additionally , more severe and symptomatic patients may have been prescribed more inhalers , resulting in a bias by indication . second , this cohort study only included asian patients and most of the patients were male with gold stage ii or iii copd . , the low proportion of female patients in this study limits generalization of the results . third , as we used a mixed - effect linear regression for this study , this may have oversimplified the trend of changes into a linear model . our analysis could not accurately account for a more complex trend in lung volumes in individual patients . fourth , there may have been overuse of inhaled corticosteroids because ~80% of the patients were prescribed inhaled corticosteroids during follow - up . fifth , this cohort study did not include healthy aging individuals as a control group . if the trajectories of change in lung volumes could be compared between copd patients and healthy individuals , this would provide more robust results . finally , variability in measuring lung volumes as described earlier this study has value , in that , to our knowledge , it is the first to present longitudinal data , which were acquired over an extended period , from annual plethysmographic lung volume measurements . the rates of change in rv / tlc and ic / tlc , as indicators of lung hyperinflation , were highly variable in copd patients . frequent exacerbations were associated with progression of lung hyperinflation over time , as determined by changes in rv / tlc and ic / tlc . a progressive increase in rv

purposecopd is characterized by an accelerated and progressive decline in forced expiratory volume in 1 second ( fev1 ) and lung hyperinflation . although lung hyperinflation is the hallmark of copd , data on the longitudinal changes in lung hyperinflation and any association with the decline in fev1 are lacking . the aim of this study was to evaluate the longitudinal changes in lung hyperinflation and to investigate its relationship with fev1 decline.patients and methodswe conducted a prospective cohort study and studied 176 copd patients with annual lung volume measurements over a period of 5 years or more . we used a random coefficient model to calculate the annual changes in lung volumes and to evaluate the factors associated with changes in lung hyperinflation . additionally , the relationship between the change in lung hyperinflation and fev1 was assessed.resultsresidual volume ( rv ) , inspiratory capacity ( ic ) , and total lung capacity ( tlc ) declined at a mean rate of 39.5 , 49.6 , and 63.8 ml / year , respectively . while ic / tlc declined at 0.70%/year , rv / tlc also declined at 0.35%/year . changes in both ic / tlc and rv / tlc varied significantly . frequent exacerbations led to an increase in rv / tlc and faster decline in ic / tlc over time . rv / tlc declined in 59.7% and increased in 40.3% of the patients . a significant negative correlation was found between the rates of change in fev1 and rv / tlc , and the rate of decline in fev1 was greater in patients with an increase in rv / tlc than in those with a decline in rv / tlc ( 54.2 vs 10.7 ml / year , p<0.001).conclusionthe rate of change in lung hyperinflation varied greatly among copd patients . progression of hyperinflation was associated with frequent exacerbations and a faster decline in fev1 .

A new leukemia immune treatment being developed by Novartis AG (NOVN) led to the disappearance of cancer in 90 percent of patients, a study showed. The therapy, a process that involved taking a patient’s T cells and reprogramming them to hunt cancer cells, resulted in complete remission of 27 of 30 patients with acute lymphoblastic leukemia, a deadly pediatric cancer, according to the study published today by the New England Journal of Medicine. The early-stage trial of CTL019 engineered cells conducted by researchers at the University of Pennsylvania indicates the potential of the complicated treatment, which analysts have estimated may generate $10 billion a year if its uses expand beyond leukemia. The therapy can provoke serious side affects, however, and eight of the 30 patients required intensive care for severe cytokine-release syndrome. “We are excited by these results, which indicated how effective CTL019 may be in fighting ALL, a leading cause of childhood cancer deaths,” said lead investigator Stephan Grupp, a professor at the university. Immune therapies, which harness the body’s own defense system to fight cancer and other diseases, have taken the pharmaceutical industry by storm, with analysts estimating $35 billion in annual sales. Unlike products on the market such as Bristol-Myers Squibb Co. (BMY)’s Yervoy, CTL019 therapy involves removing a patient’s blood to modify their blood cells. Breakthrough Therapy The published study updated trial data first reported in December at the American Society of Hematology’s annual meeting. A further update will be released at this year’s meeting. The therapy is now in the second of three stages of human trials for acute lymphoblastic leukemia, with studies for other forms of cancer planned for next year. Novartis, based in Basel, Switzerland, received a breakthrough therapy designation from the U.S. Food and Drug Administration in July. The company will seek FDA approval in 2016. Patients in the trial -- 25 children and five adults -- received infusions between April 2012 and February of this year. Of the 27 patients who were successfully treated, 19 remained in remission and 15 of them received no further therapy. Seven patients died after a relapse of the disease. In 2013, more than 43,000 adults and 5,000 children and teens in the U.S. were diagnosed with leukemia, with about 6,000 having acute lymphoblastic leukemia. To contact the reporter on this story: Oliver Staley in London at ostaley@bloomberg.net To contact the editors responsible for this story: Phil Serafino at pserafino@bloomberg.net Kristen Hallam, Bruce Rule ||||| NEW YORK (Reuters Health) - Ninety percent of people facing death because conventional treatments had failed to destroy their leukemia have responded to an experimental therapy that trains their cells to kill out-of-control blood cells, doctors in Philadelphia report. Twenty seven of the 25 children and 5 adults initially responded to the new therapy. Nineteen - including a 9-year-old treated two and a half years ago - have remained cancer-free and 15 of those 19 have not receive any subsequent therapy. "We're astonished how well it turned out," senior author Dr. Stephan Grupp of Children's Hospital of Philadelphia told Reuters Health. Doctors are often happy if a treatment can improve the remission rate by 3 percent to 5 percent. "In our wildest dreams, we didn't think it would work as well as it did for the patients we've treated so far," Grupp said. "It's equally impressive in both the adult and pediatric population," said Dr. Noelle Frey of the University of Pennsylvania, who directed the adult portion of the study. "These are patients where the chances of cure are close to zero, if not zero," she said. "This is a therapy that not only gives hope, but is also correlated with tremendous success." The treatment results, reported in the New England Journal of Medicine, are part of a broader effort to reprogram the cells of cancer patients so they reproduce rapidly and attack the rogue cells responsible for tumors. "If this has curative potential - which we don't know yet, but seems to be the case - it's a game changer," said Dr. Michael Sadelain of Memorial Sloan Kettering Cancer Center, part of a separate team that previously used the technique to produce complete remissions in 14 out of 16 adults who had acute lymphoblastic leukemia (ALL) of a stage "where nobody would go into complete remission." "The good news is, this therapy can work just as well in children as it was reported to do in adults," he told Reuters Health. In the Philadelphia study, other treatments - as many as four - had failed in the 30 patients. Conventional therapy typically cures 80 percent to 85 percent of children with ALL and those children "don't need this," said Grupp. "The other 15 percent or so are candidates for this." Adults with ALL are tougher to treat, "so 50 percent or more might need this," he said. In July, the U.S. Food and Drug Administration gave the treatment, known as CTL019, a Breakthrough Therapy designation designed to expedite its development for ALL. The Philadelphia researchers have also been experimenting with CTL019 for chronic lymphocytic leukemia and Hodgkin's lymphoma,. The remission rates in those tests have been high, but not nearly as high as with ALL, Frey told Reuters Health. Those findings have not been published. The ALL treatment involves training disease-fighting blood cells known as T-cells. Once removed from a patient's body, they are programmed to hunt cancer cells that have a telltale protein on their surface. The specially-trained cells are then re-injected into the patient. The re-engineering process currently costs about $25,000. Of the initial 30 patients, 27 were in complete remission by the one-month mark, but seven relapsed over a period ranging from 6 weeks to 8.5 months after treatment. Twenty three were alive at the six-month mark. Five of the 23 left the study to receive other treatments, including stem cell transplantation. The treatment is not without serious risks. The most common is cytokine release syndrome, where the body appears to react to the mass killing of tumor cells. Patients "become tired, achy and nauseous," said Frey. "You can also get low blood pressure and breathing difficulties. Unfortunately, it can be life-threatening. But we have, in most cases, been able to reverse it. Yet in most situations it’s very manageable." “For our patients who have already relapsed after stem cell transplants, or don’t have any options for donors," she said, "this option has provided new hope.” In eight of the 27 cases where there was a response, cytokine release syndrome was judged to be severe and the patients ended up in intensive care. At least part of the technique involved in the Philadelphia study has been licensed to Novartis. Sloan Kettering has teamed up with a start-up company, Juno Therapeutics, which will conduct a multicenter study of adults with ALL, Sadelain said. "That's a sea change in the field because, until now, this realm of cell therapy was almost exclusively in the hands of academic centers," he said. "Now you see a whole host of companies moving into this space. Investors have been impressed by these results and will take them far beyond what academic centers will do." SOURCE: bit.ly/1syxUeI New England Journal of Medicine, October 15, 2014.

– An experimental therapy labeled the "holy grail" of cancer treatment a few years ago has produced amazing results in a group of leukemia patients who had been given a few months or even a few weeks to live, researchers say. Some 30 patients with an acute form of leukemia were given the treatment, which "trains" a patient's immune cells to kill rogue cells and spawn more cancer-killing cells. Of those, all but three went into remission, and 23 were still alive six months or more later. Multiple other treatments had failed in the five adults and 25 children and young adults who received the treatment. Seven of those who got the treatment have since died, but 19 are still cancer-free, including 15 who have had no other treatment, reports the New York Times. "We're astonished how well it turned out," a researcher at the Children's Hospital of Philadelphia tells Reuters, which notes that a 3% improvement in the remission rate is considered a success for a new therapy, while this one achieved a stunning 90%. "In our wildest dreams, we didn't think it would work as well as it did for the patients we've treated so far." The treatment has its drawbacks—serious side effects put eight of the patients in intensive care, reports Bloomberg—but researchers say the latest trial proves early successes were no fluke and that the treatment holds promise for fighting other kinds of cancer. (Another experimental cancer treatment involves bee venom.)

454 is a powerful flat - spectrum radio quasar located at a redshift @xmath3 . this source is very bright in the gev energy range ; during strong flares , its apparent ( isotropic ) luminosity can reach @xmath4 erg s@xmath5 ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? the mass of the central black hole ( bh ) in 454 is estimated in the range @xmath6 @xcite . this implies an eddington luminosity @xmath7 , which is several orders of magnitude below @xmath8 . although the large gap within @xmath9 and @xmath8 is naturally explained by relativistic doppler boosting , the estimates of the jet power during these flares appear , in any realistic scenario , close to or even larger than the eddington luminosity @xcite . being quite extreme , `` super - eddindton '' jets can not be nevertheless excluded for accreting black holes with very high accretion rates but low radiation efficiencies . although 454 is an exceptional case ( e.g. discussion in * ? ? ? * ) , data from other objects provide additional evidence in favor of jets with super - eddington mechanical power @xcite . the gev emission from 454 is highly erratic , with variability timescales as short as 3 hr , as reported , in particular , for the december 2009 flare @xcite . the most spectacular flare regarding both variability and gamma - ray luminosity was observed in november 2010 by and @xcite telescopes . during this high state , with the most active phase lasting for 5 days , the apparent luminosity in gev achieved @xmath10 . around the flare maximum , the rising time was @xmath11 hr , and the decay time , @xmath12 hr . the detection of photons with energies up to @xmath13 gev , the short variability , and the contemporaneous x - ray flux constrain the doppler boosting of the emitter to @xmath14 to avoid severe internal @xmath15 absorption in the x - ray radiation field @xcite . a remarkable feature of the gamma - ray emission from 454 is the so - called plateau phase revealed during the bright flare in 2010 . it is characterized by a long - term brightening of the source , a few weeks before the appearance of the main flare . such plateau states have been observed by for three flares ( e.g. * ? ? ? * ; * ? ? ? * ) , with the plateau emission being about an order of magnitude fainter than that of the main flare . remarkably , the rapid gamma - ray variability of 454 is accompanied by an activity at lower energies . the simultaneous multiwavelength observations of the source during flares have revealed a strong correlation with optical and x - rays . it has been interpreted as evidence that the gamma - ray source is located upstream from the core of the 43 ghz radio source , which is at a distance @xmath16 few pc from the central bh ( see , e.g. , * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) . over the recent years , several works have attempted to explain the flaring gamma - ray activity of 454 within the framework of the standard synchrotron self - compton ( ssc ) or external inverse - compton ( eic ) models @xcite . in the ssc scenario , it is possible to reproduce the spectral energy distribution ( sed ) from optical wavelengths to gamma - rays . in these models most of the jet power is ( unavoidably ) carried by protons , and only a small fraction is contained in relativistic electrons and the magnetic field . the required proton - to - poynting flux ratio of @xmath17 is quite large . such a configuration would be hard to reconcile , at least in the gamma - ray emitting region close to the central bh , with an undisturbed jet which is launched by the blandford - znajek @xcite type ( bz ) process , in which the luminosity of the jet is dominated by poynting flux and the jet consists of @xmath18-pairs ( see also * ? ? ? * ; * ? ? ? in this regard we should mention that recent relativistic magnetohydrodynamical ( mhd ) simulations of jet acceleration yield much less efficiency of conversion of the magnetic energy into bulk motion kinetic energy ; these calculations @xcite predict a quite modest ratio @xmath19 . as stars and clumpy matter are expected to be present in the jet surroundings , they could be behind the powerful gamma - ray events in agn ( see , e.g. , a discussion in * ? ? ? in particular , a red giant ( rg ) can enter into the jet , lose its external layers , and in this way generate a strong perturbation inside the jet . this perturbation can accelerate particles and produce high - energy radiation . the jet - rg interaction ( jrgi ) scenario has been invoked to explain the day - scale flares in the nearby non - blazar type agn m87 @xcite , it has been applied also to the tev blazar @xcite to demonstrate that the jet - driven acceleration of debris from the rg atmosphere can explain ultra - fast variability of very high - energy gamma - ray emission on timescales as short as @xmath20 s. a distinct feature of the jrgi scenario is the high magnetization ( @xmath21 ) of the relativistic flows located at sub - parsec distances , where the gamma - ray production supposedly takes place . although the strong magnetic field , @xmath22 g , dramatically reduces the efficiency of the inverse compton scattering of electrons , it opens an alternative channel of gamma - ray production through synchrotron radiation of protons @xcite . the latter can be effectively realized only in the case of acceleration of protons to the highest possible energies , up to @xmath23ev . thus the second ( somewhat hidden " ) requirement of this model is a very effective acceleration of protons with a rate close to the theoretical limit dictated by the classical electrodynamics @xcite . although somewhat speculative , this condition does agree with rather model - independent ( derived from first principles ) arguments that the relativistic jets in agn present the best candidate sites of production of the highest energy cosmic rays @xcite . the large magnetic field and acceleration of protons to the highest possible energies , coupled with strong doppler boosting in relativistic outflows , not only provide an extension of the gamma - ray spectra up to tev energies , but also provide variability as short as 1 h @xcite . it is interesting to note that also inverse compton models can be accommodated , at least in principle , in the jrgi scenario . moreover , unlike most of the leptonic models of powerful blazars , in which the requirement of a very low magnetic field , implying a deviation from the equipartition condition by orders of magnitude , generally is not addressed and explained , the jrgi scenario can offer a natural way for leptonic models to be effective assuming that the gamma - ray emission is produced through the inverse compton scattering in shocked clouds originally weakly magnetized ( see * ? ? ? * ) . in this work , we show that the jrgi scenario gives a viable mechanism for the explanation of the flares seen in 454 . we also argue that within this model the plateau state can form due to the interaction of the jet with a stellar wind excited by nonthermal ( accelerated ) particles that penetrate into the red giant atmosphere . given its extreme nature and importance , we will use the very powerful gev flare of 454 occurred in november 2010 as a template for our interpretation . we will show that this active period of 454 , consisting of a day - long flares with variability as short as a few hours on top of a weeks - long plateau state , can be explained by the interaction of a rg with the jet relatively close to the central black hole . the possibility that some exceptional flares in agn may originate from star - jet interactions has been proposed and discussed in our recent papers @xcite . in this work we explore the question whether the extremelly bright and short gamma - ray flares detected by the _ fermi _ large area telescope ( _ fermi_/lat ) from 454 in november 2010 can be explained by this model . it is important to note that these flares provide us information of exceptional quality concerning both the temporal behavior of the source and its energy spectrum . in this regard we should note that the operation of _ fermi_/lat in scanning mode allows continuous monitoring of the source , so its temporal behavior can be studied without interruptions , including the pre- and post - flare epochs . before considering the case of 454 , in this section we discuss different implications of the jrgi scenario regarding the general temporal structure of the active phase in a blazar - type agn . when a star enters into an agn jet , some stellar material is expected to be released inside the jet flow , eventually forming a population of blobs that will be accelerated by the jet ram pressure . during this process , depending on the local magnetic fields , different types of shocks and plasma waves can be produced and propagate through both the jet material and the blobs . these waves may accelerate particles to relativistic energies the interaction of which with the ambient radiation and magnetic fields would result in a broadband nonthermal emission . generally the properties of this emission depend on the specifics of the acceleration and radiation mechanisms and the details of the target fields . however , in the case of extremely effective particle acceleration and radiation , i.e. when the corresponding acceleration and radiative cooling times are shorter than other timescales characterizing the dynamics of the system ( a mandatory condition given the enormous luminosity of the emission ) , the lightcurve of the emission will be essentially determined by the jet / blob interaction model . in the _ fast cooling regime _ , the proper intensity of the nonthermal emission , i.e. the intensity in the blob co - moving reference frame , is proportional to the energy released at the jet - blob interface . this energy release can be characterized by a simple dynamical model , which describes the acceleration of the blob by the jet ram pressure . in this model there are just a few relevant parameters that describe the basic properties of the jet and the blob : the jet ram pressure ( @xmath24 ) and bulk lorentz factor ( @xmath25 ) , and the blob mass ( @xmath26 ) and radius ( @xmath27 ; or , equivalently , its cross - section : @xmath28 ) ( for details , see * ? ? ? the time dependence of the intensity of the jet / blob interaction corrected for the doppler boosting can be treated as a first - order approximation for the radiation lightcurve . there are several important stages in the jrgi scenario that may have an important impact on the observed lightcurve of radiation : ( i ) first , the removal of the star external layers ; ( ii ) the formation of a cloud from the removed stellar material , which under the jet impact suffers heating and expansion , and eventually fragments into a set of smaller blobs '' , `` @xmath29 '' , and `` @xmath30 '' to characterize the parameters of the initially formed cloud , of the blob , and of the jet at the star crossing height , respectively . ] ; ( iii ) the acceleration of the blobs in the direction of the jet flow to a lorentz factor equal or smaller than the jet lorentz factor . the intensity of the nonthermal processes associated with the blob motion has a strong time dependence . at the start of the acceleration of the blob , its lorentz factor is modest , yielding a small ( but growing with time ) boosting of the flux . at later stages , when the blob lorentz factor approaches the lorenz factor of the jet , the radiation intensity decreases because of the weakening of the jet - blob interaction . according to the results obtained in @xcite in the fast cooling limit , the maximum of the apparent luminosity , accounting for the doppler boosting of the emission , occurs when the blob bulk lorentz factor achieves @xmath31 . during the penetration of the star into the jet , strong shocks are induced in the stellar atmosphere and a significant part of the envelop can be removed . although the details of this process might be very complicated and depend on the radial density profile of the star and the structure of the jet outer boundary , here , for simplicity , we assume an instantaneous penetration . to a certain extent , this simplification is justified by the stellar proper motion , which is expected to be faster than the initially induced shock waves . nevertheless , independent of the details of the star penetration , one can expect that when the star is fully within the jet , a dense cloud will be released . later , as the cloud propagates through the jet , the star may still release an intense wind or a sequence of small clouds due to ablation of the stellar atmosphere by the jet . the mass of the cloud @xmath32 formed at the initial stage can be estimated by comparing the jet ram pressure , @xmath33 with the gravitational force . here , @xmath34 is the jet cross - section at the star crossing height . this gives the following estimate : @xmath35 where @xmath36 and @xmath37 are the rg mass and radius , respectively . the absolute upper limit on the continuous mass - loss rate can be estimated comparing the energy flux density of the jet @xmath38 and the gravitational force work density for removing matter from the stellar surface @xmath39 . the maximum continuous mass ejection from the star is @xmath40 a more precise estimate of this rate requires a detailed study of the interaction process , which is out of the scope of this paper . nevertheless , in sect . [ pla ] we discuss whether a sufficiently strong stellar wind can be excited by the penetration of nonthermal ( accelerated ) particles . since the initial size of the expelled cloud should be comparable to the size of the star , it is possible to estimate the cloud expansion time as @xmath41 , where @xmath42 is the sound speed of the shocked material : @xmath43^{1/2}$ ] . the cloud expansion time is @xmath44 where @xmath45 is the plasma adiabatic coefficient , and @xmath46 is a constant of about a few @xcite . according to the rhd simulation by @xcite , a value of @xmath47 can be adopted for @xmath48 . the blob acceleration occurs on a timescale of ( see e.g. * ? ? ? * ) @xmath49 the @xmath50parameter that will be often used in the paper has a simple meaning . it is a dimensionless inverse mass of the blob : @xmath51 the above timescale corresponds to the blob acceleration in the laboratory reference frame . however , since the blob gets accelerated towards the observer , the emission delay , as seen by the observer , should be approximately corrected by a factor of @xmath52 . thus , the observed peak of the emission should be delayed by a time interval of @xmath53 there are some uncertainties in this equation . in particular , for @xmath54 , the blobs can travel a distance comparable to @xmath55 and the jet properties at the dominant emission blob location may differ significantly from the blob formation site . thus , the detailed evolution of the emitter can only be addressed properly through numerical modeling . however , despite the adopted simple approach , some important conclusions can be derived . namely , given the dependence of the two components at the rhs of equation ( [ eq : delay ] ) on the stellar material mass ( @xmath56 and @xmath26 , respectively ) , the radiation associated with the heavy cloud expelled first will be delayed with respect to the emission produced by lighter clouds formed later . the emission produced by lighter clouds allows an estimation of the time required for the star to cross the jet . once the star enters into the jet , the process of jet - star interaction should proceed steadily , with the production of these lighter clouds being roughly constant on average thus , the whole duration of the light cloud - associated emission , if observed , can be taken as a direct measurement of the jet crossing time @xmath57 , where @xmath58 is the star velocity . this yields the following relation : @xmath59 where @xmath60 is the bh gravitational radius . adopting the paradigm of magnetically - accelerated jets ( see appendix , equations ( [ eq : ap_mdj ] [ eq : ap_mdj2 ] ) ) , it is possible to derive a very simple expression for this timescale : @xmath61 in this way , the duration of the jet - star interaction is determined by the interaction distance from the central bh . the physical properties of the emitting blobs determine the available energetics and the maximum flux reachable in the considered scenario . in the blob comoving frame , the jet - star interface energy flux is defined by @xmath62 assuming a fixed efficiency @xmath63 in the blob reference frame for the transfer of jet power to nonthermal gamma rays ( where @xmath64 ) , and correcting for doppler boosting , one can estimate the luminosity of a blob : @xmath65 where the correction function @xmath66 depends on time ; or , equivalently , on the blob location in the jet ( for a mathematical definition of this function , see appendix , equation [ eq : ap_lum ] ) . we note that the structure of the jet , i.e. , the dependence of the jet lorentz factor on @xmath55 , determines the actual dependence of @xmath66 on @xmath55 ( see also appendix for details ) . the maximum value of @xmath66 monotonically depends on the @xmath50 parameter , approaching a value of @xmath67 if @xmath68 and being @xmath69 for @xmath70 . this relatively weak dependence allows us to derive the maximum blob luminosity . also it is possible to obtain an estimate of the total energy emitted by a blob or an ensemble of sub - blobs as a result of the fragmentation of the original cloud ( @xmath71 ) , @xmath72 which accounts for the total energy transferred by the jet to a blob during the acceleration process , @xmath73 , and for the anisotropy of the emission due to relativistic effects represented by the factor @xmath74 ( see appendix [ ap : energy ] , in particular equation [ eq : toten_ap ] , for details ) . the total apparent energy of the gev gamma - ray radiation detected during the flare observed from 454 in november 2010 was about @xmath75 . the exceptionally high flux during this period allows the derivation of a very detailed lightcurve , as seen from figure 1 in @xcite . the nonthermal activity lasted for @xmath76 days . the onset of the activity period was characterized by a plateau stage . during the first @xmath77 days , a rather steady flux was detected , with an apparent luminosity @xmath78 erg s@xmath5 . the plateau stage was followed by an exceptionally bright flare , the total duration which was @xmath79 days , with a rise time of @xmath80 h. the maximum flux reached was @xmath81 , which corresponds to a luminosity of @xmath82 . the final stage of the flare phase was characterized by variable emission with a flux approximately a factor of @xmath83 weaker than the main flare , but still a factor of @xmath84 above the plateau level . the observed luminosity of the plateau phase allow us to determine a lower limit on the star mass - loss rate , which can be derived by differentiating equation ( [ eq : toten ] ) : @xmath85 where @xmath86 . comparing this requirement to equation ( [ mdot ] ) , it is easy to see that for typical parameters of rg stars , equation ( [ mdotw ] ) represents a modest ( a few percent ) of the maximum possible mass - loss rate . in sect . [ pla ] we will return to this issue . to evaluate the feasibility of the jrgi scenario for the 454 main flare , it is necessary to check whether the flux , the total energy release , and the flare delay with respect to the onset of the plateau , are well described by equations , , and for a reasonable choice of jet / star properties . for example , equation can be rewritten as @xmath87 where @xmath88 is the peak luminosity of the flare normalized to @xmath89 , and @xmath90 the blob cross - section . a total energy budget of the flare of @xmath91 is feasible , according to equation ( [ eq : toten ] ) , if @xmath92 where @xmath93 g is the mass of the blown up rg envelop ( i.e. the initially formed cloud ) . this requirement appears to be very close to the one provided by equation , where the jet ram pressure is now substituted using equation : @xmath94 where @xmath95 and @xmath96 , respectively . the second term in equation is expected to be short compared to the duration of the plateau phase , even for @xmath97 , and thus the duration of the initial plateau phase constrains the expansion time ( see equation ( [ eq : expansion ] ) ) : @xmath98 @xmath99 @xcite found that the emission of the main flare consisted of 5 components ( see figure 2 in that work ) : a nearly steady contribution , like a smooth continuation of the plateau emission , and 4 sub - flares of similar duration and energetics . although the uniqueness of such a fit is not statistically assessed , it looks a good empirical description of the data . in the framework of the jrgi scenario , such a description is very natural . the steady component would be attributed to light clouds , continuously ejected by the star , and the four sub - flares would correspond to much heavier blobs formed out of the blown - up stellar envelop during the initial stage . on the other hand , the decomposition of the main flare in four sub - flares implies a strict limitation on the variability timescale . the flare rise / decay timescales should be longer than the blob light crossing time corrected for the doppler boosting . since the shortest variability scale was @xmath100 s , the maximum possible size of the emitting blobs can be estimated as : @xmath101 if the jet is magnetically driven , this size constraint can be expressed through the mass of the central bh ( see equation [ eq : ap_mdj ] ) : @xmath102 which is restrictive only in the case of @xmath103 . for @xmath104 , the blobs can cover the entire jet without violating the causality constraint . in summary , if the flare detected with was produced by an rg entering into the jet , the jet properties should satisfy equations , and , which correspond to the restrictions imposed by the flux level , total energy release , and the duration of the plateau stage , respectively . interestingly , this set of equations allows the derivation of a _ unique _ solution , which can constrain all the key parameters through the value of the @xmath50 parameter : @xmath105 @xmath106 @xmath107 and @xmath108 the value of the ram pressure determined by equation ( [ eq : lum_final ] ) can be compared to the value achievable in a magnetically - driven jet : @xmath109 where @xmath55 is the distance from the central bh . it is seen from the comparison of and that the solution found implies a jet with luminosity exceeding by a factor of @xmath110 the eddington limit . this requirement is also consistent with the lower limit on the jet luminosity @xmath111 which exceeds the eddington limit for the mass of the central bh @xmath112 ( see * ? ? ? * and references therein ) . to assess the feasibility of such a strongly super - eddington jet remains out of the scope of this paper , although we note that @xcite have presented observational evidence indicating that such jets may not be uncommon . we also note that the requirement of a high luminosity is less severe in the case of small @xmath50-values and that in this limit one can derive a constraint on the central black hole mass combining equations and : @xmath113 the coherent picture emanating from the jet properties derived above suggests that the jrgi scenario can be responsible for the flare detected from 454 for a solution of the problem with a reasonable set of model parameters . this solution is designed to satisfy the requirements for ( i ) the total energy ; ( ii ) the peak luminosity ; and ( iii ) the duration of the plateau phase . therefore , some additional observational tests are required to prove the feasibility of the suggested scenario . to address this issue , we discuss in sect . [ sec : proc ] the feasibility of different radiation mechanisms to explain the observations under the inferred emitter conditions . also , in sect . 3.2 we explore whether the stellar wind induced by the rg - jet interaction can be responsible for the flux level detected during the plateau stage . recall that , as already shown , the required mass - loss rate is well within the limitations imposed by equation . finally , the flare raise time , which is related to the blob acceleration timescale ( see equation [ dtpeak ] ) , can be calculated for the obtained solution . interestingly , in the limit of small @xmath50-values , this timescale appears to be independent on @xmath50 , the only remaining free parameter , and matches closely the detected raise time of @xmath114 : @xmath115 this agreement can be treated as a cross - check that shows the feasibility of the proposed scenario . when the star penetrates into the jet , strong perturbations are generated in both the jet structure and the star external layers . strong shocks and other processes of energy dissipation take place in the impacted jet and stellar material , generating conditions under which nonthermal particles can be accelerated . here we will not specify the acceleration mechanism , which depending on the acceleration region may be such as fermi i , stochastic acceleration , or magnetic reconnection . the accelerated particles can either be advected away , while radiating , from the perturbed jet region , or penetrate into the stellar atmosphere and thermalize heating the ambient plasma . the heating can induce a strong wind that will significantly enhance the stellar mass - loss rate . a similar enhanced mass loss can occur as well through compton - heated winds in high - mass x - ray binaries and agn due to heating by x - rays from an accretion disc ( e.g. * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) , although for the mass - loss rate required to explain the plateau phase ( see equation [ mdotw ] ) , the accretion disk x - ray flux seems to be too small . on the other hand , the nonthermal particles produced at the star - jet interaction region can be enough to heat the stellar atmosphere . since even nonthermal particles with low energy can effectively heat the atmosphere . the nonthermal emission may be undetectable during the heating process . the heating energy flux can be estimated as @xmath116 where @xmath117 is the normalized jet ram pressure , and @xmath118 the nonthermal particle - to - jet power ratio within the stellar atmosphere , a combination of the fraction of jet power channeled into nonthermal particles @xmath119 , and the fraction of the nonthermal particles diffusing into the rg atmosphere @xmath120 . in the case of a jet interacting with a heavy obstacle , the value of @xmath119 could be potentially close to 1 . the entrainment of particles into the rg atmosphere could be also high due to a strongly asymmetric diffusion process : whereas the strong magnetic field in the jet may prevent particles from crossing back , the weaker magnetic field in the other side would stimulate particles to diffuse deep into the stellar atmosphere . for all this , the effective value of @xmath121 may be of order 1 . the mass flux of a stellar wind excited by nonthermal particles of flux @xmath122 can be estimated as : @xmath123 @xmath124 where @xmath125 is related to the properties of the plasma heating and cooling . in the case of x - ray heating , one finds that @xmath126 or @xmath127 ( i.e. * ? ? ? . however , for nonthermal - particle heating , the efficiency of transferring jet energy into the stellar wind can be higher because these particles can penetrate deeper into the stellar wind . thus , in this case @xmath128 can significantly exceed 1 . the induced mass - loss rate therefore will be @xmath129 , or @xmath130 to explain the plateau emission by the interaction of this induced stellar wind with the jet , the mass flux from equation ( [ mdotx ] ) should be greater than the one from equation ( [ mdotw ] ) . adopting the typical parameters of the november 2010 flare , this requirement can be satisfied if the following condition holds ( the function @xmath131 here characterizes the main flare episode ) : @xmath132 formally , for the adopted rg normalization parameters , the required heating efficiency should be rather high @xmath133 ( accounting for @xmath134 , as found for conical jets see appendix for details ) . however , a significantly lower heating efficiency can be sufficient to fulfill equation ( [ rrg ] ) under certain circumstances ; @xmath121 could be easily reduced if @xmath135 ( @xmath136 in this regime ) , or assuming that nonthermal particles contribute strongly to the pressure of the stellar atmosphere ( @xmath137 ) , or for a rg radius exceeding the fiducial value @xmath138 . for instance , to reduce @xmath121 to @xmath139 , one may adopt either @xmath140 ; or @xmath141 and @xmath142 ; or @xmath143 . a combination of all these factors could further decrease the required heating efficiency to lower values . therefore , an induced stellar wind seems to provide a feasible way to generate the plateau emission component . in this section we discuss the feasibility of different radiation mechanisms for the conditions in the production site inferred in the previous section ( see equations [ eq : lum_final ] [ eq : size_final ] ) . the efficiency of the radiation channels is determined by the presence of nonthermal particles with the required energy and targets . several types of target fields are related to efficient high - energy processes : matter in the case of proton - proton or bremsstrahlung mechanisms ; magnetic field for synchrotron radiation ; and photons for inverse compton and photo - meson emission . the obtained solution for the properties of the jet , plus observational constraints , allow two of these targets to be properly characterized . since the mass and size of the blobs are estimated , one can derive the matter density in the production regions : @xmath144 this density estimate allows one to discard the proton - proton channel , since the expected cooling time , @xmath145 s , is too long . this conclusion is also valid to exclude the bremsstrahlung channel , with a similar cooling time . the derived ram pressure of the jet allows the derivation of an upper limit on the magnetic field strength : @xmath146 in fact , from equipartition arguments , the actual strength of the magnetic field should be close to that value ; i.e. one may take @xmath147 as the fiducial value for the fraction of the jet luminosity carried in electromagnetic form . also , accounting for the relation @xmath148 , valid in the range of feasible values of the @xmath50 parameter for the conical jet model , one can derive a lower limit on the jet magnetic field of @xmath149 more detailed calculations of this value are presented in fig . [ fig : rad_limits ] . in this figure we also show the value of the magnetic field in the comoving system ( @xmath150 ) , which was calculated using the jet lorenz factor equation as a function of the value of @xmath50 . it can be seen that for the @xmath50-range of interest , there is a lower limit on the magnetic field strength : @xmath151 regarding the density of the target photon field , it can not be constrained in general . however , in the specific case of the synchrotron - self compton scenario , it is possible to put certain limitations . namely , the high - energy component detected by exceeds by two orders of magnitude ( @xmath152 ) the flux detected at other wavelengths . this implies that the energy density of the target field should exceed by this factor the energy density of the magnetic field : @xmath153 ( these are co - moving reference frame values ) . the luminosity of such a field can be estimated as @xmath154 @xmath155 since @xmath156 and @xmath157 , one obtains @xmath158 thus , the ssc scenario can be realized only in a specific region of the jet , where the magnetic field is significantly lower than the characteristic one ( i.e. , @xmath159 ) . the blobs themselves may have a magnetic field quite different from the field in the jet , and therefore may serve as good sites for ssc . however , this assumption involves further complexity , e.g. regarding internal shock acceleration within the blobs , and is therefore deferred to future studies . also , we note that the radiation efficiency of photomeson production is low ( e.g. see discussion in * ? ? ? if photomeson production were the radiation mechanism , it would imply a very low value of @xmath63 and an uncomfortably high power of the jet . we focus now on the following radiation mechanisms : electron and proton synchrotron , and external inverse compton . the analysis of the synchrotron channel is straightforward , since the density of the target is determined . indeed , to produce a gamma ray of energy @xmath160 gev it is required either an electron or proton of energy @xmath161 we note that the weak d - dependence in these equations is neglected for simplicity . to obtain such a high - energy particles a few conditions should be satisfied , the most critical ones being the _ hillas criterion _ and the efficiency of the acceleration process . the hillas criterion requires the gyroradius of the highest energy particles to be smaller than the size of the acceleration region . since the acceleration region size is determined by the blob cross - section , one can derive the following requirements : @xmath162 this estimate allows one to illustrate that for the derived jet parameters the hillas criterion appears to constrain the acceleration of particles in neither the lepton nor the proton synchrotron scenarios . regarding the efficiency of the acceleration process , it is convenient to present the nonthermal particle acceleration time in a form independent of the specific acceleration mechanism : @xmath163 where @xmath164 is the energy of particle , @xmath165 the acceleration efficiency , and @xmath166 the particle gyroradius . this timescale should be compared to the dominant cooling time ( synchrotron ) to determine the highest achievable energy : @xmath167 accounting for the energy of the emitted gamma - rays , @xmath168 , one can obtain an upper limit on the acceleration efficiency : @xmath169 where @xmath170 is the blob lorentz factor . since the red - shift corrected energy of the spectral break appears to be close to @xmath171 gev , the leptonic scenario can be realized only if @xmath172 . in the case of proton - synchrotron models this constraint gets significantly relaxed yielding @xmath173 . however , given the relatively small values of the obtained lorentz factors ( see equation [ eq : gamma_final ] ) , the derived limits on the acceleration efficiency are very tight , especially for the leptonic case ( @xmath174 ) . the feasibility of such a scenario should be addressed with a detailed acceleration model , which remains out of the scope of the present paper . we note that this limitation can be relaxed adopting a scenario with a highly turbulent magnetic field ( see more details in * ? ? ? since the proton synchrotron scenario fulfills the basic requirements for the production mechanism , it is worthy to check whether one can reproduce the observed basic spectral properties . has reported a broken powerlaw spectra with a nearly constant break energy . the change of the powerlaw index is varying being between 0.5 and 1 . whereas index changes of 0.5 , thought to be cooling breaks , are typical in synchrotron scenarios , other values for the powerlaw index change may be hard to explain through cooling . on the other hand , one can attribute this spectral feature to absorption ( as suggested for this source * ? ? ? * ) . regarding the uncooled part of the synchrotron spectrum , it is typically characterized by a power - law index of 1.5 ( @xmath175 ) . interestingly , the extrapolation of such a slope from the level found by _ swift _ in x - rays gets close to the spectral points reported by the collaboration . therefore , it is natural to expect that the cooling break is located at energies @xmath176 mev . the synchrotron cooling time of protons in the comoving frame can be expressed as @xmath177 this timescale should be compared to the timescale characterizing the comoving blob acceleration time : @xmath178 in figure [ fig : rad_limits ] ( bottom left panel ) we show the numerical computation of these timescales for the case of a conical jet . one can see that for the typical model parameters , these time scales are comparable . this allows us to obtain three important conclusions for the considered scenario . namely , that ( i ) the fast cooling regime assumption should not be strongly violated in proton - synchrotron models for gev emitting protons ; ( ii ) one should expect a cooling break in the high - energy domain ; and finally that ( iii ) the proton synchrotron mechanism appears to be an efficient radiation channel . indeed , it is often argued based on the comparison of the proton cooling and jet dynamical time scales ( see , e.g. , * ? ? ? * ) that proton synchrotron is characterized by a very low efficiency as gamma - ray production mechanism in agn jets . however , as it can be seen from figure [ fig : rad_limits ] ( bottom left panel ) , for the inferred jet properties , proton synchrotron can render a high radiation efficiency . the external inverse compton channel is not strongly constrained in the jrgi scenario , since the properties of the photon target are not well known and can vary within a broad range . similarly to the ssc case , the density and luminosity of the target photons can be estimated based on the ratio of the synchrotron and ic luminosities . this yields the following luminosity @xmath179 the value of this luminosity as a function of @xmath50 is shown in figure [ fig : rad_limits ] ( bottom right panel ) . it is seen that the photon field luminosity required for the eic scenario to work appears to be very high ( accounting for @xmath180 . ] ) , exceeding the reported luminosity of the blr unless @xmath181 is very small or the interaction region is located far enough from the central black hole ( @xmath182 ) . there is another constraint related to the process of gamma - ray absorption through pair creation in the local radiation fields . the peaking energy of the radiation component detected with should be close to 100 mev . otherwise , the lower energy spectrum should be very hard not to violated the x - ray flux detected with _ swift _ @xcite . in the emitter comoving system this would correspond to @xmath183 i.e. relatively close to the electron - positron creation threshold . assuming a photon spectrum @xmath184 below the peak ( it may be even harder ; see sect . [ sedlc ] ) , it is possible to compute the luminosity transferred to the secondary pairs : @xmath185 where @xmath186 is the normalized blob radius . substituting here the obtained solutions for the jet parameters ( equations [ eq : lum_final]-[eq : size_final ] ) in the limit of small @xmath50 , one gets @xmath187 this energy should be emitted either via synchrotron or inverse compton radiation . the obtained estimate of the proper magnetic field from equation allows one to estimate the peaking energy for the synchrotron channel to be @xmath188 this component can be constrained with the infrared flux detected during the flare @xcite . if the dominant channel is inverse compton scattering , the peak energy can be estimated as : @xmath189 where @xmath190 is the target photon energy . although this component would peak above the x - ray energy band , the lower energy tail may give an important contribution to the reported flux level . also , it is important to note that the inverse compton photons may serve as targets for the absorption of primary gamma - rays leading to a non - linear regime of the emission formation . this , in particular , may make a self - consistent treatment of the eic scenario very complex , and thus we leave this possibility for future dedicated studies . nevertheless , we wil account for internal gamma - ray absorption in the blob own synchrotron field , and comment on radiation reprocessing outside the blob in sect . [ sedlc ] . despite being not very detailed , and order - of - magnitude , the above analysis shows that explaining the november 2010 flare detected from 454 in the framework of the jrgi scenario requires a jet with a very high ram pressure . consequently , a magnetic field with a strength not far from equipartition , say a factor of 10 below , appears to be too strong for radiation processes other than synchrotron . on the other hand , leptonic synchrotron emission requires an extremely efficient acceleration process with an acceleration parameter @xmath191 , which can not be discarded but is perhaps unrealistic . thus , _ proton synchrotron _ emission seems the most comfortable radiation channel given the restrictions imposed by data and the jrgi scenario . in what follows we test this process using a simple radiation model . to check whether jrgi plus synchrotron radiation can explain the observations in the case of magnetically dominated jets ( i.e. , @xmath192 ) , we have computed the lightcurve of the november 2010 flare and the sed for one of its subflares . the radiation output was assumed to be dominated by proton synchrotron , being external or synchrotron self - compton neglected due to the strong magnetic field ( see sect . [ genan ] ) . to derive the lightcurve , equation [ eq : lum ] has been used ( see the determination of @xmath193 in the appendix ) . in figure [ lc ] , a computed lightcurve that approximately mimics the november 2010 flare is presented . the lightcurve has been obtained assuming four subflares of total ( apparent ) energy of @xmath194 erg each , plus a plateau component with luminosity of @xmath195 erg s@xmath5 . for each subflare , we have adopted @xmath70 . the normalization of the lightcurve has been determined adopting the following values : the lorentz factor @xmath196 , the ram pressure @xmath197 erg @xmath198 , blob radius @xmath199 cm and @xmath200 . these parameters imply a minimum jet luminosity of @xmath201 erg s@xmath5 . the remaining parameters for the emitter are @xmath202 cm and @xmath203 g. the corresponding mass of the matter lost by the rg to explain the four subflares is @xmath204 g , not far from the upper - limit given in equation [ dms ] . to calculate the sed , we have adopted a spectrum for the injected protons @xmath205 , and an homogeneous ( one - zone ) emitter moving towards the observer with lorentz factor @xmath206 . the minimum proton lorentz factor has been taken equal to the shock lorentz factor in the blob frame , i.e. @xmath207 . the cutoff energy , @xmath208 , has been obtained fixing @xmath209 ( see equation for details ) , i.e. , a modest acceleration efficiency . for the maximum proton energy , i.e. how far beyond the cutoff the proton energy is considered , we adopted two values : @xmath210 and @xmath211 . regarding the latter case , we note that assuming a sharp high - energy cut is very natural . the injection spectrum was selected to be hard , @xmath212 , to optimize the required energetics . interestingly , magnetic reconnection , in particular in magnetized jet - cloud interactions , has been postulated to provide hard particle spectra ( see , e.g. , * ? ? ? * and references therein ) . in figure [ sed ] , the sed of a subflare is shown . the impact of the internal absorption on the gamma - ray spectrum is negligible , although the emission of the secondary pairs appears in the energy band constrained by optical measurements @xcite . for the chosen model parameters , the synchrotron secondary component goes right through the optical observational constraints , and for slightly higher @xmath213-values , the secondary emission will be well below the optical points ( see equation ) . also , we note that the obtained spectrum does not violate the x - ray upper - limits obtained by _ swift_. to illustrate the impact of external @xmath15 absorption , we have introduced a photon field peaking at 40 ev with a luminosity @xmath214 erg s@xmath5 , produced in a ring with radius @xmath215 cm at @xmath216 around the jet base . two photon fields have been adopted , a black body and one represented by a @xmath217-function , to simulate the impact of a dominant spectroscopic line . as seen in figure [ sed ] , the impact of such an external field can be important . the treatment of the secondary emission of the produced pairs is beyond the scope of this work . however , we note that the ambient magnetic field energy density could be well below that of radiation , allowing electromagnetic cascades to develop , effectively increasing the gamma - ray transparency . in fact , if it were not the case , the secondary synchrotron emission would likely violate the constraints from swift data ( see , e.g. , * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) . ebl absorption is not relevant in the energy range of interest . as seen in figure 4 , the spectral breaks induced by external absorption are very sharp and do not fit the data points . however , the properties of the external photon field can vary in a quite broad range , and it is expected that for some feasible photon field one could achieve a very good agreement between the emission spectrum and measurements ( see , e.g. , * ? ? ? * ) . instead of searching for such a field configuration , here we consider an alternative possibility . as mentioned above , we assume that the injection spectrum has not only an exponential cutoff at @xmath208 , but also a sharp upper limit at @xmath218 . as seen in figure 4 , this assumption , natural accounting for the fact that particles can not have arbitrarily high energies in the source , allows one to qualitatively model observations without invoking additional assumptions regarding external absorption . in addition to optical photons , radio emission was also detected at the flare epoch and thought to be linked to the gamma - ray activity @xcite . this radiation is strongly sensitive to the details of the flow dynamics , and at this stage we will not try to interpret radio observations . however , we note that the energetics involved in gamma - ray production is very large , and jrgi comprehends complex magnetohydrodynamical and radiative processes , so it could easily accommodate the presence of a population of radio - emitting electrons at @xmath219 . _ swift _ x - rays could be also linked to the jrgi activity . as stated in sect . [ genan ] , x - rays may come from secondary pairs produced via pair creation , or from a primary population of electrons(/positrons ) . however , as with radio data , given the complexity of the problem we have not tried at this stage to explain the x - ray emission contemporaneous to the gev flare . erg s@xmath5 , @xmath220 cm @xmath221 , @xmath222 g , @xmath223 cm , and @xmath200 . we show 4 subflares ( dashed lines ) , plateau background ( dot - dashed line ) , and the sum of all of them ( solid line ) . the observational data points and error bars are obtained from the 3h binned count rates and photon index using luminosity distance of @xmath224 and assuming a pure powerlaw spectrum between 0.1 and 5 gev.,scaledwidth=43.0% ] . dotted and dot - dot - dashed line shows gamma - ray spectra corrected for internal absorption only for @xmath210 and @xmath211 , respectively . the thin solid and the dot - dashed lines correspond to the cases when absorption is dominated by a black body and a monoenergetic photon field , respectively . the computed synchrotron sed of the secondary pairs produced via internal pair creation is also shown ( dotted line ) . the parameters of the flare are the same as in figure [ lc ] . the shown observational data are from , swift @xcite , and the flux in the r band @xcite.,scaledwidth=43.0% ] observations in the vhe domain put severe constraints on the size of the gamma - ray production site , supporting a scenario of a very compact emitter . the concept of a blob as a compact emitter inside jets is often used to interpret the nonthermal emission of agn . this paradigm is supported by a broad range of observations , in particular bright knots moving downstream the jets . the origin of such blobs is not clear . it was suggested that the blobs can form when an external object ( e.g. star or a cloud ; see @xcite and references therein ) penetrates into the jet and can lose its atmosphere due to the jet impact . because of the much larger obstacle density and the velocity difference , the intruding matter can not immediately dilute within the jet but has to be first heated and accelerated , which in supersonic jets will lead to strong shocks that can accelerate particles . therefore , this scenario naturally presents specific characteristics that are hard to introduce in pure jet models . for instance , the large blob density makes possible the formation of a radiation component typically suppressed in agn , i.e. emission generated at proton - proton collisions ( suggested to be behind the tev emission detected from m87 by hess * ? ? ? * ) . moreover , since the size of the blobs produced in this scenario is not constrained by the gravitational radius of the central black hole , it was proposed that this process could be responsible for the very rapidly variable tev emission detected from pks 2155 - 304 @xcite . the jrgi scenario may have quite general applications , but the properties of the emission expected within its framework are quite strictly constrained . in particular , the available energy budget and expected lightcurve shape can be determined with a simple dynamical model , which describes the evolution of the blob in the jet . depending on the jet properties and other factors like the viewing angle , the dominant emission channel can vary . however , the majority of the physical conclusions that can be inferred in the jrgi scenario are quite general because they concern the dynamics of compact blobs in relativistic jets , independently of the origin of the former and the nature of the radiation channel . the observations of 454 with _ fermi _ revealed several quite puzzling features , in particular the peculiar lightcurve , with a nearly steady plateau phase that was interrupted by an exceptionally bright flare . the detected flux corresponds to an apparent luminosity of @xmath225 , which almost unavoidably implies a presence of a very powerful jet ( see e.g. * ? ? ? * ) . in the case of powerful jets , the jrgi scenario should proceed in a quite specific way as compared to other cases already considered in the literature @xcite . in particular , the mass of the material initially removed from the star might be very large , resulting in rather long cloud expansion and acceleration timescales , the main flare being significantly delayed with respect to the moment of the star entrance into the jet . the plateau emission would otherwise start just after the jet penetration , and come from the jet crushing of lighter clouds ejected from the stellar surface while the star travels through the jet . the duration of the plateau phase would be determined by the time required by the main cloud to expand and accelerate . we have studied the lightcurve obtained with _ fermi _ in the context of the jrgi scenario aiming to satisfy three main properties of the flare : total energy , maximum luminosity and duration of the plateau stage . it was shown that the key properties of the jet , i.e. the jet ram pressure ( linked to its luminosity ) and lorentz factor , as well as the cloud / blob characteristics , i.e. mass and cross section , can be reconstructed as functions of the dimensionless parameter @xmath50 . it was also shown that in the limit of small @xmath50-values , the parameter space is less demanding concerning the jet luminosity , and the key characteristics of the model saturate at values independent of @xmath50 , which allows conclusive cross - checks of the scenario . in particular , the flare raise time appeared to be an independent parameter , with its value of @xmath226h closely matching the rising time of of @xmath227h obtained observationally . furthermore , it was shown ( see sec . [ pla ] ) that for the inferred jet properties the jet - induced stellar wind can provide a mass - loss rate large enough to generate a steady emission component with a luminosity comparable to that of the plateau . although the analysis of different radiation channels involves additional assumptions regarding the spectrum of the nonthermal particles and density of the target fields , it was possible to show that for magnetic fields not far below equipartition ( as expected in a magnetically launched jet ; see appendix for details ) all the conventional radiation channels can be discarded , and the emission detected with _ fermi _ can be produced through proton synchrotron emission ( unless @xmath228 , making electron synchrotron also feasible ) . we note that in this case the emission from pairs created within the blob may also explain the reported optical enhancement at the flare epoch . if the studied scenario is behind the november 2010 flare from 454 , it has some important implications on the properties of agn jets . on one hand , the obtained solution implies a super eddington jet . although this requirement may appear somewhat extreme , given the exceptional properties of the source it can not be ruled out ( and in fact super eddington jets might be a rather common phenomenon ; @xcite ) . in addition , the obtained solution ( eqs . ( [ eq : lum_final ] ) ( [ eq : size_final ] ) ) implies a lower limit on the central black hole mass that , for a location of the interaction region at @xmath229 , is roughly consistent with the measured values . also , adopting a magnetically launched jet model , it is possible to infer the mass of the central black hole as @xmath230 , which is again consistent with the measurements . at the initial stage of the cloud acceleration , the intensity of the jet - cloud interaction is the highest , but the associated emission is not doppler boosted and therefore very hard to detect in the high - energy regime . nevertheless , there are other manifestations of the jrgi scenario that may be observed . in particular , as reported by @xcite , a significant enhancement of the line emission from the source was recorded during the flare epoch . the detected flux was @xmath231 , implying an ionizing luminosity at the level of @xmath232 . according to our estimates , the initial blob acceleration period should be characterized by luminosities of @xmath233 , so only 1% of this luminosity would be required to explain the ionization line component . with the acceleration of the blob , its radiation gets beamed along the jet , thus reducing its impact on the blr and thereby weakening any related line emission . since the duration of the expansion phase determines the delay between the onset of the plateau phase and the flare itself , it is important to check whether the suggested scenario is consistent with other flares registered with _ fermi _ from the source , e.g. , in december 2009 and april 2010 @xcite . this issue can be addressed through a simple scaling that relates the duration of the plateau phase to the total energy released during the active phase : @xmath234 ( assuming a steady jet one can obtain from equations and that @xmath235 , which yields in the scaling dependence ) . therefore , for the previous events , with energy releases 1 - 2 orders of magnitude smaller than that of the november 2010 flare , a rough estimation of the plateau duration gives plateau durations between @xmath236 and @xmath237 days , consistent with observations . the amount of rgs or young protostars in the vicinity of the central bh may be enough to expect about one jrgi event per year ( see estimates in * ? ? ? * ; * ? ? ? * and references therein ) . however , these estimates are unfortunately strongly dependent on the stellar density in the region , a quantity still highly uncertain . nevertheless , our study ( and before @xcite ) shows that the penetration of a star into the base of the jet in a powerful blazar leads to a very characteristic dynamical evolution . in fact jrgi has a quite constrained physics with basically one free parameter : the nonthermal efficiency . the specific conditions in the jet / blob interaction region will determine , as long as particle acceleration occurs , the dominant radiation process , but in any case powerful high - emission seems natural in the proposed scenario . although the process of jet formation is not fully understood , recent hydrodynamical studies by different groups have shown that the bz process may be at work in agn , and suggest that , once formed , jets may be magnetically accelerated . in that scenario , the jet base is expected to be magnetically dominated at @xmath238 @xcite . during the jet propagation , the magnetic field energy can be transformed into bulk kinetic energy , with a simple prescription for the bulk lorentz factor at the linear acceleration stage of the form @xcite @xmath239 where @xmath240 and @xmath60 are the jet and the bh gravitational radius , respectively . the opening angle of the jet is expected to be @xmath241 @xcite . this leads to few useful relations between different jet parameters : @xmath242 it is also useful to express the above relation in the units used all through the paper : @xmath243 @xmath244 the jet magnetic field in the comoving frame can also be derived : @xmath245 if the mass of the blob is high , implying a low value of the @xmath50 parameter , then blobs can travel a significant distance along the jet . therefore , the jet properties can change , and this should have an impact on the emission associated with the blobs . these effects can be estimated via the approach suggested by @xcite . the dynamics of the blob is characterized by @xmath246 where @xmath24 is the ram pressure of the jet . since the emission of the blob is important only when it moves relativistically , it is safe to take @xmath247 and the initial condition @xmath248 . the above equation can be modified to a dimensionless form : @xmath249 where @xmath250 ; @xmath34 , @xmath251 and @xmath252 are the jet radius , ram pressure and lorentz factor at @xmath253 ; @xmath254 ; and the dimensionless parameter @xmath50 is determined as @xmath255 this approach is nearly identical to the one developed earlier , but here one accounts for the possible change of the properties of the jet ( e.g. for the increase of the jet lorentz factor ) . if @xmath256 , the blob gets rapidly involved into the jet motion , so the solution is identical to the one obtained in @xcite even if the properties of the jet are changing with z. however , if @xmath54 , the structure of the jet may have some influence on the properties of the emission . in particular , for purely magnetically driven jets , i.e. with a parabolic shape , the above equation can be simplified , since the following relations hold @xmath257 @xmath258 @xmath259 thus , the equation of motion ( [ eq : motion_eq ] ) yields @xmath260 with the boundary condition @xmath261 . although this equation does not have any analytical solution , an _ asymptotic _ solution can be derived for @xmath135 ( i.e. the jet structure is important ) : @xmath262^{1/3}\,.\ ] ] for the case of a conical jet ( i.e. , @xmath263 , @xmath264 and @xmath265 ) , the equation of motion is reduced to the equation : @xmath266 which allows an analytical solution ( for details , see * ? ? ? however , since the analytical solution is rather bulky , we use the asymptotic solution : @xmath267^{1/3}\,.\ ] ] which is valid for @xmath135 . since the models of parabolic and conical jets correspond to the most feasible jet model , we will consider the realization of the jrgi scenario for these two cases . the obtained asymptotic solutions allow one to clearly estimate the differences that depend on the specific jet configuration . the intensity of the nonthermal emission of the blob , corrected for doppler boosting , has the following form : @xmath268 where @xmath269 is the correction function . the maximum value of the correction function , @xmath270 , depends on the value of the @xmath50 parameter and on the structure of the jet . if @xmath271 it saturates on a constant value of @xmath272 independent of the jet properties . in the case of @xmath135 , the asymptotic solutions show that the maximum of the correction function is reached at @xmath273 , with @xmath274 for a parabolic jet , and for a conical jet , @xmath275 and @xmath276 . in the intermediate range , @xmath277 , @xmath270 is @xmath278 and @xmath279 for the parabolic and conical jets , respectively . the location of the maximum @xmath280 has a weak dependence of @xmath50 in this regime ; i.e. depending on the structure of the jet , the maximum intensity , @xmath270 , can vary by a factor of @xmath84 in the case of @xmath54 . the total energy emitted by a blob can be obtained via the integration of the luminosity over the observer time ( @xmath281 ) : @xmath282 this equation _ defines _ the function @xmath131 . for large values of the @xmath50 parameter , the integration term in the above equation can be obtained analytically if one accounts for the relation @xmath283 : @xmath284 here we note that , in the case of an accelerating jet , the integral determining the total emitted energy is divergent . formally , this is so because of @xmath285 . therefore , the integration should be artificially truncated at some point . physically , this point would correspond to the moment when the blob gets homogenized in the jet . for large values of @xmath50 , the blob speed rapidly reaches the jet velocity , and one should adopt @xmath286 . for small @xmath50 values , we use @xmath287 , which is a precise identity for the case of a conical jet , and corresponds to a truncation at @xmath288 for a parabolic jet . therefore , for the present order - of - magnitude estimates , one can estimate the energy emitted by the blob as @xmath289 since the structure of the jet only imposes uncertainties of the order of 2 , for the order - of - magnitude estimates presented in this paper we use the solution obtained for the conical jet structure . to use the solution obtained for the parabolic structure of the jet one should properly describe the process of the blob homogenization in the jet , which is out of the scope of this work . one can obtain a simplified analytical solution which allows the determination of the jet parameters . ignoring the weak dependence on @xmath37 in equation , one obtains : @xmath290 from equation ( [ mass_condtion ] ) , one can infer the mass of the cloud : @xmath291 and equation ( [ eq : super_edd ] ) can be re - normalized as @xmath292 finally , the definition of the @xmath50 parameter , equation ( [ dd ] ) , provides the fourth required equation to determine the parameters @xmath293 , @xmath294 , @xmath295 and @xmath251 . here we assume that the flare was the result of the superposition of 4 subflares ( i.e. , @xmath296 ) : @xmath297 equations ( [ eq : ap_flux ] [ eq : ap_dd ] ) have a unique solution , which characterizes the parameters @xmath293 , @xmath294 , @xmath295 and @xmath251 as functions of @xmath50 : @xmath298 @xmath299 @xmath300 and @xmath301 the values @xmath270 and @xmath131 depend on the value of the @xmath50 parameter and the structure of the jet . to illustrate the feasibility of the derived solution , in figure [ fig : solution ] we show the jet parameters as functions of the @xmath50 parameter . the authors are thankful to s. kelner for useful discussions and benoit lott for providing observational data . the research leading to these results has received funding from the european union seventh framework program ( fp7/2007 - 2013 ) under grant agreement pief - ga-2009 - 252463 . r . acknowledges support by the spanish ministerio de ciencia e innovacin ( micinn ) under grants aya2010 - 21782-c03 - 01 and fpa2010 - 22056-c06 - 02 . r . acknowledges financial support from mineco through a ramn y cajal fellowship . this research has been supported by the marie curie career integration grant 321520 . bmv acknowledges partial support by rfbr grant 12 - 02 - 01336-a .

we propose a model to explain the ultra - bright gev gamma - ray flares observed from the blazar 454 . the model is based on the concept of a relativistic jet interacting with compact gas condensations produced when a star ( red giant ) crosses the jet close to the central black hole . the study includes an analytical treatment of the evolution of the envelop lost by the star within the jet , and calculations of the related high - energy radiation . the model readily explains the day - long , variable on timescales of hours , gev gamma - ray flare from 454 , observed during november 2010 on top of a weeks - long plateau . in the proposed scenario , the plateau state is caused by a strong wind generated by the heating of the star atmosphere by nonthermal particles accelerated at the jet - star interaction region . the flare itself could be produced by a few clouds of matter lost by the red giant after the initial impact of the jet . in the framework of the proposed scenario , the observations constrain the key model parameters of the source , including the mass of the central black hole : @xmath0 , the total jet power : @xmath1 , and the doppler factor of the gamma - ray emitting clouds , @xmath2 . whereas we do not specify the particle acceleration mechanisms , the potential gamma - ray production processes are discussed and compared in the context of the proposed model . we argue that synchrotron radiation of protons has certain advantages compared to other radiation channels of directly accelerated electrons . 4543c454.3 501

many experiments aiming at recording so - called `` molecular movies '' the atomic - resolution imaging of the intrinsic structural dynamics of molecules rely on molecules fixed - in - space , , aligned or oriented samples of molecules @xcite . one of the most promising approaches is coherent x - ray diffractive imaging , for instance , using short - wavelength free - electron lasers or synchrotrons @xcite . these modern light sources , especially upcoming free - electron lasers with very large photon fluxes such as the european xfel @xcite or lcls ii @xcite , but also synchrotrons @xcite as well as table - top laser systems based on optical - parametric chirped - pulse amplification ( opcpa ) @xcite , operate at very high repetition rates with ten - thousands to millions of pulses per second , sometimes in burst modes , which have to be matched by the high - intensity optical control lasers . the alignment of gas - phase ensembles of molecules exploits the interaction between the anisotropic polarizability of the molecule and non - resonant linearly or elliptically , polarized electric fields @xcite . the electric field strengths necessary for strong ( quasi ) adiabatic alignment are on the order of @xmath9 , even when exploiting very cold samples @xcite , and must be applied over durations longer than , or at least comparable to , the rotation periods of the molecules @xcite . these range from tens of picoseconds for small molecules to nanoseconds or even microseconds for larger molecules . adiabatic mixed - field orientation requires the addition of a moderate dc electric field and even longer laser pulses @xcite . three - dimensional control requires elliptically polarized fields with fully controllable ellipticity @xcite . traditionally , injection - seeded nd : yag lasers operating at a repetition rate of some 10 hz were used to provide the necessary fields . recently , we have demonstrated the use of chirped pulses from amplified ti : sapphire laser systems at 1 khz @xcite and the implementation of this amplified - chirped - pulse technique at the linac coherent light source ( lcls ) at 120 hz @xcite . continuous - wave ( cw ) lasers would allow for the control of molecules at arbitrary repetition rates . furthermore , they would enable long interaction times . for instance , molecules or particles traveling through a 50 laser beam with a velocity of 100 m / s @xcite would experience an effective pulse duration of 0.5 . however , the use of cw lasers to provide the envisioned field strengths with focal beam waists in excess of @xmath10 would require optical power levels of 30300 kw , respectively , with a beam quality that allows for such tight focusing with a rayleigh length comparable to the molecular beam diameter on the order of 1 mm . 100-kw - class cw lasers have been realized as fiber lasers @xcite , as co@xmath5 lasers @xcite and as chemical deuterium fluoride lasers @xcite . coherent beam combining @xcite is also a viable approach to achieve laser output at this power level @xcite . the thin - disk laser ( tdl ) geometry has been shown to be suited for very high cw output powers in combinition with yb@xmath8-doped gain materials @xcite . outputs exceeding 27 kw were demonstrated @xcite and 100-kw - systems are anticipated @xcite . so far these high output powers of thin - disk lasers and fiber lasers are only available at beam qualities @xcite that do not allow for the tight focusing necessary to achieve the envisioned focal intensities . in contrast , carbon dioxide and chemical lasers have good beam qualities at even higher output power , but their demanding space requirements and the possibly toxic gain materials are a significant drawback for using the setup as a mobile user facility at modern x - ray light sources . moreover , operating and propagating any laser at such high output power levels imposes serious safety risks . here , we propose to provide the necessary field strength in an intracavity focus of a cw tdl resonator . a resonator with low losses , low output coupler transmission , and high intracavity power has a low stored excitation energy in the crystal , a high photon energy storage in the resonator and comparably low output power . the required pump power levels are reasonably low due to the strong enhancement in the active cavity and allow for a cost efficient system , without an exceptional laser - safety risk . in combination with its small spatial footprint , such a system is an ideal candidate for flexible and safe employment at modern light sources . a long multiply - folded resonator allows for tem@xmath11 operation and enables to focus the beam with the necessary rayleigh length of 1-mm . operation , focused inside of a vacuum chamber leads to the required focal intensities for alignment of molecules . ( b ) : mode averaging in the resonator yields in smooth intensity distribution and avoids spatial hole burning . ] the envisioned aligned - molecule - imaging experiments impose a number of design criteria on the tdl . these arise partly from the actual molecular physics and partly from the need for integration of the alignment laser into the complex and constraining machinery of the experimental setup , schematically shown in fig . [ fig : resonator - scheme ] . the ultra - high - vacuum needs impose further restrictions on the design of the setup . in order to ensure the alignment of all probed molecules , the electric field intensity of @xmath12 utilized to control the molecules , has to be spatially and temporally smooth and nearly constant over the diffraction volume . the latter is defined by the overlap of the few - mm - diameter molecular beam and the 10 - -diameter x - ray - beam . such a homogeneous field can be achieved inside the tdl resonator through multi - longitudinal - mode operation , as depicted in the inset of fig . [ fig : resonator - scheme ] . the different modes average out the field distribution around the interaction point . for a few ten modes a longitudinally practically homogeneous field is achieved in the resonator . under these conditions , spatial hole burning could only occur close to the end mirrors . multi - longitudinal mode operation does not impose a serious challenge for the bandwidth of the laser material or the resonator design . at a typical lengths of a tem@xmath11 tdl of 1 m , hundreds of longitudinal modes fit into 1 pm of laser emission bandwidth in the 1 wavelength range . yb@xmath8-doped lasers typically exhibit emission bands with much broader bandwidths in the nanometer range . the laser beam needs to be focused to create the necessary field strength . at the same time , the tdl beam needs to be larger than the x - ray beams , which are typically kept on the order of 10 to avoid radiation damage @xcite , and its rayleigh length needs to be long enough to provide the necessary field strength over the width of the molecular beam of typically a few mm . this results in an envisioned focal waist of the tdl of approximately 2040 . such small focal spot sizes require sophisticated astigmatism compensation , which has to be considered in the resonator design . furthermore , a stable linear or elliptical polarization state is required . the cold molecular beam has to be delivered to the intracavity focus and the degree of alignment needs to be monitored , for instance , through velocity map ion imaging ( vmi ) @xcite . at the current state , the dimensions of the delivery mechanics and the vmi device require a clear space of tens of @xmath13 around the focus . moreover , the x - ray beam must pass the focus nearly collinear with the tdl intracavity mode to achieve a good overlap with the volume of strongly aligned molecules . finally , the laser wavelength must be off - resonant with respect to the molecular sample to avoid excitation and radiation damage from the control beam . as the electronic transitions of molecules are typically in the ultraviolet or visible spectral range and vibrational excitations in the mid - infrared range , this requirement is usually fulfilled by yb@xmath8-based lasers with emission wavelengths around 1 . in a first proof - of - principle experiment a tdl was set up in a short longitudinal resonator . this allowed to characterize different gain materials at low output coupler transmissions with respect to their losses and their efficiencies . the experiments were carried out utilizing a yb(7 % ) : y@xmath14al@xmath15o@xmath7 ( yb : yag ) disk ( dausinger+giesen ) with a thickness of 0.22 mm and a yb(3 % ) : lu@xmath16o@xmath14 disk with a thickness of 0.25 mm @xcite . due to the different cation densities @xcite in both host materials , the different values for the yb@xmath8-doping correspond to a similar yb@xmath8-density of ~10@xmath17 @xmath18 . both disks were soldered onto copper - tungsten - alloy heat - sinks ( 20/80 for @xmath2and 10/90 for @xmath3 ) , which were cooled at a water temperature of during the experiments . the disks were pumped by 600 -core multimode fiber coupled ingaas laser diodes , which were imaged onto a 1.2 mm diameter pump spot on the disk . for the @xmath2disk a pump wavelength of 940 nm corresponding to a broad @xmath2absorption band in this wavelength range was chosen . the jenoptik jold-75-cpxf-2p laser diode utilized for this purpose had a maximum output power of 75 w and up to 56 w were used in the experiments . in contrast , @xmath3provides a much stronger absorption at the zero - phonon line around 976 nm@xcite . the corresponding jold-50-cpxf-2p pump laser diode provided up to 50 w of output power which was fully utilized . the temperature of the pump diodes was adjusted to fine - tune the emission wavelength for an optimum absorption of the pump power . after the 24 pump - light passes in our tdl module , more than 99 % of the pump power was absorbed . a simple plane - concave resonator with a length of 60 mm and different output coupling mirrors with radii of curvature ( roc ) of 100 mm ( roc of the disks @xmath19 2 m ) was set up for efficient multimode laser operation . the output - coupling mirrors had transmissions between @xmath20 and @xmath21 for all wavelengths between 1 and 1.1 . the output coupler transmissions were initially measured with a spectrometer ( varian cary 5000 ) and cross - checked by measuring the transmission of the output of a @xmath3tdl operating at wavelength of 1080 nm through these mirrors . the laser output power was measured with a coherent lm-100 power meter . to avoid damage of the disks we limited the maximum pump power to the value which resulted in a disk surface temperature of @xmath22 . for this purpose we monitored the surface temperature of the laser disks with a sc645 thermographic camera ( flir systems ) . the measured values were corrected by the temperature dependent emissivity of the respective gain material . the emission spectra of the lasers were measured with a spectrometer ( ocean optics hr2000 ) , suitable for the wavelength range between 950 nm and 1100 nm . disk and a 0.25 mm thick @xmath3disk for different output coupler transmissions . ( b ) slope efficiency and surface temperature ( @xmath23 = 50 w ) for different output coupler transmissions . ] in fig . [ fig : laserperformance](a ) the laser performance of the @xmath2and the @xmath3disks are shown for three output coupler transmissions of @xmath20 , @xmath24 , @xmath21 . the observed slope efficiencies as well as the measured surface temperatures for these and other mirrors for a pump power of 50 w are shown in fig . [ fig : laserperformance](b ) . as the surface temperature of @xmath3exceeded a damage - critical temperature of for the lowest output coupler transmission , the maximum pump power was limited to 47 w for this mirror . for @xmath2and @xmath3maximum slope efficiencies of 67 % and 72 % were measured at the highest output coupler transmission rate of @xmath21 with a maximum output power of 36 w and 34 w , respectively . in this configuration , the maximum optical - to - optical efficiency was 66 % and 68 % , respectively . it should be noted that these @xmath25 are significantly below the optimum @xmath25 for maximum laser output for these materials @xcite . thus , the efficiencies reported here are lower than previously reported @xcite . however , from the measured efficiencies it can be concluded that the losses through the output coupling mirror are significantly higher than the losses in the disks at these output coupler transmissions . for both materials , this results in low surface temperatures even at pump powers of 50 w , which range from around for large output coupler transmissions to the highest surface temperatures of and for @xmath2and @xmath3 , respectively , measured at the lowest output coupler transmission rate of @xmath20 . here , the losses in the disks mainly cause a strong heating of the laser disks as they dominate over the output coupler transmission losses . despite this relatively strong heating , for both lasers no thermal roll over could be observed , and maximum output powers @xmath26 of 13 w and 10 w were reached , respectively . from these numbers the intracavity power @xmath27 was derived from the known output coupler transmission @xmath28 as @xmath29 both disks achieved their highest cw intracavity power of @xmath30 kw for @xmath2and 105 kw for @xmath3at minimized total resonator losses , , at the lowest output coupler transmission rate of @xmath20 . at such low output coupler transmissions the laser spectrum of @xmath2covers wavelengths between 1050 nm and 1085 nm , while the @xmath3laser oscillates at wavelengths between 1078 nm and 1082 nm . from the laser performance at different / lowest output coupler transmissions , we derived the resonator round - trip losses by the caird analysis @xcite . the slope efficiency @xmath31 of a laser follows from @xmath32 with the the output coupling efficiency @xmath33 , the stokes efficiency @xmath34 , the pump absorption efficiency @xmath35 , and the pump - laser mode overlap efficiency @xmath36 . the product of the latter three can be abbreviated as total efficiency @xmath37 . trivial rearrangements lead to @xmath38 which allows to derive the resonator losses from a linear fit of the inverted slope efficiencies versus the inverted output coupler transmission . it is known that the caird plot may not lead to reasonable results at higher output coupler transmissions , where the slope efficiency decreases due to loss processes at high inversion densities which are not covered by the underlying rate equations @xcite . however , at the low output coupler transmissions used in our experiments , these effects are negligible . and @xmath3disk according to eq . [ eq : caird ] . ( b ) calculated intracavity power for internal losses of @xmath39 for fixed pump powers against additional losses . ] the fit according to eq . [ eq : caird ] is shown in fig . [ fig : calculations](a ) and results in very low round - trip losses of @xmath40 for @xmath2and only slightly higher losses of @xmath41 for @xmath3 . the total efficiency amounts to 71 % for @xmath2and 77 % for @xmath3 . considering the slope efficiencies @xmath42 approaching the stokes efficiencies @xmath43 previously observed in tdls @xcite one might argue that the absorption efficiency @xmath44 and the overlap efficiency of pump and laser mode @xmath36 should be approaching unity . this condition is fulfilled by deriving the intracavity losses from the ratio of the stokes efficiency @xmath45 and the slope efficiency @xmath31 at the lowest output coupler transmission from @xmath46 despite the higher stokes efficiency of @xmath47 , even in this case the corresponding losses are only slightly higher and amount to @xmath48 for @xmath2and @xmath49 for @xmath3 . nota bene , this is an upper level for the intracavity losses due to energy conservation . the intracavity power considering realistic resonator losses of @xmath50 plus additional losses @xmath51 between @xmath52 and @xmath53 due to output coupler transmission or other intracavity elements required e.g. for the polarization selection were calculated for pump powers @xmath54 between 100 w and 600 w with @xmath55 this equation can be simplified by assuming a threshold power @xmath56 of zero , which is appropriate as pump thresholds @xmath57 w were observed in all experiments . the resulting intracavity powers are depicted in fig . [ fig : calculations](b ) . all measurements were performed in a short linear laser resonator to allow for both , efficient multi - mode lasing and for easy evaluation of losses , which require knowledge of the specific loss of all optical components . under these conditions the gain - medium - specific resonator losses @xmath58 can be nearly exclusively attributed to losses in the tdl assembly , , the laser - medium disk with its dielectric coatings and the metallic contacting layer . while the @xmath2disk showed in general better performance , our experiments do not provide conclusive evidence about the material - specific advantage of @xmath2or @xmath3 . using a pump power of 54 w we achieved an intracavity power of @xmath59 for @xmath2 . this is to the best of our knowledge the highest documented cw intracavity power for a pump power lower than 100 w. typically , such cw intracavity powers are only achieved using pump powers of 10 kw . the slope efficiencies obtained with @xmath2and @xmath3of 0.66 and 0.72 , respectively are in good agreement with previous results at such low output coupling transmissions @xcite . the measured laser performance at various low output coupler transmissions below @xmath21 allows to precisely determine an upper limit of the internal resonator losses of a few @xmath60 , which is about an order of magnitude lower than previously assumed @xcite . this also demonstrates the low losses of the thin - disk laser resonator and the excellent quality of the utilized disks , which benefited from improvements in the crystal growth and in optical coating methods over the last decade . the results in fig . [ fig : calculations](b ) reveal that intracavity power levels in excess of 0.5 mw can be achieved at pump powers of a few 100 w , even at total resonator losses in the order of @xmath61 , which would be five times higher than the intracavity losses of @xmath39 we determined for multi - mode linear tdls using state - of - the - art processed gain materials and standard resonator mirrors . at such intracavity power levels , the required focal intensities for molecular alignment in the order of @xmath62@xmath63 could be achieved at realistic intracavity focal diameters of 2040 . such diameters can be obtained between two concave cavity mirrors and do not impose a particular challenge for the resonator design . slightly larger intracavity foci have already been demonstrated e.g. in enhancement cavities and conventional resonators @xcite . figure 3 ( b ) also shows that minimized resonator losses are of crucial importance for achieving high intracavity power levels at moderate pump power levels . we note that we operated our tdl at output coupler transmissions in the order of @xmath60 . however , in the upcoming experiments the resonator losses will be increased by additional resonator elements , for instance a brewster plate . at intracavity powers in excess of 100 kw even a very low transmission of 10@xmath64 results in leakage of more than 10 mw , which allows for a reliable determination of the intracavity power . moreover , we expect the main additional losses to occur due to depolarization at polarization control elements , , reflections at brewster elements or transmission losses at mirrors with a polarization dependent reflectivity . both should increase resonator extraction efficiency and thus avoid hot - spots in the cavity . therefore , the disk temperatures should remain lower than demonstrated here , even when using hr mirrors . the considerations so far were independent of the pump spot diameter on the disk . we have shown that further scaling of the intracavity power may lead to strong heating of the disk . this can be circumvented by choosing larger pump spot diameters , which allows to use significantly higher pump powers . even though the alignment sensitivity increases strongly with the laser mode diameter on the disks @xcite , tdl with centimeter - scale pump spot diameters are reported @xcite . even in fundamental mode operation , a 4.7 mm pump spot diameter has been reported at a pump power of up to 830 w @xcite ; this corresponds to pump power intensities on the order of @xmath65 . in this case the output coupler transmission was optimized for high extraction efficiency , but at the maximum output power of 430 w the remaining pump power deposited in the disk was still as high as 400 w. this pump power level should be sufficient for our experiments . the application of the laser for molecular alignment requires operation in vacuum and polarization control . preliminary results in vacuum ( @xmath66 mbar ) point towards an increased operation stability due to the lack of atmospheric turbulence , in agreement with previous reports @xcite . further experiments are required to explore further challenges , , the corresponding lack of convection cooling of the optical elements and mounts . for the alignment experiments it would be sufficient to keep only the focal area of the resonator in a vacuum chamber , but the required additional brewster windows and polarization optics would add complexity and increase the total resonator losses . when operated in ultra - high - vacuum ( @xmath67 mbar ) and combined with a continuous cold supersonic molecular beam @xcite , the demonstrated laser system will allow to strongly align and orient molecules at `` arbitrary '' repetition rates . the continuous presence of aligned molecules will enable the envisioned application of strongly controlled molecules in modern imaging experiments at high - repetition rate x - ray facilities @xcite . we have demonstrated a thin - disk laser providing 135 kw of cw intracavity laser power . this corresponded to an enhancement by a factor of 2500 with respect to the incident pump power of 54 w , enabled by the low losses of state - of - the - art - processed gain disks . the internal round - trip losses of @xmath2and @xmath3disks were determined to be about @xmath39 . calculations show that our approach is scalable and will allow for megawatt - level cw intracavity powers , thus , enabling field - strengths in excess of @xmath68 in a few-10 - -diameter focus . such ac electric field strengths allow for adiabatic laser alignment or mixed - field orientation of molecules . while pulsed lasers at comparably low repetition rates have been used for this purpose @xcite , our approach allows for adiabatic alignment at arbitrary repetition rates . coupled to a continuous molecular beam , such a setup could allow for the implementation of reactive , chemical scattering investigations of aligned or oriented molecules @xcite , albeit limited to the very small focal volume ( @xmath69 ) . moreover , we point out that our laser would also allow for the trapping of atoms and molecules using the polarizability interaction @xcite . it would allow for few - kelvin deep traps for typical small molecules @xcite and even deeper traps for larger , more polarizable molecules . this could also be utilized for _ in - vacuo _ trapping and guiding of nanoparticles @xcite . the setup could be useful for many more strong - field experiments in atomic and molecular physics , for instance , at high - repetition - rate fels @xcite . this work has been supported by the excellence cluster `` the hamburg center for ultrafast imaging structure , dynamics and control of matter at the atomic scale '' ( cui ) of the deutsche forschungsgemeinschaft ( dfg exc1074 ) .

we propose a novel approach for strong alignment of gas - phase molecules for experiments at arbitrary repetition rates . a high - intracavity - power continuous - wave laser will provide the necessary ac electric field of @xmath0@xmath1 . we demonstrate thin - disk lasers based on @xmath2and @xmath3 in a linear high - finesse resonator providing intracavity power levels in excess of 100 kw at pump power levels on the order of 50 w. the multi - longitudinal - mode operation of this laser avoids spatial - hole burning even in a linear standing - wave resonator . the system will be scaled up as in - vacuum system to allow for the generation of fields of @xmath4 . this system will be directly applicable for experiments at modern x - ray light sources , such as synchrotrons or free - electron lasers , which operate at various very high repetition rates . this would allow to record molecular movies through temporally resolved diffractive imaging of fixed - in - space molecules , as well as the spectroscopic investigation of combined x - 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obesity and overweight are regarded be the most common metabolic disorders and an important disease of the recent decades . obesity is the predisposing factor of most non - contagious diseases , which allotted a considerable contribution of diseases and disabilities . since 1977 , who has announced obesity as a major problem in developed and developing countries ( 1 ) . different studies have been carried out to examine the dimensions and spread of this phenomenon . these studies indicate the high incidence of obesity , overweight , and abdominal obesity in different parts of iran with obesity rate reported greater for women than man ( 25 ) . to prevent most diseases and obesity - induced disorders in nationwide , we have felt that implementation of applied researches to recognize the prevalence patterns of this phenomenon as the most important rubric in health science researches . drawing the geographic maps to recognize the grounding reasons and related data for obesity can be the first stop . in fact , disease mapping is a collection of statistical methods , which is applied to gain careful estimates of incidence of mortality or disease , and to compile them in geographic maps ( 6 ) . disease mapping has a long history in epidemiology , which may be defined as the estimation and presentation of summary measures of health outcomes . disease mapping are valuable tools to determine the regions with high risk of infliction , which need therapeutic or intervention programs . in the problems of disease mapping , disease distribution has a spatial form . to find the deviation from the expected value of disease in the society and determine the regions , which have risk higher than the expected one , are the goals of mapping . traditionally , standardized mortality ratio ( smr ) was used for the disease map presentation , but has many drawbacks . it is the ratio estimate of observed and expected , which yield produce large changes in estimate while small changes in expected value . furthermore , when a minimum expectation is found , the smr will be very large , so this smr is a saturated estimate of relative risk ( 7 ) . therefore , crude risks are not trusty values to map the diseases since they are inaccurate in very small regions , also rates with large chance variation tend to highlight the map and such map does not yield meaningful / useful interpretation(8 ) . disease mapping has a long history in epidemiology as part of the classic triad of person / place / time . john snow , 19 century used point map technique to investigate the epidemics of plague in london(9 ) . the scattering of data and possible correlation of the observed data in adjacent regions is a great barrier for which formulating data in bayesian hierarchical model has been proposed . model - based disease mapping ( bayesian ) predict the local area risks ensemble in an optimal way , separate systematic variability from random noise and produce clean maps from random noise and any outcomes of population variation ( 10 ) . clayton and kaldor proposed the hierarchical models and related empirical bayesian inference for standardized mortalities when there is a spatial correlation between the observations in neighboring regions ( 11 ) . in the recent years , different spatial models have been proposed for hidden hierarchical levels . since the nearby regions have the same rates of disease or mortality , the spatial pattern must be considered in map parameter s estimation . therefore , to evaluate such cases , bayesian method has been proposed , which incorporates the information related to deaths and the cases observed in each region and that related to relative risks of the whole region in terms of the prior distribution ( 6 ) . in another word , in the bayesian spatial models , the purpose is to obtain the smooth estimates of odds ratio ( or ) . bayesian hierarchical models are typically used to produce such maps , where the spatial pattern in disease risk is represented by a set of random effects . these random effects are often assigned by a conditional autoregressive ( car ) prior ( 1213 ) . there have been carried out some studies via bayesian methods like mapping geographical variations related to acute heart infarcts , parkinson , the diabetes type i ( 6 ) . due to the lack of specific mapping health symptoms such as obesity through spatial bayesian methods , we have set out to draw a geographical map based on bayesian spatial method to recognize the pattern of obesity in iran . the aim of this study was to produce accurate map of obesity based on estimated odds ratio in iran . the data on this study consist of the number of obese people in the population of provinces in terms of gender based on the latest published report of risk factors of non contagious diseases in 30 provinces in 2007 presented by the disease center of health , treatment and medical education of iran ( 14 ) . obesity and overweight evaluation have been , based on the criterion of who , the body mass index ( bmi ) , obtained by dividing weight ( kg ) on height squared ( m2 ) . the index greater than 30 is considered the represent of obesity , in addition , the data on the location of each province expressed as the adjacency matrix , was used . the population of men ( women ) was shown in each province by ni and the number of people with bmi>30 as yi assume that the number found obese people at the location i is yi out of ni sampled , then yi is a binomial random variable , yi bin ( ni , pi ) , where pi is the proportion infected at each location . the ordinary logistic model is given by log ( pi1pi)=0+biwhere 0 ( the intercept ) indicates the logarithm of global mean odds of the entire country . bi is the random effect specific to the region which shows the logarithm of remaining or unexplained odds ratio of obesity in the i - th province . in addition , to consider spatial correlation between spatial effects of bi in neighboring provinces , the conditional auto regression was used and monet carlo markov chain ( mcmc ) algorithm and gibes and metropolis hasting sampling was used for prior distribution . in these conditions , the estimation of prevalence of obesity in the i - th province was calculated by : pi = exp ( 0+bi)1+exp ( 0+bi)we refer to or = exp(bi ) an odds ratio , which is a ratio of the local area odds over the global mean odds ( 10 ) . the results of a bayesian disease - mapping analysis are presented in the form of a map displaying a point estimate of the odds ratio for each province . the data analysis was carried by r and open bugs software . in addition also we assessed mcmc convergence of all model parameters by trace plots and autocorrelation plots of the mcmc output after burn - in . furthermore , we look at different diagnostics to check the convergence of an mcmc algorithm such as the geweke s convergence diagnostic ( z - score ) . this is supported in the coda package in r. the result showed that the mcmc algorithm is convergent . the result of this study related to prevalence of obesity and obesity rank of the provinces are presented in table 1 . based on the findings , the greatest percentage of the obese people in all age ranges ( 1564 yr ) was in mazandaran ( 17.8 ) and the lowest in sistan and baluchestan ( 4.0 ) for men . the figure for women was 29.4 and 1.9 for women in mazandaran and hormozgan , respectively . the odds ratio of obesity in various provinces of the country is shown in terms of men and women in the table 1 . based on the results , mazandaran ( or=1.71 ) , tehran ( 1.56 ) and gilan ( 1.51 ) was recognized to be the provinces of the greatest odds ratio for women followed by khozestan ( 1.48 ) , east azerbaijan ( 1.47 ) , west azerbaijan(1.44 ) , ardabil ( 1.34 ) and kermanshah ( 1.26 ) as high risk provinces and qom(1.23 ) , ghazvin ( 1.22 ) , golestan ( 1.17 ) , zanjan ( 1.04 ) , kordestan ( 1.02 ) , semnan ( 1.01 ) and yazd ( 1.00 ) as medium risk and other provinces as low risk . for men , mazandaran ( 2.02 ) was the province of the greatest odds ratio followed by tehran ( 1.57 ) and ardabil ( 1.50 ) , qom ( 1.48 ) , zanjan ( 1.36 ) , west azerbaijan ( 1.32 ) , yazd ( 1.27 ) , khozestan ( 1.26 ) , semnan ( 1.24 ) , east azerbaijan ( 1.20 ) , golestan ( 1.19 ) , esfahan ( 1.19 ) , gilan ( 1.08 ) , razavi khorasan ( 1.00 ) , ghazvin ( 1.00 ) and respectively and other provinces have low risk . the mapping of estimation of the obesity or for men and women in the provinces , based on bayesian spatial method and the results of table 1 are presented in fig.1 and fig.2 . the results show that bayesian spatial method can illustrate the odds ratio of obesity in the country geographically . the estimates of bayesian spatial model are taken from 10000 iterations and the map is drawn through the mean of iterative estimates . with the emerge of medical and health data expressed in terms of geographical areas , the study of mapping diseases in small areas has been suggested as a new technique in geographical epidemiology ( 7 ) . as the geographical areas usually consist of populations with different sex and age structure , using crude estimates in drawing geographical maps is misleading . today , mapping diseases are of great interest for health authorities , due to its significance to diagnose the risk factors . if we know a special disease occurs in some areas more than in others , we want to provide better medical facilities in these areas . mapping spatial distributions of disease occurrence can serve as a useful tool for recognizing exposures of public health concern ( 13 ) . application of lately developed bayesian hierarchical models facilitates the prediction of spatial patterns for recognizing areas in need and the estimation of risk associations for informed health service plan and resource allocation . in this article , we present such an application . bayesian conditional autoregressive model is a disease mapping method , which is used for smoothening of the odds ratio . this model gives some shrinkage and spatial smoothing of the crud estimate , which gives a more stable estimate of the pattern of underlying risk of disease than that provided by the raw estimates . this method efficiently lends information from neighboring areas than from areas far away and smoothing local rates toward local , neighboring values . this reduces the variance in the related estimates and allows for the spatial effect of regional differences in province populations ( 8) . this study discussed bayesian spatial modeling and spatial smoothing of relative odds ratios where local information relevant to the rate odds for each individual province and global information relevant to the overall dispersion of the underlying spatial disease rates are integrated via a conditional autoregressive prior . we used bayesian spatial model to draw the geographical map of obesity in iran in which the data related to observed cases of obesity in each province were determined by logistic distribution . we incorporated the data of prevalence of the country summarized in prior distribution with the spatial pattern of observations to provide more accurate estimates for odds ratio of obesity so that a more trustworthy map could be obtained . in fact , one of the benefits of bayesian spatial models is to estimate the auto correlations simultaneously by using fitted regression model parameters ( 612 ) . many studies used classical and frequentist method to disease mapping ( 15 , 16 ) . the bayesian allows the modeling of both sources of over dispersion , heterogeneity and spatial dependence or clustering in the model ( 17 ) ; however , it is not independent of selected prior distribution ( 15 ) . the limitation of the study is absence of registered auxiliary variables such as lifestyle to adjust the odds ratio of obesity . it is worthy to state that there is not any possibility of comparing our findings with other studies . the studies carried out in iran have focused on the incidence of cardio - vascular diseases and obesity factors with a few paying attention to drawing geographical maps of disease based on statistical techniques . gharibzadeh et al . , tried to draw the nationwide map of acute flaccid paralysis by using mixture models ( 18 ) . drew the map of relative mortality of infants under one year in rural areas by using bayesian methods and maximum likelihood ( 19 ) . drew the geographical map of gastric cancer in the caspian sea region by this method ( 21 ) . in finland , ( 2008 ) drew the geographical map of obesity by bayesian hierarchical methods with gis software ( 22 ) . johnson ( 2004 ) drew the incidence pattern of prostate cancer in new york by bayesian hierarchical methods ( 23 ) . in ireland , avril et al . ( 2010 ) used bayesian spatial models of conditional auto regression and multiplied partition model to map cancer ( 24 ) . in this study , the geographical distribution of obesity was drowning so that regions at high risk of obesity are considered for the main prerequisite of managerial decision making and planning in health system . the results can be used to allocate the resources for different regions of the country to offer the health services more accurately . these maps can be used to determine the factors related to diseases in epidemiologic studies . ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc ) have been completely observed by the authors .

backgroundone of the methods used in the analysis of data related to diseases , and their underlying reasons is drawing geographical map . mapping diseases is a valuable tool to determine the regions of high rate of infliction requiring therapeutic interventions . the objective of this study was to investigate obesity pattern in iran by drawing geographical maps based on bayesian spatial model to recognize the pattern of the understudy symptom more carefully.methods:the data of this study consisted of the number of obese people in provinces of iran in terms of sex based on the reports of non - contagious disease s risks in 30 provinces by the iran msrt disease center in 2007 . the analysis of data was carried out by software r and open bugs . in addition , the data required for the adjacency matrix were produced by geo bugs software.results:the greatest percentage of obese people in all age ranges ( 1564 ) is 17.8 for men in mazandaran and the lowest is 4.9 in sistan and baluchestan . for women the highest and lowest are 29.9 and 11.9 in mazandaran and hormozgan , respectively . mazandaran was considered the province of the greatest odds ratio of obesity for men and women.conclusion:recognizing the geographical distribution and the regions of high risk of obesity is the prerequisite of decision making in management and planning for health system of the country . the results can be applied in allocating correct resources between different regions of iran .

investigation of the transport of small particles through narrow constrictions is of essential importance in many physical systems . the transport properties of tiny particles have been studied with use of both experimental and simulation methods ( see , e.g. , @xcite ) . an ideal model system for studying strongly interacting electrons is a system of electrons floating on the surface of superfluid @xmath1he @xcite . the wigner solid , or wigner crystal , was predicted theoretically by wigner in 1934 @xcite . in 1970s , the interest in the wigner crystal as a real physical object grew significantly due to the new developments and discoveries in the studies of two - dimensional low - density electron systems in semiconductors and on a surface of liquid helium @xcite . in 1979 the wigner solid was first observed experimentally in a two - dimensional electron system on the surface of liquid helium @xcite . a system of electrons on a surface of liquid helium provides an opportunity for investigating concerted effects between electrons and a soft interface . a number of distinct phenomena associated with the interaction with a free surface of liquid @xmath1he have been observed , in particular , in an electron crystal or the wigner solid phase , where electrons are self - trapped in a commensurate surface deformation called the dimple lattice . on a flat surface of liquid @xmath1he , the wigner solid moves as a whole keeping the hexagonal lattice under a driving force parallel to the surface . the electron motion on liquid helium is associated with surface excitations , or ripplons ( see , e.g. , @xcite ) . when travelling faster than the ripplon phase velocity , as in the case of the cherenkov radiation , an electron radiates surface waves and the ripplons emitted by different electrons interfere constructively if the wave number of the ripplons equals the reciprocal lattice vector of the wigner solid ( the bragg condition ) . this resonant bragg - cherenkov emission of ripplons gives rise to the limitation of the electron velocity , which was first observed in @xcite and analyzed in @xcite . another intriguing nonlinear phenomenon , a sharp rise in mobility at a much higher excitation , was found in @xcite . this effect was attributed to decoupling of the wigner solid from the dimple lattice , and the observed features were qualitatively understood by decoupling from a rigid dimple lattice . later a simple hydrodynamic model was proposed @xcite based on the assumption that decoupling occurs from the dimple lattice that deepens due to the bragg - cherenkov scattering thus bridging the two above - mentioned phenomena . for a finite 2d wigner model of particles with @xmath2 interacting potential , the equation of state and some of the ground state configurations were reported in @xcite . within a more realistic model using a coulomb potential , it was shown in @xcite that circularly confined electrons arrange themselves in ring configurations ( wigner molecules , or `` wigner islands '' ) , which were recently visualized in experiment @xcite . using monte carlo simulations , the structural , dynamical properties and melting of a quasi - one - dimensional system of charged particles , interacting through a screened coulomb potential were studied in @xcite . recent advances in microfabrication technology have allowed the study of the wigner solid in confined geometries using devices such as microchannel arrays @xcite , single - electron traps @xcite , field - effect transistors ( fet ) @xcite and charge - coupled devices @xcite . however , a `` quantum wire '' regime when the effective width of a conductive channel is less than the thermal wavelength of the electrons has been only accessed recently , in experiments @xcite where the transport properties of electrons were measured in a microchannel , with the confinement potential controlled on the scale of the inter - electron separation ( @xmath3 0.5 @xmath4 m ) . here , we focus on the electron transport in a microchannel with a width of the order of the inter - electron separation @xcite . we employ molecular dynamics simulations to study an externally driven wigner solid ( similarly to the system of charged colloidal particles driven in a quasi-1d channel @xcite or diffusing in a circular channel @xcite ) . to understand the role of wigner solid melting in the electron transport through a small microchannel , we refer to the results of the experiments @xcite , where the current was found to be dependent on a tunable potential barrier formed in the channel by a split - gate electrode beneath the helium surface , as well as the intrinsic resistance of the electron system . the latter effect is more pronounced for small or zero gate voltage when the threshold in the transport current may be induced by the melting of the 2d wigner solid in the microchannel . this effect is investigated in detail for different ratios of the inter - electron spacing to the channel width and varying temperatures , and the _ iv_-curves are calculated , without and in the presence of a gate voltage . next , we propose an experimental set - up that includes a set of asymmetric constrictions along the channel . this structure is shown to function as a fet - like device : the electron current can be easily controlled in this device by applying a transverse bias . the electron flow induced by the external driving , can be directed either toward the side of the channel without constriction ( and thus flow freely ) or toward the constrictions where the particle motion is suppressed . in both cases , the electron transport is characterizied by striking oscillations in the average velocity of the particles . the paper is organized as follows . in sec . ii , we introduce the model system . iii is devoted to the study of symmetric channels with various types of constrictions and the relevance of the simulation results to the experiments with electrons in the `` quantum wire '' regim . in sec . iv , we introduce an asymmetric fet - like structure , as a proposal for an experimental set - up , and investigate the trasport properties of this structure . finally , in sec . v , we summarize our findings . we study the dynamics of electrons floating on surface of superfluid @xmath1he driven by an external force in a channel with a constriction ( see fig . [ channelsketch ] ) . the equations of motion of the electrons in the @xmath5-plane are as follows : @xmath6 where @xmath7 and @xmath8 stand for the mass and charge of an electron ( or , in general , a charged particle ) , @xmath9 is an effective viscous damping constant , and @xmath10 is the dielectric constant of the medium . the electron - electron interaction is modeled by the screened coulomb potential ( see , e.g. , @xcite ) . then the interparticle interaction force can be written as : @xmath11 where @xmath12 , @xmath13 is the screening length , and @xmath14 is @xmath15 or @xmath16 . here @xmath17 is the driving force ( applied along the channel , i.e. , in the @xmath15-direction ) , and @xmath18 is a random thermal force obeying the following conditions : @xmath19 and @xmath20 it is convenient to choose @xmath13 as a unit length . then eqs ( [ motioneq ] ) can be rewritten in standard ( see , e.g. , @xcite ) dimensionless form , @xmath21 where we used the transformation @xmath22 , @xmath23 ( and omit primes in the dimensionless equations ) and the units of time and force , @xmath24 and @xmath25 . in addition , without loss of generality , the dimensionless viscosity is set to unity in our simulations . the interaction of particles with the walls of the channel is modeled as hard - wall . the geometry of the channel and the constriction are defined by the parameters @xmath26 , @xmath27 , which are a half - length and half - width of the channel , respectively , and @xmath28 , @xmath29 which are a half - length and half - width of the constriction , respectively , as shown in fig . [ channelsketch ] . we impose periodic boundary conditions in the @xmath15-direction . using computational methods of molecular dynamics , we investigate the transport of electrons for different constrictions and model parameters . the initial state of the system is prepared using simulated annealing simulation ( sas ) . for this purpose , we initially set some value of temperature which is high enough to avoid trapping of the system in a metastable state , and then gradually decrease the temperature . the obtained initial state then is either the ground state of the system or a low - energy state close to the ground state . to study the dynamics of the particles , we apply a weak driving force which can be obtained for each specific constriction and particle configuration from the corresponding @xmath30-curve ( i.e. , the average velocity versus driving force curve ) , similar to the experimental procedure . in this section , we consider channels with different types of constrictions . let us start with investigating the dynamics of electrons in a channel with a constriction with inclined boundaries forming an angle of 45@xmath31 with the lateral boundaries of the channel ( see fig . [ channelsketch ] ) . the electrons form the wigner crystal structure inside the channel , and when we decrease the constriction width , the number of the electrons rows in the constriction decreases . ultimately for very narrow constriction the regimes of `` zigzag '' and `` quantum wire '' when only two or one row of the particles is formed in the constriction ( i.e. , the _ single - file _ regime ) can be observed . consequently , density of the electrons and the number of rows in the rest of the channel grow as we decrease the width of the constriction . our goal is to study the quasi - one - dimensional transport with additional driving force applied in the @xmath15-direction @xmath32 . therefore , we apply the driving force in the @xmath15-direction and consider very narrow constriction in the channel such that the electrons pass the constriction in one row . examples of the electron distributions in the channel with constriction are shown in fig . [ 1rowexl5](a ) ( when no driving force is applied ) and in fig . [ 1rowexl5](b ) ( when a weak driving is applied leading to a transport current ) . as one can see in the first figure ( fig . [ 1rowexl5](a ) ) , the particles are ordered in rows both to the left and to the right from the constriction . the row structure is only destroyed near the constriction where the width of the channel is decreased . turning on the driving force destroys the symmetric electron distribution and creates gradients in the electron density ( fig . [ 1rowexl5](b ) ) . in order to remain close to the equilibrium state , the driving force therefore is chosen as weak as possible . this allows us to remain within the quasi - stationary regime and to model the experimental situation with a minimal transport current . this will allow us to achieve a better understanding of the phenomena observed in the experiments @xcite . for a fixed value of the driving force @xmath32 , the average velocity of the electrons in the constriction in the @xmath15-direction exhibits a correlation with the number of the electrons in the constriction . the oscillations in the average velocity are due to single - electron entry / exit in / from the constriction . the corresponding functions of the average velocity in the @xmath15-direction and the number of the particles versus iteration time are shown in fig . [ numpveloc ] . as one can see from the plot , there is a pronounced correlation between the change in the number of particles in the channel and in the average velocity . thus an increase ( decrease ) in the number of particles by one or two , is associated with an increasing ( decreasing ) jump in the average velocity . it is clear , however , that the life - time of a state with @xmath33 particles should be not too short to have an impact on the average velocity . below , we assume some weak driving such that it provides electron transport through the constriction but does not significantly influence the equilibrium particle distributions . let us now analyze how the electron transport through the channel with constriction can be influenced by changing driving force @xmath32 , i.e. , calculate the `` average velocity @xmath34 vs. driving force @xmath35 '' which is the analog of the `` @xmath30-curve '' of the system . in this section , we address the phenomenon recently observed in the experiment @xcite where the conductance of the classical point contact revealed pronounced oscillations for small conductance values . the oscillations were observed for short constrictions while for long constrictions , instead , a monotonic behavior was revealed . the experiment @xcite suggests that in case of narrow constrictions the gate potential has a shape of a saddle point . in this section we consider a narrow channel with a constriction which is modeled as a saddle - point potential , as shown in fig . [ saddlepointpotential ] . in our model , the saddle - point potential is defined as follows : @xmath37 where parameters @xmath38 and @xmath39 define the height of the potential : @xmath40 we choose the potential to extend over the interval @xmath41 and we calculate the average velocity of the particles in the interval @xmath42 . to be consistent with the experimental situation @xcite , we choose very low values of the driving force @xmath32 such that they do not destroy the equilibrium wigner crystal configurations but provide the motion of electrons through the constriction . first , we consider a relatively short constriction with length @xmath43 . [ mvfromvgsmooth ] shows the resulting average velocity as a function of the gate voltage @xcite , while the electron distributions corresponding to the values of @xmath38 marked with characters ( a to f ) , are shown in fig . [ snshl2f015 ] . the analysis of the electron distributions indicates that the oscillations in the average velocity curve are caused by the changing number of rows of electrons in the constriction . thus the first and the second peaks in the @xmath44-curve correspond to one ( fig . [ snshl2f015](e ) ) and two ( fig . [ snshl2f015](c ) ) rows of electrons moving through the constriction . clearly , in case of a saddle - point constriction where the electrons are distributed generally non - uniformly along the @xmath15-direction , these rows are best defined in _ very short _ constrictions , there they are formed just by a few electrons ( or ultimately just by one electron ) . therefore , a change in their number results in a pronounced oscillation in the average velocity of electrons . in order to obtain a better insight in the transitions between the dynamical regimes with different numbers of the rows , we track the @xmath16-coordinates of the electrons passing through the center of the constriction at @xmath45 during some time interval , e.g. , @xmath46 , for gradually changing @xmath38 . the results are summarized in fig . [ bifdl2f015 ] . from these plots one can see that the transition points between the states with different numbers of rows in the constriction correspond to the peaks of the average velocity curve ( lower panel ) . for long constrictions there are no well pronounced oscillations unlike in the above case of shorter constrictions . although the transitions between the states with different numbers of rows are still observed , they do not result in pronounced features in the velocity curve . the reason for this behavior is that the particle distributions in longer saddle - point constrictions are not formed by rows which are uniform along the constriction and thus can not be characterized by a unique number of rows . instead , the number of rows varies along the length of the constriction resulting in a smooth monotonic change of @xmath47 versus @xmath38 , as shown in fig . [ bifdl5f015 ] . this result is in agreement with the observations of the experiment @xcite . next , we consider a slightly modified model potential such that the central part of the constriction contains a short _ plateau _ thus stabilizing the rows : @xmath48 using this modified saddle - point - like potential results in more pronounced different regimes , as shown in figs . [ bifdl4lp4f015 ] and [ snshl4f015 ] . it is worth noting that in this phase diagram ( i.e. , the number of rows versus @xmath38 ) we observe the transition `` 1 - 2 - 4 - 3 - 6 - 4 - 5 '' with the striking inversions `` 2 - 4 - 3 '' and `` 3 - 6 - 4 '' ( cp . to refs . these transitions have not been observed ( nor found in calculations ) in similar classical systems , e.g. , colloids moving in narrow channels or vortices in superconducting narrow stripes . let us consider now a channel with asymmetric constrictions . in our model , three constrictions are placed such that they divide the channel into three equal in length compartments , as shown in the sketch in fig . [ chan3consketch ] . the lateral walls of the constrictions are vertical , and all three constrictions have the same width that is denoted with @xmath29 . the interaction of the particles with the boundaries of the channel and the constrictions is hard - wall . as before , the longitudinal driving force @xmath32 is applied , and we also introduce the additional _ transversal _ force in the @xmath16-direction @xmath49 . in this structure with geomteric constrictions , we vary the width of the constriction @xmath29 and we study how this change influences the transport of the particles . the resulting average velocity of the particles in the channel as a function of the gap @xmath50 exhibits stair - like structure , as shown in fig . [ 3constairsw ] . here , we apply a constant weak driving force @xmath51 . the characters ( a to i ) mark the parameter values for the corresponding electrons distributions shown in fig . [ examples3con ] . the electron distributions shown in fig . [ examples3con ] allow us to understand the dynamics and to explain the appearance of the stairs in the average velocity curve . thus each transition to the lower stair ( e.g. , a to b , c to d , etc . ) in principle occurs when the constriction gap @xmath50 decreases by the value corresponding to one spacing between the adjacent rows in the particle distribution . in practice , however , the situation appears to be more complicated since the perfectly ordered row structure ( observed for a channel without constrictions ) is strongly influenced by the asymmetric constrictions . for example , as one can see in fig . [ examples3con](a ) , even in case of a wide gap @xmath50 the four - row structure ( including the rows of particles near the boundaries ) is modified near the constrictions . the row near the constriction is locally split into two , and the next row is cuvred . as a result , a significant drop in the @xmath47 is observed , although the gap @xmath50 is still wide enough to allow a free motion of the _ undisturbed _ row of particles ( i.e. , in the absence of the constrictions ) . therefore , the reason for the observed drop in the @xmath47 is that the row of particles splits near the constriction , and the particles of one branch of the splitted area become blocked by the constriction ( see fig . [ examples3con](b ) ) . as a consequence , some additional decrease of the gap @xmath50 ( such that the geometrical line connecting particles in the row away from the constrcition crosses the constriction ) does _ not _ result in any decrease in the @xmath47 ( see fig . [ examples3con](c ) and fig . [ 3constairsw ] ) . in a similar manner , other stairs in the function @xmath52 shown in fig . [ 3constairsw ] are explained by analyzing the particle distributions presented in fig . [ examples3con ] . as we argued above , it is important to apply a very weak driving force that provides a quasi - stationary transport regime when the particle distribution is characterized by a row structure . as we just showed , this is the row structure that is responsible for the stair - like @xmath52-curve . to check this statement , we applied slightly stronger driving : @xmath53 and we found that the stairs become smoothened as shown in fig . [ 3constairswdiff ] . on the other hand , we can control the depth of the steps by applying additional transversal force @xmath49 . let us discuss this effect . we fix the constriction width @xmath29 and the longitudinal force @xmath32 , and investigate the effect of varying the transversal force @xmath49 on the average velocity of the particles @xmath54 . we apply a relatively large value of the driving force @xmath53 @xcite , and in this case the average velocity of all the particles in the channel does not exhibit pronounced stairs , but this effect can be enhanced if we consider the average velocity of the particles in the constriction , as shown in fig . [ 3condifw ] . in this figure , we plotted the average velocity for different values of the total number of particles in the channel @xmath55 , 300 , 400 , and 500 , and we found that the stairs are more pronounced for the case of the narrow constriction with @xmath56 , fig . [ 3condifw](a , b ) rather than for a wide constriction . the important result is that we can control the particle flow through the channel with asymmetric constrictions not only by changing the size of the constriction but , more strikingly , by tuning the transversal force @xmath49 applied to the channel ( for a fixed constriction size ) . the latter is an analog of electronic fet - devices and it can be easily realized in experiment . finally , fig . [ examples3confy ] shows the particle distributions corresponding to the above case of @xmath57 particles shown in fig . [ 3condifw](b ) . the distributions indicate that the electron distributions is rather far from the quasi - equilibrium , it is characterized by pronounced gradients in the particle density . nevertheless , the calculated distributions reveal local row structure which is responsible for the appearance of the steps in the @xmath58-curve . by numerically solving the langevin equation of motion for a system of interacting charged particles , we investigated the transport properties of the wigner crystal driven by an external force on the surface of a superfluid @xmath1he in narrow channels with constrictions . the width of the constriction varied such that it could accommodate from a few rows of electrons ( i.e. , the quasi - one - dimensional regime ) to ultimately just one row , i.e. , the `` quantum wire '' regime , when the channel width is comparable to the inter - electron separation . we analyzed the average velocity of the moving electrons through the constrictions as a function of the parameters : the strength of the driving force , the shape of the constriction ( i.e. , with either inclined or normal boundaries with respect to the channel walls ) and the strength of the model gate voltage . we considered two different types of constrictions : symmetric with respect to the central axis of the channel , and asymmetric constrictions . in case of symmetric constrictions , we addressed a recent observation revealed in the experiments on measuring the conductance of a classical point contact , for long and short constrictions . in particular , in our simulations we revealed a significant difference in the dynamical behavior for long and short constrictions . namely , the oscillations of the average velocity of particles in case of short constrictions exhibited a clear correlation with the transitions between the states with different numbers of rows of particles in the constriction , while for the systems with longer constriction these oscillations are suppressed . the obtained results are in agreement with the recent experimental observations . we also proposed to use a narrow channel with asymmetric constrictions as a fet - like device for an effective control of the electron transport throuth the constriction . it was demonstrated that the particle flow through the channel with asymmetric constrictions can be controlled not only by changing the size of the constriction but , more strikingly , by tuning the transversal force @xmath49 applied to the channel . the latter can be easily realized in experiment . our study brings important insights into the dynamics of electrons floating on the surface of superfluid @xmath1he in channels with constrictions . in addition , the present analysis of the charged interacting particles moving through narrow constrictions could be useful for a better understanding of the quasi - one - dimensional and single - file dynamics in other interacting soft - matter or biological systems such as , e.g. , colloids or proteins in narrow channels . we are thankful to david rees for providing us with helpful insights in details of the experiments and the corresponding references . this work was supported by the flemish science foundation ( fwo - vl ) and by the odysseus " program of the flemish government and fwo - vl . a. kristensen , k. djerfi , p. fozooni , m. j. lea , p. j. richardson , a. santrich - badal , a. blackburn , and r. w. van der heijden , hall - velocity limited magnetoconductivity in a classical two - dimensional wigner crystal . lett . * 77 * , 1350 ( 1996 ) . p. glasson , v. dotsenko , p. fozooni , m. j. lea , w. bailey , g. papageorgiou , s. e. andresen , a. kristensen , observation of dynamical ordering in a confined wigner crystal . * 87 * , 176802 ( 2001 ) . g. papageorgiou , p. glasson , k. harrabi , v. antonov , e. collin , p. fozooni , p. g. frayne , m. j. lea , d. g. rees , y. mukharsky , counting individual trapped electrons on liquid helium . . lett . * 86 * , 153106 ( 2005 ) . g. sabouret , f.r . bradbury , s. shankar , j.a . bert , s.a . lyon , signal and charge transfer efficiency of few electrons clocked on microscopic superfluid helium channels . lett . * 92 * , 082104 ( 2008 ) . we show absolute values of the dimensionless gate voltage ; these values can be recalculated to the experimentally measured values by multiplying to a negative constant which can be extracted from fitting the simulation results to the experimental data . the larger value of the driving force is chosen in order to ensure the passing of the particles through the constriction even for moderate values of the transversal force @xmath49 . otherwise , if we restrict ourselves to very weak driving at @xmath60 then applying even a very weak @xmath61 will result in zero transport current throuth the constriction .

when floating on a two - dimensional surface of superfluid @xmath0he , electrons arrange themselves in two - dimensional crystalline structure known as wigner crystal . in channels , the boundaries interfere the crystalline order and in case of very narrow channels one observes a quasi - one - dimensional ( quasi-1d ) wigner crystal formed by just a few rows of electrons and , ultimately , one row , i.e. , in the `` quantum wire '' regime . recently , the `` quantum wire '' regime was accessed experimentally [ d. rees _ et al . _ @xcite ] resulting in unusual transport phenomena such as , e.g. , oscillations in the electron conductance . using molecular dynamics simulations , we study the nonlinear transport of electrons in channels with various types of constrictions : single and multiple symmetric and asymmetric geometrical constrictions with varying width and length , and saddle - point - type potentials with varying gate voltage . in particular , we analyze the average particle velocity of the particles versus the driving force or the gate voltage . we have revealed a significant difference in the dynamics for long and short constrictions : the oscillations of the average velocity of the particles for the systems with short constrictions exhibit a clear correlation with the transitions between the states with different numbers of rows of particles ; on the other hand , for the systems with longer constrictions these oscillations are suppressed . the obtained results are in agreement with the experimental observations by d. rees _ et al . _ @xcite . we proposed a fet - like structure that consists of a channel with asymmetric constrictions . we show that applying a transverse bias results either in increase of the average particle velocity or in its suppression thus allowing a flexible control tool over the electron transport . our results bring important insights into the dynamics of electrons floating on the surface of superfluid @xmath1he in channels with constrictions and allow an effective control over the electron transport .

"So this is not good for any cooking quantity of spices if you ask me.., I put a tablespoon of thyme in it and ground and shook and ground and shook.., etc.., and some came out a fine powder, other came out near untouched," a reviewer named Don Wade wrote. "I had hoped this was for the kitchen, but after trying it on rosemary, thyme and black pepper i've decide this thing must be for cooking up something else and not your favorite family friendly recipe.., Only for very small amounts of spices, like a teaspoon.., not enough for the recipes I use..., In hind-site I should have known this was not really a kitchen tool.., but a recreational tool.., I have no use for it..., If you- do,pe-rhaps it will work :)" ||||| We’ve all been there, ordered something online only to receive something that isn’t quite what the description made it out to be. Please, Burger King, bring your fried halloumi burger to the UK But when one woman ordered a herb grinder, ready to grind her rosemary for a wonderful dinner, she wasn’t quite counting on receiving a product that’s actually meant for grinding weed. And just to clarify: she’s totally not into that. And just to clarify: she’s totally not into that. Amazon user A.Maddox left a hilariously innocent review on a product which was tagged: ‘Ohuhu Tobacco Grinders Herb Grinder /Weed Grinder/ Plant Grinder / Pollen Collector/ 4 Pieces 2.38″ Heavy Duty Zinc Alloy, Magnetic Top, Elegant Black’. The description for the product reads: ‘This Ohuhu® Herb Grinder is a small, but powerful device with sharp teeth that you can use to grind up herbs, tobacco, marijuana, and other small plant materials.’ Advertisement Advertisement Now, I know what you’re thinking – it blatantly states that the grinder is meant for grinding weed. But let’s just give A.Maddox a break here, not everyone goes as far as to read the description of what they’re buying – especially if at first glance the product looks to suit your needs. However, the Amazon user learned the hard way to always read the description for future buys when her ‘rosemary fell right through’ the grinder. In a face-palm-worthy review, the user wrote: ‘The rosemary just fell right through. I’m sure it works well for nugs but I actually need a spice grinder and it’s impossible to find now thanks to the weed industry. ‘I wish they would call them something else so I don’t have to sort through 89679376 products like this to find an actual spice grinder.’ Of course, she also finished the review by giving the product just one star – which really, is quite generous considering it didn’t even grind her rosemary. A.Maddox, if you’re out there, we’ve found a lovely herb grinder for you here for just £4.99. Hopefully, this one will work and all of your rosemary-grinding needs will be fulfilled. MORE: Crosstown doughnuts are about to launch a vegan range MORE: Man accidentally buys a cow off the internet while on sleeping pills Advertisement Advertisement

– It's important we not lose focus on the victims of marijuana legalization: home chefs. Metro reports a woman looking for a kitchen accessory to grind rosemary accidentally bought a device to grind marijuana instead. And she was none too pleased in her one-star review, saying "the rosemary just fell right through" and complaining it's "impossible to find" an actual spice grinder "thanks to the weed industry." The reviewer says she wishes the marijuana industry would find a new name for the devices so she doesn't have to "sort through 89,679,376 products" just to find a real spice grinder. The disappointed Amazon shopper could perhaps be forgiven for her confusion. The $9.99 Ohuhu Herb Grinder she purchased not only has the ambiguous word "herb" right in its name, but boasts it can "grind up herbs, tobacco, marijuana, and other small plant materials." Rosemary is certainly small plant material. And Refinery 29 reports the reviewer wasn't the only one misled by the device; it appears at least three other Amazon customers thought they were getting a spice grinder. Regardless, the review has been removed from Amazon, according to Munchies.

the poincar group provides the fundamental kinematic symmetry of a relativistic particle . as a non - compact group , all its unitary representations are infinite dimensional , but in a famous paper @xcite wigner showed that the physically interesting representations can be induced from finite - dimensional unitary representations of a _ little group _ , which is the subgroup of homogeneous lorentz transformations that leaves some reference four - momentum @xmath1 invariant . the representation space of the little group is the hilbert space for the particle s spin . if the particle has positive mass @xmath2 , we may take as reference the four - momentum in the particle s rest frame where @xmath3 . the little group then consists of the space rotations @xmath4 . for a massless particle there is no rest frame and the reference momentum must be a null vector @xmath5 . the little group now consists of space rotations @xmath6 about the three - vector @xmath7 , together with operations that are generated by infinitesimal lorentz boosts in directions perpendicular to @xmath7 combined with compensating infinitesimal rotations . remarkably the combined operations mutually commute , possess all the algebraic properties of euclidean translations , and the resulting little group is isomorphic to the symmetry group @xmath0 of the two - dimensional euclidean plane . what is being moved by these translation operations ? the answer given by wigner is that they move : if the translation generators had a physical effect , the little - group representation would be infinite dimensional and the particle being described would have `` continuous spin '' a property possessed by no known particle . indeed the wigner translations have no effect when applied to plane - wave solutions of the massless dirac equation , and act as gauge transformations when applied to the vector potentials of plane - wave solutions of maxwell s equations @xcite . consequently they act as the identity on the momentum eigenstates created by the operator - valued coefficients of the plane - wave modes , thus ensuring that the spin of a massless particle is entirely specified by a finite - dimensional representation of the @xmath8 helicity subgroup @xcite . it is the purpose of this paper to show that , while they have no effect on _ infinite _ plane waves , when applied to _ finite - size _ wave packets of non - zero helicity and in particular to circularly polarized gaussian packets the wigner translations do have an effect : they shift the wave packet trajectory parallel to itself . this shift is related to the relativistic hall effect of light @xcite and to the observer dependence of the location of massless particles @xcite . it gives rise to the unusual lorentz covariance properties found @xcite in the chiral kinetic theory approach to anomalous conservation laws @xcite and is also the source of the difficulty of obtaining a conventionally covariant classical mechanics for a massless spinning particle in a gravitational field @xcite . in section [ sec : poincare ] we will provide a suggestive algebraic argument for a sideways shift . in section [ sec : paraxial ] we will show that the shift actually occurs in finite - width beam solutions to maxwell s equations . in section [ sec : discussion ] we will discuss and resolve a potential paradox implied by the trajectory displacement . as an indication that wigner translations can have a physical effect , we briefly review a well - known @xcite realization of the poincar algebra for massless particles of helicity @xmath9 in terms of quantum mechanical position and momentum operators . we start from the familiar commutators [ x_i , p_j]=i _ ij , = 0 , [ eq : canonical ] and use the fact that the spin of a massless particle is slaved to its direction of motion to motivate the definition of the angular momentum operator as j_k= _ klm x_lp_m + . [ eq : qm - ang - mom ] this unconventional definition preserves the usual commutation relation = i _ klm p_m . however , in order to recover [ j_k , x_l]= i _ klm x_m , and [ j_k , j_l]= i _ klm j_m , we need to modify the commutator of the position - operator components to [ x_k , x_l]= -i _ klm . accepting that the position - operator components no longer commute , we can still use @xmath10 to define a generator of lorentz boosts in direction @xmath11 as k_k=12(x_k|| + ||x_k ) . these generators satisfy the remaining relations of the lorentz lie algebra [ j_k , k_l]&= & i_klm k_m , + [ k_k , k_l]&= & -i_klm j_m , [ eq : lorentz ] and act as expected on the momentum components : [ k_k,||]&=&i p_k , + [ k_k , p_l]&=&i_kl|| . [ eq : p - boost ] we have therefore constructed a representation of the poincar algebra on a quantum - mechanical hilbert space . when we extend the algebra to include the position operators , things become more complicated . we find ( at @xmath12 ) [ k_k , x_l]=-i\ { 12(x_k + x_k ) + _ klm } . [ eq : x - boost ] neither term is immediately familiar . the expression in parentheses arises because the underlying hamiltonian formalism automatically maintains the non - lorentz invariant condition @xmath13 @xcite . the term containing the helicity @xmath9 will be more interesting . we select a reference four - momentum @xmath14 where @xmath15 and obtain the corresponding wigner translation generators as the boosts and compensating rotations given by _ 1&=&k_1 + j_2 , + _ 2&=&k_2-j_1 . [ eq : wigner ] from ( [ eq : lorentz ] ) we see that these generators obey the @xmath0 lie algebra [ _ 1,_2]=0 , = i_2 , = -i_1 . from ( [ eq : p - boost ] ) and ( [ eq : x - boost ] ) we also see that @xmath16 , @xmath17 , and the @xmath0 generators collectively leave invariant the eigenspace with eigenvalues @xmath18 and any fixed @xmath19 . acting within the particular invariant subspace with @xmath20 , we find that [ _ k , x_l]= - i _ kl3 , ( k , l=1,2 ) . [ eq : wigner - subspace ] in ( [ eq : wigner - subspace ] ) the wigner `` translations '' seemingly effect a genuine infinitesimal translation of the @xmath21 , @xmath22 coordinates in the @xmath20 plane , and hence a translation of the particle trajectory @xmath23 parallel to itself . is this apparent displacement merely an artifact of an unconventional representation of the poincar algebra , or does it have something to do with physics ? in the next section we will use solutions of maxwell s equations to illustrate that this sideways shift is not just a mathematical curiosity , but corresponds to what occurs in nature the trajectory of a circularly polarized photon is observer - dependent and is translated parallel to itself by an infinitesimal lorentz boost and aberration - compensating rotation . we wish to consider the action of boosts and rotations on a finite - size photon wavepacket . it will serve to consider their effect on finite - width laser beam in the paraxial approximation . we will use units in which @xmath24 . the scalar paraxial wave equation + + 2ki = 0 [ eq : paraxial - equation ] is obtained from the full scalar wave equation + + - = 0 by writing ( * r*,t)= ( * r * ) e^ik(z - t ) and assuming that @xmath25 is sufficiently slowly varying that we can ignore its second derivative @xmath26 in comparison to the remaining terms in ( [ eq : paraxial - equation ] ) . the simplest solution of eq . ( [ eq : paraxial - equation ] ) is the gaussian - beam @xcite ( * r*)= \ { - + i k } , [ eq : scalar - paraxial ] where w^2(z ) = ; r(z)= . in this solution the beam is propagating in the @xmath27 direction , the quantity @xmath28 is the width of the beam at a distance @xmath29 away from its waist , and @xmath30 is the radius of curvature of the wavefront passing through the point @xmath31 . the width grows linearly with @xmath29 once @xmath32 , and the angular half - width is @xmath33 . the condition for the paraxial approximation to be accurate ( @xmath34 ) is equivalent to the beam having small asymptotic divergence . we will always be interested in the region @xmath35 where the beam is narrow and almost parallel sided . , @xmath36 . a ) density plot of original beam amplitude @xmath37 ; b ) beam amplitude after lorentz transformation ( eq . ( [ eq : lorentz - transform ] ) ) with rapidity @xmath38 ; c ) beam amplitude after both lorentz transformation and aberration - compensating rotation though @xmath39 . _ , width=672 ] from any two independent solutions @xmath40 , @xmath41 of the scalar paraxial equation we can find @xcite vector @xmath42 and @xmath43 fields that are internally consistent solutions of maxwell s equations up to accuracy of order @xmath44 , where @xmath45 is some charateristic length such as @xmath46 e_x(*r*,t)&=&f(*r*,t ) + 14k^2(- ) + , + e_y(*r*,t)&=&g(*r*,t)- 14k^2(- ) + , + e_z(*r*,t)&=&(+ ) , [ eq : paraxiale ] and b_x(*r*,t)&=&-g(*r*,t ) + 14k^2(- ) + , + b_y(*r*,t)&=&f(*r*,t)- 14k^2(- ) - , + b_z(*r*,t)&=&-(- ) . [ eq : paraxialb ] to obtain a gaussian @xmath47 beam that is circularly polarized with positive helicity we take @xmath48 and @xmath49 , with @xmath25 given by eq . ( [ eq : scalar - paraxial ] ) . using mathematica^tm^ to manipulate the resulting rather lengthy expressions we find , for example , that the time - average energy density in the beam is t^0012 = e^-kz_0(x^2+y^2)/(z^2+z_0 ^ 2 ) , and the three components of the time - averaged poynting vector @xmath50 are s_x&=&t^10= e^-kz_0(x^2+y^2)/(z^2+z_0 ^ 2 ) , + s_y&=&t^20=e^-kz_0(x^2+y^2)/(z^2+z_0 ^ 2 ) , + s_z&= & t^30=e^-kz_0(x^2+y^2)/(z^2+z_0 ^ 2 ) . the energy - flux streamlines twist in the direction of the beam helicity @xcite , consequently the @xmath29 component of the angular momentum density _ z = xs_y - ys_x is non - zero . if we integrate over the plane @xmath51 we find that p_z _ z=0 s_z dxdy= = \{1 + o ( ) } , and j_z_z=0 _ z dxdy== 1 k \{1 + o()}. the ratio @xmath52 is equal to @xmath11 in region ( @xmath34 ) where paraxial aproximation is accurate . this is what is to be expected : @xmath53 gives the linear momentum per unit length , which should be @xmath54 per photon ; @xmath55 gives the angular momentum per unit length of the beam , which should be @xmath56 per photon . we now compute the @xmath42 and @xmath43 fields as seen from a reference frame moving along the @xmath57 axis at rapidity @xmath58 . the corresponding lorentz transformation takes e_x(x , y , z , t ) & & e_x(x , y , z , t ) , + e_y(x , y , z , t ) & & e_y(x , y , z , t ) s - b_z(x , y , z , t , ) s + e_z ( x , y , z , t ) & & e_z(x , y , z , t ) s + b_y(x , y , z , t ) s , + b_x(x , y , z , t ) & & b_x(x , y , z , t ) + b_y(x , y , z , t ) & & b_y(x , y , z , t ) s + e_z(x , y , z , t ) s , + b_z(x , y , z , t ) & & b_z(x y , z , t ) s- e_y(x , y , z , t ) s , [ eq : lorentz - transform ] where x & = & x s+ t s + t & = & ts- x s. the lorentz transformation changes the wave vector from @xmath59 to @xmath60 , so the direction of propagation has been rotated though an aberration angle of @xmath61 . the wavefronts are therefore tilted . the beam envelope , however , still lies parallel to the @xmath29-axis , and is moving towards the observer at speed @xmath62 ( see figure [ fig : fig1]-b ) . the lorentz transformation also affects the energy density distribution and the poynting - vector flux though the @xmath51 plane . in addition to a lorentz contraction it noticeably shifts the position of their maxima ( see figure [ fig : fig2 ] ) . to quantify these shifts we can compute the location of the lorentz transformed energy density and energy flux centroids . the required integrals are still gaussian and can be done analytically . with the definition = _ z=0 t^00 dxdy , we have _ density&= & _ z=0 y t^00 dxdy , + & = & , + & = & 1 k s\{1+o ( ) } , and _ flux&=&1p_z_z=0 y s_z dxdy , + & = & , + & = & 1 2k s\{1+o()}. for positive helicity , both centroids are displaced to the left when seen from an observer moving towards the upward - propagating beam . the centroids do not coincide , the energy - flux centroid moving only half as far as the energy - density centroid . such displacements are not restricted to gaussian beams . a similar boost - induced sideways shift and centroid separation was exhibited in @xcite for bessel beams possessing orbital angular momentum . it was also explained there that the centroid separation arises solely from the geometrical effect pointed out in @xcite : because of their corkscrew trajectories , energy - flux streamlines passing through a surface rotated away from perpendicular to the direction of propagation find themselves inclined at different angles to the surface to the right and left of the plane of rotation . consequently , even in the absence of a lorentz boost , the energy - flux centroid of a tilted beam is displaced with respect to its energy - density centroid @xcite . we wish to obtain a finite - displacement version of the wigner translations , so , after performing the boost , we rotate the lorentz transformed beam about @xmath63 though an aberration - compensating angle of @xmath64 . after the rotation the wavevector becomes @xmath65 and the wavefronts again lie parallel to the @xmath66-@xmath67 plane . consequently the energy - flux streamlines no longer possess a left - right asymmetry . we find numerically that the position of the energy centroid in the @xmath51 plane is unchanged by the rotation ( @xmath68 is a scalar under space rotations ) while the energy - flux centroid moves into coincidence with the energy - density centroid . thus , as result of the combined boost and compensating rotation _ both _ centroids have been shifted though a distance @xmath69 , where @xmath70 . the beam spot is restored to its pre - boost appearance , and we could repeat the operation and translate the beam spot through a further distance . if we reverse the helicity , we change the sign of this shift . plane for @xmath71 , @xmath72 . a ) original intensity @xmath73 ; b ) lorentz transformation of @xmath74 under eq . ( [ eq : lorentz - transform ] ) with rapidity @xmath75 . the spot center is at @xmath76 ; c ) poynting energy flux @xmath77 after lorentz transformation . the spot center is at @xmath78 ; d ) poynting energy flux @xmath79 after aberration - compensating rotation . the flux maximum is at @xmath76 . the rotated intensity distribution has similar appearance , and its maximum is also at @xmath76.__,title="fig:",width=480 ] [ fig : fig2 ] in the absence of the lateral shift , the combination of boost and compensating rotation would leave the trajectory of a short wavepacket emitted from @xmath63 at @xmath12 unchanged . the continuous beam , which can be though of as arising from a stream of sequentially emitted wavepackets , is _ not _ left invariant , however . how it changes is shown in fig . [ fig : fig1]-c . we see that the transformed beam can be though of as a sequence of pulses each fired in the @xmath27 direction by an emitter that is moving rapidly to the left . it is reminiscent of a diagonal steam of strictly upward - moving projectiles fired from a horizontally moving gun in the old atari^tm^ game `` space invaders . '' any particular packet continues to move parallel to the @xmath29 axis , but as a result of the lateral shift in the @xmath51 plane , its entire trajectory is shifted sideways by @xmath80 . figure [ fig : fig1]-c also shows why the action of the wigner translations take their simple form ( [ eq : wigner - subspace ] ) only in the plane @xmath81 . in any other plane the translations get mixed up with the geometric effect of the rotation . the finite-@xmath58 boosts considered in this section have effects on the photon energy and intensity that appear at quadratic order in the rapidity @xmath58 . if we alternate a sequence of infinitesimal boosts and compensating rotations , the quadratic terms can be neglected and only the sideways shift ( now equal to @xmath82 times the total rapidity change ) remains . we are in effect assembling a trotter - product approximation that converges to exponentials of the wigner translation generators ( [ eq : wigner ] ) . the direction and magnitude of the boost - induced lateral shift can be understood from a geometric picture ( see @xcite for a related argument ) . consider two massless particles , both possessing helicity @xmath83 and heading directly towards one another parallel to the @xmath66 axis . because they will collide head - on , they have no relative orbital angular momentum and the two spin angular momenta @xmath84 also sum to zero . seen from a frame moving along the @xmath67 axis towards the collision point , however , the unit vectors in the direction of the particles motion have components @xmath85 . because the spin of a massless particle is slaved to its direction of motion there is now a net spin component of @xmath86 directed towards the observer . nonetheless , in the new frame , the total angular momentum will remain zero so the spin contribution must be offset by an orbital angular momentum of @xmath87 . this orbital angular momentum can only come from a lateral shift of each particle s trajectory by @xmath88 ( see fig . [ fig : collision ] ) . for a photon @xmath89 and @xmath90 , so we recover the shift seen in our gaussian beam . of course , if two particles collide and produce two pions in one frame they must produce two pions when seen from another frame . that the particles apparently miss each other because of the sideways shift can not affect the pion production . the incipient paradox is resolved by the fact that partial - wave scattering amplitudes depend only on the total relative angular momentum @xmath91 of the particles , and this quantity is not affected by the shift . the shift still has physical consequences , though . if we move a detector such as a photographic emulsion though the beam , it will be sensitive to either the energy density or the energy flux in its own rest frame , and these quantities have been displaced by the motion . collide head - on ; b ) the particles viewed from above in a frame moving towards the collision ; c ) a front view from the moving frame shows the particles miss one another . _ , title="fig:",width=211 ] collide head - on ; b ) the particles viewed from above in a frame moving towards the collision ; c ) a front view from the moving frame shows the particles miss one another . _ , title="fig:",width=211 ] collide head - on ; b ) the particles viewed from above in a frame moving towards the collision ; c ) a front view from the moving frame shows the particles miss one another . _ , title="fig:",width=211 ] this work was supported by the national science foundation under grant number nsf dmr 13 - 06011 . in the course of this work ms has exchanged many useful emails with peter horvthy and christian duval . ms would also like to thank konstantin bliokh for discussions about the observer dependence of the location of light rays , and for drawing our attention to @xcite . we also thank the authors of @xcite for sending us an early version of their work . d. han , y. s. kim , d. son , _ gauge transformations as lorentz - boosted rotations _ , physics letters * 131b * , 327 - 329 ( 1983 ) ; _ photons , neutrinos , and gauge transformations _ , am . j. phys . bf 54 , 818 - 821 ( 1986 ) . s. weinberg , _ feynman rules for any spin . ii . massless particles _ , phys . rev . * 134 * , b882-b896 ( 1964 ) ; _ photons and gravitons in s - matrix theory : derivation of charge conservation and equality of gravitational and inertial mass _ , * 135 * , b1049-b1056 ( 1964 ) ; see also _ the quantum theory of fields , vol . 1 _ , cambridge university press , massachusetts ( 1996 ) .

the wigner little group for massless particles is isomorphic to the euclidean group @xmath0 . applied to momentum eigenstates , or to infinite plane waves , the euclidean `` wigner translations '' act as the identity . we show that when applied to finite wavepackets the translation generators move the packet trajectory parallel to itself through a distance proportional to the particle s helicity . we relate this effect to the hall effect of light and to the lorentz - frame dependence of the position of a massless spinning particle .

in this paper is to prove the existence of solutions of @xmath0 that satisfy the following behaviour @xmath1 this equation has been deduced in @xcite ( see also @xcite ) . it arises in a two dimensional model describing steady coating of a bumpy surface by a thin - film approximation . in particular ( [ s2e3 ] ) results in the particular case that the motion of the fluid is driven by a balance of capillarity and gravity effects . in some regions the curvature of the substrate induces capillary forces of the same order of magnitude than the gravitational ones . in the steady regime the model describing such flows has the form ( cf . ( @xcite ) ) : @xmath2 where we have neglected some non - relevant terms . the variable @xmath3 stands for the arc - length that parametrises the substrate , and @xmath4 is the height of the fluid over this surface . the parameter @xmath5 is the ratio of the characteristic height of the fluid and the characteristic radius of curvature of the substrate . the function @xmath6 describes the balance between gravitational and the capillary forces induced by the geometry of the substrate , it measures the tendency of the fluid to move in the tangential direction to the substrate as a result of the afore mentioned forces . if the function @xmath6 has a constant sign , the motion of the fluid takes place always in the same direction . in such case , ( [ a1 ] ) can be approximated by the leading order term of ( [ a1]):@xmath7 however , this approximation breaks down and it can not be uniformly valid for arbitrary values of @xmath3 if @xmath6 changes sign . in such cases ( [ a2 ] ) predicts the onset of regions , where @xmath6 is close to zero , with infinite height @xmath4 , i.e. the fluid accumulates in those regions . as a consequence , the approximation ( [ a2 ] ) must be replaced by the model ( [ a1 ] ) . in the particular case in which in most of the substrate @xmath6 is positive , but there exists a sufficiently small region ( of size @xmath8 to be precise ) , where @xmath9 , a boundary layer analysis shows that , under suitable non - degeneracy conditions , the height of the fluid can be approximated by means of ( [ s2e3 ] ) , the height of the fluid becoming of order @xmath10 . this asymptotic analysis shows also that the solutions of ( [ s2e3 ] ) describing the stationary flows in those regions must satisfy ( [ s2e7 ] ) . equations similar to ( [ a1 ] ) where the main driving terms are the gravity and the curvature of the substrate , have been obtained , in a slightly different context , in @xcite and @xcite . this model can be obtained also as a particular case of the ones considered in @xcite for specific choices of the parameters . see also @xcite for a model that neglects gravity . similar problems have been investigated in relation with industrial applications , such as the drainage of ( metal ) foams ( e.g. @xcite ) , manufacture of lenses ( e.g. @xcite and @xcite , although in the later case the effect of gravity can be neglected . these works offer numerical as well as formal ( using perturbation methods ) results . it is our aim to study the solutions of ( [ s2e3])-([s2e7 ] ) rigorously . the main result of the paper is the following : [ main ] for any @xmath11 there exists a solution of ( [ s2e3 ] ) satisfying ( [ s2e7 ] ) . we sketch the main ideas in the proof of theorem [ main ] . we first observe that the terms @xmath12 and @xmath13 in ( [ s2e3 ] ) give the natural scaling @xmath14 with @xmath15 ( cf . ( [ s2e7 ] ) ) , which gives the leading order behaviour of ( [ s2e3 ] ) , namely , @xmath16 as @xmath17 gives the dominant balance problem @xmath18 in such set of variables @xmath19 and @xmath20 ( [ s2e3 ] ) becomes an autonomous dynamical system of the form @xmath21 that we shall denote by @xmath22 , for the unknown @xmath23 $ ] . here @xmath24 is defined by @xmath25 and the function @xmath26 is a linear combination of @xmath19 and its derivatives with coefficients that depend only on @xmath24 and that vanish at @xmath27 . thus , this system has the property that the three dimensional subspaces @xmath28 are invariant and the flow on them is described by the ode @xmath29 the system associated to ( [ odetapas ] ) for the unknown @xmath30 was studied in @xcite . it has one single critical point , @xmath31 and therefore @xmath22 has two critical points , @xmath32 and @xmath33 . then , the solutions of ( [ s2e3 ] ) satisfying the matching conditions ( [ s2e7 ] ) correspond to solutions of @xmath22 contained in the trajectories that connect the critical point @xmath34 as @xmath35 to @xmath36 as @xmath37 . or equivalently , they are contained in heteroclinic orbits connecting these two critical points . the existence of a heteroclinic orbit for @xmath22 is proved by means of a shooting argument in the direction of decreasing @xmath20 . the shooting starts close to the invariant manifold @xmath38 and the final argument will require information of the flow on the invariant manifold @xmath39 . for that reason we shall need the following information on ( [ odetapas ] ) . first , that the critical point @xmath40 is hyperbolic and has a one - dimensional stable manifold and a two - dimensional stable manifold . secondly , we proved in @xcite that the only possible asymptotic behaviour of solutions on the stable manifold correspond to either @xmath41 or to @xmath42 we shall also recall later that ( [ odetapas ] ) has a increasing lyapunov function , and that this in particular guarantees the non - existence of periodic orbits . to start the shooting we first prove that there exists an invariant two - dimensional centre - stable manifold @xmath43 locally defined near the point @xmath36 . all the trajectories associated to @xmath22 whose starting initial data is contained in @xmath43 converge to @xmath36 as @xmath37 . we can parametrise the set of trajectories in @xmath43 by means of one real parameter @xmath44 taking values in some large interval . the behaviours ( [ b1 ] ) and ( [ b2 ] ) define two sets of values @xmath44 . we prove that for very large values of @xmath44 the corresponding trajectory satisfies ( [ b1 ] ) . on the contrary , if @xmath44 is very negative we show that there exists a @xmath45 such that ( [ b2 ] ) . it turns out that the sets of values @xmath44 such that the corresponding trajectories satisfy either ( [ b1 ] ) or ( [ b2 ] ) are disjoint open sets . this implies , the existence of @xmath44 s for which the corresponding trajectory does not satisfy neither ( [ b1 ] ) nor ( [ b2 ] ) . the final step is to show that the trajectories associated to such @xmath44 are globally defined in @xmath46 and that they satisfy @xmath47 for some @xmath48 , and that @xmath49 the idea is that if ( [ b3 ] ) and ( [ b4 ] ) are satisfied we can use the fact that the dynamics of @xmath22 become close to the ones associated to the trajectories contained in the unstable manifold of @xmath40 for the system associated to ( [ odetapas ] ) and the trajectories have no alternative but to approach @xmath34 as @xmath35 . the most technical part of the paper is the proofs of ( [ b3 ] ) and of ( [ b4 ] ) . these require to show that oscillatory behaviours with large amplitude for the solutions of @xmath22 as @xmath35 must have a decreasing amplitude for decreasing @xmath20 if neither ( [ b1 ] ) nor ( [ b2 ] ) take place . the key point is that the structure of oscillatory solutions can be identified by looking at the several asymptotic regimes of ( [ s2e3 ] ) . there are , in particular , two very distinctive ones . for instance , the balance @xmath50 for very negative @xmath51 will be relevant in our analysis . in this case the behaviour of solutions is described by @xmath52 this equation can be integrated giving that , in such regions , @xmath53 behaves like a fifth order polynomial . the solutions of ( [ ecuacionminima1 ] ) are in fact a two - parameter family of polynomials , as we shall see . on the other hand , if @xmath54 on bounded intervals , the dominant balance there is given by the equation @xmath55 the analysis of ( [ ecuacionminima2 ] ) plays a crucial role in our proofs and was already studied in @xcite . the possibility of alternating regions where either ( [ ecuacionminima1 ] ) or ( [ ecuacionminima2 ] ) dominates , builds up a scenario where solutions with large oscillations exist : the bouncing region of the oscillations are described by ( [ ecuacionminima2 ] ) and the maximum amplitude regions are close to solutions of ( [ ecuacionminima1 ] ) . this phenomenon has been already observed for ( [ odetapas ] ) in @xcite and explored rigorously in @xcite . in order to prove ( [ b1 ] ) and ( [ b2 ] ) we exploit this mechanism of oscillation . we argue by contradiction and assume first that ( [ b3 ] ) does not hold . this gives ( after a number of technical lemmas ) that there exists a sequence @xmath56 with @xmath57 such that @xmath58 is a local maximum and @xmath59 . we use that the oscillatory solutions with very large amplitude for very negative values of @xmath20 can be approximated , after a suitable rescaling , by a sequence of functions @xmath60 where each @xmath61 solves ( [ ecuacionminima1 ] ) in intervals @xmath62 $ ] . the values @xmath63 being such that @xmath64 is the minimum in @xmath65 . in particular , in such intervals @xmath66 are close to a fifth order polynomial solving ( [ ecuacionminima1 ] ) . the matching between two consecutive such functions is done into the inner region where @xmath19 and @xmath61 become close to @xmath67 , as it turns out , this inner regions lies around @xmath63 . as we have mentioned the dynamics in such bouncing region are dominated by ( [ ecuacionminima2 ] ) and the rigorous matching can be adapted from that performed for ( [ odetapas ] ) ( see @xcite ) : the study of ( [ ecuacionminima2 ] ) reduces to the one of a phase - plane analysis in which the bouncing can be encoded into the behaviour of a separatrix . this object attracts trajectories for increasing @xmath51 , implying that its behaviour is generic . reading off this behaviour into the functions @xmath61 implies that in the outer region they behave as a polynomial with a double zero near @xmath68 . this in particular reduces the family of polynomials that give the outer region around each @xmath69 to a one - parameter family . moreover , this analysis allows to get information on the relative size of consecutive maxima and minima , namely that the sequence of the maximum values decreases and that the sequence of minimum values increases ( as @xmath70 ) and these contradict the assumption that ( [ b3 ] ) does not hold . the paper is organised as follows . section [ sec : preliminaries ] is divided in three preliminary parts . first in section [ sec : summary ] we give some results concerning ( [ odetapas ] ) , most of which are proved in @xcite . in section [ sec : ds ] we reformulate ( [ s2e3 ] ) as a four dimensional dynamical system and reformulate theorem [ main ] in this setting . the third part is section [ sec : loc - analysis ] where we prove the existence of the centre - unstable manifold around @xmath36 . section [ sec:3 ] is devoted to the analysis of the behaviours ( [ b1 ] ) and ( [ b2 ] ) for @xmath22 ; in section [ sec : stability ] we show stability under small perturbations of solutions that satisfy either of these properties , and in section [ sec : classes ] we give necessary conditions on solutions of ( [ s2e3 ] ) to satisfy either ( [ b1 ] ) or ( [ b2 ] ) . with the analysis carried out up to here we can then prove in section [ sec:4 ] that there exist solutions on @xmath43 that do not satisfy neither ( [ b1 ] ) nor ( [ b2 ] ) . we continue by proving that these trajectories of @xmath43 do satisfy ( [ b3 ] ) and ( [ b4 ] ) . in order to do that we first find in section [ sec : dynamics ] that if ( [ b3 ] ) is not satisfied the sequences @xmath56 and @xmath71 , described above , are well defined . second , in section [ sec : proof : osci ] we find the contradictory results that @xmath72 is decreasing and that @xmath73 is increasing . this part is very technical and needs by itself a few steps . thus , in section [ sec : aux ] we identify the scales of the outer region and the approximating polynomials near local maxima . this is based on the analysis of the solutions of ( [ ecuacionminima1 ] ) that is carried out in appendix [ sec : polynomials ] . in section [ sec : rescale : h ] we perform the right scaling of the solutions under consideration and identify the range in which they are approximated by the polynomials . in this section we also prove that the approximating polynomials must have a double zero . this step requires the analysis of ( [ ecuacionminima2 ] ) given in appendix [ sec : summary : ii ] as well as the _ matching lemma _ given in appendix [ sec : control ] ( a result that has been adapted from @xcite ) . in section [ sec : formal ] , with detailed information of the matching regions , we derive an ( iterative ) expression that relates the elements of the sequence of local maxima and another that relates the local minima , and that contradict that ( [ b3 ] ) is not satisfied . finally , in section [ sec:6 ] we finish the prove of theorem [ main ] . finally , we recall that equations similar to ( [ odetapas ] ) have been studied intensively , see @xcite , @xcite , @xcite , @xcite , @xcite , @xcite , @xcite , @xcite and @xcite ) , to mention a few , where similar equations arise in several related physical situations . rigorous results concerning such equations can be found also in @xcite and , concerning travelling wave solutions , in @xcite , @xcite , @xcite , @xcite and @xcite . it is interesting to note that many of these models yield higher order odes describing oscillatory fluid interfaces . we refer to @xcite , where this aspect and related works are put into context . we now summarise some properties of ( [ odetapas ] ) , most of which have been proved in @xcite and will be used later in the proof of theorem [ main ] . it is convenient to rewrite ( [ odetapas ] ) in the equivalent form@xmath74 we then have the following result . [ tapas1 ] 1 . there is a unique critical point for ( [ s3e1 ] ) in the domain @xmath75 given by:@xmath76 2 . the point @xmath40 is hyperbolic . the stable manifold of ( [ odetapas ] ) at the point @xmath40 is tangent to the vector : @xmath77{c}3^{-\frac{2}{3}}\\ -3^{-\frac{1}{3}}\\ 1 \end{array } \right)\ ] ] and the corresponding eigenvalue is @xmath78 . 3 . at @xmath40 there is a two - dimensional unstable manifold locally spanned by the eigenvectors @xmath79 and @xmath80 . the eigenvalues associated to the plane spanned by @xmath81 are @xmath82 and @xmath83 . 4 . the trajectories associated to ( [ s3e1 ] ) that are contained in the stable manifold and satisfy @xmath84 , behave in one of the two following ways for decreasing @xmath20 : either they are defined for all @xmath46 and satisfy @xmath85 or , alternatively , there exists a @xmath86 such that @xmath87 moreover , the points of the stable manifold associated to @xmath40 with @xmath88 satisfy ( [ p1 ] ) and those with @xmath89 satisfy ( [ p2 ] ) . suppose that there exist @xmath90 and @xmath91 such that @xmath92 for all @xmath93 , then @xmath94 and the corresponding trajectory is contained in the unstable manifold of @xmath40 . all the statements of this proposition have been already proved in @xcite except for _ ( v)_. in order to prove this , we use an argument similar to the one used to prove lemma 2.4 in @xcite . we first recall that there exists an increasing lyapunov functional @xmath95 associated to ( [ odetapas ] ) : @xmath96 this and the assumptions made imply that @xmath97 using ( [ s3e1 ] ) , it then follows that @xmath98 . indeed , arguing by contradiction , one can construct a sequence @xmath99 such that there exits a @xmath100 such that either @xmath101 or @xmath102 . then ( [ s3e1 ] ) implies that @xmath103 , so either @xmath104 for @xmath105 or @xmath106 for @xmath105 . but this contradicts ( [ finite : integral ] ) ) since either @xmath107 or @xmath108 for all @xmath109 . now the second equation in ( [ s3e1 ] ) implies that @xmath110 remains approximately constant as @xmath35 in any finite interval of arbitrary fixed length @xmath111 . therefore , if there is a subsequence @xmath112 with @xmath113 satisfying @xmath114 , we obtain that @xmath115 } |w(\tau)| \geq\varepsilon_{0}>0 $ ] for @xmath109 sufficiently large . it then follows from the first equation in ( [ s3e1 ] ) that the condition @xmath116 fails if @xmath111 is assumed to be sufficiently large ( integration on the interval @xmath117 for sufficiently large @xmath109 gives that @xmath118 , but @xmath119 for all @xmath109 and @xmath111 ) . therefore @xmath120 . using the last equation in ( [ s3e1 ] ) as well as the fact that @xmath98 it then follows in a similar way that @xmath121 . this gives ( [ s3e3b ] ) and the result follows . the next lemma gives the detailed asymptotic behaviour in both cases ( [ p1 ] ) and ( [ p2 ] ) : [ tapas2 ] the trajectories associated to ( [ s3e1 ] ) that are contained in the stable manifold and satisfy @xmath122 satisfy that either they are defined for all @xmath46 and ( [ p1 ] ) holds with @xmath123 or , alternatively , there exists a @xmath86 such that ( [ p2 ] ) holds with @xmath124 that either ( [ p1 ] ) or ( [ p2 ] ) hold is just the statement _ ( iv ) _ of proposition [ tapas1 ] . then , ( [ p1:prime ] ) follows from ( [ p1 ] ) and integrating the equation . indeed , for all @xmath125 there exist a @xmath126 with @xmath127 large enough so that for all @xmath128 , then @xmath129 thus @xmath130 and integrating this expression with @xmath131 we obtain @xmath132 for @xmath127 large enough . then dividing by @xmath133 and taking the limit @xmath35 implies ( [ p1:prime ] ) , since @xmath126 can be made arbitrarily negative and @xmath134 arbitrarily large . in order to prove ( [ p2:prime ] ) we use the phase - plane analysis of the appendix [ sec : summary : ii ] . we employ the transformation ( [ sephi0-trans ] ) with @xmath135 replaced by @xmath20 for ( [ s3e1 ] ) ( see also @xcite ) that gives the system @xmath136 which corresponds to ( [ phi0system ] ) with @xmath137 in the last equation . for further reference , the flow field of the phase plane of ( [ phi0system ] ) is also depicted in figure [ phase - plane ] where , in particular , the direction of the field , the critical point @xmath138 and the attractive separatrix @xmath139 are shown . using lemma [ tozero - bwds ] and the behaviour of trajectories of the system ( [ phi0system ] ) entering the only critical point @xmath138 as @xmath140 it is easy to show that if @xmath141 then , by a bootstrap argument , the trajectory @xmath142 remains close to @xmath138 , in particular the estimate ( [ w3e6e ] ) holds for @xmath143 large enough . that ( [ hyp1 ] ) and that @xmath144 are satisfied is a consequence of the proof of ( [ p2 ] ) in @xcite and the transformation ( [ sephi0-trans ] ) . using the first equation in ( [ phi - z - system ] ) one obtains that there exists positive constants @xmath145 and @xmath146 such that @xmath147 with @xmath148 , for all @xmath149 where @xmath150 and @xmath151 is sufficiently large . and this in particular implies that @xmath152 using now the last equation of ( [ sephi0-trans ] ) and ( [ phi:0:esti ] ) one can infer that , considering @xmath20 as a function of @xmath143 @xmath153 ( where we use @xmath154 to compute the explicit coefficient ) . finally , this and ( [ phi:0:limit ] ) imply ( [ p2:prime ] ) . as anticipated in the introduction , in this section we reformulate the main result in terms of a dynamical systems approach . we first transform ( [ s2e3 ] ) into a suitable systems of four autonomous odes , and ( [ s2e7 ] ) into its corresponding boundary conditions . since we are interested in solutions for which @xmath155 remains bounded for all @xmath51 it is convenient to introduce the following change of variables @xmath156 where the variable @xmath20 is defined by means of @xmath157 with this transformation , we have that @xmath158 and ( [ s2e3 ] ) becomes @xmath159\ ] ] with @xmath160 where @xmath51 is given as a function of @xmath20 by means of ( [ s2e8 ] ) . in other words , we use @xmath20 as independent variable , while @xmath51 becomes a dependent one , making the system autonomous . it is convenient to transform @xmath51 further into a new variable that takes values in a compact set , namely , we define the variable @xmath24 by @xmath161 \ , . \label{xi}\ ] ] finally , we can reformulate ( [ s2e8 ] ) and ( [ s2e9])-([s2e9bis ] ) as @xmath162 \,,\label{compact3}\\ \frac{d\theta}{d\tau } & = ( \cos\theta)^{\frac{26}{9 } } \ , , \label{compact4}\ ] ] that has critical points @xmath163 we aim to prove the following theorem : [ hetcon ] there exists a heteroclinic connection of the system ( [ compact1])-([compact4 ] ) between the points @xmath34 and @xmath36 given in ( [ stst ] ) . we notice that theorem [ main ] is just a corollary of theorem [ hetcon ] ; this is implied by ( [ s2e7 ] ) and ( [ s2e8a ] ) . we point out that the system ( [ compact1])-([compact4 ] ) reduces to ( [ s3e1 ] ) on the subspaces @xmath164 and @xmath165 . we shall take advantage of this fact in some of the arguments that follow . we now proceed to describe in detail the construction of a centre - stable manifold at @xmath36 that we denote by @xmath43 . let us first define a set of transformations @xmath166 for any given @xmath167 $ ] by means of @xmath168 where @xmath169 solves ( [ compact1])-([compact4 ] ) with @xmath170 . classical ode theory ascertains that the family of transformations @xmath171 is well defined in some suitable interval @xmath172 . we have the following result . [ set : shooting ] there exists a two - dimensional @xmath173 manifold @xmath43 contained in the ball @xmath174 $ ] for some @xmath175 sufficiently small , tangent to the subspace spanned by the vectors @xmath176{c}3^{-\frac{2}{3}}\\ -3^{-\frac{1}{3}}\\ 1\\ 0 \end{array } \right ) \,,\quad\tilde{v}_{4}=\left ( \begin{array } [ c]{c}0\\ 0\\ 0\\ 1 \end{array } \right ) \ , . \label{stable : eigenvec}\ ] ] if @xmath177 , the flow @xmath178 defined in ( [ c1 ] ) is defined for any @xmath179 and @xmath180 with @xmath181 in order to apply standard results it is convenient to extend the range of values of @xmath24 , replacing @xmath182 by @xmath183 , where the system ( [ compact1])-([compact4 ] ) is defined . the resulting system can be defined in a neighbourhood of @xmath36 and the right hand side of ( [ compact1])-([compact4 ] ) is in @xmath184 . since @xmath185 we can apply the results in @xcite . in our setting , this means the existence of a two - dimensional manifold @xmath186 tangential to the plane spanned by @xmath187 at @xmath36 that remains invariant under the flow @xmath178 if one can prove that the corresponding trajectories on this manifold remain inside a ball @xmath188 for some small @xmath175 . let us show that @xmath43 is invariant . let us consider a four - dimensional cube @xmath189\times[-\delta/2,\delta/2]^{2}\times [ \pi/2-\delta/2,\pi/2]$ ] contained in a ball @xmath188 . the cube has four pairs of parallel -@xmath190 dimensional- sides . one pair with normal direction @xmath191 , another pair with normal direction @xmath192 , the other two pairs of parallel sides contain a plane parallel to the one spanned by @xmath191 and @xmath192 . the set @xmath193 gives four @xmath173 curves and , due to the tangency of @xmath43 to the plane spanned by @xmath191 and @xmath192 , two are contained in each of the parallel sides of the cube that are orthogonal to @xmath191 , and the other two are contained in parallel subspaces orthogonal to @xmath192 . more specifically , one of later is contained in the subspace @xmath194 . notice that @xmath195 gives a portion of the stable manifold associated to ( [ s3e1 ] ) for @xmath196 small enough . therefore , if @xmath197 , @xmath198 for arbitrary values of @xmath179 . on the other hand , for the curve contained in a subspace with constant @xmath199 and orthogonal to @xmath192 , we use the fact that @xmath24 is increasing , thus trajectories could only scape the cube through the other boundaries that intersect @xmath43 . but the points @xmath200 on the other two boundary curves satisfy @xmath201 for some @xmath202 ( small or at most of order one ) . we then use that @xmath203 since the manifold @xmath43 is tangent to the plane spanned by @xmath191 and @xmath192 it follows , using _ ( iii ) _ in proposition [ tapas1 ] as well as ( [ stable : eigenvec ] ) that @xmath204 therefore , if @xmath196 is sufficiently small this quantity is negative and the trajectories in @xmath43 remain always in the ball @xmath188 and ( [ mansta ] ) follows . it only remains to show ( [ limman ] ) . to this end , we observe that ( [ compact4 ] ) implies @xmath205 . using ( [ c2 ] ) we then obtain ( [ limman ] ) . for further reference , let us denote by @xmath206 the affine plane spanned by the stable eigenvectors at @xmath36 , namely , @xmath207 with @xmath191 and @xmath192 as in ( [ stable : eigenvec ] ) . every @xmath208 can be identified by its coordinates , thus we write @xmath209 and @xmath210 with this set of coordinates . since @xmath43 is tangent to @xmath211 at @xmath36 , there exist local differentiable parametrisation of @xmath43 . [ trivia ] let @xmath211 be given by ( [ parplane ] ) . there exists a @xmath212 and a differentiable mapping @xmath213 that maps a neighbourhood of @xmath211 into @xmath214 . moreover , @xmath215 , @xmath216 . we now prove that both asymptotic behaviours ( [ b1 ] ) and ( [ b2 ] ) represent two disjoint open sets of solutions of ( [ compact1])-([compact4 ] ) . more precisely , we have the following results : [ continfinity ] suppose that @xmath217 is a solution of ( [ compact1])-([compact4 ] ) with @xmath218 . let us also assume that for such a solution @xmath219 . then , there exists a @xmath220 sufficiently small such that for any @xmath221 @xmath222 satisfies @xmath223 it is convenient to use , in order to prove the result , the original equation ( [ s2e3 ] ) that is equivalent in the set @xmath224 to the system ( [ compact1])-([compact4 ] ) by means of the change of variables ( [ s2e8a ] ) , ( [ s2e8 ] ) . we first recall that ( [ compact4 ] ) implies that @xmath225 as @xmath35 . therefore , by ( [ xi ] ) , @xmath226 . on the other hand our hypothesis on @xmath19 as well as ( [ s2e8a ] ) and ( [ s2e8 ] ) imply that @xmath227 then this and ( [ s2e3 ] ) yields the existence of a @xmath228 with @xmath229 large enough such that @xmath230integration this expression gives@xmath231 therefore , there exist a @xmath232 with @xmath233 large enough such that @xmath234 we assume , without loss of generality , that @xmath235 by taking @xmath236 even larger is necessary . now for @xmath237 with @xmath238 we define @xmath239 . since the changes of variables ( [ s2e8a ] ) and ( [ s2e8 ] ) are smooth , it follows , using ( [ b7 ] ) and ( [ b7a ] ) and standard continuous dependence arguments for odes , that @xmath240 integration of ( [ s2e3 ] ) for the unknown @xmath241 and ( [ b8 ] ) imply that for all @xmath242 @xmath243 suppose that @xmath244 therefore , it would follow from ( [ b9 ] ) that:@xmath245 where we use that @xmath246 . we can then extend the inequality ( [ f1 ] ) to a larger range of values of @xmath51 and therefore the inequality ( [ f2 ] ) also follows for all @xmath247 with @xmath51 in the extended interval . since the integral term on the right - hand side of ( [ f2 ] ) tends to infinity as @xmath248 , we obtain ( [ b5 ] ) as well . [ contzero ] suppose that @xmath217 is a solution of ( [ compact1])-([compact4 ] ) with @xmath249 . let us also assume that there exists a @xmath86 such that @xmath250 . then , there exists a @xmath220 sufficiently small such that for any @xmath238 there exists a @xmath251 such that @xmath252 satisfies @xmath253 as in the previous proof , it is more convenient to use the original formulation ( [ s2e3 ] ) . we again use the smooth transformations ( [ s2e8a ] ) and ( [ s2e8 ] ) to interpret the results between either formulation . thus let @xmath53 be the solution of ( [ s2e3 ] ) associated to @xmath217 . let also @xmath254 be defined by @xmath255 , we observe that @xmath86 implies that @xmath256 , and the hypothesis on @xmath19 becomes @xmath257 thus in regions close to @xmath254 we expect that the solutions are described by ( [ ecuacionminima2 ] ) and we employ the change of variables(cf . appendix [ sec : summary : ii ] , ( [ ecuacionminima ] ) and ( [ sephi0-trans ] ) ) , namely , @xmath258 where @xmath259 is defined by means of @xmath260 then , @xmath261 and @xmath262 are defined for any @xmath263 where @xmath264 is given by @xmath265 . notice that @xmath266 may or may not be finite . moreover , @xmath267 satisfy @xmath268 where all functions , including @xmath269 , are functions of @xmath143 . the hypothesis on @xmath19 translates into @xmath270 the phase - plane analysis associated to ( [ v1e3 ] ) with @xmath271 is included in appendix [ sec : summary : ii ] . relevant to the current analysis are lemma [ separa ] ( where @xmath139 is defined ) and lemma [ tozero - bwds ] that describes the overall flow . we claim that there is a sequence @xmath272 such that @xmath273 as @xmath274 and that @xmath275 for all @xmath109 large enough . before we prove this we note that for any sequence @xmath272 such that @xmath273 as @xmath274 , the trajectory @xmath276 must be in the half - plane @xmath277 for @xmath278 if @xmath109 is large enough . indeed , otherwise the first equation in ( [ v1e3 ] ) implies that @xmath279 for all @xmath51 near @xmath254 and this contradicts ( [ h:2:zero ] ) . let us now prove that we can select such a sequence and that it also satisfies @xmath280 for all @xmath109 large enough . let @xmath272 be such that @xmath273 as @xmath274 and suppose that @xmath281 . then , the third equation in ( [ v1e3 ] ) implies that @xmath282 and since the last term converges to zero as @xmath274 , it follows that @xmath262 becomes negative for some @xmath278 close to @xmath283 for @xmath109 large enough . thus we can construct another sequence @xmath284 with @xmath285 , @xmath286 as @xmath274 and such that @xmath287 for @xmath109 large enough . suppose now that @xmath288 for large enough @xmath109 . then , the second equation in ( [ v1e3 ] ) implies that @xmath276 arrives to the half - line @xmath289 at some @xmath290 . for otherwise , the last equation in ( [ v1e3 ] ) implies that @xmath276 crosses the line @xmath291 , and the argument of the previous case applies . therefore , there exists a sequence @xmath284 with @xmath292 as @xmath274 such that one of the following possibilities take place:@xmath293 in the case ( [ cs1 ] ) , we can approximate the evolution of @xmath276 in intervals of the form @xmath294 $ ] by the system ( [ phi0system ] ) using standard continuous dependence results and lemma [ tozero - bwds ] implies that @xmath276 enters @xmath295 at some @xmath296 for @xmath109 large enough , and the claim follows . suppose now that ( [ cs2 ] ) takes place . using again continuous dependence we obtain that @xmath297 for some @xmath296 and @xmath109 large enough . in this region , and with @xmath143 close to @xmath264 , then @xmath298 increases for decreasing @xmath143 . therefore , @xmath299 remains positive and @xmath300 is negative as long as @xmath276 stays in @xmath301 . moreover , due to the second equation in ( [ v1e3 ] ) @xmath302 increases for decreasing @xmath143 . this implies that the inequality @xmath303 remains valid during all the evolution until @xmath304 , thus also the inequalities @xmath305 , @xmath306 remain valid . however , this contradicts ( [ h:2:zero ] ) and ( [ cs2 ] ) can not hold . it remains to study the case ( [ cs3a ] ) . in this case there exist a small @xmath111 such that for @xmath307 @xmath276 remains close to the separatrix @xmath139 . on the other hand , @xmath276 must return to @xmath277 infinitely often as @xmath308 . thus the trajectory must remain close to @xmath309 for @xmath143 close to @xmath264 , or otherwise the trajectory enters @xmath301 giving a contradiction as before , or it enters the region @xmath310 which contradicts ( [ cs3a ] ) . then lemma [ separa ] _ ( i ) _ implies that @xmath305 and @xmath306 remain valid during all the evolution for decreasing @xmath311 for @xmath109 large enough , and this contradicts ( [ h:2:zero ] ) . as in the proof of lemma [ continfinity ] for @xmath237 with @xmath238 we define @xmath239 and the transformed functions @xmath312 by means of the transformations ( [ v1e1 ] ) and ( [ v1e2 ] ) with the obvious changes of notation . we then notice that , by continuous dependence of solutions on the initial data , if @xmath175 is chosen sufficiently small then @xmath313 enters the region @xmath314 for some @xmath315 close to @xmath264 and therefore @xmath316 and @xmath317 for some @xmath318 close to @xmath254 with @xmath319 . we have that @xmath320 is small and @xmath321 as long as @xmath320 is small . integrating this inequality for @xmath322 we obtain that @xmath323 , @xmath324 and @xmath325 remains small for @xmath322 as long as @xmath241 is defined . then , @xmath325 vanishes for some @xmath326 , so the lemma follows . we now give necessary conditions for the solutions of ( [ s2e3 ] ) to either satisfy that @xmath327 or that @xmath328 observe that these behaviours imply ( [ b1 ] ) and ( [ b2 ] ) respectively , for the corresponding function @xmath329 given by ( [ s2e8a ] ) and ( [ s2e8 ] ) . we start by giving necessary conditions for ( [ b1:h ] ) , but first we need the following auxiliary calculus result . [ polyn ] given the polynomials @xmath330 then , they are strictly decreasing and positive for @xmath331 . moreover , if @xmath332 satisfies @xmath333 , then @xmath334 if @xmath335 then @xmath336 for @xmath331 , but @xmath337 if @xmath338 . the monotonicity properties of @xmath339 and @xmath340 are just an elementary calculus exercise . the inequality ( [ in2 ] ) is a consequence of the fact that the polynomial@xmath341 is non - negative and decreasing if @xmath342 , in particular @xmath343\ ] ] is non - negative if @xmath344 , thus ( [ in2 ] ) holds . if @xmath345 ( i.e. @xmath346 ) then @xmath347 in @xmath348 . but there the polynomial is larger than or equal than the value of the minimum in @xmath331 , namely , @xmath349 and ( [ in3 ] ) follows . we now give necessary conditions for ( [ b1:h ] ) to hold . [ linf ] let us assume that there exists a positive constant @xmath350 and some @xmath351 with @xmath352 and @xmath353 such that a solution of ( [ s2e3 ] ) satisfies @xmath354 , @xmath355 and @xmath356 . then ( [ b1:h ] ) holds . integrating ( [ s2e3 ] ) three times for @xmath357 we obtain : @xmath358 given the polynomials defined in lemma [ polyn ] and letting , for every @xmath357 , @xmath359 then , we can write @xmath360\,.\ ] ] clearly @xmath361 if @xmath357 and @xmath362 and @xmath363 if @xmath357 and @xmath364 , thus in either case @xmath331 and the polynomials are in the range of values considered in lemma [ polyn ] . we can now distinguish two cases . suppose first that @xmath365 . then a gronwall type of argument shows that for any @xmath357 with @xmath366 $ ] then @xmath367 . indeed , as long as @xmath368 then ( [ in1 ] ) can be estimated from below by @xmath369\ ] ] ( using ( [ xi0:int ] ) ) . then we can apply ( [ in3 ] ) with @xmath370 , hence @xmath371 using this in ( [ in4 ] ) yields @xmath372 and ( [ bigness1 ] ) implies the claim by a continuity argument . let us assume now that @xmath373 . using ( [ xi0:int ] ) we obtain @xmath374 by lemma [ polyn ] . applying now this inequality to ( [ in1 ] ) we obtain the following estimate for @xmath373 : @xmath375 now , we can use a gronwall type of argument to prove that if @xmath376 satisfies ( [ bigness2 ] ) then ( [ g1 ] ) implies @xmath377 we observe that ( [ g2 ] ) holds by hypothesis and that it also holds for @xmath51 close to @xmath378 by continuity . then , as long as ( [ g2 ] ) is satisfied , ( [ g1 ] ) implies that @xmath379 we can apply lemma [ polyn ] , and this implies that the last term in ( [ g3 ] ) can be estimated by the previous one for any @xmath357 if @xmath376 , @xmath380 and @xmath378 satisfy @xmath381 and ( [ g2 ] ) follows . let us then prove ( [ cond : c1:2 ] ) . if @xmath382 , ( [ bigness2 ] ) implies ( [ cond : c1:2 ] ) . if @xmath383 we consider two further cases . for @xmath384 we obtain that the last two terms in ( [ g3 ] ) can be bounded from below by @xmath385 . but this quantity can be absorbed by the first term if @xmath386 , which is satisfied if ( [ bigness2 ] ) is satisfied . therefore ( [ g2 ] ) holds for this range of values . on the other hand , if @xmath387 , then the second term of ( [ g3 ] ) can be estimated from below by @xmath388 , while the last term in ( [ g3 ] ) can be estimated by @xmath389 . then , we can absorb the last term in ( [ g3 ] ) into the second one if @xmath390 which is guaranteed by ( [ bigness2 ] ) . thus , the inequality ( [ g3 ] ) holds for arbitrary values of @xmath391 , and this implies ( [ b1:h ] ) by taking the limit @xmath248 . we end this section by giving necessary conditions for ( [ b2:h ] ) to hold [ lext ] let us assume that there exist positive constants @xmath392 and @xmath393 , depending on @xmath380 , and some @xmath351 with @xmath394 such that a solution of ( [ s2e3 ] ) satisfies @xmath395 , @xmath396 and @xmath397 . then there exists @xmath398 such that ( [ b2:h ] ) holds . suppose that @xmath392 is sufficiently small . then , as long as @xmath399 we obtain from ( [ s2e3 ] ) that @xmath400 . integrating this equation over @xmath401 once we obtain that , as long as @xmath402 is satisfied for @xmath357 , then @xmath403 and , integrating a second time , also that @xmath404 . then this concavity implies that @xmath405 vanishes at some @xmath406 . but a third integration implies that @xmath407thus @xmath408 . finally the condition ( [ smallness ] ) implies that we can replace @xmath378 by @xmath409 , thus @xmath402 follows in this interval and the result follows by a classical continuation argument . in this section we apply a standard shooting argument to prove the existence of solutions of ( [ compact1])-([compact4 ] ) such that ( [ b4 ] ) holds , and such that @xmath19 remains positive and bounded for all @xmath410 . specifically , the main result of this section is : [ existence:1 ] there exists a solution of ( [ compact1])-([compact4 ] ) @xmath411 defined for all @xmath412 such that @xmath413 and satisfying @xmath414 for all @xmath410 , ( [ b4 ] ) and @xmath415 the proof of proposition [ existence:1 ] is divided in several steps . first we prove that points placed in the curve @xmath416 with @xmath417 sufficiently small , yield solutions of the equation ( [ s2e3 ] ) satisfying the hypotheses of proposition [ linf ] if @xmath418 and those of proposition [ lext ] if @xmath419 : [ start : shooting ] let @xmath420 and @xmath421 be as in lemma [ trivia ] . then there exist @xmath422 and @xmath417 , such that for @xmath423 with @xmath424 and @xmath425 the trajectory associated to ( [ compact1])-([compact4 ] ) starting at @xmath421 satisfies ( [ b1 ] ) . moreover , if @xmath426 and @xmath425 the corresponding trajectory of ( [ compact1])-([compact4 ] ) satisfies ( [ b2 ] ) . the dynamics induced by the system ( [ compact1])-([compact4 ] ) on the invariant subspace @xmath194 have been summarised in proposition [ tapas1 ] and lemma [ tapas2 ] . in particular , the trajectory starting at @xmath427 with @xmath418 sufficiently small satisfies ( [ p1:prime ] ) and , as it can be easily deduced , also that @xmath428 then , classical continuous dependence results for odes imply that for any @xmath429 arbitrarily small and @xmath422 small enough there exists @xmath5 sufficiently small such that , for @xmath430 the trajectory starting at @xmath431 at @xmath432 satisfies:@xmath433 for some @xmath434 . using ( [ g4 ] ) and ( [ s2e8a])-([2nd : dh ] ) to get @xmath53 , @xmath435 and @xmath436 at the value @xmath378 ( given by ( [ s2e8 ] ) ) , we obtain @xmath437 where @xmath438 can be made arbitrarily large choosing @xmath5 sufficiently small and @xmath127 sufficiently large to guarantee that ( [ bigness2 ] ) is satisfied . then we apply proposition [ linf ] to obtain ( [ b1:h ] ) and hence ( [ b1 ] ) follows . on the other hand the trajectories starting at @xmath439 with @xmath440 satisfy @xmath441 , for some @xmath442 . moreover , ( [ p2:prime ] ) is satisfied , as well as @xmath443 suppose now that @xmath444 , @xmath445 . assuming again that @xmath5 is sufficiently small we obtain that the numbers @xmath446 can be made arbitrarily small for @xmath126 close to @xmath447 , @xmath448 . we can use this approximation to obtain that @xmath449 where @xmath450 and @xmath451 , thus they can be chosen to satisfy ( [ smallness ] ) by taking @xmath417 sufficiently small . we can now apply proposition [ lext ] to conclude the proof of the result . next we prove that if for every compact set @xmath452 we have that @xmath453 for some @xmath86 , then @xmath250 . therefore , we will be in the situation stated in lemma [ contzero ] and it will be possible to prove continuity of this behaviour for small changes of the initial values . [ l1 ] let @xmath329 be a solution of ( [ s2e9])-([s2e9bis ] ) defined in some interval @xmath454 with @xmath86 , @xmath455 , @xmath414 for @xmath456 . then @xmath457 implies ( [ b2 ] ) for this value @xmath458 . it is easier to work with the original equation ( [ s2e3 ] ) , observe that then , ( [ f1e1:2 ] ) is equivalent to @xmath459 for @xmath254 given by @xmath460 . let us then prove that ( [ f1e1 ] ) implies ( [ b2:h ] ) , and therefore ( [ b2 ] ) will follow . we argue by contradiction . we then assume that ( [ f1e1 ] ) is satisfied , but ( [ b2:h ] ) does not hold , this means that also @xmath461 on the one hand ( [ f1e1 ] ) gives the existence a decreasing sequence @xmath462 such that @xmath463 as @xmath274 , @xmath464 and @xmath465 . and ( [ f1e3 ] ) implies the existence of a sequence with elements @xmath466 such that @xmath467 . then there exists another sequence @xmath468 with @xmath469 and @xmath470 , where local minima are attained , i.e. satisfying @xmath471 let also @xmath472 be the sequence where local maxima are attained , such that @xmath473 and satisfying @xmath474 let us now show that @xmath475 indeed , from ( [ s2e3 ] ) we obtain that @xmath476 if @xmath477 $ ] and integrating this inequality , we also obtain @xmath478 now , if ( [ f3e5 ] ) fails , it follows that @xmath479 for some subsequence , and this contradicts ( [ f3e4:i ] ) and ( [ f3e4 ] ) . thus ( [ f3e5 ] ) holds . we now claim that ( [ f3e5 ] ) implies that @xmath405 vanishes for some @xmath480 $ ] . indeed , since @xmath476 we then have that , for @xmath109 large enough , @xmath481\,.\ ] ] this implies that @xmath482 for @xmath109 large enough with @xmath483 $ ] , but this contradicts the definition of @xmath484 , and so for @xmath109 large enough there is a first value @xmath485 $ ] such that @xmath486 , i.e. ( [ b2:h ] ) holds . [ positivity ] notice that a classical gronwall argument implies that any solution @xmath329 can be extended for arbitrary negative values of @xmath20 as long as @xmath329 remains away from zero . more precisely , if @xmath487 for any @xmath488 , it is possible to extend @xmath329 as a solution of ( [ compact1])-([compact4 ] ) for times @xmath489 and some @xmath175 . reciprocally , the maximal existence time , due to lemma [ l1 ] , is finite and it is given by @xmath86 if @xmath490 . we are now ready to prove proposition [ existence:1 ] . we consider the one - dimensional family of solutions of ( [ compact1])-([compact4 ] ) obtained choosing in lemma [ start : shooting ] the parameters @xmath491 with @xmath417 small enough and @xmath492 . we define as @xmath493 the set of values of @xmath44 such that the corresponding solution of ( [ compact1])-([compact4 ] ) satisfies ( [ b1 ] ) . on the other hand , we denote by @xmath494 the set of values of @xmath44 such that the corresponding solution of ( [ compact1])-([compact4 ] ) satisfy ( [ b2 ] ) for some @xmath86 . due to lemma [ start : shooting ] we have that @xmath495 and @xmath496 . moreover , by definition @xmath497 . due to lemmas [ continfinity ] and [ contzero ] we have that the sets @xmath493 and @xmath494 are open sets . therefore , there exists @xmath498 such that @xmath499 . the corresponding solution of ( [ compact1])-([compact4 ] ) associated to the parameter @xmath500 has the property that , for any @xmath501 we have @xmath502 , since otherwise @xmath503 due to lemma [ l1 ] . this implies also that @xmath504 because the right - hand side of ( [ compact1])-([compact4 ] ) is bounded in compact sets if @xmath505 . therefore , this solution is globally defined for @xmath412 . moreover , ( [ f4e3 ] ) holds , since otherwise @xmath506 and the result follows . we recall that the final aim is to prove that the solutions found in proposition [ existence:1 ] have no alternative but to approach the invariant subspace @xmath164 as @xmath35 and they remain uniformly bounded while @xmath19 stays positive ( see ( [ b3])-([b4 ] ) ) . the argument is by contradiction and in this section we prove the following lemma that is the first step in the argument . [ char : max ] suppose that @xmath411 is a solution of ( [ compact1])-([compact4 ] ) defined for all @xmath412 and satisfying @xmath507 and that @xmath508 then , there exists a decreasing sequence @xmath56 with @xmath57 and a sequence @xmath509 with @xmath510 small enough such that @xmath511}\phi(\tau)\ ] ] and that @xmath512 before we prove this result prove three auxiliary lemmas . first we show that there exists a decreasing sequence of local minima attained at certain @xmath513 with @xmath514 . [ l2 ] let @xmath515 satisfy the assumptions of proposition [ char : max ] . then , there exists a decreasing sequence @xmath112 such that @xmath113 and that @xmath516 first , we claim that @xmath517 indeed , suppose first that @xmath518 . then , there exists @xmath100 and @xmath126 sufficiently negative , such that @xmath519 for @xmath520 . then , ( [ s2e8a ] ) and ( [ s2e8 ] ) imply @xmath521 for @xmath391 , where @xmath378 is related to @xmath126 by means of ( [ s2e8 ] ) . this inequality applied to ( [ s2e3 ] ) gives @xmath522 for @xmath391 and some @xmath523 ( by taking a more negative @xmath126 if necessary ) . integrating ( [ g1e4 ] ) three times for @xmath391 gives @xmath524 ( where @xmath339 is as in lemma [ polyn ] ) . thus @xmath525 , but this contradicts ( [ f5e1 ] ) . we now prove the second inequality in ( [ g1e3 ] ) . suppose on the contrary that @xmath526 , then @xmath527 for some @xmath100 and for @xmath520 if @xmath434 with @xmath127 large enough . the transformation ( [ s2e8])-([s2e8a ] ) , with the obvious correspondence in notation , implies that @xmath528 for @xmath391 , whence ( [ s2e3 ] ) yields @xmath529 for some @xmath530 and @xmath391 . integrating ( [ g1e5 ] ) for @xmath391 we obtain @xmath531 . this implies the existence of a @xmath256 such that @xmath532 . this contradicts the assumption that @xmath533 ( see remark [ positivity ] ) and ( [ g1e3 ] ) follows . suppose now that @xmath534 we define a sequence of functions @xmath535 with @xmath536 $ ] as follows . for every @xmath537 the variable @xmath538 is given by , cf . ( [ s2e8a ] ) , @xmath539 then , each @xmath540 is defined by , cf . ( [ s2e8 ] ) , @xmath541we observe that then @xmath542where @xmath19 solves ( [ s2e9])-([s2e9bis ] ) . also , for every @xmath536 $ ] the corresponding sequence @xmath543 converges to @xmath544 as @xmath274 , since @xmath545 . on the other hand , the functions @xmath540 solve ( cf . ( [ s2e9])-([s2e9bis ] ) ) @xmath546\ ] ] where @xmath547 is given by the expression of @xmath26 in ( [ s2e9bis ] ) with @xmath19 and @xmath51 replaced by @xmath548 and @xmath549 , respectively . consider now the result of integrating ( [ g2e1 ] ) : @xmath550{ll } \phi_{n}(s ) & = \displaystyle { \phi_{n}(0 ) + \frac{d\phi_{n}(0)}{ds}s + \frac{d^{2}\phi_{n}(0)}{ds^{2}}\frac{s^{2}}{2 } } \\ & \\ & \displaystyle { -\int_{s}^{0}\int_{s_{1}}^{0}\int_{s_{2}}^{0 } \left [ \frac{1}{(\phi_{n}(s_{3}))^{3}}-\frac{|\xi_{n}(s_{3})|^{2}+a}{|\xi_{n}(s_{3})|^{2}+1 } \right ] ds_{3}ds_{2}ds_{1 } } \\ & \\ & \displaystyle { -\int_{s}^{0}\int_{s_{1}}^{0}\int_{s_{2}}^{0}f_{n}(s_{3})ds_{3}ds_{2}ds_{1 } } \ , . \end{array}\ ] ] we now pass to the limit in the integral terms . observe that the assumption ( [ lim:1 ] ) implies that @xmath551 uniformly on @xmath552 $ ] . moreover , ( [ g1e9 ] ) yields @xmath553 uniformly on @xmath552 $ ] . the first term in ( [ phi : n : inte ] ) can be seen to converge to zero using the limit properties of @xmath540 and @xmath538 . in the last term we integrate by parts where necessary in order to get integrands with @xmath540 as a coefficient ( this gives boundary terms with a double or single integral , but these are estimated similarly , because @xmath536 $ ] ) . the resulting integrands have @xmath540 multiplied by a function of @xmath538 and its derivatives , which can be computed using ( [ g1e9 ] ) : @xmath554 and @xmath555 . then , one can conclude that the limit of the last term in ( [ phi : n : inte ] ) tends also to zero as @xmath274 , and we are left with @xmath556 but this contradicts ( [ g1e6 ] and ( [ lim:1 ] ) can not hold . then @xmath557 . we can now construct a sequence that satisfies ( [ g1e7 ] ) . we first take the following quantity @xmath558 ( that might be infinite if @xmath559 ) . due to the continuity of @xmath19 , there exist decreasing sequences @xmath560 and @xmath561 such that @xmath562 , @xmath563 and that @xmath564 . we define another sequence @xmath112 by @xmath565 } \phi(\tau)\,,\ ] ] and this one satisfies ( [ g1e7 ] ) . we continue with another consequence of assuming ( [ g1e6 ] ) , namely , [ l3 ] suppose that @xmath411 satisfies the assumptions of proposition [ char : max ] . then , at least one of the following identities holds : @xmath566 we argue by contradiction . suppose that @xmath567 then , there exists a @xmath568 and a @xmath126 sufficiently negative such that @xmath569 then , ( [ g1e6 ] ) implies the existence of a sequence @xmath570 with @xmath571 and such that @xmath572 we now define a sequence of functions @xmath573 by means of @xmath574 and observe that they solve ( [ s2e9])-([s2e9bis ] ) with the obvious changes in notation and with @xmath575 defined by @xmath576 they also satisfy , due to ( [ g2e2 ] ) , that @xmath577 this allows us to introduce , for every @xmath109 , the length scale @xmath578 which clearly satisfies @xmath579 . we now set @xmath580 , @xmath581 , @xmath582 and @xmath583 , to obtain that @xmath584 satisfies @xmath585 + ( \gamma_{n})^{3 } \bar{f}_{n}(\bar{z } ) \,,\quad n\in\mathbb{n}\,.\ ] ] it is clear that there exists a @xmath586 such that for @xmath109 large enough @xmath587 we can now use classical continuous dependence results for odes . let @xmath588 denote a function that solves the limiting problem @xmath589 with initial conditions close to @xmath590 for @xmath109 large enough , and thus also satisfying ( [ init : bdd ] ) ( with @xmath591 ) , then @xmath592 as well as its derivatives , uniformly in compact sets of @xmath315 . since @xmath588 is a polynomial at most of second order that is not identically constant , there exist values of @xmath593 such that either @xmath594 or @xmath595 . but this contradicts ( [ g2e2a ] ) . the third auxiliary lemma is the following : [ l4 ] suppose that @xmath411 satisfies is the assumptions of proposition [ char : max ] . then , @xmath596 suppose that @xmath597 then , due to lemma [ l3 ] we have @xmath598 , and there exists a sequence of points @xmath112 such that ( [ g1e7 ] ) and that @xmath599 . for every @xmath109 we introduce the changes of variables @xmath600 observe that if @xmath549 is related to @xmath601 by means of ( [ s2e8 ] ) . in particular , this reflects that when @xmath602 remains bounded as @xmath603 , then @xmath17 as @xmath274 , a fact that we shall apply below . we write ( [ s2e9 ] ) in the new variables , then @xmath604 solves @xmath605 with ( cf . [ s2e9bis ] ) @xmath606 \varphi(s ) \\ & + & \varepsilon_{n}^{\frac{4}{3 } } \frac{1}{(\xi^{2}+1)^{\frac{17}{9}}}\left [ \frac{208}{81}\frac{\xi^{2}}{\xi^{2}+1 } -\frac{10}{9}\right ] \frac{d\varphi(s)}{ds } + \frac{2}{3}\frac{\xi}{(\xi^{2}+1)^{\frac{13}{9 } } } \frac{d^{2}\varphi(s)}{ds^{2}}\ , , \end{aligned}\ ] ] and subject to @xmath607 the coefficients involving @xmath51 are functions of @xmath3 ; @xmath608 . then , since @xmath609 , we can use classical continuous dependence results for odes to approximate the solutions of ( [ g4e2])-([g4e3 ] ) by the solutions @xmath610 of the limiting problem ( with @xmath611 ) @xmath612 on compact sets of @xmath3 . clearly , @xmath613 is increasing for @xmath614 , and there exists a @xmath175 such that @xmath615 for all @xmath616 . thus , @xmath617 increases at least linearly for @xmath3 large enough and one can find a value @xmath618 such that @xmath619 . continuous dependence results then imply that @xmath620 if @xmath109 is sufficiently large ( see ( [ g4e2 ] ) ) . we now return to the original variables and get estimates on @xmath329 for every @xmath109 in an interval around the local minimum . using ( [ g4e2a ] ) , ( [ g6e2 ] ) and the notation @xmath621 we obtain that @xmath622for @xmath109 large enough and @xmath20 such that @xmath623 , there exists a positive sequence @xmath624 with @xmath625 and such that @xmath626 let us denote by @xmath627 where the function @xmath628 is given by ( [ s2e9bis ] ) , and let also @xmath629 then , integrating ( [ s2e9 ] ) we can write for @xmath630 $ ] that @xmath631 then , taking @xmath109 large enough and combining the inequalities ( [ g5e1 ] ) we obtain that @xmath632 and that @xmath633 for some sequence @xmath634 with @xmath635 and for all @xmath636 $ ] . we now observe that @xmath26 has the form @xmath637 where the functions @xmath638 , @xmath639 and @xmath640 converge uniformly to zero on sets @xmath641 for every @xmath109 ( cf . ( [ s2e8 ] ) and ( [ s2e9bis ] ) ) . this allows to get estimates on the integral terms ( those involving @xmath642 ) as follows : @xmath643 for all @xmath109 with @xmath20 such that @xmath644 and where @xmath645 . applying this to ( [ g5e1tris ] ) and to ( [ low : bdd ] ) we obtain , taking @xmath109 sufficiently large , that @xmath646 for @xmath647 . choosing , say @xmath648 , we obtain that @xmath649 , but this contradicts ( [ g6e2 ] ) , whence the lemma follows . we are now ready to prove proposition [ char : max ] . the assumptions imply that we can use the statements of lemmas [ l2 ] and [ l4 ] . in particular , by rolle s theorem , we can guarantee the existence of local maxima in each interval @xmath650 where @xmath112 is the sequence of minima defined in lemma [ l2 ] . we then observe that the regularity of a solution @xmath19 of ( [ s2e9 ] ) guarantees that the points at which @xmath19 attains local maxima or minima are isolated . otherwise @xmath19 would take constant values on closed intervals , but constants are not solutions of ( [ s2e9 ] ) . hence , we can define the sequence such that ( [ def : max ] ) holds . on the other hand , lemma [ l4 ] implies ( [ g5e3 ] ) . in this section we proof the following proposition : [ max : increase ] let the assumptions of proposition [ char : max ] hold and let @xmath56 be the sequence found in this proposition . then there exists @xmath651 large such that for all @xmath652 @xmath653 we observe that this result is in contradiction with ( [ g5e3 ] ) . we now define a sequence @xmath71 as follows @xmath654 i.e. @xmath19 reaches the minimum in the interval @xmath65 at @xmath655 . then as part of the construction necessary to prove ( [ g5e4 ] ) it will follow that : [ min : decrease ] let the assumptions of proposition [ char : max ] hold . then the sequence @xmath71 given in ( [ def : min ] ) is well - defined , @xmath656 and there exists @xmath657 such that for all @xmath652 then @xmath658 the proofs of these propositions are divided in several steps that we outline below for clarity . we first identify a two - parameter family of polynomials that approximate @xmath53 near a large maximum of @xmath19 . most part of this analysis is done in appendix [ sec : polynomials ] , where we identify and give some properties of the polynomials that solve ( [ ecuacionminima1 ] ) ( with the reverse sign ) . then for each @xmath109 and around @xmath69 we identify a length scale that transform these polynomials into polynomials of order one . we then translate the properties found into the rescaled polynomials . we also rescale accordingly the function @xmath53 near each @xmath659 defined by ( [ s2e8a ] ) for @xmath660 and give the approximating lemma that in particular implies that @xmath53 will get close to @xmath67 in a linear decreasing way . next we adapt the _ matching lemma _ , lemma [ matchinglemma ] in appendix [ sec : control ] , that gives the behaviour of the solutions in the inner regions near each @xmath661 . from this result we can conclude that the approximating polynomial in the outer region must have a double zero in order to match . this , in particular , reduces the class of approximating polynomials to a one - parameter family . we finally derive an iterative relation between the elements of the sequence @xmath72 if @xmath109 is large enough that implies proposition [ max : increase ] , as well as a relation for the elements of @xmath73 that implies proposition [ min : decrease ] . given the sequence of @xmath56 found in proposition [ char : max ] , see ( [ def : max ] ) , and the sequence of local minima @xmath71 defined in ( [ def : min ] ) , we define the sequences @xmath662 , @xmath663 , @xmath664 and @xmath665 by means of ( see ( [ h6 ] ) and ( [ s4e3 ] ) ) : @xmath666@xmath667observe that the definition of @xmath69 implies that @xmath668 , that @xmath669 and that @xmath670 . observe that @xmath671 is the value of the maximum of @xmath19 at each @xmath69 rescaled appropriately with the position of the maximum in the variable @xmath51 , @xmath659 ( this scaling near a maximum resembles that @xmath672 there and that @xmath53 is approximated by a fifth order polynomial , cf . ( [ p : z : eq ] ) and ( [ s4e3 ] ) in appendix [ sec : polynomials ] ) . the definition of @xmath673 results from similar considerations , but is a parameter that captures the value of the second derivative of @xmath19 at @xmath69 . following appendix [ sec : polynomials ] , associated to every @xmath69 we construct the two - parameter family of polynomials @xmath674 that solve ( [ p : z : eq ] ) with @xmath675 replaced by @xmath676 , and that are given by ( [ s4e4 ] ) . we recall that they satisfy that @xmath677 . we shall see later that these polynomials are close to @xmath678 for @xmath51 close to @xmath659 in an interval contained in @xmath679 $ ] . thus we have to consider @xmath676 in some interval containing @xmath680 and where @xmath681 stays positive . moreover , since @xmath682 the approximation will be applicable for @xmath683 only . in this regard , for each @xmath109 , we have derived a number of properties that are outlined in lemmas [ pol2 ] , [ pol4 ] , [ pol5 ] and [ new : pol ] . these give , in particular , that the largest root of @xmath684 in @xmath685 is attained at a value @xmath686 for every @xmath687 and every @xmath668 . it is also shown that for every @xmath687 there exists a unique value @xmath688 such that @xmath689 has a double zero at some @xmath690 . in these lemmas the asymptotic behaviour as @xmath691 and as @xmath692 of @xmath693 , @xmath694 and @xmath695 is also given . but , as we shall see later and assume now , the sequence @xmath696 is bounded . taking these considerations into account , we now introduce a rescaling of @xmath684 for every @xmath109 in order to have values of order one in the relevant range of parameters . namely , we set @xmath697 observe that now the variable @xmath698 is meaningful in an interval around @xmath699 and with @xmath700 . we note that @xmath701 is a characteristic length scale which measures the distance between @xmath680 and @xmath702 , relevant if @xmath671 is very small , see lemma [ pol4 ] . we also observe that the polynomials @xmath703 are explicitly given by @xmath704 it is natural to define the following values of @xmath698 : @xmath705 ( see lemma [ pol5 ] , ( [ max : zroot ] ) ) , thus clearly @xmath706 . and if @xmath688 we define also @xmath707 therefore @xmath708 has a double zero at this value ( see lemma [ pol2 ] ) . when @xmath688 and for simplicity of notation , we shall write:@xmath709 and @xmath710 the following result follows easily : [ apppolynomials ] for every @xmath109 and @xmath671 the polynomial @xmath703 solves @xmath711 with initial conditions @xmath712 we now reformulate the results of appendix [ sec : polynomials ] for these approximating functions : [ scaled : pols ] let @xmath703 be given by ( [ s5e6 ] ) . they satisfy that if @xmath713 , then @xmath714 in @xmath715 and if @xmath716 then there are two zeros of @xmath717 in @xmath715 . the derivative of @xmath703 with respect to @xmath698 is positive at the largest root in @xmath715 . if @xmath688 there is only one double zero in @xmath715 and is placed at @xmath718 . moreover , @xmath719@xmath720 also , the value ( [ min : zeta : root ] ) is well - defined for every @xmath109 and @xmath671 , and if @xmath688 , then @xmath721 finally , we have also that [ new : pol : rescale ] the value @xmath722 is the unique root of @xmath703 in @xmath723 . moreover , if @xmath724 , there exists a positive constant @xmath725 independent of @xmath671 and @xmath673 such that @xmath726 we point out that the case @xmath727 corresponds to the the approximating polynomials obtained for ( [ odetapas ] ) in @xcite . the asymptotics ( [ zeta : plus : m0 ] ) are in agreement with this observation . in order to compare @xmath53 with a polynomial @xmath703 we need to apply the scaling ( [ s6e1 ] ) to @xmath53 around @xmath728 . we then obtain : [ h : rescaling ] let us assume that @xmath19 satisfies the assumptions of proposition [ char : max ] , so that the sequence ( [ def : max ] ) is well - defined . let @xmath405 be the solution of ( [ s2e3 ] ) related to @xmath19 by means of ( [ s2e8a ] ) and ( [ s2e8 ] ) . let the sequence of functions @xmath729 be defined by @xmath730 then , for each @xmath109 , @xmath61 solves @xmath731 where @xmath732 with initial conditions @xmath733 and latexmath:[\[\label{s6e5}\frac{d^{2}\mathcal{h}_{n}(0)}{d\zeta_{n}^{2 } } = \frac{\beta_{n}}{m_{n}^{\frac{1}{3}}}\frac{|\xi_{n}^{\ast}|^{\frac{2}{3}}}{(|\xi_{n}^{\ast}|^{2}+1)^{\frac{1}{3 } } } + \frac{2m_{n}^{\frac{2}{3}}}{3 } \left ( \frac{\left ( \frac{5}{3}|\xi_{n}^{\ast}|^{2}-1\right ) that each @xmath61 solves ( [ s6e2a ] ) follows by changing variables in ( [ s2e3 ] ) . the initial conditions follow from ( [ def : max ] ) and ( [ s5e3 ] ) . the following lemma will be used in the following to approximate the functions @xmath735 by polynomials @xmath736 . [ approximationlemma ] for each @xmath109 let @xmath737 solve ( [ s6e2a])-([s6e5 ] ) . then , for every @xmath417 there exists @xmath651 such that for all @xmath652 the estimates @xmath738 @xmath739 hold in @xmath740 and as long as @xmath741 the proof of this result is a standard bootstrap argument similar to the ones that has been used repeatedly . the idea is that the initial conditions ( [ s6e4 ] ) and ( [ s6e5 ] ) tend to the ones for @xmath708 as @xmath742 , see ( [ s6e62 ] ) . also the term @xmath743 in ( [ s6e2a ] ) is negligible if @xmath109 is sufficiently large since @xmath744 as @xmath274 ( observe that @xmath745 ) . on the other hand , the term @xmath746 can be approximated by @xmath747 as @xmath274 . the resulting limiting equation is then ( [ s6e6 ] ) and the values of @xmath61 and of its derivatives can be approximated at @xmath699 by those of @xmath736 and its derivatives there . the difference between @xmath737 and @xmath703 can then be approximated arguing as in , for example , lemma [ continfinity ] as well as in lemma 4.3 of @xcite . we observe that , as in @xcite , ( [ w1e9 ] ) implies upon integration of ( [ s6e2a ] ) , that a condition on @xmath748 of the form @xmath749 must be satisfied for @xmath109 large enough . then for every @xmath5 we can choose @xmath657 large enough to obtain that the @xmath5 is larger than the solution of @xmath750 and that the initial data are close enough to those of @xmath708 . we now prove that @xmath751 as @xmath274 . the idea is to use the fact that the derivative of the approximating polynomial @xmath703 at @xmath722 is of order one ( and negative ) by lemma [ new : pol : rescale ] . then , we can use lemma [ matchinglemma ] of appendix [ sec : control ] that gives the behaviour in the boundary layer where @xmath61 becomes small ( near @xmath752 ) , to conclude that the next polynomial in the outer region is close to one having a double zero in the matching region near @xmath752 . [ lemmadoublezero ] suppose that the @xmath19 and its derivatives satisfy the assumptions of proposition [ char : max ] and let @xmath56 be the sequence found there . let the sequences @xmath662 , @xmath664 and @xmath665 be defined by means of ( [ s5e2 ] ) and ( [ s5e3 ] ) , and let the functions @xmath693 be as in ( [ s5e8 ] ) and the sequence of functions @xmath61 be given by ( [ s6e2 ] ) . then , for any @xmath417 , there exists a @xmath753 and a @xmath657 large enough such that if @xmath754 and @xmath755 then @xmath756 also , for all @xmath652 @xmath757 @xmath758 and @xmath759 where @xmath760 is proportional to @xmath761 by a constant of order one , and there exist @xmath762 and @xmath763 independent of @xmath671 such that @xmath764 . moreover , for all @xmath652 there exists @xmath100 small enough an @xmath765 such that @xmath766 and @xmath767 @xmath768 suppose that @xmath109 is very large . we apply lemma [ approximationlemma ] for @xmath109 , thus starting @xmath699 or at @xmath728 . it then follows that we can approximate @xmath61 by the polynomial @xmath703 in intervals of the form @xmath769 $ ] with @xmath523 small but fixed and @xmath109 large enough . this in particular implies ( [ linear : entry ] ) and ( [ linear : entry2 ] ) . the fact that @xmath770 is bounded from above and below follows from lemma [ new : pol : rescale ] . using then lemma [ matchinglemma ] we obtain that @xmath771 can be approximated as a quadratic polynomial for @xmath772 . this implies @xmath773 for some @xmath530 small enough and @xmath774 of order one , and thus ( [ quadratic : exit ] ) follows . we can then replace the variables @xmath698 by @xmath775 and @xmath61 by @xmath776 using ( [ s6e2 ] ) and applying again lemma [ approximationlemma ] we can then approximate the function @xmath777 by one polynomial which has a double root at the value of @xmath775 corresponding to @xmath778 . this implies ( [ quadratic : exit ] ) , but also ( [ j3e7 ] ) follows by the definition of @xmath779 , and therefore also ( [ j1e2 ] ) , ( [ quadratic : exit3 ] ) and ( [ quadratic : exit2 ] ) follow . in order to prove the propositions we derive information from lemma [ lemmadoublezero ] in the matching region around @xmath780 for @xmath109 large enough . let us then assume that @xmath19 satisfies the assumptions of proposition [ char : max ] , so that the sequence ( [ def : max ] ) is well - defined . let @xmath405 be defined by means of ( [ s2e8a ] ) and ( [ s2e8 ] ) , and satisfies ( [ s2e3 ] ) . let the sequence of functions @xmath61 be defined by ( [ s6e2 ] ) , so that , by lemma [ h : rescaling ] , each such function satisfies ( [ s6e2a ] ) with initial conditions ( [ s6e4 ] ) and ( [ s6e5 ] ) . we further assume in the following that the approximating polynomials have @xmath688 thus they are as described in lemma [ scaled : pols ] and we drop the dependency on @xmath673 in the notation . lemma [ lemmadoublezero ] ( [ j1e2 ] ) and the definition of the variables @xmath676 give @xmath781 we can now argue that @xmath664 is a bounded sequence . indeed , if @xmath671 is very large , ( [ z0:minfty ] ) implies that @xmath782 is very negative . this would imply , using ( [ j1e1 ] ) that @xmath783 ( notice that @xmath784 by definition ) . however , we can not have @xmath783 for large @xmath109 , because @xmath785 . using now the definition of @xmath698 ( see ( [ s6e2 ] ) ) and ( [ j1e2 ] ) we can compute @xmath786 and @xmath787 to get @xmath788 on the other hand , the definition of the sequence @xmath61 ( in ( [ s6e2 ] ) ) gives @xmath789 we then change variables according to ( [ j1e3 ] ) and ( [ j1e4 ] ) in ( [ quadratic : exit ] ) in order to write it in terms of the variables @xmath775 and @xmath776 . this gives the asymptotic formula , for @xmath109 large enough , @xmath790 but comparing this to ( [ quadratic : exit3 ] ) implies that the approximation @xmath791 is valid for @xmath109 large enough ( here we have also used ( [ parameters ] ) ) . using the fact that @xmath671 is bounded , and also that @xmath760 can be estimated from above and below by a constant independent on @xmath109 , we obtain:@xmath792 for @xmath793 . using ( [ s5e3 ] ) , then @xmath794 using now ( [ j1e1 ] ) as well as the fact that @xmath782 and @xmath795 are bounded from above and below for @xmath671 and @xmath796 bounded ( cf . ( [ s5e4 ] ) , ( [ z0:mzero ] ) ) , we obtain , for different @xmath145 and @xmath146 if necessary , that @xmath797 using now ( [ zeta : gamma : m0ii ] ) for @xmath798 we can estimate @xmath799 from above and below by positive constants independent on @xmath109 . then:@xmath800 for some @xmath48 . we are now in the position of proving proposition [ max : increase ] . due to lemma [ lemmadoublezero ] we can assume that ( [ j3e7 ] ) holds for @xmath109 large . in a similar fashion as in @xcite we can make rigorous the argument outlined above by combining the lemmas [ matchinglemma ] and [ approximationlemma ] and prove indeed that ( [ j3e8 ] ) hold . since by hypothesis @xmath801 as @xmath274 it then follows that @xmath802 and this gives proposition [ max : increase ] . for each @xmath109 , let now @xmath63 be the value of @xmath20 at which @xmath19 reaches the minimum in the interval @xmath65 as defined in ( [ def : min ] ) . we can now prove proposition [ min : decrease ] : as before , we only give the formal steps of the proof and refer to @xcite for details . let @xmath661 be defined by means of ( [ s2e8a ] ) . then , by lemma [ approximationlemma ] , the fact that @xmath803 and lemma [ matchinglemma ] we can write , to leading order for @xmath109 large enough , @xmath804 and that , @xmath805 it is clear that for @xmath109 large enough @xmath64 approaches @xmath67 by lemma [ approximationlemma ] and employing the scaling @xmath806 ( that is analogous to the one used in the proof of lemma [ matchinglemma ] ) , give that the following is a valid approximation @xmath807 for @xmath109 large enough . here we also use that de definition of @xmath671 ( see [ s5e3 ] ) and that @xmath808 ( see ( [ parameters ] ) ) . thus for @xmath109 large enough one also has , by ( [ j3e8 ] ) , that @xmath809 for some order one constant @xmath48 . we finally observe that the values @xmath810 are of order one if @xmath109 is large enough , by lemma [ matchinglemma ] . also , we can approximately write the quotients @xmath811 . but each @xmath782 is an order one constant , since the sequence @xmath671 is uniformly bounded . then , since @xmath812 , we have that @xmath813 . moreover , there exists a constant @xmath48 ( different from the one above ) such that , for @xmath109 large enough , @xmath814 and thus ( [ min : decrease ] ) follows . in this section we finish the proof of theorem [ hetcon ] . first we prove the following [ controloscillations ] suppose that @xmath411 is a solution of ( [ compact1])-([compact4 ] ) as found in proposition [ existence:1 ] and satisfying ( [ f5e1 ] ) . then , there exist positive constants @xmath145 and @xmath146 depending only on @xmath380 such that @xmath815 we recall that the solutions found in proposition [ existence:1 ] are defined for all @xmath412 and satisfy @xmath816 . moreover , @xmath817 , @xmath414 for any @xmath412 and @xmath818 . we now claim that ( [ f5e2 ] ) holds for some @xmath819 . indeed , otherwise , due to proposition [ char : max ] and proposition [ max : increase ] there would exist a sequence @xmath56 such that @xmath57 and @xmath59 but such that there exits @xmath657 with @xmath820 for all @xmath652 . then , since @xmath821 ( cf . ( [ g5e3 ] ) ) it follows that @xmath822 , this yields a contradiction and , therefore , ( [ f5e2 ] ) is satisfied . suppose now that ( [ f5e3 ] ) is not satisfied , then in particular this implies , probably taking a subsequence , that @xmath823 but this contradicts ( [ g5e5 ] ) of proposition [ min : decrease ] . we can now finish the proof of the main result . due to proposition [ existence:1 ] there exists a solution of ( [ compact1])-([compact4 ] ) defined for all @xmath412 such that @xmath816 . moreover , @xmath817 , @xmath414 for any @xmath412 and @xmath818 . then proposition [ controloscillations ] gives that ( [ f5e2 ] ) and ( [ f5e3 ] ) hold . we now define a sequence of functions:@xmath824 using ( [ compact1])-([compact4 ] ) , ( [ f5e2 ] ) , ( [ f5e3 ] ) , standard compactness arguments and the fact that @xmath817 we can show that there exists a subsequence @xmath825 satisfying @xmath826 and such that @xmath827 converges uniformly in compact sets of @xmath20 to a bounded solution of ( [ s3e1 ] ) , say @xmath828 . moreover , we have @xmath829 , @xmath830 . due to proposition [ tapas1 ] it follows that @xmath828 is close to @xmath40 if @xmath831 and @xmath832 is large enough . using the stable manifold theorem it then follows that @xmath833 is contained in the unstable manifold of @xmath40 . however , due to proposition [ tapas1]_(v ) _ it follows that the only bounded trajectory contained in the unstable manifold of @xmath40 is the is the critical point itself , thus @xmath834 . this implies that the sequence @xmath835 converges to the equilibrium @xmath34 as @xmath836 . therefore the points @xmath837 are contained in the centre - unstable manifold of @xmath34 , whence @xmath838 and the result follows . * acknowledgements * this work was supported by the hausdorff center of the university of bonn . cuesta was also partially supported by the dges grant mtm2011 - 24 - 109 . we recall here the results concerning the following equation @xmath839 ( cf . ( [ ecuacionminima2 ] ) ) that have been shown in @xcite . for simplicity , we henceforth use the same notation for the dependent and independent variables as for ( [ odetapas ] ) . the following holds . [ matchsolution ] there exists a unique solution of ( [ ecuacionminima ] ) with the matching condition : @xmath840moreover , the asymptotics of @xmath329 for large @xmath20 is given by : @xmath841 finally , the exists a unique solution of ( [ para : match ] ) with matching condition @xmath842 it also satisfies that there exists a finite @xmath447 such that @xmath843 all other solutions satisfy ( [ para : match ] ) for increasing @xmath20 , and , for decreasing @xmath20 , either ( [ back : zero ] ) or @xmath844 holds . the proof of theorem [ matchsolution ] is done by a series of lemmas . the crucial step is to apply the transformation @xmath845 that reduces ( [ ecuacionminima ] ) to the system @xmath846 the lemmas then give the behaviour of the corresponding trajectories and are given below for reference . the last two equations in ( [ phi0system ] ) can be studied independently by means of a phase - plane analysis . the isoclines of this system are @xmath847 , that has @xmath848 , and @xmath849 , that has @xmath850 . the only critical point is @xmath851 , and linearisation gives two complex eigenvalues with positive real part , namely @xmath852 . we distinguish five regions , @xmath853 to @xmath301 , in the phase plane that are separated by the isoclines . these are depicted in figure [ phase - plane ] where the direction field is also shown . standard arguments imply that any orbit on the phase plane eventually crosses the isoclines into the region @xmath854 forwardly in @xmath143 . we recall that @xmath855 and the field in it satisfies @xmath856 . if , however , an orbit has @xmath857 at some value of @xmath143 , it is possible to discern from which of the regions is coming from for smaller values of @xmath143 by identifying the separatrices of the system . we have the following result . [ separa ] 1 . there exists a unique orbit @xmath139 in the phase plane associated to system ( [ phi0system ] ) that is contained in @xmath854 for all @xmath858 . moreover , @xmath859 has the following asymptotic behaviour @xmath860 2 . there exists a unique orbit @xmath861 in the phase plane associated to system ( [ phi0system ] ) that has the following asymptotic behaviour @xmath862and @xmath863 [ tozero - bwds ] all orbits associated to solutions of ( [ phi0system ] ) enter @xmath854 . those that are below the separatrix @xmath139 come from the critical point @xmath864 as @xmath865 and satisfy ( [ w3e6e ] ) . all other orbits , except for @xmath309 , come from the region @xmath301 . we identify the functions giving the leading order behaviour of the solutions of ( [ s2e3 ] ) if @xmath866 becomes large on a bounded interval around some negative value @xmath867 that gives a large local maximum of @xmath19 ( after the change of variables ( [ s2e8a ] ) ) . due to ( [ s2e8 ] ) , these approximating functions , if @xmath248 and @xmath868 is large , are @xmath869 where @xmath870 solves ( [ ecuacionminima1 ] ) . let @xmath871 be such that @xmath872 is a local maximum . we shall derive in the following some properties of these functions , such us conditions to ensure that they have a double zero at a point @xmath873 . but first we need to normalise them in an adequate way . we can readily integrate ( [ ecuacionminima1 ] ) with given initial conditions at @xmath867 . this gives a family of fifth order polynomials that depend on @xmath874 , @xmath875 and the first and second derivatives of @xmath876 evaluated at @xmath867 . using that @xmath877 we can write @xmath878 thus we can eliminate one parameter and obtain that @xmath879 we want to characterise the functions @xmath880 in terms of the parameters @xmath874 , @xmath872 and @xmath881 , however . in order to do that we first compute @xmath882 and then define a family of polynomials @xmath681 that normalises @xmath876 as follows : @xmath883thus @xmath681 solves @xmath884 and the parameters @xmath885 and @xmath886 are defined by @xmath887 then , ( [ q1e3 ] ) implies that @xmath888 changing to these variables in ( [ int : h : bar ] ) we obtain @xmath889 we point out that @xmath675 has the opposite sign as @xmath51 and thus we shall be interested in the region @xmath890 , or that one ahead of the local maximum of @xmath891 . we next show the existence , for each @xmath892 , of a unique @xmath893 such that @xmath894 has a unique and double root in @xmath895 . [ pol2 ] let @xmath894 be as in ( [ s4e4 ] ) with @xmath892 as in ( [ s4e3 ] ) . then , there exists a @xmath896 such that 1 . if @xmath897 , @xmath894 is strictly positive in @xmath898 . 2 . if @xmath899 there exists a unique @xmath900 such that @xmath901 in @xmath902 , @xmath903 and @xmath904 . 3 . if @xmath905 there exists @xmath906 that is a double zero of @xmath894 , and @xmath901 for @xmath907 . the polynomial @xmath894 is monotonically increasing in @xmath886 . since @xmath908 , it follows that @xmath901 if @xmath890 and @xmath909 . on the other hand given @xmath892 and @xmath910 , @xmath911 for negative values of @xmath886 if @xmath912 is large enough . for each @xmath885 we define @xmath913 then , by continuity in @xmath886 there exists a @xmath914 such that @xmath915 . moreover , @xmath916 , since otherwise there would exists @xmath897 and @xmath890 such that @xmath917 . we now claim that @xmath918 . indeed , otherwise the definition of @xmath893 would imply that @xmath919 is a zero of @xmath920 of order four and , in particular , that @xmath921 . but @xmath681 solves ( [ p : z : eq ] ) , thus @xmath922 suppose that @xmath899 . the monotonicity of @xmath894 in @xmath886 , combined with the fact that @xmath923 and @xmath924 imply that there exists at least two zeros of @xmath894 in @xmath925 . actually , there are exactly two zeros of @xmath894 in @xmath925 . for otherwise , there would be four zeros in @xmath925 counting multiplicities , and this would imply , by rolle s theorem , the existence of three zeros of @xmath926 in @xmath925 , and iterating the argument , also the existence of two zeros of @xmath927 in @xmath925 and at least one zero of @xmath928 in @xmath925 . but this contradicts ( [ s5e1 ] ) . therefore , @xmath894 has exactly two zeros in @xmath925 . the smallest of which , @xmath929 , satisfies @xmath904 ( by continuity since @xmath892 ) . we now compute the asymptotic behaviour of @xmath893 in the limits @xmath930 and @xmath931 . [ pol4 ] for every @xmath892 let @xmath893 and @xmath914 be as in lemma [ pol2 ] . then , they satisfy that @xmath932 and @xmath933 , and have the following asymptotic behaviour : @xmath934 and @xmath935 in order to determine @xmath914 and @xmath893 we have to solve the system that results from imposing that @xmath894 has a double zero:@xmath936 subtracting the second equation of ( [ double : zero2 ] ) multiplied by @xmath937 to ( [ double : zero1 ] ) we obtain@xmath938 the solution of which gives @xmath914 , the position of the double zero . now @xmath893 can be computed from either ( [ double : zero1 ] ) or ( [ double : zero2 ] ) by substituting @xmath919 . it is clear that @xmath939 for any @xmath892 , since the left - hand side of ( [ double : zero3 ] ) is positive for @xmath910 . it then follows from ( [ double : zero3 ] ) that , if @xmath940 , @xmath941 is of order @xmath942 and that , using ( [ double : zero1 ] ) , @xmath943 behaves like @xmath942 . on the other hand , if @xmath931 , we obtain that @xmath944 and that @xmath893 is of order @xmath885 . the precise asymptotic behaviours stated in ( [ s5e4 ] ) and in ( [ s5e5 ] ) follow easily from ( [ double : zero3 ] ) and ( [ double : zero1 ] ) by using the leading order behaviour of @xmath914 in both limits @xmath930 and @xmath931 . finally , we identify the largest root of @xmath681 in the region @xmath945 : [ pol5 ] for all @xmath892 and @xmath946 the following value is well defined @xmath947 if @xmath905 then , setting @xmath948 @xmath949 and @xmath950 moreover , in this case , @xmath951 is the only real root in @xmath945 . the proof follows by continuity , lemma [ pol2 ] and the implicit function theorem . we need to derive some information concerning the derivative of the polynomial @xmath952 at @xmath953 . [ new : pol ] the value @xmath954 is the unique root of @xmath894 in @xmath955 . moreover , if @xmath956 , there exists a positive @xmath725 independent of @xmath885 and @xmath886 such that @xmath957 using ( [ p : z : eq ] ) , and differentiating @xmath894 then @xmath958 and we obtain that @xmath894 is strictly concave for @xmath945 if @xmath959 . on the other hand , if @xmath960 we obtain that @xmath894 is strictly concave for @xmath961 and strictly convex if @xmath962 . then , since @xmath963 it follows that there exists a @xmath964 such that @xmath965 if @xmath966 and @xmath967 if @xmath968 . using now that @xmath969 it then follows that @xmath894 attains a positive maximum in the interval @xmath970 at @xmath971 . therefore , since @xmath972 and the concavity , the function @xmath973 has a unique zero @xmath974 . it is easy to prove that for @xmath885 bounded @xmath975 uniformly for @xmath976 , uniformly on @xmath977 ( differentiating ( [ s4e4 ] ) ) . in fact , one can actually show that for @xmath885 small enough there exists a positive constant @xmath725 such that @xmath978 if @xmath977 . in order to obtain ( [ j1e6 ] ) for large @xmath885 we first consider the case @xmath979 with @xmath980 sufficiently small , and then ( [ j1e6 ] ) follows easily @xmath977 suppose then that @xmath981 . then , if @xmath885 is large we can approximate @xmath894 and its derivatives in the interval @xmath977 by @xmath982 and its derivatives respectively . observe that then @xmath983 is a quadratic polynomial with bounded coefficients satisfying @xmath984 . suppose that @xmath985 . notice that we can not have any other zero of @xmath983 in the region @xmath945 because then , by continuity , @xmath894 would have more than one zero in the domain @xmath986 and this would contradict the statement above . then , using also that @xmath984 , we can write @xmath987 with @xmath988 bounded and @xmath989 . therefore @xmath990 , uniformly for large @xmath885 . it then follows that @xmath991 . then , since @xmath992 , @xmath993 and the result follows . we seek to reformulate the results concerning the region of very small @xmath53 ( or @xmath19 ) that can be approximated by ( [ ecuacionminima2 ] ) , that were obtained in @xcite . the result here is more general , namely the class of equations under consideration is @xmath994 where , if @xmath135 belongs to some given bounded interval , then @xmath995 [ matchinglemma ] suppose that the equation ( [ order1:eq ] ) is satisfied in an interval @xmath996 for some @xmath523 independent of @xmath196 and where @xmath997 satisfies ( [ j3e1 ] ) . suppose that : @xmath998 for @xmath999 , @xmath1000 and some @xmath530 . for any @xmath1001 , there exists @xmath100 independent of @xmath196 and @xmath1002 , but in general depending on @xmath725 , and a real constant @xmath1003 such that if @xmath1004 there exists a @xmath1005 such that for @xmath1006 we have:@xmath1007 for @xmath1008 . this result can be adapted from the results proved in @xcite . more precisely , the result follows from arguing as in the proof of the lemmas 4.4 , 4.5 , 4.6 and 4.7 of this article . we recall the main ideas of the argument here . we introduce the variables @xmath1009 and @xmath1010 and obtain that @xmath4 satisfies the equation @xmath1011 with the matching condition @xmath1012 we can then reformulate ( [ h : eq ] ) by the transformation ( [ sephi0-trans ] ) of appendix [ sec : summary : ii ] , thus , to leading order of approximation and due to the assumption ( [ j3e2 ] ) , the solution of the resulting perturbation of ( [ phi0system ] ) follows the separatrix @xmath859 ( see lemma [ separa ] ) . a key point in the argument is that the system of odes ( [ phi0system ] ) is integrated forward , the direction for which the separatrix is stable . this allows to prove that @xmath1013 as @xmath1014 for some @xmath1003 ( see theorem [ matchsolution ] ) , thus the asymptotics of the resulting solution for @xmath1015 can be described by means of ( [ j3e2 ] ) .

we consider a third order non - autonomous ode that arises as a model of fluid accumulation in a two dimensional thin - film flow driven by surface tension and gravity . with the appropriate matching conditions , the equation describes the inner structure of solutions around a stagnation point . in this paper we prove the existence of solutions that satisfy this problem . in order to prove the result we first transform the equation into a four dimensional dynamical system . in this setting the problem consists of finding heteroclinic connections that are the intersection of a two dimensional centre - stable manifold and a three - dimensional centre - unstable one . we then use a shooting argument that takes advantage of the information of the flow in the far - field , part of the analysis also requires the understanding of oscillatory solutions with large amplitude . the far - field is represented by invariant three - dimensional subspaces and the flow on them needs to be understood , most of the necessary results in this regard are obtained in @xcite . this analysis focuses on the understanding of oscillatory solutions and some results are used in the current proof , although the structure of oscillations is somewhat more complicated .

vibrational properties in amorphous solids are ill - understood compared to those in crystalline solids . in crystalline solids , the debye model explains that their vibrational density of states ( vdos ) is expressed as @xmath0 where @xmath1 is vibrational frequency and @xmath2 is dimensionality @xcite . on the other hand , in amorphous solids , the low frequency vdos shows excess mode spectra over that obtained from the debye model . although such low frequency vibrational modes are responsible for the anomalous dynamics and statics in amorphous materials , their physical origins remain elusive . such low frequency excess vibrational modes are most often observed in athermal jammed solids @xcite . the jammed solids are categorized as one class of amorphous solids . experimentally , such jammed solids are , in many cases , composed of soft materials such as emulsions @xcite , foams @xcite and large colloids @xcite . interestingly , the vdos in such systems shows a plateau of modes spectra in the low frequency region which extends to @xmath3 as the volume fraction approaches the jamming transition point from above @xcite . furthermore the low frequency vibrational modes in athermal jammed solids ( which are called soft modes ) are also highly non - trivial . here , some modes appear to be collective and extended throughout the space and others are quasi - localized @xcite , as in low temperature glasses @xcite . to characterize the spatial distribution and correlation of such vibrational modes is significant in jammed soft materials . actually , it has numerous applications such as predicting where plastic deformations ( leading to mechanical failure ) might occur in space , which is called soft spot @xcite . to obtain the spatial distribution and correlation of vibrational eigen modes in dense particle assemblies , normal mode analysis is frequently used @xcite . in such analysis , the vibrational modes are approximated as harmonic oscillators . here , they are characterized by diagonalizing the hessian matrix , which is composed of second derivatives of the potential energy with respect to the coordinates of the particles . unfortunately , its computational and memory costs tend to be huge , because even when rotational motions are neglected , the matrix size is @xmath4 , where @xmath5 is the particle number . thus in previous studies @xcite , small system sizes tend to be used . on the other hand , in order to study very low frequency modes , larger system sizes will be inevitable , and thus , another innovative method with low computational costs will be desired . to characterize these spatial properties , the participation ratio is often measured @xcite . on the other hand , the participation ratio alone is not sufficient to characterize the degree of collectivity in the particles vibrations it only measures the degree of localization in the particles vibrations . thus , in this study , we shall introduce the average local polarization as a measure of collectivity in the vibrations of the particles . in this paper , we outline a novel method to characterize the spatial distribution and correlation of vibrational modes without diagonalizing a huge hessian matrix . although our case study is a small system size of @xmath6 , this method can be easily extended to much larger system sizes . it should also be noted that our method can not directly obtain vdos , it only tells us the spatial properties of the vibrational modes . a method to obtain vdos without computing hessian matrix has already been described @xcite . therefore , combined with our new method , we can obtain most of the basic vibrational quantities in stead of the normal mode analysis . in our method , we excite a specific vibrational mode by giving active oscillation in each particle s diameter with an identical driving frequency . the response is then obtained as the real time displacements of the particles , which can be compared to the conventional normal modes obtained from static hessian matrix . we show high degree of correlation between the real time displacements and the static normal modes . furthermore , we also characterize the spatial structure of these vibrational normal modes by measuring the participation ratio @xcite and the polar order parameter . the results of these measurements are again found to be consistent for both the real time displacements and the static normal eigen mode . more importantly , from these measurements we can distinguish three distinct frequency regimes based on the spatial distribution of the particles vibrations ( whether they are extended and/or collective in space ) . finally by directly measuring the real time displacements of the particles , we may obtain dynamical quantities such as the mean squared displacement ( msd ) . the msd gives us the relative amplitude of particles vibrations . in particular we find that particles vibrate over larger distances at lower frequency excitation . this is consistent to the experiments of colloidal particles @xcite where they find large vibrations of the particles at lower frequency in the disordered structural regions . this paper is organized as follows : in sec . ii , we will explain the numerical methods on the oscillatory driven particle dynamics and the normal modes analysis . in sec iii , we will show the results especially on the comparisons between the normal mode analysis and our new method . in sec iv , we will give the summary and discussion of the present study . we consider a dense suspension of @xmath5 soft spherical particles at zero temperature in a two - dimensional square box of linear size @xmath7 with periodic boundary conditions on each side . the interaction between the particles is modelled by a short - ranged , purely repulsive , harmonic potential ( similar to foams @xcite ) : @xmath8 where @xmath9 and @xmath10 . @xmath11 and @xmath12 are the diameter and position of particle @xmath13 respectively . @xmath14 is the energy scale in the system and @xmath15 is the heaviside function , defined such that @xmath16 if @xmath17 and @xmath18 if @xmath19 . the dynamics of each particle is described by the following equation of motion : @xmath20 where @xmath5 is the total number of particles in the system , @xmath21 is the mass of the particles and @xmath22 is the friction constant between the particles and the solvent . we can define the natural frequency to be : @xmath23 and the damping coefficient to be : @xmath24 where @xmath25 is the typical diameter of the particles . physically if @xmath26 , the vibration of the particles will be overdamped , and if @xmath27 , the vibration is underdamped . in this paper we shall fix @xmath28 ( underdamped regime ) and @xmath29 . thus @xmath30 sets the timescale of our simulations . the dynamical equation ( [ eq : ] ) is integrated numerically using the velocity verlet scheme @xcite ( see suppl . info . for more detail ) . the system is then forced out of equilibrium by oscillating each particle s diameter @xmath31 around its mean value @xmath32 @xcite : @xmath33 , \label{eq : diameter}\ ] ] where @xmath34 is the driving frequency and @xmath35 is the amplitude of oscillation . the average diameter @xmath36 is taken from a bidisperse distribution of sizes @xmath37 and @xmath25 with proportion @xmath38 to avoid crystallization . we also introduce a fixed phase difference @xmath39 for each particle @xmath13 so that the area fraction @xmath40 is constant in time . throughout this paper , we consider an area fraction close to jamming transition with @xmath41 @xcite and a particle number @xmath42 . here , we use a small system size , because we calculate the hessian matrix to compare the conventional normal mode analysis to our new method . in simulations , we also set the typical diameter of the particles as the unit of length such that @xmath43 . we start from a random initial configuration at time @xmath44 . we then introduce active oscillation in the particles diameters according to eq . ( [ eq : diameter ] ) with some fixed amplitude @xmath35 and driving frequency @xmath34 . if the amplitude of oscillation is large enough ( above some critical value @xmath45 ) , the motion of the particles will be diffusive and the system will explore all the configurational space ( ergodic ) at steady state @xcite . on the other hand if the amplitude of oscillation is less than @xmath45 ( the regime in which we are interested in ) , the motion of all the particles will be periodic at steady state . thus in this vibrational state , the system is trapped in a local minimum of the total potential energy landscape . the total potential energy is defined to be : @xmath46 where @xmath47 is a @xmath48-components vector describing the configuration of the system at time @xmath49 . for a small oscillation amplitude @xmath50 , the phase - trajectory of the system @xmath51 oscillates around some local minimum @xmath52 at steady state . at the local energy minimum @xmath53 , the hessian matrix is defined to be the second derivative of the potential energy with respect to the particles positions ( see suppl . info . for more detail ) : @xmath54 the vibrational normal mode @xmath55 is associated to the eigen frequency @xmath1 according to the following equation : @xmath56 note that there is a set of @xmath48 eigen frequencies @xmath57 and @xmath48 corresponding eigen modes @xmath58 for a given hessian matrix . the soft modes are the set of eigen modes @xmath58 whose eigen frequencies @xmath57 are small compared to the natural frequency @xmath29 . these soft modes are usually characterized by long - range spatial correlation in the eigen vectors @xmath59 of the particles . soft modes are typical of a disordered system close to jamming transition @xcite . in summary , from a given static configuration @xmath52 , we may calculate the hessian matrix and subsequently a set of vibrational normal modes . however this information is not sufficient to predict how the particles will move in real time . thus as one of the aims of this paper , we will make some comparisons between the vibrational normal modes and the real time particles displacements . since we are only interested in the vibrational steady state , we fix the oscillation amplitude to be much smaller than the critical amplitude @xmath45 ( @xmath60 in all our simulations ) . we then vary the driving frequency @xmath34 from @xmath61 to @xmath62 . in this regime , the system will evolve into a vibrational steady state where all the particles move or vibrate periodically with a frequency close to the driving frequency @xmath34 . therefore , the total potential energy @xmath63 oscillates with frequency @xmath34 ( see fig . [ fig : u ] ) . note that in few cases , the system can also evolve into a vibrational steady state with a frequency double the driving frequency ( period doubling ) @xcite . we do not consider these cases in this paper since they occur much less frequently in the limit @xmath64 . here , we also note that the configurations obtained from the vibrational steady states are not fully distorted with the active vibrations in any frequencies @xmath34 as the vibrational amplitude @xmath35 is extremely small . at steady state , we may look at the displacements of the particles between time @xmath49 and @xmath65 : @xmath66 , where the initial time @xmath49 is larger than the time it takes for the system to reach a steady state and the delay time @xmath67 is less than the period of oscillation @xmath68 . ( note that the displacements of the particles are zero when @xmath69 since the motion of the particles is periodic . ) throughout this paper , we fix @xmath70 and @xmath71 in simulation units ( unless mentioned otherwise ) . this delay time of equal to half the period of oscillation corresponds to the maximum displacements of the particles during one full oscillation cycle . in fig . [ fig : dr ] top row , we plot the real time displacement fields of the particles for increasing driving frequencies from left to right . from these plots , we can distinguish three distinct frequency regimes based on two properties : collectivity and extensivity . here , we categorize the representative modes as performed in ref . @xcite , but with additional new definition of the collective measure . for small driving frequency or regime i ( @xmath72 in fig . [ fig : dr ] ) , the displacements of the particles appear to be collective and extended throughout the space . however for intermediate driving frequency or regime ii ( @xmath73 in fig . [ fig : dr ] ) , the displacements of the particles become disordered but still extended throughout the space . finally at high driving frequency or regime iii ( @xmath74 in fig . [ fig : dr ] ) , the displacements of the particles become localized in space and disordered . see below for the quantitative definitions of these regimes by using the degrees of participation @xmath75 and polarization @xmath76 in the present study . here , we note that @xmath76 is a newly introduced degree of criterion , which has never been used in the previous studies . to make comparison with the vibrational normal modes , we compute the hessian matrix from a single static configuration at steady state . more specifically , we drive the system with a fixed oscillation amplitude @xmath60 and fixed driving frequency @xmath34 as before . the value of the driving frequency @xmath34 is not important since they will all give the same distribution of normal modes as we shall see later . we wait until the system reaches a vibrational steady state and then we take a snapshot of the system . from this snapshot , we compute the hessian matrix according to eq . ( [ eq : hessian ] ) , and after diagonalizing the hessian matrix , we obtain a set of eigen modes ( or normal modes ) @xmath58 and a set of corresponding eigen frequencies @xmath57 . note that since the system is still evolving periodically , the configuration of the system at this instantaneous time is not strictly at the local energy minimum , and thus , we found a small fraction ( around @xmath77 ) of imaginary eigen frequencies ( @xmath78 ) which does not affect results that will be discussed below . the distribution of the eigen frequencies or vibrational density of states ( vdos ) @xmath79 is plotted in fig . [ fig : dos](a ) for different driving frequencies @xmath34 ( the data is averaged over @xmath80 independent simulations for a given @xmath34 and binned with bin size @xmath81 on the @xmath1-axis ) . @xmath79 is normalized such that the area under the curve is equal to @xmath82 . as expected , vdos does not depend on the driving frequency @xmath34 . it only depends on the natural frequency @xmath30 and packing fraction @xmath83 of the system , as long as we are sufficiently close to the local energy minimum ( _ i.e. _ @xmath35 is small enough compared to @xmath45 ) . moreover from the plot , we can identify a region of soft modes which is typical of disordered system close to jamming density . from the hessian matrix above , we also plot the static vibrational normal modes @xmath84 in the bottom row of fig . [ fig : dr ] for increasing eigen frequencies @xmath1 from left to right . note that , the vibrational normal modes plotted in the bottom row of fig . [ fig : dr ] are obtained from the static configurations directly above them . for instance , the vibrational normal modes of @xmath85 ( fig . [ fig : dr ] bottom right ) is obtained by diagonalising the hessian matrix of the instantaneous particles configuration in fig . [ fig : dr ] top right . incidentally , we may also identify three distinct eigen frequency regimes depending on the collectivity and extensivity of the normal modes , analogous to the real time displacement fields which we have observed in the top row of fig . [ fig : dr ] . moreover , when we compare fig . [ fig : dr ] bottom right to fig . [ fig : dr ] top right , we may recognize a region of large overlap ( dotted oval ) , signifying some degrees of correlation between real time displacements and vibrational normal modes obtained from a static configuration . also note that when diagonalising the hessian matrix , there exist several values of @xmath1 s which are very close to @xmath74 . each of these eigen modes contributes to multiple localized regions of large displacements that we see in fig . [ fig : dr ] top right ( one of them is the region bounded by the dotted oval ) . to quantify the collectivity of the displacement field @xmath86 or the normal modes @xmath84 , we introduce a local polar order parameter @xmath87 in the neighbourhood of particle @xmath13 . more precisely , for the displacement field @xmath86 , the local polar order parameter @xmath88 is defined to be : @xmath89 where the subscript @xmath90 indicates summation over all particles @xmath91 whose distance from particle @xmath13 is less than @xmath92 and @xmath93 is the total number of such neighbours around @xmath13 . here , we fix @xmath94 ( in simulation units ) , although the result does not depend strongly of the value of @xmath92 . physically @xmath95 if all the particles in the neighbourhood of particle @xmath13 move in the same direction and @xmath96 if they all move in random direction ( disordered or isotropic ) . finally @xmath97 corresponds to anti - ferromagnetic order which is not considered here . similarly we define the local polar order parameter for the normal modes @xmath98 to be : @xmath99 finally , the average local polarization is then defined to be : @xmath100 in fig . [ fig : dos](b ) , we plot the average polarization of the displacement fields @xmath101 ( green points ) and of the normal modes @xmath102 ( green line ) as a function of driving frequency @xmath34 and eigen frequency @xmath1 respectively . ( again , the data is averaged over @xmath80 independent simulations and the @xmath103-errorbar is the standard deviation from the ensemble average . the bin size for the @xmath1-axis is @xmath104 as before . ) as can be seen from these plots , both @xmath101 and @xmath102 overlap each other , indicating high degree of correlation between the real time displacements and the static normal mode . furthermore , we also see @xmath105 for all frequencies above @xmath106 in the plot , indicating disordered phase in the particles displacements / eigen vectors in normal modes . on the other hand , @xmath76 starts to increase ( in the positive direction ) as the frequency decreases below @xmath106 indicating increasing collective behaviour in the diplacement / eigen vectors . this coincides with the soft modes region as defined in jamming phenomena ( see fig . [ fig : dos](a ) ) , and thus , we may also identify the soft modes to be the onset of collective order in the displacement or eigen vectors ( regime i in our classification ) . to quantify the degree of extensivity ( or inversely , localization ) , we calculate the participation ratio @xmath75 as defined in @xcite . the participation ratio of the particles displacements @xmath107 is defined to be : @xmath108 physically @xmath109 if the motion of the particles is extended over the whole system size , and on the other hand , @xmath110 if the motion is localized . similarly , the participation ratio of the eigen vectors @xmath111 is defined to be : @xmath112 in fig . [ fig : dos](b ) , we also plot the participation ratio of the displacement fields @xmath107 ( red points ) and of the normal modes @xmath111 ( red line ) as a function of driving frequency @xmath34 and eigen frequency @xmath1 respectively . again as before , both data almost overlap each other . finally , by studying both the participation ratio @xmath75 and the average polarization @xmath76 , we can separate the three frequency regimes seen qualitatively in fig . [ fig : dr ] more precisely : regime i ( @xmath113 and @xmath114 ) , regime ii ( @xmath115 and @xmath114 ) , and regime iii ( @xmath115 and @xmath116 ) . we also compute the correlation between the real time particles displacements ( which are dynamical quantities ) and the normal modes of the hessian matrix ( which are static quantities ) . when comparing fig . [ fig : dr ] top right to fig . [ fig : dr ] bottom right , we have already seen a region of large overlap between the real time displacements and the eigen vectors ( dotted oval in the figure ) . thus , we define the overlap function @xmath117 to be the dot product between the displacement field @xmath66 and the eigen vector @xmath84 : @xmath118 where @xmath119 . note that the eigen vector @xmath84 is obtained from the hessian matrix of the particles configuration at time @xmath49 , the initial time of the displacement vector @xmath86 . physically , the overlap function tells us how similar the displacement field is to the eigen vector @xmath84 . @xmath117 varies from @xmath82 ( maximum overlap ) to @xmath120 ( no correlation between @xmath121 and @xmath84 ) . we plot @xmath117 in fig . [ fig : dos](c ) for different driving frequencies @xmath34 from @xmath61 to @xmath62 . ( again , the data is repeated over an ensemble of @xmath80 independent simulations and then averaged . ) as can be seen from these plots , we observe a peak in the overlap function @xmath117 at exactly the driving frequency of the system @xmath122 . thus by introducing an active oscillation in the system , we can excite the normal mode of the system which corresponds to the driving frequency of the active oscillation . to quantify the relative magnitude of the particles vibrations , we also compute the mean squared displacement ( msd ) as a function of delay time @xmath67 : @xmath123 where the initial time @xmath49 is fixed . [ fig : dos](d ) shows the msd for increasing driving frequencies @xmath72 , @xmath124 and @xmath62 for the same oscillation amplitude ( @xmath60 ) . as can be seen from the figure , the msd is periodic with frequency @xmath34 as expected , however , the amplitude of the msd is larger for low frequency excitation ( @xmath72 ) compared to the higher one ( @xmath74 ) . in other words , the particles vibrate over larger distance when the driving frequency is lower . this is consistent to the experimental results in @xcite , where they observe large low - frequency vibrational amplitude in the disordered structural regions . this increasing distance over which the particles vibrate can be explained by increasing participation ratio and collective order as the frequency is lowered . to analyze the dependence on the driving frequency more fully , we measure the average msd over one period of oscillation : @xmath125 ( note that this quantity is also averaged over an ensemble of @xmath80 different simulations . ) we plot the averaged msd as a function of driving frequency @xmath34 for a fixed driving amplitude @xmath60 in fig . [ fig : dos](e ) . indeed , we find that the averaged msd does increase as we decrease the driving frequency . ( note that the @xmath103-errorbar in fig . [ fig : dos](e ) is the standard deviation of the @xmath126 over the ensemble . ) in this study , we have constructed a new method to extract the specific vibrational modes as demonstrated in the normal modes analysis , by using oscillatory driven particles in a two dimensional dense disordered system . for the activation of the particle motions , we give a small amplitude of active oscillation in particle sizes with an identical driving frequency @xmath34 . first we have checked that the particles demonstrate reversible motion by means of the total potential energy for any input frequency @xmath34 , as shown in fig . [ fig : u ] . next we have shown the displacements of the driven particles for a half cycle ( @xmath71 ) at several @xmath34 values in the top row of fig . [ fig : dr ] . then we have revealed that the distributions of displacement vectors remarkably depend on the values of @xmath34 . for comparison , we have measured the eigen modes by means of the conventional normal mode analysis in the bottom row of fig . [ fig : dr ] . in particular , we observe overlapping regions between the real time displacements and the eigen vectors for the same frequency value , even though different techniques are applied . from the vdos shown in fig . [ fig : dos ] ( a ) , we have also checked that the normal mode analysis is not influenced by the external oscillations , because the oscillation amplitude is extremely small ( @xmath60 ) . in fig . [ fig : dos ] ( b ) we have presented the degrees of spatial polarization and participation ratio for both methods , presented respectively as @xmath127 and @xmath128 . it has been found that they behave respectively very similar , comparing the results obtained from both methods . furthermore we have measured the direct correlations between the real time displacement vectors of the particles driven with @xmath34 and the eigen vectors of the arbitrary modes @xmath1 obtained from the normal mode analysis by means of the overlap function @xmath117 . as shown in fig . [ fig : dos ] ( c ) , we have indeed found clear correlation where @xmath129 . this means that our new method works well as performed in the normal mode analysis . from these analysis , we have revealed that both of the real time displacements for the oscillatory driven particles and the eigen vectors of normal mode analysis are composed of at least three different regimes such as regime i : the correlated extended regime ( @xmath130 ) due to @xmath131 with @xmath132 , regime ii : the disordered extended regime ( @xmath133 ) due to @xmath134 with @xmath135 , and regime iii : the disordered localized regime ( @xmath136 ) due to @xmath137 with @xmath138 in the athermal amorphous solid close to @xmath139 . finally we have found that the typical amplitude of real time vibrations driven with low frequency oscillation is much larger than those with high frequency by measuring the one cycle mean squared displacement @xmath140 as shown in figs . [ fig : dos ] ( d ) and ( e ) . these results are consistent with features of the eigen modes measured by the normal mode analysis @xcite . in this method , we are able to fully characterize the vibrational properties of amorphous materials ( such as participation ratio @xmath141 and polarization @xmath142 ) without the need of diagonalizing a large hessian matrix . nevertheless , this method appears to be unable to directly measure the vdos ( or @xmath79 ) . but , the vdos has been obtained from the fourier transform of the velocity auto correlation with respect to time without computing the hessian matrix @xcite . here , we note that the computational and memory costs for this velocity auto correlation together with the fourier transform are of the order of @xmath143 . thus combined with our new method , we can obtain most of the basic vibrational quantities . it should also be noted that when we oscillate the particles diameters , the amplitude of oscillation should be kept small enough such that the response of the particles remains linear . in our case , we always check that the total potential energy @xmath144 is approximately sinusoidal with frequency equal to the driving frequency for each simulation run . previously we also defined @xmath45 to be the critical amplitude above which the motion of the particles become irreversible . below @xmath45 , the motion of the particles is reversible , but not necessarily linear . nonlinearity in our system come in the form of period - doubling , in which , the particles vibrate with a frequency @xmath145 @xcite , but the motion of the particles remains reversible . in @xcite , finite size scaling shows that @xmath45 approaches to a finite value as @xmath146 . thus we can always find a reversible phase irrespective of the system size used . however in @xcite , it has also been shown that the window of linear regime with respect to @xmath35 in the reversible phase scales as @xmath147 , where @xmath148 . this means that the linear regime vanishes at jamming transition point . and above jamming , the linear regime becomes narrower as @xmath146 . nevertheless , above jamming , we can always find a small enough value of @xmath35 in which the response is still linear for large but finite @xmath5 . in this paper we fix @xmath60 , but , we also perform several test simulations with @xmath149 and we still find reliable results.this means we can easily extend our simulation to large system size @xmath150 and still find linear response with @xmath149 . additionally , our method may also provide a useful tool to investigate the non - linear behaviour at large system sizes , close to jamming transition . in future studies , by using our model , we will examine a much larger system size , not only for athermal jammed systems but also for thermal glasses . for instance in low temperature glasses , the scaled vdos @xmath151 shows a peak in the low frequency regime , which is called the boson peak . this has been observed in experimental systems such as oxide @xcite , metallic @xcite , and organic materials @xcite as well as numerical simulations of model glasses @xcite . as a related matter , the low frequency vibrational modes in thermal glasses appear to be quasi - localized and collective based on theoretical arguments @xcite , as well as numerical simulations @xcite and experiments @xcite . according to the experiments of colloidal particles @xcite , such characteristic behaviours of low frequency modes may originate from large vibrations due to structural defects , analogous to crystals . it is indicated that such low frequency modes could play a significant role in the appearance of boson peak @xcite . at even lower frequency , debye modes also appear to be restored @xcite . to study such crossover behaviour , a much higher resolution of the frequency space will be needed , which requires much larger system sizes . however , conventional normal mode analysis requires a huge computational cost and thus a more efficient computational method will be desired . to perform such studies , we propose a model where thermal noise is applied in addition to the active oscillations in the particles diameters . in particular , by using our analysis of both participation ratio @xmath141 and average polarization @xmath142 , we may identify multiple frequency regimes in low temperature glasses , which may coincide with the appearance of boson peak at low frequency @xcite as well as debye modes at extremely low frequency @xcite . our model can also be easily extended to other forms of two - body potentials such as lennard - jones , gaussian core _ etc_. in such case , we oscillate the interaction range and then we expect the same results . it might also be interesting to consider other models of deformations which can excite a particular vibrational mode with a specific frequency . for instance , we might apply an oscillatory shear on the system . it is expected that the response of the system will correspond to the frequency of the oscillatory shear . however in the case of oscillatory shear , the response of the system might not be as isotropic as compared to our mode of deformation . finally our model also represents a unique example of active matter where the system is driven with a characteristic driving frequency @xmath34 . comparison of our actively oscillating particle system to the more mainstream self - propelled active particle system @xcite might also be illuminating , since self - propelled particles do not possess such a characteristic vibrational frequency . in conclusion , by means of our new method to excite the specific modes , we have acquired results consistent with those of the normal mode analysis . here the numerical costs for our new method is much lower than the normal mode analysis because we do not need to diagonalize a huge hessian matrix . this makes us possible to perform vibrational analysis for much larger systems in near future , which will significantly contribute to the studies of the vibrational properties in any solids including soft materials . we are grateful to maxime clusel who provided us with the initial ideas and for the illuminating discussions . we thank ludovic berthier , kunimasa miyazaki , akira onuki , atsushi ikeda , misaki ozawa , and kyohei takae for variable discussions and comments . tk gratefully acknowledges funding from jsps kakenhi ( no . 15h06263 and 16h06018 ) . et gratefully acknowledges funding from the european research council ( erc ) under the european union s ( eu ) seventh framework programme ( fp7/2007 - 2013)/erc grant agreement no . 306845 . j. mewis and n. j. wagner , colloidal suspension rheology ( cambridge university press , cambridge , uk , 2012 ) . f. boyer , e. guazzelli , and o. pouliquen , unifying suspension and granular rheology _ phys . lett . _ * 107 * , 188301 ( 2011 ) . a. widmer - cooper , h. perry , p. harrowell , and d. r. reichman localized soft modes and the supercooled liquid s irreversible passage through its configuration space . _ j. chem . _ * 131 * , 194508 ( 2009 ) . k. chen , w. g. ellenbroek , z. zhang , d. t. n. chen , p. j. yunker , s. henkes , c. brito , o. dauchot , w. van saarloos , a. j. liu , and a. g. yodh , low - frequency vibrations of soft colloidal glasses , _ phys . lett . _ * 105 * , 025501 ( 2010 ) .

we propose a new method to characterize the spatial distribution of particles vibrations in solids with much lower computational costs compared to the usual normal mode analysis . we excite the specific vibrational mode in a two dimensional athermal jammed system by giving a small amplitude of active oscillation to each particle s size with an identical driving frequency . the response is then obtained as the real time displacements of the particles . we show remarkable correlations between the real time displacements and the eigen vectors obtained from conventional normal mode analysis . more importantly , from these real time displacements , we can measure the participation ratio and spatial polarization of particles vibrations . from these measurements , we find three distinct frequency regimes which characterize the spatial distribution and correlation of particles vibrations in jammed amorphous solids . furthermore , we can possibly apply this method to a much larger system to examine the low frequency behaviour of amorphous solids with a much higher resolution of the frequency space .

infrared radiation from molecules and grains in space is usually or mostly attributed to heating by visible and uv light absorption . while this may be justified by the ubiquity of light radiation , it must be remembered that the ism ( interstellar medium ) is also permeated with atomic hydrogen . h atoms are also found in abundance in the limbs of molecular clouds illuminated by bright young stars ( pdrs or photodissociated regions ) . this paper accordingly explores the relative importance of deposition of energy by atomic hydrogen impacts on the same targets . as is well known , the formation of molecular hydrogen by two isolated h atoms is forbidden by energy and momentum conservation ; it is therefore associated instead with recombination in presence of a third body * ( see spitzer 1977 ) . the most readily available such body is a hydrocarbon molecule or grain . the latter is made of a carbon skeleton to which peripheral h atoms are attached . an incident h radical , if moderately energetic , will attract one of the h atoms at the grain periphery forcefully enough to capture it and form an h@xmath0 molecule which readily escapes into space ; this is called h abstraction " in surface physics language . it will be shown below that this process does not leave much energy in the grain . however , it does leave an unoccupied dangling " c - bond . when the next incident h atom meets that free bond , it is most likely to form a strong chemical bond with the host c atom . this recombination " deposits in the grain nearly 4 ev , * half of which is available in the form of kinetic energy to excite the vibrations of the hydrocarbon particle ( the other half going into potential energy ) . although this is no more energy than is carried by a visible photon , it is totally expendable in vibrational excitation , by contrast with photonic energy , which is first delivered to electrons , to relax thereafter into continuum and vibrational radiation . the emission of vibrational bands following h - impact excitation is a type of chemiluminescence . * the basics of this process were first put forward by guillois et al . it may be considered as a special case of the radical reactions " previously envisioned by allamandola and norman @xcite ; but these authors did not treat any process in particular , dwelling instead on relaxation times and emission probabilities . * * * the present work is also motivated by several astronomical observations which hint at the need to complement the photon flux with another excitation agent for the emission of uibs ( unidentified infrared bands ) . one is the fact that the relative intensities of the bands in the spectrum of uibs do not change notably with the average photon energy of the ambient radiation ( uchida et al . 1998 ) ; besides , neither the paucity of uv radiation ( as in galaxy m31 ; pagani et al . 1999 ) nor the absence of starbursts ( see haas et al . 2002 ) precludes uib emission . another hint was the comparison , by onaka et al . @xcite , using the irts satellite , of uib emission ( 5 to 12 @xmath1 m ) at various galactic latitudes throughout the galaxy : the intensity of emission decreases quickly with increasing latitude , but its spectral profile remains unchanged . while there are no hot stars at these latitudes ( and therefore much less far uv photons ) , the uib intensity follows the trend of h atom density , which extends farther from the galactic plane than does molecular hydrogen density ( see imamura and sofue 1997 ) . earlier on , boulanger and prault @xcite , studying the solar environment by means of the iras satellite , found that , away from heating sources and molecular clouds , the ir emission from the cirruses of the ism is well correlated with the column density of hi gas . pagani et al . @xcite reached the same conclusion from the study of a large number of sight lines through the near - by andromeda nebula ; by contrast , they found no correlation of ir emission with uv flux . still another remarkable fact is the occurrence of the uib intensity peak , in pdrs ( photo - dissociation regions ) seen edge - on , in between the peak of recombination radiation ( signaled by h@xmath2 lines , e.g. br @xmath3 ) , on the star - illuminated side ( hii region ) , and the peak of h@xmath0 de - excitation radiation at 2.42 @xmath1 m . this is precisely where maximum atomic h density is to be found . the generic example is the orion bar ( see roche et al . 1989 ) , sellgren et al . 1990 , graham et al . 1993 ) . * an idealized illustration of the succession of regions and of the distribution of densities and radiative fluxes was given by guillois et al . @xcite . * * finally , the need for some excitation process other than photon absorption to understand available observations seems to have been felt by other workers ; e.g. duley and williams @xcite reconsidered briefly another type of chemical excitation of ir vibration : the sudden and violent release , upon mild heating , of potential energy stored in molecules in the form of radicals . * in sec . 2 , i describe the elementary processes which create conditions under which h atom excitation becomes operational . in sec . 3 , rate equations coupling the relevant physical quantities are laid down and the statistical equilibrium values of the variables are determined . the latter are used in sec . 4 to determine the energy build up in a grain , under h atom bombardment . section 5 displays expressions for the uib reemission power . at this stage , it becomes possible to compare uv and h impact excitation of grains , which is done in sec . finally , sec . 7 compares predictions of the chemiluminescence model with observations in various environments and measurements of different physical quantities . when an h atom ( radical ) impinges upon a hydrocarbon target , a number of processes may occur ( see lohmar et al . 2009 , cazaux and tielens 2002 , papoular 2005 ) : a)recoil ; this is usually nearly elastic , i.e. it involves little energy exchange . b)recoil with expulsion of an h atom off the target ; this breaking of a c - h bond requires an unusually energetic h projectile ( @xmath430 000 k ) . c)h abstraction , in which the incoming h atom is attracted by a target h atom to form a h@xmath0 molecule which readily leaves the target with a high velocity ; this leaves a dangling ( unoccupied ) c bond at the target surface , together with a fraction of the c - h bond energy . d)surface recombination of the h projectile with a target dangling bond ( chemisorption ) ; this may occur over a large range of projectile energies , and leaves the whole c - h bond energy in the target . \e ) sticking ( physisorption ) of the incoming h atom at the target surface , over which it can wander until it goes through ( a ) , ( c ) or ( d ) . the steady state coverage of the target depends on all 5 processes but the energy balance is not the same for all , as shown below , * using version 7.5 of hyperchem , the chemical simulation code commercialized by hypercube , inc . earlier versions of this code were used and described in detail by , for instance , papoular @xcite and @xcite . here , i used the semi - empirical pm3 method of molecular dynamics calculation provided by the package . this method uses quantum - mechanical calculations , supported where necessary by empirical constants from the chemistry laboratory , which are kept up to date . in pm3 , the empirical part was tailored by comparison with carbon - bearing molecules , so the energies given by this code agree with experiment to a few percent , better than necessary for present purposes . * first , the c - h bond energy was determined in several different structures . this was done by first optimizing the structure of interest ( at 0 k ) , i.e. minimizing its potential energy as a function of geometry , and measuring this energy . the h atom was then extracted and the new , higher , potential energy measured . the difference is the required bond energy , @xmath5 . for h@xmath0 , this is 109.4 kcal.mol@xmath6 . for an aliphatic chain ( -ch@xmath0-ch@xmath7 ) , @xmath5=98 ; in methyl ch@xmath8 , 101 to 106 ; in benzene , 116 to 118 , all in kcal.mol@xmath6 ( 1 ev=23 kcal.mol@xmath6 ) . * in the following , we take @xmath5=4 ev , uniformly , as higher accuracy is not warranted in describing the general properties of the present model . consider first case ( d ) . the target is assumed to be initially at rest at 0 k. in a simplified semi - classical picture , the representative point of this state is the bottom of a parabolic potential well * as in fig . 1.when the incoming h atom is captured by a dangling bond , the potential well is suddenly depressed by @xmath5 , so the representative point is now found above the new bottom by the same quantity , with zero ke ( kinetic energy ) . it is compelled to slide down the well , rise on the other side , fall down again and repeat this sequence indefinitely . in this new , dynamic , state the average ke and pe ( potential energy ) are both equal to @xmath9 . this energy is initially localized in the new c - h bond in the form of large amplitude stretching vibrations , but it quickly spreads to other , closely coupled , vibrations of the structure * * the average life time of this state before energy is lost through ir radiation is usually longer than 1 ms * ( see radzig and smirnov 1980 ) . so the posibility must be considered that , before this happens , another h radical is captured by the same target . the representative potential well will again be depressed . assume , for simplicity , that the transition to the new , third , state occurs at the moment when the representative point is at its peak height in the well with pe=@xmath5 and ke=0 . its instantaneous pe above the bottom of the new well will therefore be @xmath10 , and the average pe and ke will rise to @xmath5 . thus for each successive h recombination , the target particle gains @xmath11 ev in vibrational energy . if this energy were shared equally between , say n=100 atoms of the target , this would correspond to a * vibrational temperature of @xmath12170 k. * * consider now case ( c ) . here , the gain in pe of the target upon loosing an h atom is partially compensated by the loss of pe associated with the formation of a h@xmath0 molecule , because the h bond energies involved are almost equal . moreover , the h@xmath0 molecule carries away vibrational , translational and rotational kinetic energies . typical values for an aliphatic chain , for instance , are , respectively , 19 , 15 and 0.3 kcal / mol for the h@xmath0 molecule , leaving only a few kcal / mol in the target . for case ( b ) , one can develop the same argument as for ( d ) , except that , here , the target potential well is suddenly raised , instead of depressed , upon losing an h radical . * assume , in fig . 1 , that the system is given more energy than what is necessary to break a ch bond . after a while , half this extra gain in ( potential ) energy is converted into ke , as in case ( d ) . however , this process clearly requires an unusually energetic h projectile . * in estimating the overall vibrational energy gain , below , we will therefore neglect the contributions of recoil and h absraction by comparison with that of h recombination . by hi region is meant , here , a region of space permeated with photons energetic enough to dissociate molecular hydrogen without ionizing the atoms . this excludes dense molecular clouds but includes , for instance , cirruses in the diffuse ism . let @xmath13 be the number densities ( @xmath14 ) of atomic , molecular and nuclear hydrogen , respectively , with @xmath15 . assume the average velocity of the h atoms is @xmath16 cm.s@xmath6 , and the flux of dissociating photons is @xmath17 @xmath18s@xmath6 . let @xmath19 and @xmath20 be the number of c and h atoms in each hydrocarbon grain , and @xmath21 the number density of such grains ( @xmath14 ) . assume , for simplicity , that , in the ism , the mass ratio between grain and gas is 1/300 . ignoring heteroatoms , which are quite rare in fact , and h atoms which are much lighter , this implies @xmath22 , or @xmath23 . since we are interested in h recombination with naked c atoms ( those exhibiting a dangling bond ) at the grain surface , we have to distinguish between the naked and the h - covered " c atoms . this is illustrated in fig . 2 , for an aromatic and an aliphatic skeleton . roughly speaking , a covered c atom may anchor one or two h atoms according to whether the skeleton is aromatic or aliphatic ; so there is 0.5 to 1 covered c atom for every bound h atom . taking 0.75 for simplicity , and assuming the carbon skeleton is not too compact , we may therefore write @xmath24 on average . now , the relative numbers of covered and naked c atoms depend on the density of gaseous h atoms above the grain , and on the various c - s ( cross - sections ) of the gas - grain reactions . in statistical equilibrium , the number of gaseous h atoms captured by a grain is equal to the number of bound h atoms liberated from the grain by h impact . this can be written @xmath25 where @xmath26 are c - s s for recombination , abstraction and expulsion , respectively ; @xmath27 is the c - s for recombination after sticking ( indirect recombination " ) ; a factor @xmath28 was omitted from each side as it is the same for all reactions , so this equilibrium is independent of the ambient gas density . then , defining @xmath29 , we get @xmath30 and , hence , @xmath31 . the c - s s * involved in gas - grain interactions have been estimated , computed , modelled or measured ( see cazaux and tielens 2002 , * mennella et al . 2002 , papoular 2005 , lohmar et al . the results concur only approximately . here , we read from papoular @xcite , with @xmath32 cm.s@xmath6 : @xmath33 @xmath34 , @xmath35 @xmath34 and @xmath36 . equation 2 then gives @xmath37 , indicating that the hydrogen coverage of the target is @xmath38 . * by way of comparison , in a study of gaseous atomic hydrogen interactions with carbon grains , papoular @xcite found that the h coverage of hydrocarbon grains varies between @xmath39 and @xmath40 , depending mainly on the kinetic temperature of the h gas . in a recent study of the hydrogenation of hac ( hydrogenated amorphous carbon ) duley and williams @xcite estimated the coverage at 0.3 - 0.5 . * * * turning to the gas densities , let @xmath41 be the h@xmath0 molecule c - s for dissociation by photons . the rate equations for gaseous atomic and molecular hydrogen densities can be written @xmath42 the terms in the r.h.s . of the first of these equations are for photodissociation , abstraction , recombination and expulsion respectively ; in the second line , the terms are for photodissociation and abstraction respectively . * in statistical equilibrium , the derivatives in the l.h.s . must be set to 0 . defining * @xmath43 , * and using the second rate equation , * @xmath44 * finally , using @xmath15 , we obtain * @xmath45 note that , while @xmath46 depends only on c - s s , @xmath47 also depends on the radiative flux and on the velocity of h radicals . as for the dissociating photon flux which enters the rate equations , its value * varies considerably with the wavelength in the spectral region of interest ( lyman continuum , 900 - 1100 ) , and so does the dissociation rate @xmath48 ( see draine 1978 , fig . 3 , and references therein ) . it is therefore usual to replace the latter by an estimated average value , @xmath49 , in this wavelength range . we adopt @xmath50 s@xmath6 for the galactic ism ( see stecher and williams 1979 , jura 1974 ) . nearer to hot stars , @xmath51 , where @xmath52 is the galactic fuv ( far ultra - violet ) flux , and @xmath53 may reach up to @xmath54 . we shall take @xmath55 , assuming that the * uv spectral profile does not change as the radiation varies in intensity . using these parameter values , eq . 3 then becomes * * @xmath56 thus , _ the ratio of molecules to atoms , z , is proportional to the total number density of h nuclei , and inversely proportional to the uv flux_. this simplistic treatment neglects the extinction of dissociating light by molecules and grains along its path , as well as self - shielding of the h@xmath0 molecules against uv due to their excitation out of their ground level ( see draine and bertoldi 1996 , fig . 8) . when these effects are included , it is found that , for given density and radiation flux , the light is almost unaffected up to a critical column density , beyond which it is quickly extinguished while the molecular fraction increases steeply . the elaborate theory helps understanding the earlier observations of molecular cloud limbs ( see savage et al . 1977 , fig . 6 ) , which set the critical column density at a few times @xmath57 @xmath18 . the fortunate conclusion for our present purposes is that our treatment is acceptable below the critical column density , i.e. in most environments from which the uibs are usually observed to originate : cirruses , molecular limbs and pdrs . assuming the frequency of collisions between grains to be much lower than the frequency of h impacts on a particle , the energy deposited by the latter accumulates in the particle until it is reemitted in the form of ir radiation , which is its sole outlet . a fundamental quantity is , therefore , the total kinetic energy deposited per atom during the radiative lifetime . from eq . 2 , the total number of atoms per particle is @xmath58 from sec . 2 , the vibrational energy deposited by an impinging h atom that recombines on the particle is @xmath9 . the number of such events that occur before ir emission is proportional to the radiative lifetime , @xmath59 , to the ambient h atom influx , to the dangling bond coverage over the particle surface and to the c - s for direct and indirect recombination . on average , the final ( or maximum ) vibrational energy _ per target atom _ will be @xmath60\,,\ ] ] or , * using eq . 2 and 3,@xmath61 * the characteristic behaviour of this function is determined by the factor ( @xmath62 ) . as @xmath47 tends to 0 ( high @xmath63 ) , @xmath64 which is proportional to @xmath65 but no longer depends on @xmath53 . as @xmath47 increases beyond 1 ( low @xmath63 ) , @xmath66 which is proportional to @xmath53 but no longer depends on @xmath65 . for the parameters of our numerical example , and @xmath67 s , @xmath68 and @xmath69 , if @xmath65 is in @xmath14 and @xmath70 in ev for a direct comparison with observations , the total uib emission per unit volume and time is needed . assume that all the chemical energy carried by the impinging h atoms is converted into ir emission . but , for the grains to distinctly emit the uibs , they must be * neither too small ( in which case , they could not contain all the functional groups that carry the uibs ) , nor too large ( in which case most of the energy would go into the continuum ) : this is demonstrated by emittance mesurements on carbonaceous particles of different compositions and sizes ( see , for instance , solomon et al . thus , only a fraction , @xmath71 , in mass , of the is carbonaceous grains ( as defined by these two constraints ) must be included in our calculation . using eq . 8 , the uib emission can then be written * @xmath72 since @xmath70 is proportional to @xmath59 ( see eq . 6 ) , @xmath73 no longer depends on the latter . figure 3 displays @xmath74 , the uib power emitted per ambient h nucleus . again , we distinguish regions of low and high illuminations and write @xmath75 @xmath76 where @xmath65 is in units of @xmath14 and @xmath73 is in w.m@xmath77 ( choices imposed by observational practice ) in a given is environment , it may be helpful to determine which of the two cases applies . equation 8 clearly shows that this depends on whether @xmath47 is much larger or much smaller than 1/2 . the critical condition , @xmath78 , can be expressed in terms of @xmath53 and @xmath65 , using eq . 5 : @xmath79 which is displayed in fig . it is apparent , from eq . 5 and 11 , and fig . 4 , that , in the local ism ( @xmath80 ) , dissociation is rather high and that eq . 9 and 12 are the better approximations . it is instructive to determine the relative contributions of h atoms and dissociative uv photons to grain heating . this is done here by considering the ratio of the rates of h atom recombinations ( on grains ) and uv photon absorptions per unit grain surface , * multiplied by the corresponding energies deposited in the grain , @xmath81 where @xmath82 is the fuv absorption cross - section per c atom . for c - h bonds , this is @xmath83 ( turro 2009 ) , while for c = c bonds it rises to @xmath84 @xmath34 ( see roche et al . @xcite ) . for graphite , it is @xmath85@xmath34 . let us adopt @xmath86 . also take , as above , @xmath9=2 ev , @xmath32 cm.s@xmath6 , @xmath35 @xmath34 and @xmath87=0.5 . the average energy of dissociating ( lyman continuum ) photons will be taken to be 12 ev , and @xmath88 photons . @xmath18.s@xmath6 for the diffuse ism ( @xmath80 ; see draine 1978 and references therein ; mezger et al . 1982 ) . this gives @xmath89 , or , using eq . 4 for @xmath90 , in the two extreme cases ( @xmath47 large or small ) : * @xmath91 @xmath92 the determining factor in eq . 15 is @xmath93 . thus , _ in small fuv fluxes , indirect heating by h atom impacts is much more efficient than radiative heating , independent of @xmath53 ; this is essentially because there are so many fast hydrogen atoms that their flux is larger than that of fuv photons . but , in high fuv fluxes , hydrogen is almost totally dissociated , so @xmath94 decreases because , as @xmath53 increases , @xmath90 no longer increases while radiative heating still increases and ultimately becomes dominant . _ this conclusion holds even if some less energetic photons ( 1100 to 2400 @xmath95 ) are included ; it is even strengthened when it is recalled that photon absorption is intrinsically less efficient than h impact in producing uib emission , as some of its energy is diverted into ionization and another part into continuum emission . the ratio ( 15 ) can be slightly modified to become the ratio of total uib emission to total ir emission . to that effect , assume , as in sec . 5 , that total conversion of the chemical energy into uib emission occurs only in a fraction @xmath71 , in mass , of the carbonaceous grains . then , the numerator of eq . 15 must be multiplied by @xmath71 in order to represent total uib emission . on the other hand , note that not only dissociating photons ( 900 to 1100 @xmath96 ) , but also weaker uv photons ( 1100 to 2400 @xmath96 , according to the definition of the habing uv unit of flux ) , contribute to the radiative heating of grains , and must also be included in the photon flux , @xmath17 ; for the latter , we now take @xmath97 * ( based on fig . 3 of draine 1978 ) , so the denominator now nearly represents the total ir emission . expressions 15 to 17 are thus multiplied by @xmath98 . this will be compared with observations in sec we seek now to compare the predictions of the model with relevant observations . consider first the diffuse infrared emission " from the galaxy , as measured by boulanger and prault @xcite in the solar neighbourhood . they compared the ir measurements of the iras satellite , in its 4 bands , 12 , 25 , 60 and 100 @xmath1 m , with the hi radio emission from the same regions of the solar neighbourhood , away from heating sources and outside dense molecular clouds , where @xmath80 by definition . noting that the radio emission is proportional to the h atoms number density , they deduced the band emission per h atom , in each band , and found 1.1 , 0.7 , 1.1 and 3.2 , respectively , in units of @xmath99 w per h atom , for a total of 6.1 . boulanger and prault @xcite also derived an estimate of the emission per h atom of the diffuse ism , in the uib range ( 2 to 15 @xmath1 m ) : @xmath100 w.h atom@xmath6 . from these data , @xmath71 can be deduced . for the contribution of uv photons to direct grain excitation is negligible in the diffuse ism ( see sec . 6 ) , so both uib and total ir emissions are excited by h impact ( in the present model ) . as a consequence , their ratio is precisely equal to @xmath71 , according to our definition of the latter ( sec . 5 ) , so @xmath101 this considerable fraction is a necessary consequence of the assumption that uib and other ir emissions are excited by the same agent . this constraint can be met with h atom excitation because even relatively large grains can be excited ; the upper limit to their size is several thousands of c atoms per grain , before the continuum confiscates most of the chemical energy . in fact , the grain efficiency in exciting uibs must be a decreasing function of grain size , so the transition between uib - emitting and non - uib - emitting must be gradual rather than a sharp cut - off . pagani et al . @xcite made a similar study of the diffuse ism of the andromeda nebula , m 31 . they considered the signal from the lw2 ( 5 - 8 @xmath1 m ) filter of isocam on board the iso satellite as a tracer of uibs and found that _ it is extremely well correlated , across the galaxy , with the distribution of neutral gas as mapped by the hi ( 21 cm radio ) and co(1 - 0 ) signals ( @xmath65 in our model ) , which they also plotted . by contrast , the correlation is poor with the ionized gas as seen through its h@xmath3 emission , and non - existent with the uv emission_. they conclude that the mid - ir emission can be excited by the ambient visible and near - ir radiation . here , i argue that , if that were the case , there would still be a much tighter correlation with the young stars of the nebular ring than shown by the maps . instead , i set out to interpret quantitatively the findings of pagani et al . @xcite by means of the present model . pagani et al . analyzed their images , pixel by pixel , and plotted their measurements as a graph of i(lw2 ) as a function of the column density , n(h ) , in their fig . 6 . from this , they deduced the regression line @xmath102 * where @xmath103 , and i(lw2 ) is in mjy / pixel and @xmath104 , in @xmath18 . given the size of the pixel ( 6``x6 '' ) , and neglecting the ordinate at the origin , -0.23 , we deduce @xmath105 * since the isocam images cover mainly the general ( diffuse ) ism of m 31 , this number can be compared with the value , 1.5@xmath106 , measured by boulanger and prault @xcite in our galaxy , in the uib range ( 2 to 15 @xmath1 m ) . they are of the same order of magnitude , but the signal from m 31 is weaker by a factor @xmath1074 . this must be due , in large part , to the fact that the lw2 filter covered the range 5 - 8 @xmath1 m , * thus excluding the strong 11.2 and 12.7 @xmath1 m bands , while the measurement of the galaxy covered the larger range 2 - 15 @xmath1 m . the remaining difference is discussed next . * figure 6 of pagani et al . exhibits a significant dispersion about the regression line . this is quantified in their fig . 9 , which plots @xmath108 ( * our @xmath109 ) as a function of the fuv flux in a band of 15 nm width around 200 nm . when translated in the units used here , their measurements extend over * the ranges 0.25 to 0.8@xmath110 erg.@xmath18.@xmath111.arcsec@xmath112 for the fuv flux , and 0.32 to 4.75@xmath113 w/ h atom , for @xmath109 . * boulanger and prault @xcite , had also found considerable patchiness in the ir emission from the solar neighbourhood in all directions ( their fig . this was associated with the notion of cirrus " imagined by low et al . @xcite by analogy with this type of tenuous clouds in our atmosphere . * * * in the present excitation model , this dispersion can be interpreted in terms of h density differences between regions having the same uv illumination . in order to * justify this proposition , we return to eq . 11 , which gives the exact expression of the power reemitted in the uibs per unit volume of space , insert 0.25 for @xmath71 and divide by 2 to take into account the smaller band width of the lw2 filter . the result can be cast as * @xmath114 where @xmath115 , * as in eq . 5 , and @xmath65 is in @xmath14 . * clearly , @xmath116 varies with @xmath65 and @xmath53 . as an example , take the minimum measured uv flux in fig . 9 * of pagani et al . @xcite ( for which the dispersion of plotted points is greatest ) : 2.4 @xmath117 erg.s@xmath6.@xmath118.arcsec@xmath112 , which is close to the value in the solar neighbourhood : 2.1 10@xmath119 ( see draine 1978 ) . for lack of better information , assume that the ratio of dissociating uv flux to the flux at 200 nm is the same in m 31 as in the solar neighbourhood . then , for the selected points , @xmath120 , according to our definition of @xmath53 in sec . 3 . for the corresponding minimum and maximum values of @xmath116 , eq . 19 gives , respectively , about 5 and 77 h at.@xmath14 . for the average @xmath116 ( eq . 20 ) , @xmath121 @xmath14 . these calculations implicitely assume that every measured ir power emanates from a limited region of space ( a cirrus ) , with a relatively homogeneous density distinctly different from that of the environment ( see also sec . * boulanger and prault @xcite also derived an estimate of the emission per h atom of the diffuse ism , within 1 kpc of the sun , in the uib range ( 2 to 15 @xmath1 m ) : @xmath100 w.h atom@xmath6 . in this case , eq . 21 gives @xmath122 @xmath14 . for densities in this range and @xmath80 , @xmath116 is much more sensitive to variations of @xmath65 rather than in @xmath53 . so , although the fuv content in m 31 may be lower than in the solar environment , as suggested by pagani et al . @xcite , the weakness of the measured @xmath116 may , in the present model , be due to the relative paucity of hydrogen rather than to that of the fuv flux . when a young , bright star ( e.g. class o or b ) , happens to be in the vicinity or inside a denser ( and hence cooler ) cloud , its fuv radiation digs into the cloud to form an hii region ( signalled by ionic radiation or h recombination radiation ; e.g. br @xmath3 , p @xmath3 ) , followed farther by an hi region ( pdr proper ; essentially h radicals , signalled by centimeter - band radio emission ) , then by a thin layer of radicals recombining into excited molecules ( signalled by several near ir lines ; e.g. 2.42 @xmath1 m ) and , farther still , by the new edge of the molecular cloud ( signalled by co molecular lines ) . this sequence has often been described ; for a recent analysis , see habart et al . for our present argument , it is essential to note that , in this type of environment , the uib are observed to come from the intermediate , hi region and the adjacent h@xmath123 region * ( where vibrationally excited h is observed ) : see , for instance , roche et al . @xcite for the 11.3- and 12.7-@xmath1 m bands , sellgren et al . @xcite for the 3.3-@xmath1 m band , all observed in the orion bar ; an and sellgren @xcite , studying ngc 7023 , compared the maps of the 3.3-@xmath1 m band with its adjacent , underlying , ir continuum as well as the 1 - 0 s(1 ) line of excited h@xmath0 ; giard et al . @xcite studied m17 at 3.3 and 10 @xmath1 m , at 6 cm and in the c@xmath124o 2 - 1 band . this is a very strong indication of a link between h atoms and uib excitation , especially when it is remembered that , in the present model , those molecules that are formed after an h atom impact on a grain , leave the grain surface with a large amount of vibrational excitation ( see sec . 2 ) and that the h@xmath123 near ir emission is therefore generated at the interface between the hi region and the edge of the molecular cloud . * boulanger et al . @xcite later analyzed the data collected by the iso satellite from several such locations . they were thus able to quantitavely determine the brightnesses of the main uibs , at 6.2 , 7.7 , 8.6 , 11.3 and 12.7 @xmath1 m , and this for several sources for which they also determined the illumination @xmath53 . they found a common trend for all five bands : an initial rise in intensity as a function of illumination , followed by a progressive levelling - off for @xmath125 ( their fig . the brightness of the 7.7 @xmath1 m band , for instance , starts at @xmath126 w. m@xmath112.sr@xmath6 for @xmath80 ( the chamaeleon cirrus cloud in the dffuse ism ) , and terminates at 6.4 w. m@xmath112.sr@xmath6 for @xmath127 ( the omega nebula , m 17 ) . the single uv photon excitation ( also referred to as transient or stochastic heating * in the pah hypothesis ) expects a continuous rise of band brightness with @xmath53 , and the levelling - off is tentatively explained by grain destruction . the present model predicts an initial linear rise in incompletely dissociated regions followed by a levelling - off as a result of high dissociation , and limited amount , of available h gas . * for a more quantitative comparison of our model with observations , consider the emission @xmath73 given here by eq . this ir power is emitted in 4@xmath128 sr . the ir surface brightness of a source of depth @xmath129 along the line of sight is , then , @xmath130 . the results of astronomical measurements are usually expressed in the form @xmath131 , where @xmath132 . now , the spectrum of a finite material structure ( or small grain ) , as opposed to that of a homogeneous medium of infinite extent , is expressed in terms of its discrete line intensities , @xmath133 . there are @xmath134 of these for a total of @xmath135 atoms ( one for each vibrational mode ) ; they can be measured ( absorptivity ) or calculated ( electronic polarizability ) . if the line distribution is sufficiently dense , an adjacent averaging over @xmath136 makes sense , giving a continuous distribution @xmath137 assuming the excitation energy to be uniformly distributed among all vibrational modes , one can write @xmath138 , and the observed astronomical quantity becomes @xmath139 where @xmath129 is in meters , @xmath73 in w.m@xmath77 and @xmath140 in w.m@xmath112.sr@xmath6 . finally , a typical value of the pure number @xmath141 can be derived from a bright source , like ngc1482 ( smith et al . 2007 ) , for each of the main bands . this was done here by interpolating the flux spectrum with 600 points between 5 and 20 @xmath1 m , so that @xmath142 m . for the 7.65- and 11.3-@xmath1 m bands , for instance , one thus obtains 1.4 and 2.1 respectively . inserting @xmath143 in eq . ( 22 ) , together with expression ( 12 ) for @xmath73 , and @xmath144 ( as in sec . 7.2 ) , we obtain @xmath145 thus , for @xmath146 m ) to comply with the observed value of 10@xmath147 with @xmath80 , @xmath148 should be 3.3@xmath149 @xmath150 with , for instance , @xmath129=1 pc and @xmath151 @xmath14 , which seems reasonable . for this choice , @xmath152 and , in fig . 4 , the representative point falls above the critical line , which would justify the use of approximations 9 and 12 . it is tempting to use the relation between hydrogen column density and visible extinction along the same line of sight ( if available ) : @xmath153 ( see bohlin et al . 1978 ) . here , @xmath154=3@xmath155 , so @xmath156 ; but , in the case of chamaeleon , laureijs et al . @xcite measured @xmath157=1 . the discrepancy may be due to a number of causes , the most probable of which is that , for this value of a@xmath158 , the molecular hydrogen fraction in the column density may be quite high due to light extinction by molecules ( see savage et al . 1977 , fig . 6 ; draine and bertoldi @xcite , fig . 8) ; in this case , our expression 3 would underestimate @xmath47 , thus leading to a lower estimate of @xmath65 . at the high @xmath53 end of boulanger et al.s observations , for m 17 with @xmath127 , @xmath140(7.7@xmath1m)=6@xmath159 w.m@xmath112.sr@xmath6 . equation ( 26 ) then gives @xmath160 cm.@xmath161 . here , the geometry of the emitting region must be very different than that of a thin cloud , because the very strong illumination by a young , bright , star near by drives a shock in a thick cloud , thus considerably increasing the density in a region of limited extent : a bar " whose thickness along the direction to the star is a small fraction of a parsec ( see , for instance , the extensive study of the orion bar by bregman et al . @xcite ) . a more likely order of magnitude for @xmath129 , therefore , is now 0.1 pc , for which one gets @xmath162@xmath14 , again within reasonable range for this type of object . more recently , analyzing the data of the _ spitzer _ satellite , smith et al . @xcite produced a large number of good quality uib spectra from star - forming galaxies . the peak brightnesses of the main bands cover the range between 10@xmath163 and @xmath164 w.m@xmath112.sr@xmath6 , similar to the galactic data of boulanger et al . , confirming the remarkable uniformity of the uib * spectral profiles , independant of their intensity . * a crucial result of boulanger et al.s @xcite observations , among others , is that the relative intensities of the main uibs do not vary much , nor systematically , over a @xmath53 range of @xmath54 . this insensitiveness was noticed by several authors , observing various environments ( out of galactic plane , other galaxies , etc . ) : see , for instance , murakami et al . @xcite , chan et al . @xcite , mattila et al . @xcite , kahanp et al . @xcite , smith et al . it is in agreement with h - impact excitation , which , in nanoparticles , is followed by non - thermal , quasi uniform , redistribution of the same chemical energy ( 5 ev ) among those vibrational modes of the target that are strongly coupled . by contrast , the insensitiveness to photon flux is at variance with what one would expect from single uv photon excitation as noted by sellgren et al . @xcite . in this model , the grain temperature is supposed to decrease with the photon energy so the relative intensities of shorter - wavelength bands would also decrease ; the uibs should even fade out precipitously for illuminating star temperatures below @xmath165 k , as the fuv content of the illumination is then too small . but this was not borne out by their observations of several reflection nebulae illuminated by stars with temperatures ranging from 5000 to 21000 k ( see also uchida et al . 1998 ) . mattila et al . @xcite also remarked that their and others observations implied that the uib carriers are very resistant to different environments ( rne , pne and hii regions ) . none of the above is incompatible with the small spectral variations in position , intensity or width , which led to the classification of uib spactra in different classes ( see peeters et al . 2002 , tokunaga 1997 ) . in some cases , the variations are more radical , such as for the 11 - 13 @xmath1 m massif across ngc7023 ( boulanger et al . still more striking is the detection or non - detection of the 3.3-@xmath1 m band , independent of illuminating star temperature or ambiant uv content over 4 orders of magnitude of @xmath53 ( smith et al . this poses a common problem to all models , but appears to be linked with particular chemical processes or environments , rather than with the excitation process ; as such , it falls outside the scope of this work . in most uib spectra , an underlying continuum is clearly apparent , rising towards long wavelengths and often very weak at short wavelengths ( see , for instance , cesarsky et al . 2000 , peeters et al . 2004 , zhang and kwok 2010 ) . from their analysis of measurements with the iso satellite in the 6 - 12 @xmath1 m band and at 100 @xmath1 m , kahanp et al . @xcite concluded that both emissions were strongly correlated at small and large scales , which implies a strong connection ( origin , chemical composition , environment ) between the small grains responsible for the former , and the large ones , responsible for the latter . mattila et al . @xcite arrived at the same conclusion from their study of the disk of ngc 891 , which they observed at 8 wavelengths characteristic of different ism components . this conclusion is in line with the present treatment , as well as with the roughly constant ratio of uib to total ir emission ( sec . . however , it seems to be at odds with the large variations of the spectral band - to - continuum ratio , or contrast , @xmath166 , from object to object ( see also boersma et al . if the grain composition does not change with size , this may be explained as follows . the continuum brightness contribution to the band at @xmath167 can be written @xmath168 where @xmath169 is the grain emissivity , @xmath170 is planck s black - body law ( w.m@xmath112.@xmath1m@xmath6 ) , @xmath129 the object depth along the line of sight ( m ) , @xmath21 the grain number density ( m@xmath77 ) , and @xmath171 the grain optical c - s ( m@xmath172 ) . the grain temperature is estimated by assuming thermal equilibrium and equating the power absorbed by a grain from the illuminating flux @xmath173 , to the power reemitted by the same grain in the ir . for simplicity , assume the grain absorptivity ( emissivity ) varies as @xmath174 and that all the reemitted power is at the same wavelength , viz . the peak of the bb ( black body ) emission , @xmath175 , and is given by the stefan - boltzmann law , @xmath176 where @xmath177w.@xmath18.k@xmath178 . also assume the flux that heats the large grains is @xmath179 , where @xmath53 is the same as above , but @xmath180 is much larger than the dissociating flux , in order to include lower energy photons . following boulanger and prault @xcite , we take @xmath181w.@xmath18 . also , defining the photon wavelength as 0.1 @xmath1 m , one gets @xmath182 . then , equating absorbed and reemitted powers , the grain diameter and its emissivity ( at the reference wavelength ) factor away , and it is easily deduced that @xmath183 equation ( 26 ) still requires an estimate of the emissivity , @xmath169 ; it can be obtained from the consideration of the total far ir emission measured by boulanger and prault @xcite in the iras 60- and 100-@xmath1 m bands : @xmath184 w per h atom . this is to be equated with the stefan - boltzmann law . now , spitzer @xcite estimated the grain c - s at @xmath185@xmath34 per h atom . assuming the fraction associated with carbonaceous dust to be @xmath186 , then @xmath187@xmath188 . finally , taking @xmath189k , we obtain @xmath190 at the peak of the black body emission , 150 @xmath1 m and , for an opacity in @xmath174 , @xmath191 using the spitzer result again to express @xmath192 in eq . 26 , the latter becomes @xmath193 finally , the contrast becomes @xmath194 where @xmath73 is taken from eq . 11 and @xmath195 , from eq . 23 . as an illustration , fig . 5 plots @xmath196 as a function of @xmath53 , as well as @xmath166 for @xmath197 m and 11.3 @xmath1 m , both for @xmath198 @xmath14 . our model predicts that , for most environments in the ism , @xmath53 and @xmath65 are such as to deliver high contrasts , as usually observed . it also predicts that the contrast decreases as the uib wavelength increases , as observed , except for the diffuse ism ( see onaka et al . 1996 ) : this is because , there , hydrogen is dissociated although the illumination is so low that the larger grains are very cold and the continuum very weak . finally , the model predicts that the transition from high to low contrast is very swift as @xmath53 increases , due to the steep short wavelength edge of planck s law . as a result , the uibs paradoxically disappear " at high illuminations ! in the present model , this is not due to their destruction , but to the fact that the underlying continuum quickly increases , even as the uib emission levels off because all available hydrogen is already dissociated ( cf . observational examples of this behaviour of the band - to - continuum ratio can be found in giard et al . @xcite ( 3.3-@xmath1 m uib , 10-@xmath1 m continuum ) and cesarsky et al . @xcite ( 6.2-@xmath1 m uib , 16-@xmath1 m continuum ) , both observing m 17 . the predictions of our model concur with the conclusions of an and sellgren @xcite , based on their observations of the reflection nebula ngc 7023 with high spatial resolution , in the 3.29-@xmath1 m uib and its neighboring continuum at 2.18 @xmath1 m . they find the two emissions to coexist in a vast hi region between the hii region enclosing the illuminating star , and the thin h@xmath123 filament at the edge of the molecular cloud . however , the intensity distributions are distinctly different , with the 3.29-@xmath1 m peaking within the filament , while the 2.18-@xmath1 m peaks at about half this distance from the star . moreover , they measured a feature - to - continuum ratio peaking at @xmath199 , in the filament , and decreasing with the distance , @xmath94 , from the illuminating star as @xmath200 , i.e. roughly as @xmath201 ( here , @xmath53 is proportional to the star flux heating the grains ) . remarkably , this trend is very smooth , in stark contrast with the very dissimilar spatial distributions of the two emissions . as noted by the authors , both these facts are hardly understandable if both emissions are prompted by absorption of the star radiation . on the other hand , the present model predicts just this behaviour of the band contrast . however , fig . 5 suggests a much faster variation with @xmath53 . note that the @xmath200 trend is only a regression line over a large set of highly dispersed points , covering only a small range of @xmath53 : a factor 2 , which suggests high density heterogeneity . so the discrepancy may be due to the lines in fig . 5 being drawn for constant @xmath65 . but it could also be due to a number of assumptions made for the sake of simplicity : -assuming too tight relationships between the densities of large grains ( emitting the continuum ) , uib - emitting grains and h radicals ( sec . these relationships hold best in the diffuse ism , and may be invalidated in the presence of very intense uv radiation able to drive a shock front into the h cloud . -assuming that the illuminating spectrum does not change with @xmath53 , while , in fact it varies considerably from the diffuse ism to the neighbourhood of a bright star . ever since pipher @xcite discovered the diffuse ir emission ( dire ) originating in the galactic plane , the problem of its excitation has been open for discussion . based on observations by low et al . @xcite and rouan et al . @xcite , respectively , mezger @xcite estimated the total dire at @xmath202w , while ryter and puget @xcite set it at 7.5@xmath203w . given reasonable star formation rates , it has been hard to argue that this emission can be accounted for by the luminous o stars alone . mezger estimated that o stars fuelling radio hii regions contribute only 20 % of the total . he also concluded that , for uv absorption and ir reemission by the galactic grains in the diffuse medium to account for @xmath204 , these grains should be able to absorb 8 times more uv photons than they can do in fact ( this is the ir excess " ) . section 6 above suggests that h atom impacts might do the job . in order to explore this possibility in the present model , note that the total number of h atoms in the galaxy was estimated by ryter and puget @xcite and mezger @xcite , again excluding the galactic center , at @xmath205m@xmath206 , which amounts to @xmath207 h atoms . using the values of @xmath204 mentioned above , we deduce the total ir power reemitted per h atom , @xmath116=4.5 and 14 @xmath99 w / h atom . these are comparable to the value deduced from the iras data by boulanger and prault @xcite : 6.1 @xmath99 . now , @xmath204 must be compared with the value predicted by our model , i.e. eq . 11 , which gives the total ir power reemitted per unit volume of space , if @xmath71 is replaced by 1 . here , as in sec . 7.1 , we deal with a tenuous environment , so approximation ( 12 ) may be used instead . integrating this quantity over the volume of the galaxy ( excluding star forming regions ) , we obtain @xmath208 where @xmath65 is in @xmath14 . the total volume , v , of the galaxy is the ratio of the total number of h nuclei divided by the average density of the latter . this is about 1 @xmath14 ( see spitzer 1977 ) , so v@xmath209 @xmath210 . the root mean square density can then be deduced : @xmath211 where @xmath212 was set at @xmath213 w. the square root of this is 14 @xmath14 , which is typical of clouds containing optically thin h@xmath0 in the dism ( see jura 1975 ) ; the model thus proves to be sound . the difference between @xmath214 and @xmath215 is a measure of the patchiness of the diffuse ism . a model was developed for the excitation of the uibs by h atom impacts in the interstellar medium . it builds upon the fact that , in the presence of far uv radiation and hydrocarbon grains , the hydrogen gas will be partially dissociated and the grain surface will be partially hydrogenated and partially covered with free carbon bonds . under such a statistical equilibrium , h atoms from the gas will recombine with c atoms at the grain surface at some rate . at each recombination , the h atom deposits an energy of about 5 ev in the grain . half of this is directly converted into vibrational excitation , always distributed in the same way among the most tightly coupled vibration modes of the grain . absent frequent grain - grain collisions , the only outlet for this energy is ir reemission , part of it in the uibs , provided the chemical structure of the grains is adequate , and the other part in the continuum . the partition only depends upon the grain size , all grains being assumed to have the same constitution . only a fraction , @xmath216 , of the grains ( the smallest ones ) will contribute significantly to the uibs . it is shown quantitatively that h impacts are generally more efficient excitation agents than uv absorption because of the overwhelming abundance of hydrogen relative to uv photons . only very near young bright stars is this no longer true because photon flux then largely exceeds h atom flux . thus h impacts and fuv absorption are both necessary to understand the variety of observed uib * spectral intensities . * the model translates into a small number of equations enabling a quantitative comparison of its predictions with available astronomical observations , which have become exquisitely rich and accurate in the last two decades . section 7 collects some of the most crucial tests of the model : - it predicts uib emission even far from star bursts and in poor - fuv environments . - since the excitation agent and the deposited energy are always the same , uib reemission is independent of the temperature of the neighbouring illuminating stars . - in pdrs , it becomes possible to understand the observed very near spatial coincidence of hi and h@xmath123 emission with the peak of the uibs . - the model predicts the measured average power in the uibs ( 2 - 15 @xmath1 m ) emitted per ambient h atom ( in statistical equilibrium in the solar neighbourhood ) , 1.5 @xmath99 w , provided that 1/4 of the cosmic carbon be locked in uib - emitting grains , and the average h nuclei density be about 100 @xmath14 in the average emitting cloud . - agreement between computed and measured uib intensities is obtained for a given fuv illumination , provided the unknown h column densities are given adequate values , which are found to be quite plausible . this is true even for m 31 , which is presumed to be poor in fuv flux . - the assumption of a common carrier for the uibs and the underlying continuum makes it possible to quantitatively account for the observed large variations of the band - to - continuum contrast ratio : they are simply due to the steep variation of wien s law , at a given wavelength , for small variations of illumination . - the ir excess " paradox , posed long ago by the comparison of the overall galactic ir emission with the uv flux available for grain excitation , is resolved quantitatively by h atom excitation , provided the r.m.s . density of h nuclei throughout the galaxy be of order 200 @xmath217 . * in order to allow quantitative comparisons to be made with observations , a number of assumptions were necessary . the most restrictive one is the neglect of uv extinction and self - shielding of hydrogen ; the calculations are progressively invalidated as column densities along the sight lines exceed a few times 10@xmath218 @xmath18 . fortunately , this is not the case for most of the mesured uib spectra . * for lack of relevant experimental results or explicit values from theoretical computations , i relied heavily on numerical chemical simulation to obtain the values of cross - sections of grain - gas interactions . as the heating is proportional to the c - h recombination c - s ( eq . 8) , the latter needs measurement or at least confirmation by other means . it was also assumed that the importance of the dissociating uv flux relative to total uv does not depend on the total uv flux ; this only impacts the degree of dissociation of hydrogen , and most of our calculations are weakly sensitive to it . none of these assumptions notably affects the general nature and performance of this model . the notion of a fraction @xmath71 should not be taken to correspond to definite lower and upper size limits ; for the transition between emitting and non - emitting grains is progressive and likely to depend on grain structure and composition . some of the physical processes involved here are evidenced by molecular dynamic simulations . even for a 100-atom molecule , an important broadening mechanism is already at work and directly observable in chemical simulations : this is the interaction between modes and constant redistribution , between them , of the initially deposited energy . this widens lines into bands and confers wings to each line , so plateaus " appear below bands " in crowded spectral regions , and even an underlying continuum is visible ( see papoular 2000 ) . this effect is observed to increase quickly with the size , much more so than the number of modes . as the grain size increases , the number of skeletal vibration modes ( involving the whole structure ) increases more rapidly than the number of modes of functional groups ( involving only a small number of atoms of adequate chemical nature , and with adequate bonds to other atoms ) . the uibs are mainly due to the latter , while the continuum ( mainly in the farther ir ) is due to the former . thus , the fraction of energy deposited in the grain that goes into uib emission progressively decreases as the size increases . this is observed up to the largest structures attainable by the usual simulations ( of order of 10@xmath219 atoms ) . tailoring the composition and structure of the grains so that they carry the uibs is outside the scope of this paper ( it was treated at length by papoular 2011 ) . the validity of our conclusions do not depend on these properties , provided the grains bear enough carbon dangling bonds at their periphery , in steady state , so they can capture ambient h atoms . i thank the reviewer , dr c. boersma , for several useful comments . an j. and sellgren k. 2003 , apj 599 , 312 allamandola l. and norman c. 1978 , a&a 66 , 129 boersma c. , bauschlicher jr . c. , allamandola l. , ricca a. , peeters e. and tielens a. 2010 , a&a 511 , a32 bohlin r. , savage b. and drake j. 1978 , apj 224 , 132 boulanger f. and prault m. 1988 , apj 330 , 964 boulanger f. , abergel a. , bernard j. , cesarsky d. , puget j .- , reach w. , ryter c. et al . 1998 , asp conf . ser . 132 , p15 boulanger f. 1999 , les houches lxx , no 11 p253 bregman . j. , larson k. , rank d. and temi p. 1994 , apj 423 , 326 cazaux s. and tielens a. 2002 , apj lett . 575 , l29 cesarsky d. , lequeux j. , abergel a. et al . 1996 , a&a 315 , l309 cesarsky d. , lequeux j. , ryter c. and grin m. 2000 , a&a 354 , l87 chan k .- w . , rorllig t. , onaka t. et al . 2001 , apj 346 , 273 duley w. and williams d. 2011 , apj lett . 737 , l44 draine b. 1978 , apj suppl . 36 , 595 draine b. and bertoldi f. 1996 , apj 468 , 269 giard m. , bernard j.p . and dennefeld m. 1992 , a&a 264 , 610 guillois o. et al . 1998 , faraday discuss . 109 , 335 graham et al . 1993 , apj 105 , 250 haas m. , klass u. and bianchi s. 2002 , a&a 385 , l23 habart e. , boulanger f. and verstraete l. 2011 , a&a 527 , a122 imamura k. and sofue y. 1997 , a&a 319 , 1 jura m. 1974 , apj 191 , 375 jura m. 1975 , apj 197 , 575 and 581 kahanp j. , mattila k. , lehtinen k. , leinert c. and lemke d. 2003 , a&a 405 , 999 laureijs r. , chlewicki g. , wesselius p. and clark f. 1989 , a&a 220 , 226 lohmar i. , krug j. and biham o. 2009 , a&a 504 , l5 low f. et al . 1977 , apj lett . 214 , l115 low f. et al . 1984 , apj lett . 278 , l19 mattila k. , lehtinen k. and lemke d. 1999 , a&a 342 , 643 mennella v. , brucato j. , colangeli l. and palumbo p. 2002 , apj 569 , 531 mezger p. 1978 , a&a 70 , 565 mezger p. 1982 , a&a 105 , 372 murakami h. , freund m. , ganga k. et al . 1996 , pasj 48 , l41 onaka t. , yamamura i. , tanabe t. , roellig t. and yuen l. 1996 , 48 , l59 pagani l. , lequeux j. , cesarsky d. , donas j. , millard b. , loinard l. and sauvage m. 1999 , a&a 351 , 447 papoular r. 2000 , spectrocimica acta 57a/4 , 947 papoular r. 2005 , mnras 359 , 683 papoular r. 2011 , mnras 415 , 494 ; see also 2008 , arxiv 1008.5136 peeters e. , hony s. , van kerckhoven c. , tielens a. , allamandola l. , hudgins d. and bauschlicher c. 2002 , a&a 390 , 1089 peeters e. , spoon h. and tielens a. 2004 , apj 613 , 986 pipher j. 1973 , iau sympos . 52 radzig a. and smirnov b. 1980 , reference data on atoms , molecules and ions , springer - verelag berlin heidelberg roche p. , aitken d. and smith c. 1989 , mnras 236 , 485 rouan d. , lena p. , puget j .- de boer k. and wijnbergen , j. 1977 , apj lett . 213 , l39 ryter c. and puget j.l . 1977 , apj 215 , 161 savage b. , bohlin r. , drake j. and budich w. 1977 , apj 216 , 291 sellgren k. , tokunaga a. and nakada y. 1990 , apj 349 , 120 sellgren k. 2001 , spectrochimica acta 57a , 627 smith t. , clayton j. and valencic l. 2004 , astron . j. 128 , 357 smith j. , draine b. , dale d. et al . 2007 , apj 656 , 770 solomon p. , carangelo r. , best p. , markham j. and hamblen d. 1986 , 21st sympos . on combustion , 437 spitzer l. 1977 , physical processe in the interstellar medium , j. wiley & sons , n. y. stecher t. and williams d. 1979 , a&a 67 , 115 tokunaga a. 1997 , asp conf . vol 124 , 149 turro n. et al . 2009 , principles of molecular photochemistry uchida k. , sellgren k. and werner m. 1998 , apj lett . 493 , l109 zhang y. , kwok s. and hrivnak b. 2010 , apj 725 , 990

a model was developed for the excitation of the uibs by h atom impacts in the interstellar medium . it builds upon the fact that , in the presence of far uv radiation and hydrocarbon grains , the hydrogen gas will be partially dissociated and the grain surface will be partially hydrogenated and partially covered with free carbon bonds . under such a statistical equilibrium , h atoms from the gas will recombine with c atoms at the grain surface at some rate . at each recombination , the h atom deposits an energy of about 5 ev in the grain . half of this is directly converted into vibrational excitation , always distributed in the same way among the most tightly coupled vibration modes of the grain . absent frequent grain - grain collisions , the only outlet for this energy is ir reemission , part of it in the uibs , provided the chemical structure of the grains is adequate , and the other part in the continuum . the partition only depends upon the grain size , all grains being assumed to have the same constitution . only a fraction , about 0.25 , of the grains ( among the smallest ones ) will contribute significantly to the uibs . it is shown quantitatively that h impacts are generally more efficient excitation agents than uv absorption because of the overwhelming abundance of hydrogen relative to uv photons . only very close to young bright stars is this no longer true because photon flux then largely exceeds h atom flux . thus h impacts and fuv absorption are both necessary to understand the variety of observed uib spectra . the model translates into a small number of equations enabling a quantitative comparison of its predictions with available astronomical observations , which have become exquisitely rich and accurate in the last two decades . [ firstpage ]

SECTION 1. REQUIREMENT TO DISCLOSE SOURCES AND AMOUNTS OF FUNDS RAISED FOR PRESIDENTIAL ARCHIVAL DEPOSITORY. (a) In General.--Section 2112 of title 44, United States Code, is amended by adding at the end the following new subsection: ``(h)(1) Any organization that is established for the purpose of raising funds for creating, maintaining, expanding, or conducting activities at a Presidential archival depository or any facilities relating to a Presidential archival depository, shall submit to the Administration, the Committee on Government Reform of the House of Representatives, and the Committee on Governmental Affairs of the Senate on an annual basis, by not later than the applicable date specified in paragraph (2), information with respect to every contributor who, during the year-- ``(A) with respect to a Presidential archival depository of a President who currently holds the Office of President or for which the Archivist has not accepted, taken title to, or entered into an agreement to use any land or facility, gave the organization a contribution or contributions (whether monetary or in-kind) totaling $200 or more for the year; or ``(B) with respect to a Presidential archival depository of a President who no longer holds the Office of President and for which the Archivist has accepted, taken title to, or entered into an agreement to use any land or facility, gave the organization a contribution or contributions (whether monetary or in-kind) totaling $5000 or more for the year. ``(2) For purposes of paragraph (1), the applicable date-- ``(A) with respect to information required under paragraph (1)(A), shall be January 31 of each year; and ``(B) with respect to information required under paragraph (1)(B), shall be May 31 of each year. ``(3) As used in this subsection, the term `information' means the following: ``(A) The amount or value of each contribution made by a contributor referred to in paragraph (1) in the year covered by the submission. ``(B) The source of each such contribution, and the address of the entity or individual that is the source of the contribution. ``(C) If the source of such a contribution is an individual, the occupation of the individual. ``(D) The date of each such contribution. ``(4) The Archivist shall make available to the public through the Internet (or a successor technology readily available to the public) any information that is submitted in accordance with paragraph (1). ``(5)(A) It shall be unlawful for any person who makes a contribution described in paragraph (1) to knowingly and willfully submit false material information or omit material information with respect to the contribution to an organization described in such paragraph. ``(B) The penalties described in section 1001 of title 18, United States Code, shall apply with respect to a violation of subparagraph (A) in the same manner as a violation described in such section. ``(6)(A) It shall be unlawful for any organization described in paragraph (1) to knowingly and willfully submit false material information or omit material information under such paragraph. ``(B) The penalties described in section 1001 of title 18, United States Code, shall apply with respect to a violation of subparagraph (A) in the same manner as a violation described in such section. ``(7)(A) It shall be unlawful for a person to knowingly and willfully-- ``(i) make a contribution described in paragraph (1) in the name of another person; ``(ii) permit his or her name to be used to effect a contribution described in paragraph (1); or ``(iii) accept a contribution described in paragraph (1) that is made by one person in the name of another person. ``(B) The penalties set forth in section 309(d) of the Federal Election Campaign Act of 1971 (2 U.S.C. 437g(d)) shall apply to a violation of subparagraph (A) in the same manner as if such violation were a violation of section 316(b)(3) of such Act. ``(8) The Archivist shall promulgate regulations for the purpose of carrying out this subsection.''. (b) Applicability.--Section 2112(h) of title 44, United States Code (as added by subsection (a))-- (1) shall apply to an organization established for the purpose of raising funds for creating, maintaining, expanding, or conducting activities at a Presidential archival depository or any facilities relating to a Presidential archival depository before, on, or after the date of the enactment of this Act; and (2) shall only apply with respect to contributions (whether monetary or in-kind) made after the date of the enactment of this Act.

Requires any organization that is established for the purpose of raising funds for a presidential archival depository to annually submit to the National Archives and Records Administration, the Committee on Government Reform of the House of Representatives, and the Committee on Governmental Affairs of the Senate information respecting every contributor who, with regard to: (1) a presidential archival depository of a President who currently holds the Office of President or for which the Archivist of the United States has not accepted, taken title to, or entered into an agreement to use any land or facility, gave the organization monetary or in-kind contributions totaling $200 or more; or (2) a depository of a President who no longer holds such Office and for which the Archivist has accepted, taken title to, or entered into an agreement to use any land or facility, gave the organization contributions totaling $5,000 or more. Requires the Archivist to make any such information available to the public through the Internet or a successor technology.Makes it unlawful for: (1) a contributor or an organization to submit false material information or omit material information concerning the contribution; or (2) a person to make or accept a contribution made in another person's name.

we report a case of a sympathetic ophthalmia that occurred after 23-gauge transconjunctival sutureless vitrectomy for a retinal detachment . a 41-year - old japanese woman underwent combined phacoemulsification with intraocular lens implantation and 23-gauge transconjunctival sutureless vitrectomy for a rhegmatogenous retinal detachment in the right eye . four weeks after the surgery , she returned with a 5-day history of reduced vision and metamorphopsia in her left eye . slit - lamp examination showed a shallow anterior chamber in the right eye and moderate anterior uveitis bilaterally . silicone oil bubbles and pigment dispersion were observed in the subconjunctival space adjacent to the right eye s superonasal sclerotomy site . a diagnosis of sympathetic ophthalmia was made and the patient was treated with intensive topical and systemic steroids . twelve months after the onset of inflammation , the patient s condition was stable on a combination of oral cyclosporine and topical steroids . sunset glow retinal changes remain , but there has been no evidence of recurrent inflammation . we recommend that special care should be taken to inspect for adequate closure of sclerotomy sites at the end of this operation . sympathetic ophthalmia , a bilateral granulomatous panuveitis , is a rare condition that can occur after a penetrating eye injury or intraocular surgery.1 although the risk of sympathetic ophthalmia following conventional 20-gauge vitrectomy has previously been suggested,2,3 there is only one reported case of sympathetic ophthalmia following transconjunctival sutureless vitrectomy ( 23- or 25-gauge).4 we present a further case that confirms that there is a risk of developing sympathetic ophthalmia after transconjunctival sutureless vitrectomy despite its smaller sclerotomy size . her best - corrected visual acuity was 0.3 in the right eye and 1.0 in the left eye , and the corresponding intraocular pressures were 16 mmhg and 17 mmhg . anterior segment slit - lamp examination showed tobacco dust in the anterior vitreous cavity of the right eye . fundus examination revealed a right , flat , inferior , macula - off retinal detachment . several retinal holes within regions of equatorial lattice degeneration were observed in the area of the detached retina , which formed fibrous strands in the subretinal space . the patient underwent combined phacoemulsification with intraocular lens implantation and 23-gauge transconjunctival sutureless vitrectomy under local anesthesia . postoperatively she developed a massive hyphema and hypotony and underwent surgical irrigation and aspiration of the hyphema 14 days after the initial surgery . four weeks after the initial surgery , the patient returned with a 5-day history of reduced vision and metamorphopsia in her left eye . her best - corrected visual acuity was 0.03 in the right eye and 0.15 in the left eye , and the corresponding intraocular pressures were 7 mmhg and 16 mmhg . slit - lamp examination showed a shallow anterior chamber in the right eye with a moderate anterior uveitis bilaterally . silicone oil bubbles and pigment dispersion were observed in the subconjunctival space adjacent to the right eye s superonasal sclerotomy site . fundus examination revealed multifocal serous retinal detachments in both eyes ( figure 1a and 1b ) , which were confirmed by optical coherence tomography ( figure 1c and 1d ) . optical coherence tomography also showed a membranous reflex in the subretinal space of the left eye that suggests the presence of an inflammatory product such as fibrin ( figure 1d ) . fluorescein angiography of the left eye showed multiple points of dye leakage at the level of the retinal pigment epithelium during the early phase and multilobular dye pooling during the late phase ( figure 1e and 1f ) . human leukocyte antigen ( hla ) typing showed hla - a24 , hla - b54 , hla - b61 , and hla - dr4 . an association with hla - dr4 has previously been reported among japanese patients with vogt - koyanagi - harada disease and sympathetic ophthalmia.5 a diagnosis of sympathetic ophthalmia was made , and the patient was treated with two cycles of pulsed - steroid therapy ( 1 g of intravenous methylprednisolone for 3 days , followed by 40 mg of oral prednisone ) in addition to intensive topical steroids ( 0.1% betamethasone ) . the subretinal fluid cleared in both eyes following treatment ( figure 2a2d ) ; however , the hypotony and shallow anterior chamber in the right eye failed to resolve . the dose of oral prednisone was gradually reduced and eventually replaced by oral cyclosporine treatment . currently , 12 months after the onset of inflammation , she is managed with oral cyclosporine ( 150 mg daily ) and topical 0.1% betamethasone . the stigma of sunset glow fundal changes remains present , but there has been no evidence of recurrent inflammation . her best - corrected visual acuity is 0.1 in the right eye and 1.2 in the left eye , and the corresponding intraocular pressures are 7 mmhg and 17 mmhg . a prospective population - based study in the united kingdom and republic of ireland demonstrated that ocular surgery , particularly retinal surgery , has a greater risk of sympathetic ophthalmia than that of accidental trauma.6,7 the incidence of sympathetic ophthalmia reported in their population was 0.03/100,000 ; developing in 0.125% of patients following vitrectomy , and in 0.074% of patients following external retinal detachment surgery.6,7 recent advancements in microsurgical techniques have led to increased adoption of transconjunctival sutureless vitrectomy using 23- or the smaller 25-gauge microinstruments.8,9 these vitrectomy systems permit the use of smaller wounds , which theoretically results in less postoperative inflammation . however , there is also a growing concern that transconjunctival sutureless vitrectomy may be associated with an increased incidence of wound leak and subsequent ocular hypotony.10 our case emphasizes that there is a risk of sympathetic ophthalmia in patients who undergo transconjunctival sutureless vitrectomy , particularly when this technique is performed with inadequate closure of the sclerotomy sites . although the exact mechanism of developing sympathetic ophthalmia is not clear and is most likely multifactorial , lack of wound closure leads to a disturbed blood retinal barrier and exposes ocular antigens , which may contribute to the development of sympathetic ophthalmia . another possibility is that a massive hyphema with hypotony complicated the postoperative course , which may have led to wound disruption and uveal prolapse . with the rapid increase in popularity for the use of transconjunctival sutureless vitrectomy and expanding indications we may expect to see this complication more frequently over the coming years , especially in patients with specific genetic predispositions and risk factors . we recommend that special care should always be taken to check for wound leakage at the end of this surgery and when using sutures at the sclerotomy sites when self - sealing wounds are not achieved .

purposewe report a case of a sympathetic ophthalmia that occurred after 23-gauge transconjunctival sutureless vitrectomy for a retinal detachment.case reporta 41-year - old japanese woman underwent combined phacoemulsification with intraocular lens implantation and 23-gauge transconjunctival sutureless vitrectomy for a rhegmatogenous retinal detachment in the right eye . endolaser photocoagulation and silicone oil tamponade were used to manage inferior retinal holes . four weeks after the surgery , she returned with a 5-day history of reduced vision and metamorphopsia in her left eye . slit - lamp examination showed a shallow anterior chamber in the right eye and moderate anterior uveitis bilaterally . silicone oil bubbles and pigment dispersion were observed in the subconjunctival space adjacent to the right eye s superonasal sclerotomy site . fundus examination showed multifocal serous retinal detachments in both eyes . a diagnosis of sympathetic ophthalmia was made and the patient was treated with intensive topical and systemic steroids . the subretinal fluid cleared in both eyes following treatment . twelve months after the onset of inflammation , the patient s condition was stable on a combination of oral cyclosporine and topical steroids . sunset glow retinal changes remain , but there has been no evidence of recurrent inflammation.conclusionsympathetic ophthalmia can develop after 23-gauge transconjunctival sutureless vitrectomy despite its smaller sclerotomy size . we recommend that special care should be taken to inspect for adequate closure of sclerotomy sites at the end of this operation .

gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas . the hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response . the programmed death 1programmed death - ligand 1 ( pd-1/pd - l1 ) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms . we report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis . setting we demonstrate , for the first time in this type of tumor , by immunohistochemistry a strong pd - l1 expression in neoplastic cell and the presence of pd-1 positive infiltrating lymphocytes . the applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery . gastric carcinoma with lymphoid stroma ( gcl ) , also known as lymphoepithelioma - like carcinoma of the stomach , is an unusual type of gastric cancer ( gc ) that was first described by watanabe et al in 1976 and account for about 4% of gastric carcinomas . the histological hallmark of this cancer is a prominent lymphoid infiltration of the stroma with lymphocytic aggression of the neoplastic epithelial structures . this intense host lymphocytic response is associated with a better prognosis than that reported for patients with typical gastric carcinomas , suggesting an immune antitumor reaction . in this regard , despite the complexity of cancer immunology , growing evidences suggest that the coinhibitory receptors , such as cytotoxic t lymphocyte - associated antigen-4 and programmed death 1 ( pd-1 ) , play a crucial role in cancer immune - editing , especially in the equilibrium and escape stages of the immune response . human programmed death - ligand 1 ( pd - l1 ) , as a dominant ligand , plays a central role in antigen - specific t cell response mediating pd-1-dependent immune suppression . the pd-1/pd - l1 axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms . a meta - analysis addressed to the expression of pd - l1 measured by immunohistochemistry in solid tumors , reported the relationship between positive pd - l1 reaction and worse prognosis in different tumor types . however , the correlation between pd - l1 expression and clinical behavior in solid tumor is still in controversial . numerous agents targeting pd - l1/pd-1 check - point are in clinical development . here , we present a case of gcl with review of the literature and a study addressed to the assessment of both tumor pd - l1 expression and lymphocytic population phenotype in order to evaluate the role of the microenvironment in this unusual type of tumor . we report the case of a 76 years old man , with past medical history of hepatitis b virus - related liver cirrhosis , hypertension , ischemic heart disease ( treated with percutaneous transluminal coronary angioplasty ) , and carotid atherosclerosis . the patient presented epigastric pain , weight loss ( about 10 kg in 6 months ) , and lack of appetite . he underwent endoscopic evaluation at campus bio medico hospital and a gastric lesion of about 6 cm in diameter was identified on the lesser curvature ( fig . he was referred to the surgical unit for further evaluation . on physical examination , he had mild pallor with ill - defined painless swelling in his gastric region . the computed tomography scan of the patient 's abdomen showed a thickening of the stomach lining at the lesser curvature ; imaging was negative for lymph nodes enlargement , peritoneal carcinomatosis , or liver metastases . on the basis of these findings , considering the patient 's age and general condition , a gastrectomy was performed with lymph nodes dissection and a roux - en - y reconstruction . note the polypoid endophytic shape with extensive ulceration of the mucosal surface ( arrow ) . gross examination of the resected gastric specimen revealed the presence of a mass measuring about 6.5 cm in the largest diameter , partially ulcerated on the mucosal surface , located on the lesser curvature , and extending from the fundus to the esophageal margin of resection . formalin fixed , paraffin - embedded slices of the resected surgical sample , performed in agreement with international guidelines were submitted for histological examination . microscopically , the neoplastic mass corresponded to a gastric carcinoma growing in solid nests and sheets of malignant epithelial elements and it was characterized by a prominent lymphoid infiltrate . tumor cells were arranged in microalveolar and thin trabecular pattern surrounded by an abundant lymphocytic stroma showing a lympho - epithelial paradoxical lesion with small lymphocytes that invade and lyse neoplastic epithelia ( fig . neoplastic epithelial cells were atypical , medium size , and oval or polygonal in shape , with poorly defined cell borders , vesicular to clear nuclei , prominent nucleoli , and abundant light eosinophilic cytoplasm . the case was reported g3 , pt3 , and pn0 according to the 7th edition of the union for international cancer control guidelines . microscopic features of the tumor : ( a ) hematoxylin / eosin staining showed heavy lymphocytic infiltration and lymphocytic exocytosis on the neoplastic cells . ( b ) eber nuclear reactivity ( black - purple ) is evident in neoplastic cells . barr encoded small rna , pd-1 = programmed death 1 , pd - l1 = programmed death - ligand 1 . immunohistochemical characterization was achieved with automatized omnis system ( dako , carpinteria , ca ) in peroxidase method ; it was performed using the following monoclonal antibodies : cd56 ( 123c3 , dako ) , cd3 ( policlonal , dako ) , cd20 ( l26 , dako ) , and pan ck ( mnf116 , dako ) . immunohistochemistry for pd-1 ( nat105 , dako ) and pd - l1 ( pd - l1/cd274 , biosb , santa barbara , ca ) was performed on seriate paraffin sections after the diagnosis was established . in situ hybridization for ebv latent infection barr encoded small rna ( eber ) probes ( dako ) on paraffin sections . at immunohistochemistry , infiltrating lymphocytes consisted primarily of t cells that are cd3 + , cd56 and showed pd-1 positivity in more than 50% of the cellularity ( fig . lymphocytes with b phenotype ( cd20 + ) were less than 10% of lymphoid infiltrate . neoplastic cells resulted positive for pan ck and over 80% of them showed membrane positivity for pd - l1 , with variable intensity among the cancer population , ranging from marked to weak with zonal distribution ( fig . 2c ) . the patient was initially fed with enteral nutrition and then oral which was gradually increased . written informed consent was obtained from the patient for publication of this case report in the setting of a protocol for the study of biological material in oncology approved by the ethical committee ( prot . gastric carcinoma with lymphoid stroma is an uncommon type of gc and the interest for these lesions is pointed to the prognosis that for these patients is reported better than that for patients with typical cancer , independently of the tumor dimension or infiltrative stage . in this setting , gcl may represent a model of antitumor immune reaction in the host . our case showed cellular and architectural morphology similar to the previous reported for the histological diagnosis of these tumors . we focused the study on pd - l1 expression in cancer cells and on the stromal lymphocytes within the tumor mass , in order to investigate their phenotype and the possible role of the pd-1/pd - l1 checkpoint in the host immune response to tumor cells . the pd - l1/pd-1 pathways can protect tumors from cytotoxic t cells , ultimately inhibiting the antitumor immune response in 2 ways : deactivating cytotoxic t cells in the tumor microenvironment ; preventing priming and activation of new t cells in the lymph nodes and subsequent recruitment to the tumor . the mechanism is hypothesized to act by tumoral expression of pd - l1 that binds to t cell receptor pd-1 , deactivating cytotoxic t cells . this complex mechanism observed in vivo and in vitro was evidenced on tissues by immunohistochemistry . recent meta - analysis showed that overexpression of pd - l1 in solid tumor tissues , as measured by ihc , is associated with worse prognosis in different tumor types , which suggests that the development of strategies against the pd - l1/pd-1 axis would be a promising therapeutic approach for solid tumors . the strong evidence of the pd - l1/pd-1 pathway presence in a case of gcl , which is consider a tumor with a relatively good prognosis when compared with other type of gastric carcinomas , raises the thought that this checkpoint is not able to determine the immuno - escape in the tumor environment alone . recently , pd - l1 expression in gc of western patients was reported to correlate significantly with overall and tumor specific survival as well as distinct clinic - pathological patient characteristics ; the authors showed , in a large series of gastric adenocarcinoma not including cases of gcl , that patients with pd - l1 positive tumor cells had a significant better overall ( p = 0.028 ) and tumor specific survival ( p = 0.018 ) . the better prognosis of gcl has been related to the fact that the patient 's inflammatory response may prevent the spread of tumor through the gastric wall and to the lymph nodes or remote organs ; the role of pd - l1 expression however has not been previously analyzed in this subtype of cg . our results could suggest that the presence of intense pd - l1 expression on epithelial neoplastic cells may represent a way of cancer cells to inhibit the host defense reaction . other mechanisms however should be able to restore the pd-1 lymphocytes activity and act in the maintenance of the host immune - defense . the reported case showed negative nodes despite a g3 and pt3 tumor ; moreover , the patient is well without evidence of recurrent disease 10 months after surgery . the presence of diffuse ebv latent infection within cancer cells , a frequent finding in gcl , may contribute to the stimulatory action on the immune system as in the lymphoepithelioma - like carcinoma of the nasopharynx , bearing the same ebv association . the role of ebv in oncogenesis differs according to the host cell type and the immune status of the host . ebv - associated lymphoepithelioma - like carcinoma belongs to the latency i neoplasms , in which latent gene products are restricted to ebv nuclear antigen i , eber , latent membrane protein 2a , and bamhi - a rightward transcripts while viral proteins , ebna2 and lmp1 , are not expressed . the in situ hybridization finding ( strong nuclear hybridization signal in tumor cells ) in our case is consistent with the latency i type . gcl generally has a better prognosis than other forms of ebv - associated gastric carcinomas , suggesting the ebv infection alone does not serve as an independent prognostic factor . on the other hand , ebv - positive gcs are classified as a definite set of gc with related molecular alterations and are known to be associated with pd - l1 overexpression although this information was not specifically assessed for gcl subtype . the main challenge in histological diagnosis of these tumors resides in the difficult to preoperatively recognize the lymphoid pattern within small bioptic specimens , so the correct definition of this histotype is usually achieved on the final surgical sample . since these patients are known to have a better prognosis , it is of relevance for clinicians and pathologists to obtain an accurate diagnosis at the time of endoscopic evaluation . localization of ebv in malignant cells by eber in situ hybridization remains the gold standard for assigning the ebv - positive class of cancers . our results suggest that when the gcl subtype is suspected on the biopsy specimens , both pd - l1 and ebv evaluation may support the diagnosis before surgical time . in conclusion , we report a case of ebv - associated gcl with a study of the tumor microenvironment that showed significant pd - l1/pd-1 pathway expression . this uncommon type of gc has generally a better prognosis than other forms of gastric carcinomas . the advantage in clinical behavior has been related to the presence of intense lymphoid infiltrate . our results are of interest because merge the reported better prognosis for both gcl subtype and pd - l1 expression in gc and confirm the association between ebv infection and pd - l1 membranous expression ; moreover , this report is the first pd - l1 characterization of gcl subtype of gc . this case confirms that the relationship between pd - l1/pd-1 pathway and prognosis of solid tumor is a critical point for therapy and follow - up in oncological patients .

abstractintroduction : gastric carcinoma with lymphoid stroma is an unusual type of gastric tumor associated with a better prognosis than typical gastric carcinomas . the hallmark of this cancer is a prominent lymphoid infiltration of the stroma that represents an intense host lymphocytic response . the programmed death 1programmed death - ligand 1 ( pd-1/pd - l1 ) axis has recently emerged as a master immune checkpoint that controls antitumor immune responses against many neoplasms.patient's concerns case study and outcome : we report the case of a male patient with gastric carcinoma with lymphoid stroma with a large mass infiltrating the gastric wall without nodal metastasis . he is alive without disease 10 months after surgery . we focused the study on factors that potentially modulate the prognosis . in this setting we demonstrate , for the first time in this type of tumor , by immunohistochemistry a strong pd - l1 expression in neoplastic cell and the presence of pd-1 positive infiltrating lymphocytes.conclusion:the applied approach may contribute to the knowledge about host reaction in such tumor and it may also be used for tumor precise identification on the endoscopic biopsy time before excision surgery .

the successes of the quark model of the 1960 s led directly to the development of qcd in the early 1970 s . a central feature of the early quark model was the use of constituent quarks as the relevant degrees of freedom of matter fields . although the advent of qcd changed the details the light " constituent quarks of copley , karl , and obryk have become standard and one gluon exchange is typically employed to describe short range dynamics the concept of constituent quarks has remained productive and pervasive . qcd also indicates where the quark model may fail . the canonical nonrelativistic quark model relies on a potential description of quark dynamics and therefore neglects many - body effects in qcd . related to this is the question of the reliability of nonrelativistic approximations , the importance of hadronic decays , and the chiral nature of the pion . the latter two phenomena depend on the behavior of nonperturbative glue and as such are crucial to the development of robust models of qcd and to understanding soft gluodynamics . certainly , one expects that gluodynamics will make its presence felt with increasing insistence as experiments probe higher excitations in the spectrum . similarly the chiral nature of the pion can not be understood in a fixed particle number formalism . this additional complexity is the reason so few models attempt to derive the chiral properties of the pion . this is an unfortunate situation since the pion is central to much of hadronic and nuclear physics . to make progress one must either resort to numerical experiments or construct models which are closer to qcd . here we present one such model which is based on the qcd hamiltonian in coulomb gauge . the hamiltonian approach is appropriate for an examination of the bound state problem because the familiar machinery of quantum mechanics may be employed and because all degrees of freedom are physical in coulomb gauge . furthermore , an explicit time - independent potential exists which permits the construction of bound states in a fixed fock sector . the model consists of a truncation of qcd to a set of diagrams which capture the infrared dynamics of the theory . the efficiency of the truncation is enhanced through the use of quasiparticle degrees of freedom , as will be explained subsequently . finally , the random phase approximation ( rpa ) is used to obtain mesons . this many - body truncation is sufficiently powerful to generate goldstone bosons and has the advantage of being a relativistic truncation of qcd@xcite . because the hamiltonian is derived from a local density it is covariant , although the use of coulomb gauge hides this . the truncations which we will employ do not ruin this property . we remark that covariance requires a combination of boost and gauge transformations in noncovariant gauges and therefore some care must be taken in the computation of quantities such as form factors or heavy meson decay rates . here we focus on static meson properties in the rest frame where these issues do not arise . finally , we note that maintaining relativistic invariance in schemes which extend the rpa may be difficult because the interaction is no longer instantaneous at higher order . thus different terms must be summed to yield covariant results and amplitudes may arise which do not have simple wavefunction , or rpa , analogues such as amplitudes with a mixture of forward and backward moving particles . using a single framework to generate chiral symmetry breaking and the meson spectrum consistently has been attempted before . @xcite solved a simple gap equation with a quadratic interaction and then used the rpa approximation to obtain chiral pions . although the interaction is unrealistic it allowed the important simplification of turning integral equations into simple differential equations . llanes - estrada and cotanch @xcite also studied low - lying states with a linear potential while ignoring state mixing . neither paper considered the effects of the one gluon exchange potential or renormalization . an extensive literature on relativistic quark models ( which do not consider chiral symmetry breaking ) exists . for example , a preliminary study of fock sector mixing in a relativistic quark model was performed by koniuk and zhang@xcite . detailed examinations of meson and baryon properties have been carried out by the bonn group@xcite in a salpeter equation framework with a model confinement potential and dirac structure . similarly , extensive computations of pion and kaon properties have been carried out in a covariant euclidean space dyson - schwinger formalism@xcite . finally , the gluonic portion of the formalism presented here has been used to derive the quenched positive charge conjugation glueball spectrum@xcite . the results are in very good agreement with lattice computations , indicating that the method has some promise . generating the meson spectrum proceeds in three steps : ( 1 ) a quasiparticle basis for the gluonic sector of qcd is obtained with standard many - body techniques , ( 2 ) this procedure yields an instantaneous interaction which is used to construct a quasiparticle ( constituent ) basis in the quark sector , ( 3 ) bound state properties are obtained in the the random phase approximation . the first step contains an important complication : the quasiparticle interaction of qcd depends on the quasiparticles themselves ( in a way made clear below ) and hence must be solved along with the gap equation . this allows the possibility of deriving the constituent quark interaction if one can obtain the functional form of the interaction . we note that this is similar to solving coupled dyson - schwinger equations for , say , the gluon propagator and vertices . the coulomb gauge qcd hamiltonian may be written as @xmath0 with@xcite @xmath1 the interaction term contains the familiar transverse gluon color charge interaction and all of the higher order terms due to the non - abelian nature of qcd : @xmath2 - g \int \psi^\dagger \bm{\sigma}\cdot \a \psi + v_a + v_b + \nonumber \\ & + { 1\over 2}\int d\x d\y\ , \rho^a(\x ) \left [ k^{ab}(\x-\y;\a ) - \delta^{ab}k^{(0)}(\x-\y ) \right ] \rho^b(\y ) \label{hint}\end{aligned}\ ] ] the density @xmath3 entering these equations is the full color charge due to quarks and gluons @xmath4 the instantaneous non - abelian coulomb interaction in eq . [ hint ] is given by @xmath5 where @xmath6 is the covariant derivative in adjoint representation @xmath7 the electric and magnetic fields are defined by @xmath8 and @xmath9 the interaction in @xmath10 is defined as the vacuum expectation value of the coulomb interaction @xmath11 the vacuum state will be defined shortly . finally , the imposition of coulomb gauge restricts the theory to a curved gauge manifold with a metric given by @xmath12 \phi^*(\a)\psi(\a)$ ] . the factor @xmath13 is the faddeev - popov determinant given by @xmath14 the faddeev - popov determinant may be removed from the metric by rescaling the hamiltonian @xmath15 which is hermitian with respect to @xmath16 . we note that the nontrivial metric induces two new terms , denoted @xmath17 and @xmath18 , which correspond to the anomalous terms of schwinger@xcite . it has been speculated that confinement is related to the well - known gribov ambiguity@xcite . the gribov ambiguity arises because the existence of topologically inequivalent solutions to the gauge condition @xmath19 implies that the gauge is incompletely specified . gribov proposed that the ambiguities with coulomb gauge may be resolved by considering fields with @xmath20 which comprise the ` gribov region ' ( gr ) . we note that the appearance of the inverse of the faddeev - popov operator in the instantaneous coulomb potential implies that gauge configurations near the boundary of the gribov region create a strong infrared enhancement in the interaction . it is possible that this enhancement is the origin of confinement in coulomb gauge@xcite . subsequent research has shown that the gribov region actually contains gauge copies and hence gauge fields must lie in a subset of the gribov region called the fundamental modular region ( fmr ) . the fmr contains no redundant field configurations and may be defined , for example , as the set of global minima over gauge transformations of the functional @xmath21 = { \rm tr}\int d^3x ( \a^g)^2\ ] ] where @xmath22 . it is now known that the fmr contains the gr except at certain points where the regions coincide , the fmr is convex , and the gr contains the origin@xcite . furthermore , zwanziger has recently argued@xcite that observables have their support over the intersection of the fmr and the gr , thereby resurrecting the infrared enhancement argument of the previous paragraph . finally , topological aspects of qcd may be introduced to the formalism via the imposition of wavefunctional boundary conditions on the boundary of the fmr@xcite . it is clear that the interaction of quarks is strongly influenced by the instantaneous coulomb interaction of eq . [ coulk ] . it is known , moreover , that the instantaneous interaction is renormalization group invariant@xcite . this fact permits a physical interpretation of the instantaneous potential which is a central aspect of our formalism . furthermore , zwanziger has shown that the coulomb interaction provides an upper bound to the wilson loop potential and has postulated that this bound is , in fact , saturated@xcite . we remark that this saturation is crucial to the formalism presented here . this postulate may be checked with lattice computations , unfortunately the results are mixed @xcite . if the evidence to the contrary is confirmed , this approach must be abandoned . the nonpolynomial functional dependence of the coulomb interaction on the vector potential complicates computations in coulomb gauge . we proceed by separating the interaction into two parts denoted by @xmath23 ( see eq . [ k0 ] ) and @xmath24 . since @xmath23 is a vacuum expectation value it contains all diagrams in which gluons are attached to the operator @xmath25 . thus the remainder necessarily contains gluons which propagate . since gluons are quasiparticles with a dynamical mass on the order of 1 gev ( the hybrid - meson mass gap ) , matrix elements of @xmath24 are suppressed in typical hadronic observables , considerably simplifying computations . in spite of this , it is impossible to obtain a closed form expression for the the vacuum expectation value of @xmath26 . however , a procedure for obtaining dyson equations which sum the leading infrared diagrams for this matrix element has been described in ref.@xcite . an important element in the formalism is the construction of a basis which permits an efficient fock space expansion . the method proposed in ref . @xcite built this basis with the aid of a gluonic vacuum ansatz ( it is worth stressing that the vacuum need not be highly accurate , it merely provides a starting point for constructing a more general quasiparticle basis , and any sufficiently general vacuum ansatz will suffice ) . the ansatz employed is @xmath27 = \langle \a | \omega \rangle = \exp\left[-{1\over 2 } \int d\k \a^a(\k)\,\omega(k)\a^a(-\k ) \right ] . \label{varvac}\ ] ] which depends on an unknown trial function , @xmath28 . this is the simplest correlation one can build into the vacuum and corresponds to the bcs ansatz of many - body physics . note that the perturbative vacuum is obtained when @xmath29 . the trial function is obtained by minimizing the vacuum energy density @xmath30 the vacuum state obtained from this procedure is denoted @xmath31 . we refer to @xmath32 as the gap function since it is also responsible for lifting the single particle gluon energy beyond its perturbative value . of course evaluating the matrix element in eq . [ vev ] requires an explicit expression for @xmath33 which is provided by the dyson procedure described above . the result is a set of coupled nonlinear integral equations which describe the gap equation and the dyson equation for @xmath23 . solving these equations yields both the quasigluon dispersion relation , @xmath28 , and the quasigluon effective interaction , @xmath34 . renormalization is achieved by fitting the latter to the lattice wilson loop potential . the result is in excellent agreement with the lattice and provides a dynamical mass scale for the quasigluons : @xmath35 mev . it is this large mass scale which permits rapid convergence of any fock series expansion in the gluonic sector of qcd and explains why quark degrees of freedom dominate low energy hadronic physics . we remark that the emergence of a confining potential is nontrivial and indicates the robustness of the method . an analytic approximation to the solution to the coupled equations yields the following form for the vacuum expectation value of the coulomb interaction@xcite : @xmath36 this form mimics the numerical solution and the lattice results quite well . the long range potential behaves as @xmath37 , within 2% of the expected linear behavior ( the deviation is likely to be a numerical artifact ) . this allows the extraction of a string tension via @xmath38 , which implies @xmath39 gev@xmath40 . the effect of the smaller exponent is to reduce this string tension to approximately 0.21 gev@xmath40 at physically relevant scales . a fit to the standard ` coulomb plus linear ' potential ( const - @xmath41 ) yields an effective strong coupling of @xmath42 . this value is rather small with respect to expectations ( in part because there was little lattice data at small distances in the fit of ref.@xcite ) . thus we have also employed a modified potential of the form @xmath43 here @xmath44 and @xmath45 are constants which may be varied . values of @xmath46 and @xmath47 give a potential which agrees well with lattice data at short distance , but which otherwise is very close to the original form of eq.[vss7 ] . both potentials have been employed in the following to test the sensitivity of the results on the functional form of the potential . our chief goal is to examine a model of qcd which permits the simultaneous description of heavy quarkonia and chiral pions . it is clear that this may not be achieved in a potential formalism the many - body aspect of qcd is required . our approach to the quark sector therefore mimics that of the gluon sector , namely we model the quark vacuum with a gaussian wavefunctional and determine the quark gap equation . solving this yields dynamical chiral symmetry breaking and a massless goldstone boson in the random phase approximation in accord with the thouless sum rule@xcite . we note that this general approach has been used many times in the past , starting with the classic work of nambu and jona - lasinio @xcite . subsequent work has dealt with renormalization issues @xcite or with models which are closer to qcd @xcite . how the constituent quark model may be reconciled with chiral symmetry breaking is explained in ref . finally an extensive literature on the dyson - schwinger approach to this problem exists@xcite . in this approach the gap equation represents a nonperturbative one loop computation and thus must be properly renormalized . as noted in the gluonic sector , this is a nontrivial step whose implementation depends on the subset of diagrams being summed . in the bcs / rpa formalism employed here , we have found that standard renormalization is sufficient to guarantee finite results . in particular we have added mass renormalization @xmath48 and wavefunction renormalization @xmath49 terms to the hamiltonian of eq . [ h0 ] and the theory has been truncated at the scale @xmath50 . recall that the effective instantaneous interaction has already been rendered finite . proceeding with the standard bogoliubov or dyson procedure yields the following quark gap equation @xmath51c_p + { c_f \over 2 } \int { k^2 dk \over ( 2\pi)^3 } \left [ v_0(p , k ) s_k c_p - v_1(p , k ) c_k s_p\right ] \label{qgap}\ ] ] where @xmath52 the functions @xmath53 and @xmath54 are defined in terms of the bogoliubov angle @xmath55 as @xmath56 and @xmath57 . the quark gap equation is to be solved for the unknown bogoliubov angle , which then specifies the quark vacuum and the quark field mode expansion via spinors of the form @xmath58 comparing the quark spinor to the canonical spinor ( we use nonrelativistic normalization ) permits a simple interpretation of the bogoliubov angle through the relationship @xmath59 where @xmath60 may be interpreted as a dynamical momentum - dependent quark mass . similarly @xmath61 may be interpreted as a constituent quark mass . in the case of massless quarks the right hand side of the quark gap equation diverges logarithmically for potentials obeying the perturbative relation @xmath62 for large @xmath63 . the divergence may be absorbed into the wavefunction renormalization , @xmath64 , yielding a finite gap equation . it is also possible to renormalize by examining the once - subtracted gap equation . for the massive quark case two logarithmic divergences proportional to the quark mass and momentum appear . it is convenient to absorb these divergences separately into the mass and wavefunction terms respectively . for the study presented here the potential is modified by logarithmic corrections at short distances , thus all integrals are finite and the cutoff may be removed immediately . we note , however , that it still may be useful to make finite renormalizations . the numerical solution for the dynamical quark mass is very accurately represented by the functional form @xmath65 where @xmath66 is a ` constituent ' quark mass and @xmath67 is a parameter related to the quark condensate . notice that this form approaches the constituent mass for small momenta and @xmath68 for large momenta . the latter behavior is in accord with the quark gap equation which implies that@xcite @xmath69 a rough fit to the numerical solution yields @xmath70 mev and @xmath71 0.001 gev@xmath72 . the constituent quark mass is small compared to typical relativistic constituent quark model masses of roughly 200 mev . the value for @xmath67 implies a quark condensate of approximately ( -210 mev)@xmath72 , in reasonable agreement with current estimates of ( -250 mev)@xmath72 . however , we note that direct computations of the condensate typically yield results of approximately ( -110 mev)@xmath72 . these flaws undoubtedly point to inadequacies in the quark vacuum ansatz . of course , since we are working with the full qcd hamiltonian , it is possible to improve the ansatz ( for a coupled cluster approach , see ref . @xcite ; for one loop corrections see ref . @xcite ) . since one of our chief interests is the implementation of a formalism which respects chiral symmetry , and not detailed numerics , we satisfy ourselves with the present procedure . with explicit expressions for the quasigluon interaction ( and hence the constituent quark interaction ) and the dynamical quark mass in hand we are ready to obtain mesonic bound states . as mentioned above , in order to obtain a massless pion one must construct states , @xmath73 , in the random phase approximation : @xmath74 | rpa \rangle = ( e_m - e_{bcs } ) \langle m| q^{\dag } |rpa \rangle , \label{rpa}\ ] ] where @xmath75 is defined in terms of the positive and negative energy wavefunctions , @xmath76 $ ] with @xmath77 and @xmath78 being the quasiparticle operators . it is worthwhile recalling that the rpa method is equivalent to the bethe - salpeter approach with instantaneous interactions@xcite . the rpa and tda equations includes self energy terms ( denoted @xmath79 ) for each quark line and these must be renormalized . in the zero quark mass case renormalization of the tda or rpa equations proceeds in the same way as for the quark gap equation . in fact , the renormalization of these equations is consistent and one may show that a finite gap equation implies a finite rda or tda equation . this feature remains true in the massive case . the rpa equation in the pion channel reads : @xmath80 \psi^+(k ) \nonumber \\ & & - { c_f\over 2 } \int { p^2dp\over ( 2\pi)^3}\left [ v_0(k , p)(1+s_ks_p ) + v_1(k , p)c_kc_p\right ] \psi^+(p ) \nonumber \\ & & - { c_f\over 2 } \int { p^2dp\over ( 2\pi)^3}\left [ v_0(k , p)(1-s_ks_p ) - v_1(k , p)c_kc_p\right ] \psi^-(p)\end{aligned}\ ] ] a similar equation for @xmath81 holds with @xmath82 and @xmath83 . the wavefunctions @xmath84 represent forward and backward moving components of the many - body wavefunction and the pion itself is a collective excitation with infinitely many constituent quarks in the fock space expansion . we also consider a simpler truncation of qcd called the tamm - dancoff approximation . this may be obtained from the rpa equation by neglecting the backward wavefunction @xmath81 . we have computed the spectrum in the random phase and tamm - dancoff approximations and confirm that the pion is massless in the chiral limit . we also find that the tamm - dancoff approximation yields results very close to the rpa for all states except the pion : the tda pion mass is 580 mev while the first excited pion has an rpa mass of 1410 mev and a tda mass of 1450 mev . all other mesons have nearly identical rpa and tda masses . for this reason we simply present tda equations and results below . the complete hidden flavor meson spectrum in the tamm - dancoff approximation is given by the following equations . @xmath85\psi_{pc}(k ) - { c_f\over 2 } \int { p^2dp\over ( 2\pi)^3 } k^{pc}_j(k , p ) \psi_{pc}(p)\ ] ] with @xmath86 and where @xmath87 is the meson radial wavefunction in momentum space . an alternate form for the kinetic and self energies which is closer the schrdinger equation may be obtained by substituting the gap equation to obtain : @xmath88\ ] ] where @xmath89 and @xmath90 the kernel , @xmath91 in the potential term depends on the meson quantum numbers , @xmath92 . in the following possible values for the parity or charge conjugation eigenvalues are denoted by @xmath93 if @xmath94 is even and @xmath95 if @xmath94 is odd . @xmath96 @xmath97 @xmath98 @xmath96 @xmath99 [ @xmath100 , @xmath101 @xmath102 @xmath96 @xmath103 [ @xmath104 , @xmath105 @xmath106 @xmath96 @xmath107 [ @xmath108 , @xmath105 @xmath109 these interaction kernels have been derived in the quark helicity basis . we remark that in the ls basis the off - diagonal ( j-1):(j+1 ) interaction for @xmath107 mesons is proportional to @xmath110 and hence goes to zero in the heavy quark mass limit as expected . finally , we note that the authors of ref . @xcite find that the @xmath111 and @xmath112 kernels are identical . the likely reason is an error in their @xmath112 kernel which disagrees with that of eq . [ 1jj ] . our quark interaction is instantaneous , central , and obeys casimir scaling . however , it is not flavor or spin independent because the full spinor structure of the interaction has been retained . this spinor structure is specified by the hamiltonian of qcd and is of a vector nature ( specifically @xmath113 ) . a nonrelativistic reduction of this interaction yields no spin - spin hyperfine or tensor interactions . thus the present computation can not correctly describe well known spin splittings such as @xmath114 or @xmath115 ( we describe the extensions necessary to do so below ) . a spin - orbit interaction is present and is given by @xmath116 in the equal quark mass case . the spin - orbit interaction is famous for its problematic nature in the constituent quark model . quark model lore states that the spin - orbit interaction generated by one gluon exchange is too strong for phenomenology and must be softened by the addition of a spin orbit interaction from the confinement term which has an opposite sign . this can only be arranged if confinement has a scalar dirac structure ( @xmath117 ) . this is clearly at odds with the formalism presented here which insists that the confinement and coulomb potentials ( here we mean the perturbative @xmath118 tail of the static potential ) share the same dirac structure . the resolution to the conundrum is that it is too simple - minded to ascribe all of spin - orbit interactions to the dirac structure of instantaneous potentials . indeed , spin - dependence in qcd is partly generated by nonperturbative mixing with intermediate states , and need not follow the dictates of quark model lore . a specific realization of this is given in ref . finally , we note that a scalar confinement interaction leads to inconsistencies between mesons and baryons : if mesons confine then baryons anticonfine clearly an unacceptable situation ! relativistic interactions generate short range spin - dependent interactions by virtue of their spinor structure . the other sources of spin - dependence are topological effects ( for example , an instanton induced interaction ) and fock sector mixing effects . fock sector mixing is easily incorporated into the current formalism , one need only increase the size of the fock space being considered ( there is one subtlety : the mixing between fock sectors must be treated carefully since it can involve nonperturbative gluodynamics ) . one expects the leading higher fock sectors to be meson - meson ( ie . , meson loop corrections to the spectrum ) and hybrid . the latter case is the nonperturbative analogue of one - gluon - exchange , and as mentioned above , is phenomenologically important in the light meson spectrum . we shall leave the topic of fock space mixing for a future investigation and press ahead with an examination of the spectrum which arises from the central static potential generated by the non - abelian coulomb interaction , keeping in mind that large spin - dependent mass shifts may occur in the light spectrum . once the gluonic sector of the formalism has been fixed by renormalization the only remaining parameters are quark masses . in the following we have determined these by fitting the @xmath119 , @xmath120 , and @xmath121 masses . we work in the chiral limit for light ( @xmath122 and @xmath123 quark ) mesons so predictions in this sector are completely fixed . as a result there is no possibility of adjusting the spectrum presented below . thus it is possible to test the assumptions of the model throughout the spectrum . a simple way to obtain the upsilon spectrum from qcd is to insert the lattice wilson potential into the nonrelativistic schrdinger equation . one argues that the heavy @xmath45 quark mass validates the born - oppenheimer approximation ( so that the static potential may be used ) and the use of a nonrelativistic framework . precisely this approach has been taken by juge , kuti , and morningstar@xcite ( jkm ) and was subsequently justified by comparison with nonrelativistic lattice computations@xcite . since the potential we employ is essentially equivalent to that obtained from the wilson loop one may expect that the predicted upsilon spectrum will agree very closely with that of jkm . this expectation relies on two things : ( i ) the heavy quark mass must eliminate non - central contributions in the interaction kernel , ( ii ) the self energy contribution must be essentially independent of momentum . ( the authors of ref . @xcite did not include a self energy term in their model because it can not be extracted from lattice data . such a term must exist as external fermion propagator corrections . ) explicit computations show that these expectations are indeed borne out and indicate that a finite renormalization is sufficient to largely eliminate the self energy term . our predicted upsilon spectrum is given in table i. a comparison with experiment shows that the radial excitations rise too slowly with radial quantum number , and indeed our results similarly disagree with those of jkm . but , as noted above , the form for the static potential of eq . [ vss7 ] is not strongly constrained at large momenta . we have therefore computed the upsilon spectrum with the modified potential of eq . the results are shown in table ii and are in much better agreement with jkm and experiment . as expected , the detailed form of the coulomb tail of the potential is very important for low - lying heavy quark states . our results are very similar to typical quark model spectra@xcite ; with some deviation ( at the percent level ) becoming visible higher in the spectrum . this is to be expected because we employ a lattice potential with a string tension of 0.2 - 0.25 gev@xmath40 whereas the quark model of ref . @xcite takes @xmath124 gev@xmath40 . overall , the agreement with the experimental upsilon spectrum is impressive considering the simplicity of the model and that the potential was not fit to data . it is possible that deviations are seen higher in the spectrum , and indeed , one may expect this since the open flavor threshold is at 10.56 gev between the third and fourth vector s - wave states . in general mixing with higher fock components , such as hybrids ( one gluon exchange in perturbative language ) and meson - meson channels , will occur . these effects should become more important as one probes higher in the spectrum . eventually the quark + potential picture of mesons should break down entirely as an increasing number of gluonic degrees of freedom are excited . the psi spectrum predicted with the canonical potential of eq . [ vss7 ] is presented in table iii . the agreement with experiment is on the percent level . this is something of a surprise when considering that the upsilon spectrum required a careful fit to the high momentum potential . the psi spectrum computed from the modified potential ( table iv ) compares unfavorably to the data , with deviations at the five percent level . it appears that the linear and coulomb portions of the potential are equally important to the low - lying psi spectrum and that the small value of the effective strong coupling has largely cancelled against the large value of the string tension . indeed , as mentioned above , quark models typically employ a much smaller string tension than that of the wilson loop . we thus have evidence that the effective string tension is reduced for lighter quark masses . this can easily be induced by mixing with virtual meson pairs or by motion of the sources in the wilson loop . again , it should be possible to incorporate the physics of string softening in the model through fock sector mixing . the results of tables iii and iv also indicate that spin splittings are becoming important . for example the @xmath125 is roughly 100 mev lighter than the @xmath120 and this is not predicted in the model . again , this fault is easy to remedy once higher fock components are admitted . one also sees evidence for tensor splitting in the @xmath126 states which are quite well reproduced with the modified potential ( table iv ) . one concludes that the dirac structure of the interaction is becoming important and that it does a reasonable job at charm mass scales but that fock mixing must be accounted for , even for low - lying states . as indicated in the introduction , if canonical quark model lore holds , the addition of virtual hybrid states to the model will ruin the predicted tensor splittings since these will increase them an unacceptable amount . we stress , however , that nonperturbative mixing with virtual hybrid states is not equivalent to perturbative gluon exchange which only becomes relevant in hamiltonian qcd very high in the spectrum . we have seen that the formalism presented here is quite accurate for bottom quarks and reasonably accurate ( with the possibility of being very accurate once simple fock sector mixing is included ) for charm quarks . the challenge in carrying this success to the light quark sector lies in ( i ) the assumption that the static wilson loop potential is relevant to light quarks , ( ii ) the importance of chiral symmetry breaking , ( iii ) large spin - dependences which may be present , ( iv ) the possibility that topological aspects of qcd become important . one of the reasons coulomb gauge qcd is useful for constructing models of hadronic physics is that these issues may be addressed in a systematic fashion . the latter three issues have already been discussed ; for the first we note that an instantaneous interaction between quarks exists for all quark masses in coulomb gauge . the viability of this interaction can only be affected by higher order gluonic terms ( such as in the operator @xmath24 ) ; but we have seen that these contributions are suppressed by an energy denominator of the order of 1 gev . thus a static interaction should provide a good approximation low in the light spectrum . virtual light quark loops are another source of nonpotential interactions . but chiral symmetry breaking implies that the light current quarks acquire an effective mass , and this mass assists in dampening such loop effects . the success of the constituent quark model also indicates that loop effects on the interaction can be largely subsumed by renormalization . our results for the light meson spectrum are presented in figure 1 and in table v. the first feature to notice is that the pion is massless as desired . of course a finite pion mass can be obtained if a finite current quark mass is used in the calculation . we have chosen to keep the current quark mass at zero in order to test the robustness of the model in a zero parameter computation . the rho meson mass is predicted to be 772 mev , in very good agreement with data . we regard this as somewhat fortuitous since the potential has been fixed by lattice data and no parameter tuning has taken place . the first radial excitation is at 1390 mev , whereas the experimental mass is approximately 1450 mev . however , we note that already the possibility of fock mixing arises since the lowest mass vector hybrid is expected around 1900 mev . as seen in the psi spectrum , the tensor @xmath126 multiplet is sensitive to short range effects . in this case the @xmath111 state is in rough agreement with experiment . however the tensor state lies much above the data . the isoscalar scalar has a mass of 850 mev . one may be tempted to ascribe this state to the @xmath127 , which is famous for being too light in constituent quark models . however , the fact that the tensor state is much too massive is an indication that additional strong spin - orbit forces are required to obtain a satisfactory description of light mesons and that any conclusions concerning the nature of the scalar meson would be premature . the figure and table also present meson masses for high angular momentum . it is seen that the model severely overestimates the masses of these states . the likely cause for this is the large ( compared to quark model ) string tension which we have used . however , as argued above , there is little freedom in choosing the string tension and one must ascribe the discrepancy to nonpotential effects . the simplest such effects are extra quasigluons in the fock space expansion of higher lying states . thus we regard the poor quality of the predictions at high angular momentum as an indication of the range of validity of the potential approach to hadronic physics ( of course it is possible to extend this range by allowing more parameter freedom , but the degrees of freedom will be incorrect , and detailed predictions of such models must fail ) . equations ( 27 ) and ( 28 ) make it clear that meson masses form charge conjugation doublets in the pattern @xmath128 , @xmath129 , _ etc . _ in the large angular momentum limit . this pattern is clearly seen in the figure . such behavior is expected in the heavy quark limit where quark spins decouple and one may expect it to also occur for light quarks in the high angular momentum regime since the quark spin effects are local in the interaction . a central feature of chiral symmetry breaking is that quark spinors reduce to massless spinors at momenta much larger than the chiral symmetry breaking scale . thus one has @xmath130 and @xmath131 for @xmath132 . since the average quark momentum becomes large as the angular momentum increases we conclude that the interaction kernel approaches @xmath133 for all possible @xmath92 ( the off - diagonal potential in the @xmath107 sector goes to zero ) . thus the entire spectrum becomes degenerate in the large angular momentum limit ; in particular parity doubling occurs , as expected@xcite . the isovector meson spectrum . experimental masses@xcite are represented by lines to the left of each column . the attached boxes indicate the widths of each state . lines to the right are the results of this computation in the massless quark limit . narrower boxes are new results from the crystal barrel collaboration@xcite . , width=529 ] it is becoming clear that simple constituent quark models are limited in their ability to describe excitations high in the hadronic spectrum . well known flaws like nonrelativistic kinematics are exacerbated by the limitations of a fixed particle number formulation . indeed one expects fock sector mixing to become increasingly important as experiment probes high in the spectrum . for example meson loop effects can cause significant mass shifts and commensurate wavefunction distortion will affect other matrix elements . furthermore , gluons must manifest themselves about 1 gev above the ground state in a given sector and the subsequent state mixing can be important . the model constructed here is an attempt at going beyond the nonrelativistic quark model . since it is based on a truncation of qcd in coulomb gauge , it is heavily constrained , systematically improvable , and relativistic . because the instantaneous interaction is fixed by the lattice gauge wilson loop potential the model can also fail . any such failure may be regarded as an indication of the limitations of the potential approach to hadronic physics . furthermore , the dirac structure of the interaction is fixed by the coulomb gauge hamiltonian of qcd . this has important phenomenological implications ; for example the spin - orbit interaction is fixed to have the same sign as the coulomb interaction of the constituent quark model . a happy consequence is that mesons and baryons are treated on equal footing ( scalar confinement requires an additional sign change of the interaction between the sectors ) . finally , the assumption that the operator @xmath26 generates the leading quark and gluon interaction can be tested on the lattice . initial results are mixed , with ref . @xcite supporting the conjecture while ref . @xcite finds that the coulomb string tension is roughly three times larger than the wilson loop string tension . we find the latter result improbable since the coupling of gluons with static quarks is suppressed , leaving only the non - abelian coulomb interaction to mediate the wilson loop interaction . nevertheless , if the latter result is confirmed the present method will likely have to be abandoned . the issue of fock sector mixing will be vital to the success of this program . such effects are clearly needed in the light quark spectrum and are of some significance for heavy quarks . the most important such effect is the nonperturbative analogue of one gluon exchange , namely mixing with virtual hybrid states . implementing this will be a crucial test of the model since spin orbit splittings depend sensitively in the dirac structure of the mixing terms and of the central potential . it is entirely possible that the formalism proposed here will fail and that some sort of string approach will be required but this remains to be seen . we have implemented chiral symmetry breaking using standard many - body or nambu jona - lasinio methods . this is of course a truncation of all diagrams which contribute to the bound state bethe - salpeter equation , however , it is convenient and is enough to demonstrate the chiral nature of the pion and the importance of chiral symmetry high in the spectrum . it is possible to improve the computation in a systematic fashion . analogous improvements in the dyson - schwinger bethe - salpeter approach are discussed in ref . @xcite . in future we intend to examine the open flavor spectrum , strong decays , short range structure and spin splittings , and fock sector mixing effects . further research into topological aspects of the model and the isoscalar sector will also be of great interest . j. resag and d. schtte , `` rpa equations and the instantaneous bethe - salpeter equation '' , arxiv : nucl - th/9312013 . a. le yaouanc , l. oliver , s. ono , o. pene and j. c. raynal , phys . d * 31 * , 137 ( 1985 ) . f. j. llanes - estrada and s. r. cotanch , nucl . a * 697 * , 303 ( 2002 ) . t. zhang and r. koniuk , phys . d * 43 * , 1688 ( 1991 ) . u. loring , b. c. metsch and h. r. petry , eur . j. a * 10 * , 447 ( 2001 ) ; r. ricken , m. koll , d. merten , b. c. metsch and h. r. petry , eur . phys . j. a * 9 * , 221 ( 2000 ) . see also d. ebert , r. n. faustov and v. o. galkin , phys . d * 67 * , 014027 ( 2003 ) ; l. s. celenza , b. huang , h. s. wang and c. m. shakin , phys . rev . c * 60 * , 025202 ( 1999 ) . a. p. szczepaniak and p. krupinski , phys . d * 66 * , 096006 ( 2002 ) . a. p. szczepaniak and e. s. swanson , phys . d * 55 * , 1578 ( 1997 ) . a. p. szczepaniak and e. s. swanson , phys . d * 55 * , 3987 ( 1997 ) . k. j. juge , j. kuti and c. j. morningstar , nucl . suppl . * 63 * , 326 ( 1998 ) . k. j. juge , j. kuti and c. j. morningstar , nucl . suppl . * 83 * , 304 ( 2000 ) . s. godfrey and n. isgur , phys . d * 32 * , 189 ( 1985 ) . `` review of particle properties '' , k. hagiwara _ et al . _ , phys . rev . * d66 * , 1 ( 2002 ) . a. v. anisovich _ et al . _ , phys . b * 542 * , 8 ( 2002 ) . a general discussion of parity doubling is in e.s . swanson , `` parity doubling in the meson spectrum '' , arxiv : hep - ph/0309296 . see also t. d. cohen and l. y. glozman , phys . d * 65 * , 016006 ( 2002 ) and the comments in a. le yaouanc , l. oliver , s. ono , o. pne and j. c. raynal , phys . d * 31 * , 137 ( 1985 ) , especially after eq . 7.15 . a. bender , c. d. roberts and l. von smekal , phys . b * 380 * , 7 ( 1996 ) ; a. bender , w. detmold , c.d . roberts , and a.w . thomas , phys . c 65 ( 2002 ) 065203 .

a model of mesons which is based on the qcd hamiltonian in coulomb gauge is presented . the model relies on a novel quasiparticle basis to improve the reliability of the fock space expansion . it is also relativistic , yields chiral pions , and is tightly constrained by qcd ( quark masses are the only parameters ) . applications to hidden flavor mesons yield results which are comparable to phenomenological constituent quark models while revealing the limitations of such models . = 0.3 true in = -1.0 true in .5 true cm

complex networks have recently attracted a burst of interest as an indispensable tool of description of different complex systems . thus , technological webs as the internet and the world wide web , as well as other natural and social systems like intricate chemical reactions in the living cell , the networks of scientific and movie actors collaborations , and even human sexual contacts have been successfully described through scale - free networks , networks with the degree distribution @xmath3 @xcite . the degree distribution @xmath4 is one of the essential measures used to capture the structure of a network , and gives the probability that a node chosen at random is connected with exactly @xmath5 other vertices of the network . recently , it was pointed out that the existence of degree correlations among nodes is an important property of the real networks @xcite . thus , many social networks show that nodes having many connections tend to be connect with other highly connected nodes @xcite . in the literature this characteristics is usually dented as assortativity , or assortative mixing . on the other hand , technological and biological networks often have the property that nodes with high degree are preferably connected with ones with low degree , a property referred to as dissortativity @xcite . such correlations have an important influence on the topology of networks , and therefore they are essential for the description of spreading phenomena , like spreading of information or infections , as well as for the robustness of networks against intentional attack or random breakdown of their elements @xcite . in order to assess the role of correlations , especially of the assortative mixing , several studies have proposed procedures to build correlated networks @xcite . the most general of them are the ones proposed by newman @xcite , and by bogu and pastor - satorras @xcite , who suggest two different ways to construct general correlated networks with prescribed correlations . following the same goal , we however adopt a different perspective in this paper . we propose a simple algorithm producing assortative mixing , in which , instead of putting correlations by hand , we only try impose the intuitive condition that `` nodes with similar degree connects preferably '' . we then investigate the correlations which come out of our simple model . thus , we present an algorithm , governed by the only parameter @xmath0 , capable to generate assortative correlations to a desired degree . in order to study the effect of the assortative mixing , we apply our algorithm to a barabsi - albert scale - free network @xcite , the one leading to the degree distribution @xmath6 , and investigate the properties of the emerging networks in some detail . in what follows we treat undirected networks . starting from a given network , at each step two links of the network are chosen at random , so that the four nodes , in general , with different degrees , connected through the links two by two are considered . the step of our algorithm looks as follows . the four nodes are ordered with respect to their degrees . then , with probability @xmath0 , the links are rewired in a such a way that one link connects the two nodes with the smaller degrees and the other connects the two nodes with the larger degrees , otherwise the links are randomly rewired ( maslov - sneppen algorithm @xcite ) . in the case when one , or both , of these new links already existed in the network , the step is discarded and a new pair of edges is selected . this restriction prevents the appearance of multiple edges connecting the same pair of nodes . a repeated application of the rewiring step leads to an assortative version of the original network . note that the algorithm does not change the degree of the nodes involved and thus the overall degree distribution in the network . changing the parameter @xmath0 , it is possible to construct networks with different degree of assortativity . let @xmath7 be the probability that a randomly selected edge of the network connects two nodes , one with degree @xmath8 and another with degree @xmath9 . the probabilities @xmath7 determine the correlations of the network . we say that a network is uncorrelated when @xmath10 i.e , when the probability that a link is connected to a node with a certain degree is independent from the degree of the attached node . here @xmath11 denotes the first moment of the degree distribution . assortativity means that highly connected nodes tend to be connected to each other with a higher probability than in an uncorrelated network . moreover , the nodes with similar degrees tend to be connected with larger probability than in the uncorrelated case , i. e. , @xmath12 @xmath13 . the degree of assortativity of a network can thus be characterized by the quantity @xcite : @xmath14 which takes the value @xmath15 when the network is uncorrelated and the value @xmath16 when the network is totally assortative . ( note that finite - size effects and the constraint that no vertices are connected by more than one edge bound @xmath17 from above by the values lower than 1 @xcite ) . now , starting from the algorithm generator , we can obtain a theoretical expression for @xmath7 as a function of @xmath0 . let @xmath18 be the number of links in the network connecting two nodes , one with degree @xmath8 and another with degree @xmath9 , so that @xmath19 , where @xmath20 is the total number of links of the network . ( since undirected networks satisfy @xmath21 , the restriction @xmath22 can be imposed without loss of generality ) . we now define the variable @xmath23 a careful analysis of the algorithm reveals that , every time the rewiring process is applied , @xmath24 either does not change , or changes increasing or decreasing by unity . we can then calculated the probabilities that it changes , i. e. , that @xmath25 or @xmath26 . here , the effect of multiple edges can be disregarded since they are rare in the thermodynamical limit of infinite networks . taking into account all corresponding possibilities , we obtain for the probabilities of changes the following expressions : @xmath27 for @xmath25 and @xmath28\ ] ] for @xmath26 . here @xmath29 , and @xmath30 is given by : @xmath31 ( note that @xmath30 and @xmath32 vanish when one of the indices is smaller than @xmath16 , the minimal tolerated degree ) . using this , we can calculate the expected value for @xmath32 . the process of repeated applying our algorithm corresponds to an ergodic markov chain , and the stationary solution in the thermodynamical limit is given by the condition : @xmath33 @xmath28\ ] ] for all @xmath34 . for @xmath35 this condition reduces to @xmath36 \ . \label{quinta}\ ] ] using eq . ( @xmath37 ) and eq . ( @xmath38 ) we can calculate @xmath32 . the solutions reads @xmath39 with @xmath40 ^ 2 - p x^2_{1n } \left ( \frac{1+p}{2}\right ) } \ \ \ .\ ] ] applying the definition , eq.(@xmath41 ) , we obtain the correlations : @xmath42 finally , note that eq.(@xmath43 ) reduces to the corresponding uncorrelated case @xmath44 when @xmath45 , and reduces to @xmath46 for the case @xmath47 . in our simulations we apply our algorithm to the barabsi - albert network @xcite with @xmath48 nodes and @xmath49 links . we measure @xmath7 as functions of @xmath0 , and use them to calculate the corresponding values of @xmath17 . all simulation results are averaged over ten independent realizations of the algorithm as applied to the original network . [ fig1 ] shows the relation between the parameter @xmath0 and the coefficient of assortativity @xmath17 . the lower curve corresponds to the measured assortativity , and the upper to our theoretical prediction . both curves coincide for @xmath50 . however , whereas the theoretical curve reach the value @xmath16 for @xmath51 , the measured assortativity increases until the maximal value smaller than one ( @xmath52 ) is reached . this was theoretically expected , and is due to the finite - size effects mentioned above . to assess the goodness of the eq . ( @xmath43 ) we compare in the fig . [ fig2 ] the theoretical values of @xmath53 , given by eq . ( @xmath43 ) , with the simulations . the points correspond to the simulations and the curves are the corresponding theoretical results obtained based on the actual degree distribution of a particular realization of the network discussed . we note that the agreement is really excellent . _ diameter. _ the diameter of a network is the average distance between every pair of vertices of the network , being defined as the number of edges along the shortest path connecting them . uncorrelated scale - free networks show a very small diameter , typically growing as the logarithm of the network s size . for networks with @xmath54 the diameter is about @xmath55 . the results of the simulations show that the diameter grows rapidly when the assortativity of the network increases ( fig . [ fig3 ] ) , so that it becomes hundred times larger than for the uncorrelated network when the coefficient of assortativity tend to its maximal value . in the inset we plot the diameter as a function of @xmath56 , where @xmath57 corresponds to this maximal value of @xmath17 attainable in the network . for our particular barabsi - albert network we thus have @xmath58 . _ clustering coefficient. _ clustering coefficients of a network are a measure of the number of loops ( closed paths ) of length three . the notion has its roots in sociology , where it was important to analyze the groups of acquaintances in which every member knows every other one . to discuss the concept of clustering , let us focus first on a vertex , having @xmath5 edges connected to @xmath5 other nodes termed as nearest neighbors . if these nearest neighbors of the selected node were forming a fully connected cluster of vertices , there would be @xmath59 edges between them . the ratio between the number of edges that really exist between these @xmath5 vertices and the maximal number @xmath59 gives the value of the clustering coefficient of the selected node . the clustering coefficient of the whole network @xmath60 is then defined as the average of the clustering coefficients of all vertices . one can also speak about the clustering coefficient of nodes with a given degree @xmath5 , referring to the average of the clustering coefficients only over this type of nodes . we shall denote this degree - dependent clustering coefficient by @xmath61 , to distinguish it from @xmath60 . [ fig4 ] shows the variation of both clustering coefficients with the assortativity of the network . the clustering coefficient @xmath60 increases with the assortativity ( inset of the figure ) . the variation of @xmath61 shows more interesting features . the simulations show a peak around @xmath62 ( probably a finite size effect ) whose height increases with the assortativity of the network . in the uncorrelated case @xmath61 does not depend on @xmath5 @xcite , but a strong tendency to clustering ( for relatively large @xmath5 ) emerges when @xmath17 grows . we also observe in our simulations that @xmath63 when @xmath64 ( @xmath65 correspond to the minimal degree of our vertices ) . this is not surprising since in a strongly assortative case almost all nodes with degree @xmath65 are connected between themselves , forming one or several large loops of length larger than three . this means that all nodes having this minimal degree ( in our simulations the half of the total number of vertices ) do not tend to contribute to the clustering coefficient @xmath60 . in the present contribution we concentrate on the investigation of the properties of the proposed algorithm however , we suggest , in relation to real networks , a simple modification of the algorithm , that perhaps could be useful . thus , in order to generate assortativity only among highly connected vertices , one can apply the algorithm above only when at least one of the four nodes selected at the corresponding step has a degree larger than some chosen @xmath5 . provided all four nodes have a smaller degree , the the maslov - sneppen step is used . this procedure could lead to a larger value for the clustering coefficient , as it is observed in real networks ( @xmath66 ) @xcite . the last ones might , however , have a much more intricate structure , partly governed by the metrics of the underlying space , as in the models discussed in @xcite , so that caution has to be exercised when applying results of theoretical models disregarding metrical relations to real networks . _ node percolation. _ node percolation corresponds to removal of a certain fraction of vertices from the network , and is relevant when discussing their vulnerability to a random attack . let @xmath67 be the fraction of the nodes removed . at a critical fraction @xmath68 , the giant component ( largest connected cluster ) breaks into tiny isolated clusters . [ fig5 ] shows the fraction of nodes @xmath69 in the giant component as a function of @xmath67 for different degrees of assortativity of the network . we note that the behavior of @xmath70 changes gradually with @xmath17 from the uncorrelated case ( upper curve ) to a quite different behavior when @xmath71 ( lower curve ) , which indicates a very different topology in the network when it is strongly assortative . however , although the particular form of the @xmath69 dependence is different for different degrees of assortativity , the absence of the transition at finite concentrations ( @xmath72 ) and the overall type of the critical behavior for correlated networks with the same @xmath4 seems to be the same as for uncorrelated networks , namely the one discussed in refs . we also point out that in case @xmath64 , a finite network is no longer fully connected : part of the nodes does not belong to the giant component even for @xmath73 . the results suggest that , in the thermodynamical limit , the giant cluster at @xmath73 contains around a half of all nodes , and that its density then decays smoothly with @xmath67 . in summary , we present an algorithm to generate assortatively correlated networks . in the termodynamical limit we obtain a theoretical expression for the generated correlations , which only depends on the degree distribution of the network and on the turnable parameter @xmath0 of the algorithm . finally , we show that assortative correlations have a drastic influence on the statistical properties of networks , changing strikingly their diameter and clustering coefficient , as well as their percolation properties . we also indicate that with a minor change in our algorithm one can produces dissortative mixing too . the only change would be the following : after ordering the nodes with respect to their degree , one rewires , with probability @xmath0 , the edges so that one link connects the highest connected node with the node with the lowest degree and the other link connects the two remaining vertices ; with probability @xmath74 one rewires the links randomly . useful discussions with professor s. havlin are gratefully acknowledged . ims uses the possibility to thank the fonds der chemischen industrie for the partial financial support . m. e. j. newman , phys . e * 67 * , 026126 ( 2003 ) . m. e. j. newman , phys . lett . * 89 * , 208701 ( 2002 ) . a. vzquez , m. bogu , y. moreno , r. pastor - satorras , and a. vespignani , phys . e * 67 * , 046111 ( 2003 ) . a. capocci , g. caldarelli , and p. de los rios , phys . e * 68 * , 047101 ( 2003 ) . r. pastor - satorras , a. vzquez , and a. vespignani , phys . 87 * , 258701 ( 2001 ) . m. e. j. newman and j. park , phys . e * 68 * , 036112 ( 2003 ) . j. berg , and m. lssig , phys . * 89 * , 228701 ( 2002 ) . goh , e. oh , b.kahng , and d. kim , phys . rev . e * 67 * , 017101 ( 2003 ) . s. maslov , and k. sneppen , science * 296 * 910 ( 2002 ) . p. l. krapivsky , and s. redner , phys . e * 63 * 066123 ( 2001 ) . s. n. dorogovtsev , phys . e * 69 * , 027104 ( 2004 ) . d. s. callaway , j. e. hopcroft , j. m. kleinberg , m. e. j. newman , and s. h. strogatz , phys . e * 64 * , 041902 ( 2001 ) . j. park and m. e. j. newman , phys . e * 68 * , 026112 ( 2003 ) . m. bogu , r. pastor - satorras , and a. vespignani , phys . lett . * 90 * , 028701 ( 2003 ) . v. m. eguluz , and k. klemm , phys . lett . * 89 * , 108701 ( 2002 ) . m. bogu , and r. pastor - satorras , phys . e * 66 * , 047104 ( 2002 ) . n. schwartz , r. cohen , d. ben - avraham , a .- barabsi , and s. havlin , phys . rev . e * 66 * , 015104 ( 2002 ) . a. vzquez , and y. moreno , phys . e * 67 * , 015101 ( 2003 ) . y. moreno , j. b. gmez , and a. f. pacheco , phys . e * 68 * , 035103 ( 2003 ) . a. ramezanpour , v. karimipour , and a. mashaghi , phys . e * 67 * , 046107 ( 2003 ) . r. xulvi - brunet , w. pietsch , and i. m. sokolov , phys . e * 68 * , 036119 ( 2003 ) . m. bogu and r. pastor - satorras , phys . e * 68 * , 036112 ( 2003 ) .

many social networks exhibit assortative mixing so that the predictions of uncorrelated models might be inadequate . to analyze the role of assortativity we introduce an algorithm which changes correlations in a network and produces assortative mixing to a desired degree . this degree is governed by one parameter @xmath0 . changing this parameter one can construct networks ranging from fully random ( @xmath1 ) to totally assortative ( @xmath2 ) . we apply the algorithm to a barabsi - albert scale - free network and show that the degree of assortativity is an important parameter governing geometrical and transport properties of networks . thus , the diameter of the network and the clustering coefficient increase dramatically with the degree of assortativity . moreover , the concentration dependences of the size of the giant component in the node percolation problem for uncorrelated and assortative networks are strongly different . 2

next - generation sequencing technologies generate huge amount of sequences in an ever increasing speed . some of these reads contain adapters and other exogenous contents by experimental designs . on other situations , adapters were sequenced inadvertently when they should not due to operational errors and other unknown reasons . if these adapters were not trimmed out , they would interfere with the downstream data analysis , such as mapping the reads to the reference genome and _ de novo _ assembly . unlike the traditional homology search tools such as blast , nearly all the current popular mapping programs for short reads from the next - generation sequencing technologies use global matching algorithms , trying to match the whole length of the read to the reference genome if the number of mismatches or edit distance ( mismatches and indels ) is smaller than a pre - defined threshold . since the adapters are not part of the biological sequences , they are treated as matching errors and the reads containing them are not mapped . if the reads containing the exogenous contents are below the error threshold and eventually mapped , they will be the cause of many potential issues for downstream analysis . for example , the exogenous contents will increase the false positive rate for the subsequent variant analysis . they will also cause problems for _ de novo _ assembly . for most of the next - generation sequencing technologies , the quality of the sequencing reads becomes lower towards the end of the reads . if too many sequencing errors occur in the end of the reads , it would cause problem for mapping and other downstream analysis , for the same reason as mentioned above , even if the reads contain high - quality and mappable bases in the beginning . as the length of sequences becomes longer , this issue will become more serious . some experiments using the next - generation sequencing platforms utilize barcode technology : distinct barcode sequence tag representing individual samples are ligated into the dna sequences and the pooled samples are sequenced . to assign the reads back to the original samples we need to reliably identify the barcodes within the sequence reads , in the presence of possible experimental and sequencing errors in the barcodes . in practice , barcode identification can be achieved by using algorithms similar to those used in finding the adapters . the similar problem of adapter and low - quality region trimming existed for the traditional sanger sequencing technology . most people dealt with the problem using some makeshift solutions without paying much attention to their efficiency , which worked fine for small number of sequences . with the advent of next - generation sequencing technologies , the huge volume of sequences generated asks for more efficient software to handle the problem . some existing specialized packages , such as mapping program novoalign ( http://www.novocraft.com/ ) , have some built - in adapter - removal functions . a versatile stand - alone program will be very useful for flexible downstream analysis using different software packages . for example , after exogenous contents and low quality regions removed , the processed sequences can then be used as input for different mapping or assembly programs to compare their performance . on the other hand , a range of different parameters can be tried to trim the original sequences and the optimal parameter can be chosen based on the output of downstream analysis . here we present a fast and lightweight program for adapter and quality trimming . for adapter trimming , the program is based on modified myers s bit - vector dynamic programming algorithm @xcite . for quality trimming , a simple moving window algorithm is used and the reads are trimmed at the point where the average quality score within the window drops below a threshold . as one of the fastest dynamic programming algorithms available with edit distance as the error model ( each mismatch , insertion , or deletion counts as one error ) , the myers s bit - vector dynamic programming algorithm finds all locations at which the query matches a substring of the target sequence of length @xmath0 with @xmath1 or fewer errors . the algorithm scales linearly with the length of the target sequence ( @xmath0 ) when the length of the query is less than the machine word size @xmath2 ( typically , @xmath3 for 32-bit machines and @xmath4 for 64-bit machines ) , regardless of @xmath1 or query length @xcite . before the search starts , the algorithm pre - processes the query sequences . since in most cases the number of query sequences is far smaller than that of the target sequences , this pre - processing time is negligible . after the query sequences have been set up , in the subsequent search phase the algorithm scans the target sequences linearly and one - by - one , reporting any occurrences of the query with @xmath1 or fewer errors . hence our trimming program has a time complexity @xmath5 , for @xmath6 queries ( adapters or barcodes ) . the original myers s algorithm searches from the beginning of the target sequence towards the end and only reports the _ stopping _ position of query occurrences in the target sequence . for example , if the query is acgt and the target sequence is at**agt**ccgga , the position of the second `` t '' in the target sequence is reported for an occurrence with one deletion . in order to determine precisely the boundary between the insert and the adapters or barcodes , the _ starting _ position of query occurrences in the target sequence is needed ( for example , when 3-adapter is being trimmed ) . in the previous example we need to know the position of the second `` a '' . by algorithm s design no traditional trace - back could be done to find the query s starting position since no standard dynamic programming matrix is saved . furthermore a trace - back would defeat the efficiency of the algorithm . to find query s starting positions , we modified myers algorithm for the 3-adapter search . the modified algorithm carries out the search backward along the target sequence . in order to do so , the query sequences have to be set up backward also . the parameter @xmath1 , the upper limit of the number of match errors , is set equal to @xmath7 as default for 5-adapter and equal to @xmath8 for 3-adapter , but they can be changed to be based on the length of the adapters , or as user - specified . in the default mode for adapter trimming , for each pair of 5- and 3-adapters , the program searches for the locations of 5-adapter within the beginning region of the read ( default @xmath9 query length ) . if none of the 5-adapters is found , the trimming is failed for the read . if one or more of the 5-adapters are found with @xmath1 or fewer errors , the adapter with the smallest error is selected . the corresponding 3-adapter is then used as query to search the rest of the read , using the above - mentioned modified algorithm . if the selected 3-adapter is found in the region , then the location with the smallest error is used to trim the read ; otherwise , quality scores of the read are used to trim the 3-end . to use the quality scores , the average score within a moving window is calculated . the window moves from the 5 trimming point to the end of the read . if the average score drops below a preset threshold , then the 3 trimming point is found at the beginning of the moving window . other modes of adapter trimming are also available , such as passing the read to quality trimming if the adapters can not be found , or trimming based on the 3-adapters only . one of the advantages of myers s algorithm is that it can handle ambiguous and wildcard letters effortlessly . this makes it more suitable for adapter trimming , since usually the adapters are designed with degenerate bases incorporated in specific positions . to handle ambiguous bases , simply put them into square brackets , such as [ gc ] for either g or c in the same position . for wildcard letters ( which match any bases in the position ) , use `` . '' in the query . iupac codes can be incorporated easily . by default the query search is case insensitive ; it can be switched to case sensitive by a command line option . in addition to adapter trimming , btrim can do the trimming based on quality scores only . regardless of the trimming mode , as an option , all flanking fragments and their quality scores that have been trimmed off can be written into a separate file with detailed trimming information for each read , such as the trimming status , the adapters / barcodes found , the errors for the adapter / barcode , and the location of them in the read . this file can be parsed easily and may be useful for downstream analysis , such as barcode assignment . the details about how to use the program can be found in the document in the program s web site . figure [ f : err ] shows the error distribution of adapter trimming for sequences from a typical illumina lane . with two sets of 5- and 3-adapter pairs ( each for one orientation of the insert ) , 30 m 75bp illumina reads are processed in 57 seconds in a machine with a 3.16ghz intel xeon processor . as the target sequences are read in sequentially , the memory footprint of the program is very small ( less than 1 m ) . btrim supports fastq format currently ( both sanger and illumina formats ) . the program is written in c programming language and available at http://graphics.med.yale.edu / trim/. ] this work was supported by yale school of medicine .

btrim is a fast and lightweight software to trim adapters and low quality regions in reads from ultra high - throughput next - generation sequencing machines . it also can reliably identify barcodes and assign the reads to the original samples . based on a modified myers s bit - vector dynamic programming algorithm , btrim can handle indels in adapters and barcodes . it removes low quality regions and trims off adapters at both or either end of the reads . a typical trimming of 30 m reads with two sets of adapter pairs can be done in about a minute with a small memory footprint . btrim is a versatile stand - alone tool that can be used as the first step in virtually all next - generation sequence analysis pipelines . the program is available at http://graphics.med.yale.edu / trim/. next - generation sequencing ; adapters trimming ; barcode assignment ; approximate string matching ; bit - vector algorithm

SECTION 1. SHORT TITLE. This Act may be cited as the ``Access to Congressionally Mandated Reports Act''. SEC. 2. ESTABLISHMENT OF WEBSITE FOR CONGRESSIONALLY MANDATED REPORTS. (a) Requirement To Establish Website.--Not later than one year after the date of the enactment of this Act, the Director of the Government Publishing Office shall establish and maintain a website accessible by the public that allows the public to obtain electronic copies of all congressionally mandated reports in one place. The Director of the Government Publishing Office may publish other reports on such website. (b) Content and Function.--The Director of the Government Publishing Office shall ensure that the website required under subsection (a) includes the following: (1) With respect to each congressionally mandated report, each of the following: (A) A citation to the statute or conference report requiring the report. 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SECTION 1. LEVELS OF PARTICIPATION. Section 7(a)(2)(A) of the Small Business Act (15 U.S.C. 636(a)(2)(A)) is amended-- (1) in paragraph (i) by striking ``$100,000'' and inserting ``$150,000''; and (2) in paragraph (ii) by striking ``$100,000'' and inserting ``$150,000''. SEC. 2. LOAN AMOUNTS. Section 7(a)(3)(A) of the Small Business Act (15 U.S.C. 636(a)(3)(A)) is amended by striking ``$750,000,'' and inserting, ``$1,000,000 (or if the gross loan amount would exceed $2,000,000),''. SEC. 3. INTEREST ON DEFAULTED LOANS. Subparagraph (B) of section 7(a)(4) of the Small Business Act (15 U.S.C. 636(a)(4)) is amended by adding at the end the following: ``(iii) Applicability.--Clauses (i) and (ii) shall not apply to loans made on or after October 1, 1999.''. SEC. 4. PREPAYMENT OF LOANS. (a) In General.--Section 7(a)(4) of the Small Business Act (15 U.S.C. 636(a)(4)) is amended-- (1) by striking ``(4) Interest rates and fees.--'' and inserting ``(4) Interest rates and prepayment charges.--''; and (2) by adding at the end the following: ``(C) Prepayment charges.-- ``(i) In general.--A borrower who prepays any loan guaranteed under this subsection shall remit to the Administration a subsidy recoupment fee calculated in accordance with clause (ii) if-- ``(I) the loan is for a term of not less than 15 years; ``(II) the prepayment is voluntary; ``(III) the amount of prepayment in any calendar year is more than 25 percent of the outstanding balance of the loan; and ``(IV) the prepayment is made within the first 3 years after disbursement of the loan proceeds. ``(ii) Subsidy recoupment fee.--The subsidy recoupment fee charged under clause (i) shall be-- ``(I) 5 percent of the amount of prepayment, if the borrower prepays during the first year after disbursement; ``(II) 3 percent of the amount of prepayment, if the borrower prepays during the second year after disbursement; and ``(III) 1 percent of the amount of prepayment, if the borrower prepays during the third year after disbursement.''. SEC. 5. GUARANTEE FEES. Section 7(a)(18)(B) of the Small Business Act (15 U.S.C. 636(a)(18)(B)) is amended to read as follows: ``(B) Exception for certain loans.-- ``(i) In general.--Notwithstanding subparagraph (A), if the total deferred participation share of a loan guaranteed under this subsection is less than or equal to $120,000, the guarantee fee collected under subparagraph (A) shall be in an amount equal to 2 percent of the total deferred participation share of the loan. ``(ii) Retention of fees.--Lenders participating in the programs established under this subsection may retain not more than 25 percent of the fee collected in accordance with this subparagraph with respect to any loan not exceeding $150,000 in gross loan amount.''. SEC. 6. LEASE TERMS. Section 7(a) of the Small Business Act (15 U.S.C. 636(a)) is further amended by adding at the end the following: ``(28) Leasing.--In addition to such other lease arrangements as may be authorized by the Administration, a borrower may permanently lease to one or more tenants not more than 20 percent of any property constructed with the proceeds of a loan guaranteed under this subsection, if the borrower permanently occupies and uses not less than 60 percent of the total business space in the property.''. Passed the House of Representatives August 2, 1999. Attest: JEFF TRANDAHL, Clerk. By Martha C. Morrison, Deputy Clerk.

Amends the Small Business Act to authorize the Small Business Administration (SBA) to guarantee a general business loan made by a bank or other financial institution to a small business in the amount of: (1) 75 percent of the outstanding balance of such loan, if such balance exceeds $150,000 (currently $100,000); and (2) 80 percent of the outstanding balance of less than $150,000 (also currently $100,000). Prohibits any such loan from being made to a borrower if the total amount outstanding and committed to the borrower from the business loan and SBA investment funds would exceed $1 million (currently $750,000). Makes current provisions requiring the payment of accrued interest on defaulted guaranteed loans inapplicable to loans made on or after October 1, 1999. Requires a borrower who prepays any loan guaranteed by the SBA to remit to the SBA a subsidy recoupment fee (calculated under this Act) if: (1) the loan is for a period of less than 15 years; (2) the prepayment is voluntary; (3) the amount of prepayment in any calendar year is more than 25 percent of the outstanding loan balance; and (4) the prepayment is made within the first three years after disbursement of the loan proceeds. Revises loan guarantee fee amounts. Authorizes lenders participating in an SBA program to retain no more than 25 percent of such fee with respect to any loan not exceeding $150,000. Authorizes a borrower to permanently lease to one or more tenants not more than 20 percent of any property constructed using guaranteed loan proceeds, as long as the borrower permanently occupies and uses not less than 60 percent of the total business space in the property.

excitons in semiconductors have been the subject of many experimental and theoretical investigations of bose condensation . low - energy exciton - exciton interactions are characterized by the exciton - exciton scattering length , @xmath5 , which determines the thermodynamics of a low density gas and is crucial for modeling the thermalization time of a dilute exciton gas . despite its importance , the exciton - exciton scattering length is an elusive quantity , being difficult to measure experimentally or to estimate theoretically . as is well - known in atomic physics , scattering lengths can be extremely sensitive to the details of the interactions between particles . in particular , the existence of a weakly bound or nearly bound state causes the scatter length to become quite large . therefore , _ a priori _ one should suspect that exciton - exciton scattering may be a very material dependent property of semiconductors . reliable theoretical predictions of exciton - exciton scatting lengths require both a very accurate hamiltonian for the semiconductor , and an accurate solution to the ( four - particle ) scattering problem . in this paper we provide an essentially exact solution to exciton - exciton scattering for a commonly used single - band effective mass hamiltonian . this solution allows us to study three important questions : ( 1 ) how sensitive is the scattering length to the mass ratio @xmath6 , ( 2 ) how does the scattering length depend on spin states ( singlet or triplet ) of the scattering excitons , and ( 3 ) to what degree can inter - exciton exchange of electrons or holes cause excitons to scatter into different spin states ? this calculations also serve as a benchmark for the single band limit of more complicated scattering hamiltonians . one experimental method for measuring the exciton scattering cross section is to look at line width broadening of the recombination spectra in a gas of excitons . collisions between excitons increase the line width , causing the line width to depend on the exciton - exciton scattering rate , @xmath7 , where @xmath8 is the density and @xmath9 is a typical exciton velocity . extracting cross sections from a line width requires that ( 1 ) the density and velocity distribution are known , and ( 2 ) elastic scattering is the fastest process . as discussed below , @xmath10 is a good material for comparison to the model studied in this work . et al._@xcite have performed such experiments on @xmath10 and have found a line width broadening that suggests an upper bound of @xmath11 on the scattering length . although our simulations do not exactly model @xmath10 , we will compare our results to this value . theoretical approaches to this problem start with the effective mass approximation , in which the system under consideration consists of two electrons , labeled @xmath12 and @xmath13 , and two holes , labeled @xmath14 and @xmath15 . the hamiltonian is @xmath16 where @xmath17 . the hamiltonian has symmetry under exchange of electrons and exchange of holes , so eigenstates may be denoted by two exchange quantum numbers . the s - wave states are symmetric under exchange of excitons ; a condition which is satisfied by states @xmath18 and @xmath19 , where the @xmath20 signs refer to ( anti)symmetry under exchange of electrons and holes , respectively . although this hamiltonian is a well - accepted model for exciton - exciton scattering , we should point out a few of its deficiencies . for small excitons , such as those in @xmath10 , that have radii not much larger than the lattice spacing , non - parabolic terms in the kinetic energy and other corrections to the potential energy may be necessary . for many semiconductors , such as si and ge , the valence band is a mixture of three bands and can not be described by a single parabolic band . in the case of @xmath10 , the valence band is the parabolic spin - orbit split off band , and there are fewer complications . interband exchange ( virtual electron - hole recombination ) is an important effect that has been neglected , and could be modeled by an additional spin - dependent potential term . this hamiltonian also describes a family of scattering processes for other particles , including hydrogen - hydrogen , positronium - positronium , and muonium - muonium scattering . the equal mass case is at an extreme ( positronium scattering ) , where the born - oppenheimer approximation is the least applicable . there have been several theoretical estimates of exciton - exciton scattering for bulk systems@xcite and quantum wells@xcite as well as calculations on biexciton - biexciton scattering,@xcite only the bulk , elastic scattering calculations@xcite are directly comparable to the results of this paper , but the techniques presented here could be generalized to the other scattering problems . also , the results presented here provide a benchmark for evaluating the approximations used in other theoretical treatments , and could lend insight into the reliability of the approximations in more complicated situations . one standard theoretical approach is diagrammatic perturbation theory , as presented in the work of keldysh and kolsov@xcite and haug and hanamura.@xcite they estimate the exciton - exciton scattering matrix as arising from a single term , @xmath21 , where @xmath22 represents a state of two noninteracting excitons with momentum @xmath23 and @xmath24 and @xmath25 is the inter - exciton coulomb interaction . this method gives an estimate of @xmath26 ( independent of the mass ratio ) , where @xmath27 is the exciton radius , but it is an uncontrolled approximation which may have limited validity in the low energy limit . one serious drawback of the method is that it does not include effects of the biexciton in the scattering . as we show later , biexciton vibrational states cause strong dependence of the scattering length on the mass ratio @xmath6 , which is not captured by the low order perturbation theory . a second common approach was developed by elkomoss and munchy,@xcite and uses an effective exciton - exciton potential defined by @xmath28 , where @xmath29 is the wavefunction for two free excitons a distance @xmath30 apart . the effective potential @xmath31 arises from the hartree term and is used in a two - particle central - field calculation . while an exciton - exciton scattering pseudo - potential would be a very useful tool , this approximate form has some serious drawbacks . among its deficiencies are a lack of correlation , no van der waals attraction , a failure to reproduce biexciton states , and a vanishing interaction potential for @xmath32 . the cross sections calculated by this method are small and lack qualitative agreement with the results of the present work . some insight into exciton - exciton scattering can be gained by considering the bound states , biexcitons . since the number of bound states , @xmath33 , enters in the phase shift at zero energy , @xmath34 , it is necessary that a good computation method for low energy scattering be able accurately calculate biexciton binding energies.@xcite for the mass ratios considered ( and far beyond , including deuterium ) the biexcitons can not bind in the @xmath19 states , so biexcitons in rotational @xmath35 states always have @xmath18 wavefunctions . detailed theoretical descriptions of biexcitons can be found in ref . the equal mass case was shown to have a bound biexciton by hyllerass and ore using a variational argument,@xcite and a better variational estimate of the binding energy was given by brinkman , rice and bell,@xcite who found @xmath36 , where @xmath37 is the exciton binding energy . however , because of the importance of correlation energy , the latter variational treatment was missing _ half _ of the biexciton binding energy , as shown by diffusion monte carlo ( dmc ) calculations,@xcite which find @xmath38 . dmc is a quantum monte carlo ( qmc ) method that uses a random walk to project out the ground state wavefunction from a variational wavefunction , in order to stochastically sample the exact ground state energy . the success of dmc for calculating biexciton energies has been a motivation for its use in the present scattering calculations . the @xmath30-matrix approach to scattering is to examine the standing waves of the system . as shown by carlson , pandharipande , and wiringa@xcite and alhassid and koonin,@xcite by fixing nodes in the standing waves the scattering problem may be cast as a stationary state problem suitable for qmc methods . for an elastic scattering process , we label the distance between the products by @xmath30 , and the reduced mass of the products by @xmath39 . in exciton - exciton scattering there is a subtlety in the definition of r due to inter - exciton exchange , which we will address below in our discussion of the exciton - exciton scattering wavefunctions . nonetheless , for large separation @xmath30 , the relative motion of the products is free - particle like , so the many - body wavefunction depends on @xmath30 as @xmath40 , \label{asymptoticform}\ ] ] where @xmath41 is the relative angular momentum , @xmath42 is the scattering momentum , and @xmath43 is the phase shift . if we constrain the wavefunction to have a node at a large exciton separation @xmath44 , we find a discrete energy spectrum @xmath45 , which may be computed by ground state or excited state methods , such as dmc . each choice of @xmath44 gives a spectrum of states @xmath46 , with energies @xmath47 that determine values of @xmath43 , @xmath48 where @xmath49 . the scattering matrix elements are determined by the phase shifts , @xmath50 - 1.\ ] ] carlson has also proposed fixing the logarithmic derivative of the wavefunction at the boundary instead of setting wavefunction to zero , @xcite @xmath51 were @xmath52 is the normal to the boundary surface , at a fixed radius @xmath53 , and @xmath54 parameterizes the boundary condition . this formulation has the advantage of separating the choice of simulation size @xmath53 ( subject to @xmath53 lying in the asymptotic region ) , from the sampling of energy , which is handled by varying @xmath54 , and is particularly well suited for finding the scattering length . the application to vmc calculations is straight - forward , but preserving the boundary condition in dmc calculations requires a method of images . @xcite the results presented here do not use the logarithmic - derivative boundary condition . the use of excited states @xmath55 is necessary when there is a bound state and , more generally , when the scattering state being studied has its first node before the asymptotic region is reached . we use a qmc method to calculate excited states developed by ceperley and bernu,@xcite to adapt vmc and dmc methods for a hilbert space of several low energy wavefunctions . a set of @xmath56 trial wavefunctions is chosen , @xmath57 . the generalized eigenvalue equation to be solved is,@xcite @xmath58d_{k\beta}(t)=0 , \label{eq : eigen}\ ] ] where @xmath59 is the @xmath60 eigenvector with eigenvalue @xmath61 and the matrices @xmath62 and @xmath63 are the overlap and hamiltonian matrices in our trial basis , given by @xmath64 the parameter @xmath65 is the projection time . the eigenvalues @xmath61 are energy eigenvalues @xmath66 within the hilbert space spanned by the projected trial functions @xmath67 , and approach the exact energy eigenvalues in the limit of large @xmath65 . the matrices @xmath62 and @xmath63 are sampled with random walks , using a guiding function @xmath68 which must be positive everywhere . the guiding function must have significant overlap with all basis functions , and should be optimized to decrease the variance of the sampled matrices . at each step @xmath69 in the random walk , the coordinates @xmath70 of the particles are updated using @xmath71 where @xmath72 is a normally distributed random variate with zero mean and unit variance and @xmath73 is the time step . in the limit of small @xmath73 , eq . ( [ scat_step_eq ] ) describes a process for sampling @xmath74 . the matrix element of @xmath75 is estimated by integrating the local energy of the guiding function , @xmath76 , along the random walk , @xmath77}.\ ] ] the estimators for matrices @xmath62 and @xmath63 are @xmath78 where @xmath79 and @xmath80 are the local energies of the trial basis states . , at large exciton - exciton separation . the asymptotic form of the @xmath81-wave scattering states are symmetric ( @xmath18 ) or antisymmetric ( @xmath19 ) combinations of these configurations . this symmetric / antisymmetric form is used for the trial wavefunctions @xmath82 and @xmath83 , using @xmath84 and @xmath85 from eq . ( [ trial_ex_scat_psi_eq ] ) . ] we now discuss the form for the exciton scattering functions @xmath86 and @xmath87 . as mentioned before , inter - exciton exchange of particles complicates the definition of exciton - exciton separation . there are two configurations for well - separated excitons , as shown in fig . [ configfig ] . configuration i has the electrons and hole paired as @xmath88 , @xmath89 ; and configuration ii as @xmath90 , @xmath91 . we choose wavefunctions @xmath92 and @xmath93 to represent these states , @xmath94 where @xmath95 , and parameters in the function @xmath96 are variational . these wavefunctions represent two excitons in a relative s - wave state . since these are not eigenstates of the exchange operator for electrons @xmath97 or holes , @xmath98 , we take linear combinations of the two for our trial wavefunctions , @xmath99 and @xmath100 . for large separation of excitons , the exponential factors prohibit both configurations from simultaneously contributing to the wavefunction . thus , a node can be approximated in the scattering wavefunction by simply requiring that @xmath101 be zero for all @xmath102 . the error introduced by this approximation is of order @xmath103 , and is another limit on the use of small values for @xmath44 . since we only do calculations for low energy scattering , large @xmath44 , the lack of a well - defined exciton - exciton separation distance for short distances does not matter . of the dmc states relative to the vmc states as a function of dmc projection time @xmath65 , for basis states @xmath104 . the eigenvalue equation is given by eqs . ( [ eq : eigen])([eq : hmat ] ) , where the hamiltonian and overlap matrices have been sampled using eqs . ( [ eq : overlapest ] ) and ( [ eq : hmatest ] ) . ] this method for calculating scattering properties is very sensitive to the energy spectra @xmath105 . to get accurate energies , we do not try to construct and optimize elaborate variational wavefunctions , but rather use dmc to project the energy from trial wavefunctions of the form given in eq . ( [ trial_ex_scat_psi_eq ] ) . the coefficients @xmath106 , @xmath107 , @xmath108 , and @xmath109 are chosen to obey the cusp conditions on the wavefunction for small particle separations . the s - wave envelope functions @xmath101 are taken as solutions to an empirical exciton - exciton scattering potentials , @xmath110 where @xmath111 and @xmath112 have been self - consistently fit to approximate the energy spectrum of the four particle scattering states . we take the guiding function @xmath68 to have the same form as the @xmath82 wavefunctions with @xmath113^{1/2}$ ] . the parameters @xmath114 are chosen to bias sampling towards the collision : @xmath115 for @xmath18 states and @xmath116 for @xmath19 states to check for convergence of the energies in dmc , we plot the energy difference , @xmath117 , as a function of projection time in fig . [ evstfig ] . we see convergence after a projection time of 3 @xmath118 . , for ( a ) symmetric @xmath18 states , and ( b ) antisymmetric @xmath19 states , with @xmath119 . the lowest energy curve in ( a ) is the biexciton with binding energy @xmath120 . these functions @xmath121 determine the phase shifts @xmath122 and @xmath123 , by the relationship in eq . ( [ kfrome ] ) . ] we thus find two energy spectra for each value of @xmath44 , as shown in figs . [ evsrnfig](a ) and [ evsrnfig](b ) . the spectra for the symmetric states @xmath18 , show a clearly bound biexciton state , as seen in fig . [ evsrnfig](a ) . the antisymmetric states @xmath19 , as shown in fig . [ evsrnfig](b ) , have no bound state . the binding energy of the biexciton is @xmath124 , in agreement with other ground state calculations , and is insensitive to the position of the node @xmath125 because it is localized . in contrast , the delocalized scattering states are quite sensitive to @xmath125 , and their dependence on @xmath125 is a measure of the elastic scattering matrix elements . for the two @xmath35-wave scattering states , for @xmath119 , calculate using eq . ( [ kfrome ] ) and the data from fig . [ evsrnfig ] . ] .coefficients for polynomomial fit to the low energy part of the phase shift functions for the case @xmath119 . [ cols="^,^,^,^,^",options="header " , ] [ scattab ] the collision of two excitons with well defined initial and final spin states can be determined by decomposing the scattering events into the two channels , @xmath126 and @xmath127 . using the change of basis matrix ( table [ spbasistab ] ) , we find @xmath128 , where the coefficients @xmath129 and @xmath130 for all non - zero s - wave scattering processes are given in table [ scattab ] . the s - wave scattering cross sections are given by @xmath131 , where there is a factor of two enhancement due to the identical particle statistics . the spin - dependent cross sections take the form , @xmath132 , \label{eq : cs}\end{aligned}\ ] ] where @xmath133 , @xmath134 , and @xmath135 depend on the initial and final spin states and are tabulated in table [ scattab ] . the scattering lengths @xmath5 are given by @xmath136 , where the derivatives of the phase shifts are determined from the linear coefficients in table [ phasecoeftab ] . ) , for exciton - exciton scattering with @xmath119 , for the processes : ( a ) singlet - singlet @xmath137 singlet - singlet , ( b ) triplet - triplet @xmath137 triplet - triplet for total spin @xmath138 ( dashed line ) and @xmath139 ( solid line ) , ( c ) triplet - singlet @xmath137 triplet - singlet with @xmath140 , and ( d ) triplet - triplet @xmath137 singlet - singlet and singlet - singlet @xmath137 triplet - triplet , both with @xmath140 . ] the calculated spin - dependent scattering lengths for the case @xmath119 are presented in the last column of table [ scattab ] . these are the low - energy limit the cross - sections shown in fig . [ cs1fig ] . in fig . [ cs1fig ] we have plotted the s - wave scattering cross sections versus scattering momentum for the case @xmath119 and all non - zero spin configurations . fig . [ cs1fig](a ) shows scattering of two singlet - excitons . scattering of two triplet - excitons is shown in fig . [ cs1fig](b ) , where the solid line represents the spin aligned @xmath141 state , and the dashed line represents the @xmath142 state . the @xmath142 state scatters particularly strong because it has a large contribution from the @xmath143 channel , which is enhanced by the weakly bound biexciton . triplet - excitons in a relative @xmath144 state are spatially antisymmetric and thus have no s - wave scattering . we show s - wave scattering of triplet - excitons from singlet - excitons in fig . [ cs1fig](c ) . this state has two distinguishable excitons , and can scatter by both s - wave and p - wave processes . as can be seen in table [ scattab ] , the only contribution to the cross section is from the weaker @xmath145 channel . the coefficient for s - wave scattering is particularly small because only half the scattering process is symmetric ( s - wave ) , and there is an additional factor of one - half which cancels the identical particle factor . there is also an triplet- to singlet - exciton conversion cross section given in fig . [ cs1fig](d ) . although this is an inelastic process in experimental situations , it conserves energy according to our model hamiltonian because we do not have an explicit interband spin coupling . the conversion of two triplet - excitons to two singlet - excitons can be understood as an inter - exciton exchange of a pair of electrons ( or holes ) . since the spins of the individual excitons do not correspond to symmetries of the hamiltonian , they need not remain constant during scattering . this conversion process is a physical consequence of the two inequivalent scattering channels @xmath143 and @xmath145 . this effect has been reported in experimental@xcite and theoretical@xcite work on exciton scattering in quantum wells . and @xmath146 as a function of the electron - hole mass ratio . the divergence in @xmath147 near @xmath148 is due to the appearance of second bound biexciton state . solid lines are a guide to the eye . ] the dependence of the cross sections on mass may be numerically studied by our methods . in fig . [ avmfig ] we show our calculated @xmath147 and @xmath146 as a function of mass ratio , @xmath149 . we find that the scattering length is remarkably insensitive to the mass ratio for @xmath150 ( corresponding to a wide range of semiconductors ) , but then diverges near @xmath151 . this feature is lost in previously published theoretical treatments of exciton - exciton scattering . the divergence in @xmath147 near @xmath148 is due to the acquisition of a biexciton vibrational state . for @xmath119 the biexciton has no bound excited states , while a @xmath152 molecule has 15 bound vibrational states . our calculations have shown the first of these appears near @xmath148 , with dramatic effects on the scattering length . the @xmath146 curve is relatively featureless because there are are no bound antisymmetric states in this range . we interpret the upward drift of @xmath146 for larger mass ratios as a systematic error due to difficulties in projecting states in excitonic systems with very different electron and hole masses . the heavy particle determines the projection time @xmath153 while the light particle determines the diffusion time step @xmath73 . the difficulty in handling large mass ratios make the method ( as presented here ) complementary to calculations that use the born - oppenheimer approximation . it is important to realize that similar relationships must exist between the scattering length and other material parameters , such as the luttinger - kohn parameters describing realistic hole states , external strain , and spin - orbit coupling , to name a few . theoretical studies of such effects will need similar high - accuracy scattering calculations , but applied to more accurate hamiltonians , and are an area for future research . to summarize , we have shown that there are several significant elastic scattering processes for excitons , and have given numerically exact values for a widely used theoretical model . we find strong triplet - triplet and singlet - singlet scattering , with weaker triplet - singlet scattering and triplet - triplet to singlet - singlet conversion processes . scattering is relatively insensitive to the mass ratio for @xmath154 , but becomes very sensitive and actually diverges near @xmath155 . dmc has been found be a good tool for this four - particle excited state calculation , since the detection of weakly bound states requires very accurate evaluation of the correlation energy . this computational approach should be extended in many ways . the extension to higher angular momentum states would give important corrections at higher scattering energies . application to biexciton - biexciton scattering are possible , but would be a bit more difficult because the scattering wavefunction would then have to describe eight interacting particles . most importantly , the method should be adapted to better hamiltonians so that the sensitivity of the scattering length to material properties for a wide range of materials can be studied . this approach should be quite useful for quantum well problems , which have similarities to the bulk problem study here , but have many more experimental parameters that can affect exciton - exciton interaction . we would like to thank k. ohara and j. carlson for useful discussions . this work was supported by nsf grant no . dmr 98 - 02373 , computer resources at ncsa , and the department of physics at the university of illinois urbana - champaign . for example , the location of the scattering length divergence at @xmath156 , reported later in this article , is extremely sensitive to an accurate treatment of correlation energy , since it relies on the appearance of a second , weakly bound biexciton state at that mass ratio .

we calculate cross sections for low energy elastic exciton - exciton scattering within the effective mass approximation . unlike previous theoretical approaches , we give a complete , non - perturbative treatment of the four - particle scattering problem . diffusion monte carlo is used to calculate the essentially exact energies of scattering states , from which phase shifts are determined . for the case of equal - mass electrons and holes , which is equivalent to positronium - positronium scattering , we find @xmath0 for scattering of singlet - excitons and @xmath1 for triplet - excitons , where @xmath2 is the excitonic radius . the spin dependence of the cross sections arises from the spatial exchange symmetry of the scattering wavefunctions . a significant triplet - triplet to singlet - singlet scattering process is found , which is similar to reported effects in recent experiments and theory for excitons in quantum wells . we also show that the scattering length can change sign and diverge for some values of the mass ratio @xmath3/@xmath4 , an effect not seen in previous perturbative treatments .

thirty one cases of pathologically proven gastric cancer occurring from march 2002 to march 2005 were prospectively included in this study . the patient records and the pertinent clinical data are shown in table 1 and include tumor size ( greatest diameter ) , pathological tnm ( ptnm ) staging ( uicc 1997 ) and who histological grading ( 11 ) as described : well differentiated = an adenocarcinoma with well - developed glands and often resembling a metaplastic intestinal epithelium ; moderately differentiated = an adenocarcinoma intermediate between the well differentiated and poorly differentiated ; poorly differentiated = an adenocarcinoma composed of highly irregular glands that are recognized with difficulty , or single cells that remain isolated or are arranged in small to large clusters with mucin secretions or acinar structures . a ct perfusion was approved by the hospital ethics committee and a patient consent was obtained before imaging . all tumors were resected via a surgical procedure at one week after mdct scanning ( ge - lightspeed , ge medical systems , milwaukee , wi ) . following a 1,000 - 1,200 ml oral dose of water , and a 20 mg intravenous injection of scopolamine ( boehringer ingelheim , germany ) the patients were instructed to practice a gentle breathing technique while scanning , and were fixed with an abdominal belt . the lesion was localized on the non - enhanced ct scan with a 2 cm tumor region of interest defined by an experienced radiologist . the dynamic scan was acquired at this level , performed at a static table position during an intravenous bolus of 50 ml in nonionic iodinated contrast enhance medium ( iopromide , ultravist300 ; schering , berlin , germany ) via the antecubital vein at 4 - 5 ml / s . the following parameters were used : 10 s for the scan delay from the start of injection ; 5 mm slice thickness ( reconstruction slice thicknesses were 5 mm and 10 mm ) ; 1 s gantry rotation period with a 1 s temporal resolution ; 120 kv , 100 ma and a 60 sec transverse data acquisition period . next , the data were transferred to a workstation ( advantage windows 4.0 ; perfusion 3.0 ; ge medical systems ) and analyzed using commercial software . the advantages of the analytical method included a deconvolution for perfusion and blood volume , which demonstrated good temporal resolution and high spatial resolution , while high image noise and limited volume coverage appeared to be its disadvantages . each region of interest , drawn over the tumor by a radiologist section by section , was as large as possible to reduce noise ( > 50 pixels ) and to almost completely cover the whole lesion , with care to exclude peripheral fat and necrotic area . maps of tumor blood flow ( bf ) ( ml/100 g / min ) , blood volume ( bv ) ( ml/100 g ) , mean transit time ( mtt ) ( sec ) , and permeability surface ( ps ) ( ml/100 g / min ) were calculated automatically for all four sections ( with reconstruction slice thickness 5 mm ) available for each patient . the same process was repeated in the sections where reconstruction of slice thickness was 10 mm . the mvd was estimated by immunohistochemical staining of the surgical specimens with anti - cd34 monoclonal antibody ( dako , copenhagen denmark ) ( 12 ) . any single brownstaining endothelial cell or small clusters of brown - staining endothelial cells , with or without a lumen , are clearly separated from its adjacent microvessels , tumor cells , and other connective tissue elements considered as being individual vessels . vessels of a caliber larger than the approximately eight red blood cells and vessels with a thick muscular wall were excluded from the final counting . after screening the areas with intense neovascularized spots in a low power field ( 40 ) , the microvessels in the area with the highest number of discrete microvessels were counted in a 400x field . moreover , three separate areas of intense neovascularization were assessed for each sample and the mean mvd was calculated for each tumor evaluated . the bv , bf , mtt , ps , and mvds are expressed as the meanstandard deviation ( sd ) and the data were subjected to a kolmogorov - smirnov normality test . all findings were prospectively analyzed and were found to be correlated with the clinicopathological results ( histological grading , presence of lymph node metastasis , serosal involvement , tnm staging , and mvd ) . the statistical analyses ( t - test and spearman rank correlation ) were calculated in spss 11.5 ( spss inc . , for the two - tailed tests , p - values less than 0.05 were considered statistically significant . thirty one cases of pathologically proven gastric cancer occurring from march 2002 to march 2005 were prospectively included in this study . the patient records and the pertinent clinical data are shown in table 1 and include tumor size ( greatest diameter ) , pathological tnm ( ptnm ) staging ( uicc 1997 ) and who histological grading ( 11 ) as described : well differentiated = an adenocarcinoma with well - developed glands and often resembling a metaplastic intestinal epithelium ; moderately differentiated = an adenocarcinoma intermediate between the well differentiated and poorly differentiated ; poorly differentiated = an adenocarcinoma composed of highly irregular glands that are recognized with difficulty , or single cells that remain isolated or are arranged in small to large clusters with mucin secretions or acinar structures . a ct perfusion was approved by the hospital ethics committee and a patient consent was obtained before imaging . all tumors were resected via a surgical procedure at one week after mdct scanning ( ge - lightspeed , ge medical systems , milwaukee , wi ) . following a 1,000 - 1,200 ml oral dose of water , and a 20 mg intravenous injection of scopolamine ( boehringer ingelheim , germany ) , a perfusion scan was performed in a 16-section mdct cine period lasting 60sec . the patients were instructed to practice a gentle breathing technique while scanning , and were fixed with an abdominal belt . the lesion was localized on the non - enhanced ct scan with a 2 cm tumor region of interest defined by an experienced radiologist . the dynamic scan was acquired at this level , performed at a static table position during an intravenous bolus of 50 ml in nonionic iodinated contrast enhance medium ( iopromide , ultravist300 ; schering , berlin , germany ) via the antecubital vein at 4 - 5 ml / s . the following parameters were used : 10 s for the scan delay from the start of injection ; 5 mm slice thickness ( reconstruction slice thicknesses were 5 mm and 10 mm ) ; 1 s gantry rotation period with a 1 s temporal resolution ; 120 kv , 100 ma and a 60 sec transverse data acquisition period . next , the data were transferred to a workstation ( advantage windows 4.0 ; perfusion 3.0 ; ge medical systems ) and analyzed using commercial software . the advantages of the analytical method included a deconvolution for perfusion and blood volume , which demonstrated good temporal resolution and high spatial resolution , while high image noise and limited volume coverage appeared to be its disadvantages . each region of interest , drawn over the tumor by a radiologist section by section , was as large as possible to reduce noise ( > 50 pixels ) and to almost completely cover the whole lesion , with care to exclude peripheral fat and necrotic area . maps of tumor blood flow ( bf ) ( ml/100 g / min ) , blood volume ( bv ) ( ml/100 g ) , mean transit time ( mtt ) ( sec ) , and permeability surface ( ps ) ( ml/100 g / min ) were calculated automatically for all four sections ( with reconstruction slice thickness 5 mm ) available for each patient . the same process was repeated in the sections where reconstruction of slice thickness was 10 mm . the mvd was estimated by immunohistochemical staining of the surgical specimens with anti - cd34 monoclonal antibody ( dako , copenhagen denmark ) ( 12 ) . any single brownstaining endothelial cell or small clusters of brown - staining endothelial cells , with or without a lumen , are clearly separated from its adjacent microvessels , tumor cells , and other connective tissue elements considered as being individual vessels . vessels of a caliber larger than the approximately eight red blood cells and vessels with a thick muscular wall were excluded from the final counting . after screening the areas with intense neovascularized spots in a low power field ( 40 ) , the microvessels in the area with the highest number of discrete microvessels were counted in a 400x field . moreover , three separate areas of intense neovascularization were assessed for each sample and the mean mvd was calculated for each tumor evaluated . the bv , bf , mtt , ps , and mvds are expressed as the meanstandard deviation ( sd ) and the data were subjected to a kolmogorov - smirnov normality test . all findings were prospectively analyzed and were found to be correlated with the clinicopathological results ( histological grading , presence of lymph node metastasis , serosal involvement , tnm staging , and mvd ) . the statistical analyses ( t - test and spearman rank correlation ) were calculated in spss 11.5 ( spss inc . , for the two - tailed tests , p - values less than 0.05 were considered statistically significant . the perfusion parameters for gastric cancer in 31 patients ( with reconstruction slice thicknesses of 5 and 10 mm ) were compared , and revealed no significant differences ( p > 0.3 ) . in this study , the mean perfusion values and mvd for tumors are as follows : bf ( 48.1416.46 ml/100 g / min ) , bv ( 6.702.95 ml/100 g ) , mtt ( 11.754.02 sec ) , and ps ( 14.175.23 ml/100 g / min ) and mvd ( 41.711.53/400x field ) . moreover , the relationship between values and different histological grades , serosal involvement , distant metastasis , or lymphatic metastasis , and ptnm are detailed in tables 2 - 5 . a significant difference exists for the ps value between patients with or without lymphatic involvement ( p = 0.038 ) , as well as among different histological grades ( p = 0.04 ) and tnm staging ( p = 0.026 ) . however , the bf , bv , mtt , and mvd of gastric cancer revealed no significant relationship with any clinicopathological features ( p > 0.05 ) ( figs . 1 , 2 ) . currently , a perfusion ct is calculated by the deconvolution approach , which is based on the theory that immediate enhancement of the tumor is largely due to the presence of the contrast media within the intravascular space and its first - pass to the extravascular space . with the leakage to the extravascular space , the enhancement of the tumors are caused by the contrast media in both the intrasvascular and extravascular space ( 10 ) . the deconvolution model has the ability to tolerate greater image noise , is therefore rather well suited to abdominal scans , and is the preferred method for the measurement of low levels of perfusion , which are applicable to gastrocarcinoma ( 14 ) . the majority of the injected contrast media remains intravascular within 40 s ( it is also affected by cardiac output and central blood volume ) ; however , a much greater proportion later passes into the extravascular space . the duration of this process lasts around 2 to 4 min ( 15 - 17 ) . a perfusion ct scan was performed prospectively in 10 patients with histologicallyproven colorectal cancer using different acquisition times ( 45 , 60 , and 130 s ) by goh et al . ( 18 ) . no significant difference was found for bf , bv , or mtt values between any acquisition times ; however , significant differences in ps were found between 45 sec and 65 or 130 sec . by measuring the attenuation change within the input artery and tumor , an irf ( input response function ) curve can be derived . the peak of this curve is regarded as bf , while bv is represented by the area under the curve . as a result , different acquisition times do not drastically affect these three values since the shape of the curve is fixed . although the radiation dose in a perfusion ct scan is around 700 mgy ( 70% of abdominal ct ) , the extra 2 min dose may be harmful to the patient and efforts should be taken to minimize the dose . furthermore , a long acquisition time can lead to respiratory motion in an abdominal scan . when taking all of these elements into account , we determined that the 60 sec acquisition time be the most appropriate for our study . furthermore , patients who suspend their breathing will often exhale , which will lead to more motion artifacts and the temptation to take a deep breath when experiencing the " hot flush " associated with a rapid bolus of contrast medium will interrupt the perfusion scanning . therefore , a quiet respiration was requested during the scan , with patients in the prone position and fixed with a waistline to reduce the extension of respiration ( 14 ) . pathological tnm staging , histological grading , serosal involvement , lymphatic metastasis , and mvd have been identified as important predictors of the prognosis resulting from gastric cancer in our study ( 19 - 20 ) . moreover , ptnm is the conventional prognostic index as it reflects the depth of invasion as well as lymphatic or distal metastasis ( 3 ) . tumor outcome is determined by tumor size , extent , stage , and biological behavior and is largely described according to its histological grade . recent studies have acknowledged that the lymphatic metastasis status is critical in the prognosis of gastric cancer . the mortality of patients with lymphatic metastasis is 3.92x greater than patients without lymphatic metastasis . angiogenesis is a highly complex phenomenon that is essential for the growth of solid tumors , hence permitting rapid tumor growth and increased potential for tumor metastasis . furthermore , angiogenesis is a significant predictor of prognosis and hematogenous metastasis in patients with gastric cancer . mvd is currently applied as an indicator of tumor angiogenesis , and has further been demonstrated that , in some tumors , up to 15% of tumor blood vessels demonstrate the presence of cancer cells in the lumen ( 21 ) . it is proposed that these small , leaky vessels allow tumor cells to reach the circulatory system , thus increasing the probability of metastasis . the results of a multiple elements analysis in breast cancer , indicated that mvd plays a more important role in predicting invasion and metastases than other clinical indicators . also , several studies have shown a positive statistical correlation between mvd and metastasis in other solid tumors such as in the lung , uterus , cervix , and prostate . however , the relationship is controversial in gastric cancer ( 5 , 22 - 24 ) . according to the results of this study , there is a significant difference for the ps value between patients with and without lymphatic involvement . moreover , there is also a significant difference between different histological grades and tnm stages , while bf , bv , mtt , and mvd revealed no significant correlation with clinicopathological findings for gastric cancer . permeability surface represents the transmission rate of contrast media from capillary endothelium to interstitial space , reflects the integrity of endothelial cells and permeability of vessels . it is known that tumor capillaries , in general , have wide inter - endothelial junctions , a large number of fenestrate and transendocannels , and discontinuous or absent basement membrane . compared to normal vessels , they are more easily penetrated by large particles , including tumor cells . this whole process often happens along with an inflammatory reaction that accelerates permeability changes ( 22 , 25 ) . previous reports have put too much emphasis on blood flow of the tumor rather than the functional differences compared to normal vesselscapillary permeability , which appears to be of value in grading of cerebral glioma and lung cancer ( 13 , 26 ) . we believe ps to be an indicator of prognosis in gastric cancer , warranting further study in larger cohort of patients . there is no significant difference in the bf , bv , mtt and mvd between patients with and without lymphatic involvement , but also with different histological grades and tnm staging . the reasons for this may be as follows : first , this may be due to the small size of the study population , which contained many patients with poorly differentiated carcinoma , which perhaps causes some statistical bias . second , elevated tissue pressure present at the center of such tumors have caused the lumen and resulted in the underestimation of the mvd ( 3 ) . ( 10 ) that angiogenesis stimulates the opening of significant numbers of arteriovenous shunts , rather than producing a new vascular supply ( 10 ) . anything above may affect the result of bf , bv and mtt values . moreover , different tumors have different pathological features . regional cerebral blood volume is closely related to the grading of glioma ( 27 ) . fourth , tumor vessels are structurally and functionally abnormal , with uneven diameters , increased length and tortuosity , multiple arteriovenous shunts , and loss of physiological regulation of blood flow . the distribution of tumor vessels is uneven , with a large amount in the vascular area and a small amount in necrotic region . because mvd is a direct technique has a significant shortcoming as it depends on the availability of postoperative tissue or biopsy materials . additionally , a gastric ulcer is associated with cancer , thus complicating accurate calculation ( 28 ) . fifth , there is the possibility that mvd acts as an indicator of angiogenesis correlates hematogeneous metastasis . first , as the size of the study population was too small , no estimation of the absolute value of ps data could be provided for under a clinical analysis . third , the lack of control group in the study is another limitation , the normal gastric wall is more likely to be too thin for us to achieve perfusion ct values . fourth , a respiratory artifact is something hard to overcome , especially for a 60 sec free breathing scan . it has been reported that mri could aid in optimizing treatments , categorizing lesions , and influencing patient care in brain tumors ( 26 ) , which might be a hint for the futher investigation in gastrointestinal system . perfusion ct is a reproducible , objective , and feasible imaging strategy for the evaluation of oncology . furthermore , the analysis of perfusion ct in gastric cancer ( especially for the ps value ) , might be a helpful prognostic indicator , or as being useful for predicting the response to clinical treatment .

objectiveto investigate the relationship between the perfusion ct features and the clinicopathologically determined prognostic factors in advanced gastric cancer cases.materials and methodsa perfusion ct was performed on 31 patients with gastric cancer one week before surgery using a 16-channel multi - detector ct ( mdct ) instrument . the data were analyzed with commercially available software to calculate tumor blood flow ( bf ) , blood volume ( bv ) , mean transit time ( mtt ) , and permeability surface ( ps ) . the microvessel density ( mvd ) , was evaluated by immunohistochemical staining of the surgical specimens with anti- cd34 . all of the findings were analyzed prospectively and correlated with the clinicopathological findings , which included histological grading , presence of lymph node metastasis , serosal involvement , distant metastasis , tumor , node , metastasis ( tnm ) staging , and mvd . the statistical analyses used included the student 's t - test and the spearman rank correlation were performed in spss 11.5.resultsthe mean perfusion values and mvd for tumors were as follows : bf ( 48.1416.46 ml/100 g / min ) , bv ( 6.702.95 ml/100 g ) , mtt ( 11.754.02 s ) , ps ( 14.175.23 ml/100 g / min ) and mvd ( 41.711.53 ) . moreover , a significant difference in the ps values was found between patients with or without lymphatic involvement ( p = 0.038 ) , as well as with different histological grades ( p = 0.04 ) and tnm stagings ( p = 0.026 ) . however , bf , bv , mtt , and mvd of gastric cancer revealed no significant relationship with the clinicopathological findings described above ( p > 0.05).conclusionthe perfusion ct values of the permeable surface could serve as a useful prognostic indicator in patients with advanced gastric cancer .

the quantum - mechanical coupling of individual atoms and photons has been demonstrated in a series of cavity - qed experiments during the past decade . @xcite in addition to the fundamental interest in states formed by superpositions of matter and photon degrees of freedom , the development of cavity - qed has been triggered by possible applications in quantum information schemes . strong coupling of a qubit and a cavity mode allows one to convert localized qubits into flying qubits suitable for transmission of quantum information . @xcite transmission through a detuned cavity mode can be utilized for qubit readout . @xcite for several qubits interacting with a single cavity mode , the cavity can act as bus for quantum information that couples qubits with large spatial separation . @xcite in this manuscript , we consider a pair of qubits both of which are coupled to one cavity mode and , in turn , both qubits are coupled directly to one another by an exchange - type interaction . the hamiltonian of the system under study is given by @xmath0 \label{eq : gen - ham } \\ & & + \hbar \omega \hat{a}^\dagger \hat{a } + \frac{\hbar j_\perp}{2 } \left ( \hat{s}_1^+ \hat{s}_2 ^ - + \hat{s}_1 ^ - \hat{s}_2^+ \right ) + \hbar j_z \hat{s}_{1,z } \hat{s}_{2,z}. \nonumber\end{aligned}\ ] ] here , @xmath1 is the energy splitting of qubit @xmath2 , @xmath3 is the coupling strength between qubit @xmath4 and the cavity mode , @xmath5 is the energy of a cavity photon , @xmath6 are raising and lowering operators for qubit @xmath4 , and @xmath7 are pseudo - spin operators with the pauli matrix @xmath8 . extending previous work @xcite on cavity - qed with solid - state systems , we take into account an additional direct qubit coupling with amplitudes @xmath9 , @xmath10 . the interplay of direct and cavity - mediated coupling leads to intricate phenomena . for @xmath11 , the state of both qubits can be read out simultaneously from the cavity dispersion if @xmath12 and the cavity @xmath13-factor is sufficiently large . @xcite we show that a similar readout scheme remains effective even for the case of coupled qubits . for identical qubits , @xmath14 and @xmath15 , the measurement via the cavity mode projects the coupled state onto the singlet - triplet basis and thus would allow one to detect entangled two - qubit states . we show that the direct exchange coupling modifies the cavity - mediated interactions and decreases the fidelity of cavity - mediated two - qubit gates . @xcite on a more fundamental level , our model allows us to investigate the transition from cavity - mediated inter - qubit interactions at small @xmath16 to a system of two directly coupled qubits interacting with a cavity . an implementation of the hamiltonian eq . ( [ eq : gen - ham ] ) is feasible with various physical systems . for @xmath17 , eq . ( [ eq : gen - ham ] ) has been derived for superconducting qubits at the charge degeneracy point interacting with a microwave resonator . @xcite in the present work , this scheme is extended to capacitively coupled superconducting qubits . other implementations include exciton states in coupled quantum dots or coupled quantum shells in optical microcavities . @xcite we show that this model can readily be extended to electron spin states in coupled quantum dots,@xcite interacting with a microwave cavity or an optical cavity . this work is organized as follows . in sec . [ sec : dispersive ] , we calculate the optical response of the coupled qubits in the dispersive regime , where the cavity mode is far off resonance with all transitions taking place in the coupled - qubit system . we focus on the case of identical and of non - identical qubits with finite direct coupling . for identical qubits we derive the fidelity for a cavity - mediated two - qubit gate in the presence of the direct qubit interaction . in sec . [ sec : disp - control ] , we discuss the control of the direct qubit interaction via the ac stark shift for qubits with @xmath18 . in sec . [ sec : microscopic ] , we discuss possible experimental implementations of eq . ( [ eq : gen - ham ] ) in physical systems and derive explicit expressions for the energy scales in eq . ( [ eq : gen - ham ] ) for quantum dots , quantum shells , and superconducting qubits in a cavity . we conclude in sec . [ sec : conclusion ] . we consider the dispersive regime , where the cavity mode is non - resonant with all transitions of the qubit system and the coupling of cavity and qubits in eq . ( [ eq : gen - ham ] ) can be treated perturbatively . for a single qubit , the cavity resonance was shown @xcite to shift by @xmath19 , where @xmath20 is the photon detuning , depending on the state of the qubit . measurement of the cavity resonance hence provides a readout mechanism for the qubit which has been demonstrated for cooper pair boxes at the charge degeneracy point . @xcite for two qubits which are not directly coupled to each other [ @xmath17 in eq . ( [ eq : gen - ham ] ) ] , but both of which are coupled to the cavity mode with @xmath21 , the cavity - qubit coupling can be integrated out to leading order by a schrieffer - wolff transformation @xmath22 . the resulting effective hamiltonian is @xcite @xmath23 with @xmath24 . equation ( [ eq:2qubit0 ] ) implies that ( i ) photon emission of one qubit into the cavity and subsequent absorption by the other qubit gives rise to an effective cavity - mediated inter - qubit coupling ; and ( ii ) the cavity resonance is energetically shifted relative to @xmath25 by @xmath26 , @xmath27 , @xmath28 , and @xmath29 for the two - qubit states @xmath30 , @xmath31 , @xmath32 , and @xmath33 , respectively . in particular , for @xmath34 , spin flip - flop transitions between the qubits are weak and the cavity resonance can be used for the simultaneous readout of both qubits if the cavity loss rate is sufficiently small that all four frequencies can be resolved . @xcite we now turn to the limit of identical qubits ( @xmath35 and @xmath36 ) with finite direct coupling . because @xmath37 commutes with @xmath38 , the problem can be solved exactly by numerical diagonalization of the hamiltonian in the four - dimensional subspaces with given eigenvalue @xmath39 of @xmath40 ( see below ) . first , we provide a perturbative analytical solution in the limit of weak coupling where the detuning of @xmath25 relative to all transitions of the coupled qubit system is large compared to @xmath41 . for @xmath42 , @xmath38 is diagonal in the singlet - triplet basis , @xmath43 , @xmath44 , @xmath45 , and @xmath46 with energies @xmath47 , @xmath48 , @xmath49 , and @xmath50 . we now generalize the schrieffer - wolff transformation of refs . for finite @xmath51 and @xmath52 by defining @xmath53 where @xmath54 -{\rm h.c . } \right\ } \nonumber \\ & & + \frac{g}{2\delta_+}\left\ { \hat{a}\left [ \hat{s}_1^+ ( 1 + \hat{s}_{2,z } ) + \hat{s}_2^+ ( 1 + \hat{s}_{1,z } ) \right ] -{\rm h.c . } \right\ } , \nonumber\end{aligned}\ ] ] with @xmath55 , @xmath56 , and where @xmath57 denotes the energy difference between the triplet state @xmath58 and @xmath59 . by construction , the schrieffer - wolff transformation removes the cavity coupling to leading order . expanding @xmath60 to second order in @xmath61 , we find @xmath62 , \nonumber\end{aligned}\ ] ] where @xmath63 is the photon number operator . the second line of eq . ( [ eq : gen - ham - transf ] ) is diagonal in the singlet - triplet basis and can be interpreted as ac stark shift and lamb shift of the qubit states due to the cavity mode . the third line of eq . ( [ eq : gen - ham - transf ] ) describes two - photon transitions between @xmath64 and @xmath65 . the expansion in @xmath61 leading to eq . ( [ eq : gen - ham - transf ] ) is valid as long as @xmath66 . unless @xmath67 , two - photon processes described by the last term in eq . ( [ eq : gen - ham - transf ] ) can be neglected . for a cavity mode detuning which is off - resonant with all bare transition energies , eq . ( [ eq : gen - ham - transf ] ) implies that the cavity resonance experiences a shift @xmath68 similarly to two qubits with different level spacing @xmath69 and without direct coupling , @xmath70 , see eq . ( [ eq:2qubit0 ] ) , the cavity resonance splits into four lines , depending on the state of the coupled qubits . in stark contrast to qubits without a direct interaction , however , measurement of the cavity resonance projects the qubits onto the singlet - triplet basis rather than the product basis of @xmath71 eigenstates . a resonance shift by @xmath72 , corresponding to the @xmath59 state , indicates that the coupled qubits are in a maximally entangled ( and also super - radiant@xcite ) state . in contrast , the singlet state @xmath73 ( being a sub - radiant state ) decouples from the radiation field due to symmetry reasons and does not induce a shift of the cavity resonance line . however , such a proof of entanglement would be rather indirect because it relies only on the energy levels of the system rather than quantum state tomography . in order to verify the range of validity of our results , we compare the spectrum determined from eq . ( [ eq : gen - ham - transf ] ) in the dispersive regime with exact diagonalization . in fig . [ fig1 ] , we show the exact level spectrum ( solid lines ) as a function of @xmath20 for @xmath74 , @xmath75 and ( a ) @xmath76 and ( b ) @xmath77 , respectively . the analytical results valid in the perturbative regime of large detuning from all resonances are indicated as dashed lines . as is evident from fig . [ fig1 ] , the expansion in @xmath61 breaks down if the cavity mode approaches resonance with one of the triplet transitions . on varying @xmath20 , the spectrum shows three anticrossings . two strong anticrossings with splitting @xmath78 ( @xmath79 ) for @xmath80 ( @xmath81 ) , respectively , corresponding to strong mixing of the states @xmath82 and @xmath83 ( @xmath83 and @xmath84 ) by one - photon absorption . in addition , there is a weaker anticrossing with splitting @xmath85 between @xmath82 and @xmath84 at @xmath86 due to two - photon absorption processes described by the last term in eq . ( [ eq : gen - ham - transf ] ) . in fig . [ fig2 ] , we show all relevant transitions and the exact energy eigenvalues in comparison with approximate expressions of a two - state model which are obtained from a diagonalization in a truncated basis , taking only the two nearly - degenerate states into account . in fig . [ figstark ] we illustrate the ac stark shift as described by the second line of eq . ( [ eq : gen - ham - transf ] ) as a function of the cavity photon number @xmath87 and the frequency @xmath25 . as two - photon transitions are negligible , the energy eigenvalues only depend on the average photon number @xmath87 . we note that for large photon numbers in fig . [ figstark ] , @xmath88 is reached , for which the perturbative coupling to the cavity is not rigorously satisfied . we also show the ac stark shift obtained for the optical interaction without the rotating - wave approximation ( rwa ) , which we derive in appendix [ sec : sw - general2 ] . before proceeding to the more general case of non - identical qubits coupled to a cavity , we discuss the effect of the direct qubit coupling on the proposed usage of the cavity as a quantum bus to couple the two qubits.@xcite as shown in ref . , a @xmath89 two - qubit gate can be realized for @xmath90 , when the two qubits are tuned into resonance with each other ( while maintaining off - resonant coupling with the cavity ) for the interaction time @xmath91 . however , in the presence of the direct qubit interaction , the two - qubit dynamics is determined by eq . ( [ eq : gen - ham - transf ] ) rather than eq . ( [ eq:2qubit0 ] ) , and the effective interaction via the cavity is accompanied by the direct qubit coupling . for simplicity , we focus on the case @xmath92 here , which is realized , e.g. , for capacitively coupled cooper pair boxes , see sec . [ sec : mic - cpbs ] . the total effective two - qubit coupling energy in eq . ( [ eq : gen - ham - transf ] ) is given by @xmath93 , \nonumber\end{aligned}\ ] ] where the second line is valid for @xmath94 . we quantify the fidelity of the @xmath89 gate proposed in ref . as @xmath95 , where @xmath96 is the ideal gate operator and @xmath97 is the time - evolution operator for the two qubits due to eq . ( [ eq : gen - ham - transf ] ) . using the first line of eq . ( [ eq : eff2qubitcoup ] ) , we obtain for the gate fidelity @xmath98 ^ 2 . \nonumber\end{aligned}\ ] ] here , we also give the asymptotics for @xmath99 , when the cavity - mediated interqubit coupling dominates over the direct exchange - like coupling quantified by @xmath51 . we notice that @xmath100 for @xmath101 . for example , for a coupling @xmath102 ( @xmath103 ) and the parameters@xcite @xmath104 , @xmath105 , we obtain @xmath106 @xmath107 $ ] for a photon number @xmath108 , indicating that a residual direct inter - qubit coupling may lead to gate errors in cavity - mediated two - qubit gates . however , this error may be significantly reduced by adjusting @xmath109 , as discussed in the following . in order to reduce the fidelity loss discussed above , a two - qubit gate could be implemented based on the _ total _ two - qubit coupling energy eq . ( [ eq : eff2qubitcoup ] ) , in particular for systems for which the qubit interaction via the direct coupling and via the cavity are of comparable strength . if both qubit energies are strongly detuned from @xmath25 and , additionally , @xmath110 , the direct qubit interaction is strongly suppressed along with the effective interaction via the cavity . starting in such a situation , a @xmath89 two - qubit gate could be realized with eq . ( [ eq : eff2qubitcoup ] ) by tuning the two qubits into resonance and establishing simultaneously a smaller detuning of the qubits to the cavity . for the total two - qubit interaction , we readily obtain the required interaction time for a @xmath89 gate ( up to phase factors ) along the lines of ref . as @xmath111 . if a non - zero coupling @xmath52 is introduced , the block - diagonal form of @xmath97 is preserved , and the @xmath112 subspace spanned by @xmath113 and @xmath114 contains a time - dependent phase factor @xmath115 with respect to the @xmath112 subspace spanned by @xmath116 and @xmath117 . we note that for the special case @xmath118 $ ] , with a fixed photon number @xmath87 , the total coupling of the two qubits is of the heisenberg form , enabling a @xmath119 two - qubit operation rather than @xmath89 . here , we provide the schrieffer - wolff transformation for the general case of arbitrary system parameters @xmath120 , @xmath121 , @xmath122 , and @xmath123 in the hamiltonian eq . ( [ eq : gen - ham ] ) . for vanishing qubit - cavity coupling , @xmath124 , the eigenstates of the coupled qubit system are @xmath125 with eigenenergies @xmath126 respectively , where @xmath127 . in contrast to the symmetric case discussed in sec . [ sec : dispersive ] , where the singlet state decouples completely from the cavity field and only two transitions are allowed by selection rules , there are four allowed transitions @xmath128 and @xmath129 in the general case , see fig . [ fig4 ] . if the cavity mode is off resonance with all four transitions , i.e. , @xmath130 with @xmath87 the characteristic photon number in the cavity , the cavity mode can be treated perturbatively . in the eigenbasis eq . ( [ eq : gen - es ] ) , the hamiltonian eq . ( [ eq : gen - ham ] ) reads @xmath131 to first order in @xmath132 , the hamiltonian is diagonalized by the schrieffer - wolff transformation @xmath133 with @xmath134 the coefficients @xmath135 are defined by @xmath136 by assumption , @xmath137 because of the off - resonance condition . the expression for @xmath60 can then be truncated , neglecting terms of third and higher order in @xmath135 . up to second order in the coupling coefficients @xmath132 , we obtain @xmath138 here , @xmath139 is the unperturbed hamiltonian for vanishing cavity coupling . @xmath140 |\psi_s\rangle \langle \psi_s| \nonumber \\ & & + \hbar \left [ \hat{a}^\dagger \hat{a } \left(\tilde{\gamma}_2 \gamma_2 - \tilde{\gamma}_4 \gamma_4 \right ) + \tilde{\gamma}_2 \gamma_2 \right ] |\psi_a\rangle \langle \psi_a| \nonumber\end{aligned}\ ] ] denotes the stark and lamb shift of the four basis states . @xmath141 describes two - photon transitions between @xmath64 and @xmath65 . @xmath142 is a term which gives rise to _ transitions _ between the basis states @xmath143 and @xmath144 . its physical meaning will be explained in more detail in appendix [ sec : asym ] . we note that for @xmath145 the effective interaction of @xmath113 and @xmath114 via the cavity is given by @xmath146 . on a technical level , @xmath147 and @xmath146 correspond to virtual processes corresponding to the emission and re - absorption of a photon . the cavity line shift induced by @xmath147 for the coupled - qubit eigenstates is given by @xmath148 where the coupling coefficients @xmath132 are given by eqs . ( [ eq : gen - coupling - const ] ) and ( [ eq : gen - coupling - const2 ] ) , and the effective detunings @xmath149 are defined by eq . ( [ eq : swtrafo5 ] ) . however , above states are only eigenstates of the qubits coupled to the cavity when @xmath150 can be neglected . for @xmath151 , the mixing energy of @xmath143 and @xmath144 due to @xmath146 is approximately given by @xmath152/2 \tilde \delta$ ] . it is typically small due to the perturbative coupling condition and vanishes for coupled identical qubits ( @xmath153 and @xmath15 ) . similarly , in the limit @xmath154 , the mixing energy of @xmath155 and @xmath156 due to @xmath157 is proportional to @xmath158 and is therefore negligible . the above analysis has been focussed onto coherent quantum dynamics . in real systems , however , the rate @xmath159 for spontaneous photon emission and the decay rate @xmath160 of the cavity field lead to spectral line broadening . for the jaynes - cummings model in the dispersive regime , the decay rates of the two dressed states of lowest energy ( i.e. , in the subspace of one energy quantum ) are already given in ref . . similar to the readout of two qubits with no direct interaction,@xcite we expect that the line shifts for directly coupled qubits can be well resolved if they are larger than @xmath161 . a more detailed treatment of dissipation is beyond the scope of the present work . as a second application of two qubits interacting with a cavity , in addition to the readout discussed above , we show that the qubits can be tuned into and out of resonance by controlling the photon number in the cavity mode if the qubit - cavity couplings are not identical . here , we focus on the case of identical qubit level spacing , @xmath162 with strongly asymmetric cavity couplings , @xmath163 , @xmath164 . as shown in appendix [ sec : asym ] , the stark and lamb shift and mixing hamiltonian , @xmath165 , then induce a relative energy shift of the states @xmath166 and @xmath167 which can be used to control the level admixing induced by the direct coupling @xmath51 . for illustration , we focus on a cavity mode close to resonance with the transitions from @xmath155 to @xmath168 , @xmath169 , but still in the dispersive regime , @xmath170| \ll 1 $ ] . then , the ac stark shift due to qubit @xmath171 is given by @xmath172.\label{eq : starkasym}\end{aligned}\ ] ] if the number of photons in the cavity is @xmath87 such that @xmath173 the two qubits are effectively decoupled due to the ac stark shift , since level mixing due to @xmath51 is strongly suppressed . extracting the cavity photons on a time scale short compared to @xmath174 and maintaining the empty cavity state for a predetermined time ensures that , in the absence of an ac stark shift , the direct interqubit coupling @xmath51 induces quantum coherent oscillations between @xmath175 and @xmath114 . by reinserting a number of photons satisfying eq . ( [ eq : decouple ] ) faster than the time @xmath176 into the cavity , the two qubits can be decoupled again . based on the latter inequality we define a minimum photon number for optical switching of the direct coupling , @xmath177 . however , in order for the analysis leading to eq . ( [ eq : starkasym ] ) to remain valid , the perturbative coupling condition @xmath178 must be satisfied . from this follows @xmath179 and , using the definition of @xmath180 , @xmath181 . obviously , decoupling of the two qubits requires a larger photon number @xmath182 in the case when _ both _ coupling constants are non - zero ( but still satisfy @xmath183 ) . in section [ sec : microscopic ] we study three example systems for the coupled qubits : excitons in quantum dots , excitons in quantum shells , and capacitively coupled cooper - pair boxes . for those systems , we calculate the parameters @xmath51 and @xmath52 for typical coupling mechanisms . based on these estimates , we present in table [ tab : switchparam ] estimates for the switching time @xmath176 and the minimum photon number @xmath180 required to switch the direct coupling for the energy scales of @xmath184 obtained in section [ sec : microscopic ] . in table [ tab : switchparam ] , we consider detunings satisfying @xmath185 within the given range of @xmath16 , respectively . for the maximum values of @xmath16 , these detunings and @xmath180 do not strictly satisfy the condition for perturbative coupling to the cavity and thus provide a lower bound for @xmath180 . while the addition of photons to the cavity mode can be realized via external irradiation , a fast extraction requires a cavity design enabling a quick reduction of the q - factor . for optical microcavities containing bragg mirrors , this could be achieved , e.g. , via optical switching of the reflectivity.@xcite such a scheme would facilitate an all - optical control of the interaction of two qubits with possible applications as an optically controlled two - qubit gate . however , a high degree of control on the parameters of a high - q cavity is required to perform such a gate operation via a cavity mode . in particular , the quick reduction of the q - factor still needs to be demonstrated experimentally . as an interesting alternative , an ac stark shift for exciton qubits in quantum dots or shells can also be induced by a laser instead of a cavity . the switching `` on '' and `` off '' of the direct qubit coupling might then be accomplished with ultrafast optical techniques . as a recent first step into this direction , the laser - induced ac stark effect has been demonstrated experimentally for single gaas quantum dots.@xcite .switching time @xmath174 and lower bound ( see text ) for the minimum photon number @xmath186 to decouple two qubits with @xmath187 and @xmath188 via the ac stark shift in a cavity . the considered types of qubits are excitons in coupled quantum dots ( qd ) , excitons in quantum shells ( qs ) , and capacitively coupled cooper pair boxes ( cpb ) with estimates for @xmath51 and @xmath52 from sec . [ sec : microscopic ] . the estimates for @xmath189 are based on refs . .[tab : switchparam ] [ cols="<,^,^,^",options="header " , ] complementary to the decoupling of two identical qubits with asymmetric coupling to a cavity ( or laser ) mode , the ac stark shift could be exploited to bring two non - identical qubits into resonance , as already suggested by nazir _ et al . _ @xcite for excitons in quantum dots coupled to a laser . the control of the direct interaction @xmath51 could then be achieved via the shaping of microwave or laser pulses , for superconducting or exciton qubits , respectively . we note that in our work the exact schrieffer - wolff transformation is provided for the coupled system with and without the rwa for the optical interaction , while nazir _ _ provided a numerical solution within the rwa . the coupling constants @xmath122 and @xmath123 of the qubits to the cavity may be intrinsically different due to fluctuations in the composition , size , and geometry of the structure containing the qubit , which may randomly occur or might be induced on purpose in the fabrication process . in principle , asymmetric coupling of the two qubits to the cavity could also be achieved due to the different qubit locations with respect to the cavity field . still , the distance between coupled quantum dots or superconducting islands is typically much smaller than the cavity - photon wavelength , which complicates this approach . a strongly asymmetric cavity coupling could also be achieved via the misalignment of the electric dipole moment @xmath190 of one qubit relative to the electric field in the cavity , e.g. , for cooper - pair boxes in a line resonator . ideally , ( say ) @xmath191 is oriented perpendicular and @xmath192 is oriented parallel to the cavity field , such that the coupling of electric dipole transitions to the cavity is strongly asymmetric . we next derive explicit expressions for the characteristic energy scales in eq . ( [ eq : gen - ham ] ) for qubits defined in terms of exciton states of a given spin in quantum dots or quantum shells and for superconducting qubits at the charge degeneracy point . while most quantum computing schemes for quantum dots rely on the electron spin as qubit , @xcite we focus on charge - based qubits defined by the presence or absence of an exciton ( see , e.g. , ref . ) , because such states couple to the cavity mode by photon emission and absorption . here , we rely on the fact that the exciton spin relaxation time is typically much longer than the exciton lifetime in quantum dots at low temperatures and low magnetic fields . @xcite optical selection rules then ensure the coupling of the polarized excitons to a cavity mode with a suitable polarization , see , e.g. , ref . for typical optical transition matrix elements for quantum dots . the integration of quantum dots into high - q cavities is still a considerable challenge , but has been demonstrated for self - assembled quantum dots @xcite and also appears to be feasible by deposition of chemically synthesized nanocrystals onto defect modes of photonic crystals . @xcite for definiteness , we focus on the latter system in the following . the analysis can be easily extended to electron spin qubits in quantum dots , for which the electron exchange interaction leads to an effective coupling of the heisenberg form [ i.e. , @xmath193 in eq . ( [ eq : gen - ham ] ) ] , provided that the single - dot charging energy is larger than the tunnel matrix element , which has already been studied in detail in refs . . for electron spins , a static magnetic field gives rise to zeeman splittings @xmath1 , typically on the order of tens of @xmath194ev for fields on the order of 1 tesla , and the two spins couple , e.g. , via magnetic dipole transitions to a microwave cavity . alternatively , cavity - mediated spin interactions are implemented by two - photon raman transitions via trion states . @xcite we note that the spatial separation of coupled dots is typically too small to enable the application of individual laser fields to the two dots . still , effective spin interactions could be mediated via the cavity if the electrons in the two different dots have different zeeman splittings , e.g. , due to magnetic dopants@xcite ( giving different gyromagnetic factors ) , magnetic field gradients , or inhomogeneous hyperfine polarizations , since then two laser fields with different frequencies could be applied to the two dots simultaneously to establish the raman transition conditions . for the special case of identical dots , these conditions can be satisfied for both dots even by the same laser field . the confinement of electrons in nanocrystal quantum dots gives rise to well - defined quantum size levels with a spacing which is typically of order @xmath195 for the conduction band . we first consider pairs of nanocrystals interacting with a @xmath196 circularly polarized cavity mode [ fig . [ fig3](a ) ] , assuming that the symmetry axis of both nanocrystals is aligned with the propagation direction of the cavity photon . for definiteness , we will focus on materials with valence band states described by the spherical luttinger hamiltonian , which is a good approximation for , e.g. , cdse . the cavity mode is assumed to be sufficiently close to the absorption edge that only the lowest exciton transition from the @xmath197 valence band multiplet to the conduction band ground state @xmath198 must be taken into account . crystal or shape anisotropy are assumed to split the light - hole ( lh ) and heavy - hole ( hh ) states at the @xmath199 point and only transitions involving hh states are considered . the ground state of the nanocrystal , i.e. , the exciton vacuum , is denoted as @xmath200 , while the one - exciton state is denoted as @xmath201 . the transverse coupling term in eq . ( [ eq : gen - ham ] ) corresponds to coherent exciton transfer between the nanocrystals . possible microscopic mechanisms are direct transfer of electron and hole , e.g. , via a coupling molecule @xcite or resonant frster transfer . @xcite in order for eq . ( [ eq : gen - ham ] ) to capture the essential features of molecularly coupled nanocrystals , indirect exciton states must be negligible . for pairs of identical nanocrystals this implies that the transfer matrix elements for both the conduction and valence band , @xmath202 and @xmath203 , respectively , must be small compared to the exciton binding energy @xmath204 , with the nanocrystal radius @xmath205 . data for cdse nanocrystals coupled by benzene rings @xcite are consistent with @xmath206 while @xmath207 for @xmath208 . because @xmath202 and @xmath22 are of the same order of magnitude , the transfer matrix element for an exciton , @xmath209 , is determined by @xmath203 . while @xmath203 is expected to be smaller than @xmath202 because of the larger hole mass , atomistic calculations for molecularly coupled nanocrystals have shown that electron and hole transmission probabilities are comparable.@xcite the exciton transfer energy @xmath9 can thus presumably reach values of order @xmath210 . alternative mechanisms for exciton transfer are frster processes which result from the electrostatic dipole interaction hamiltonian @xcite @xmath211 , \label{eq : el - dip}\ ] ] where @xmath212 denotes the relative position of the nanocrystals and @xmath213 are the dipole transition matrix elements between the exciton vacuum and the one - exciton states in nanocrystals @xmath171 and @xmath214 , respectively . because the symmetry axes of both nanocrystals are aligned by assumption [ fig . [ fig3](a ) ] , the frster transfer in eq . ( [ eq : el - dip ] ) conserves the exciton spin . @xcite the dipole matrix element connecting the @xmath215 state of the @xmath197 valence band multiplet with the @xmath216 conduction band ground state is @xmath217 @xmath218 denotes the interband matrix element . the orbital overlap of the envelope wave functions of @xmath198 and the @xmath219 component of the @xmath197 multiplet , @xmath220 is typically of order unity . for cdse nanocrystals with a high - bandgap capping layer , @xmath221 . @xcite inserting eq . ( [ eq : dipole ] ) into eq . ( [ eq : el - dip ] ) , we find for the frster transfer energy @xmath222 for cdse , @xmath223 , such that @xmath224)^3 $ ] is of order @xmath225 for @xmath226 and @xmath227 . the longitudinal coupling term @xmath228 in eq . ( [ eq : gen - ham ] ) represents the biexciton shift . dominant contributions are the electrostatic quadrupolar interaction and van - der - waals interactions which correspond to simultaneous virtual transitions between the @xmath197 and @xmath229 valence band multiplets in both dots . the electrostatic interaction results from the charge density of the @xmath197 valence band state , @xcite @xmath230 @xmath231 are the radial wave functions for an orbital angular momentum @xmath232 of the envelope wave function . @xcite the electrostatic quadrupole moment for a spherical quantum dot with radius @xmath205 and a high - bandgap cap is @xmath233 for vanishing boundary conditions . for a spherical cdse nanocrystal with radius @xmath205 , @xmath234 . the biexciton shift resulting from quadrupolar electrostatic interactions @xcite is for @xmath235 given by @xmath236)^2}{(r[{\rm nm}])^5}. \label{eq : quadrup2}\ ] ] because the radial integral in eq . ( [ eq : quadrup1 ] ) is typically small , the electrostatic contribution to the biexciton shift is smaller than @xmath237 for characteristic parameters . for cdse nanocrystals , @xmath238 ( @xmath239 ) , and @xmath240 , @xmath241 ( @xmath242 ) . however , eq . ( [ eq : quadrup2 ] ) is no longer rigorously applicable in this parameter range and may only provide an estimate for the characteristic energy scale . for these or comparable parameters , the dominant contribution to the biexciton shift is caused by inter - dot van - der - waals interactions . because the level spacing for valence band states is small compared to the conduction band , the dominant contribution involves simultaneous transitions between the @xmath197 and @xmath229 valence band states in both quantum dots . in second order perturbation theory in the hole - hole coulomb interaction , @xmath243 the matrix element is finite only for @xmath244 , i.e. , for processes which describe simultaneous transitions from @xmath245 to @xmath246 in both dots . @xmath247 denotes the energy difference between the corresponding hole levels in quantum dot @xmath171 and @xmath214 , respectively . for a pair of identical dots , @xmath248 depends on the specific material parameters , but is typically of order @xmath249 . for cdse , @xmath250 , while @xmath251)^2 $ ] . for @xmath252 ( @xmath253 ) and @xmath226 , the van - der - waals contribution to the biexciton shift is @xmath254 ( @xmath255 ) , larger than the electrostatic contribution derived above . we conclude that for nanocrystals with radius of order @xmath256 and a distance of order @xmath257 , the energy scale for frster transfer , @xmath258 , is large compared to the inter - dot biexciton shift which is typically of order @xmath259 . similarly to quantum dots , quantum - dot quantum wells or quantum shells @xcite provide quantum confinement for electrons and holes which allows one to define a qubit by the presence or absence of an exciton with a given polarization . while experimental studies have so far focussed on individual shells , with a low - bandgap material sandwiched between a high - bandgap core and cap , synthesis of nested shells is possible . such a system is expected to exhibit properties similar to a pair of quantum dots [ figs . [ fig3](b),(c ) ] . here , we derive the characteristic energy scales for exciton transfer between shells ( @xmath260 ) and the biexciton shift ( @xmath261 ) . all energy scales typically depend on the inner and outer radius of a shell , the potential barrier , and the band masses inside the shell and the barrier . for definiteness , we consider shells with width @xmath262 small compared to their inner radius @xmath263 , where @xmath2 , in the limit of high potential barriers where both conduction and valence band states are well confined inside the shells . then , the wave functions of the lowest conduction band state is @xmath264}{r } y_{00}(\hat{\bf r } ) , \label{eq : shell - cbgs}\ ] ] while the wave function of the @xmath197 valence band states with total angular momentum quantum numbers @xmath265 and @xmath266 is @xmath267}{r } \label{eq : shell - vbgs } \\ & & \hspace*{0.5 cm } \times \left(|l=0;j=3/2;f=3/2;f_z\rangle \right . \nonumber \\ & & \hspace*{1cm}\left . + |l=2;j=3/2;f=3/2;f_z\rangle \right ) . \nonumber\end{aligned}\ ] ] the energy splitting to the @xmath229 multiplet is @xmath268 , where @xmath269 is the free electron mass and @xmath270 and @xmath271 denote the luttinger parameters of the shell material . dominant mechanisms of exciton transfer between the shells are electron and hole tunneling or frster transfer . for a finite potential barrier @xmath272 of width @xmath273 , the tunneling matrix elements for electrons ( @xmath274 ) and holes ( @xmath275 ) are exponentially suppressed with a factor @xmath276 . for realistic structures , such as cdse / zns / cdse nanocrystal heterostructures , the electron tunneling matrix element can be of order @xmath277.@xcite in order to calculate the matrix element for the frster process , we invoke the identity @xmath278 where @xmath279 , i.e. , the index @xmath171 denotes the inner shell . similarly to quantum dots , frster transfer for nested quantum shells conserves the exciton spin . in order to estimate the characteristic energy scale of the frster matrix element , we calculate the transition matrix element for the dominant @xmath280 term in eq . ( [ eq : coul1 ] ) and approximate the hole state by its @xmath219 envelope function component . then , @xmath281 \ , \label{eq : coul2}\\ & & \hspace*{1 cm } \times \int_{a_2}^{a_2+w_2 } dr \frac{\sin^2 [ \pi ( r - a_2)/w_2]}{r^3 } \nonumber \\ & & \simeq \frac{2 |\langle s|x|x\rangle|^2}{9 a_2 ^ 3}. \nonumber\end{aligned}\ ] ] the approximation in the last line in eq . ( [ eq : coul2 ] ) is valid in the limit of narrow shells considered here . @xmath218 denotes the kane interband matrix element . assuming that the dielectric constant of shells and potential barriers are comparable , eq . ( [ eq : coul2 ] ) implies @xmath282 which only depends on the radius of the outer shell but is independent of the size of the inner shell . for cdse , @xmath283 and @xmath223 , such that @xmath284)^3 $ ] . for small nanocrystals , where , e.g. , @xmath285 , the frster matrix element is of order @xmath286 . similarly to quantum dots , the dominant contributions to the biexciton shift for quantum shells are the electrostatic quadrupolar interaction caused by the non - spherical charge density of the holes and van - der - waals interactions . with the expansion eq . ( [ eq : coul1 ] ) , after integration over the angular variables , we obtain for the electrostatic quadrupolar hole interaction @xmath287 where , in the last line , the radial integrals have been evaluated for the limit of narrow shells considered here , eq . ( [ eq : shell - vbgs ] ) , and it is understood that the hole functions @xmath231 in eq . ( [ eq : shell - biexc ] ) denote the corresponding components of the hole wave functions in shells 1 and 2 , respectively . for @xmath288 , @xmath289 , and @xmath283 , @xmath290 . the van - der - waals interaction caused by simultaneous transitions between @xmath197 and @xmath229 hole multiplets in both shells can be calculated similarly to eq . ( [ eq : vw1 ] ) in second order perturbation theory in the hole - hole coulomb interaction . in terms of the radial wave functions for the @xmath197 and @xmath229 valence band multiplets , @xmath291 ^ 2 \nonumber \\ & & \times \left[\int_{a_2}^{a_2+w_2 } \!\!\!\!\!\!\!\!\!\!\!\ ! dr_2 \left(\frac{r_0 r_1}{2 } + \frac{2 r_2 r_1}{5 } + \frac{3 r_2 r_3}{10 } \right)\right]^2 \nonumber \\ & \simeq & \left(\frac{e^2}{4\pi \epsilon_0 \epsilon } \ , \frac{36 a_1}{125 a_2 ^ 2}\right)^2 \frac{1}{\delta e_1 + \delta e_2}. \nonumber\end{aligned}\ ] ] the last line is valid in the limit of narrow shells , where , again , it is understood that the hole wave functions denote the wave functions for the respective shells . for @xmath292 , @xmath293 , the characteristic hole level spacing is of order @xmath210 . for @xmath283 , the characteristic energy scale for @xmath294 is @xmath295 , significantly larger than the electrostatic quadrupolar energy derived above . extending the model of ref . , we assume that two small superconducting islands in the charge regime ( so - called cooper - pair boxes ) are located at the center of a resonator and are separated by a distance @xmath296 , see fig . [ fig3 ] ( d ) . in the charge basis , the total capacitive coupling of the two singly charged cooper - pair boxes is given by a @xmath297-@xmath297 coupling term with energy@xcite @xmath298 here , @xmath299 is the capacitance that couples the two islands and @xmath300 is the total capacitance of the single superconducting island @xmath2 , where @xmath301 ( @xmath302 ) is the capacitance of the island and the corresponding josephson junction ( the resonator ) . @xcite from the recent experiments using a single cooper - pair box in a resonator @xcite we infer @xmath303 . we give a rough estimate for @xmath299 in the following and approximate the cooper pair boxes as two rectangular plates of length @xmath304 and width @xmath273 . the electric field along the perpendicular bisector of a wire of length @xmath304 with charge density @xmath305 is calculated as @xmath306 , where @xmath307 is the distance from the wire . integrating over the width @xmath273 we obtain @xmath308\end{aligned}\ ] ] for the central electric field at a distance @xmath307 from the border of the plate [ see fig . [ fig3 ] ( d ) ] , where @xmath309 is the charge on the island . we obtain for the capacity of the two islands @xmath310^{-1 } \nonumber\\ & = & \frac{2 \pi \varepsilon \varepsilon_0 w}{k\left(\frac{2r}{l}\right)+k\left(\frac{2w}{l}\right)- k\left(\frac{2(w+r)}{l}\right)},\end{aligned}\ ] ] where we use @xmath311 . for @xmath312 , @xmath313 , and @xmath314 , we thus obtain @xmath315 , where @xmath316 should be understood as the average dielectric constant defined for the space between the cooper pair boxes . for @xmath317 , @xmath318 . using the qubit eigenstates at the charge degeneracy point , @xmath319 , @xmath200 , the capacitive interqubit coupling translates into @xmath320 with @xmath321 [ eq . ( [ eq : capacitive - energy ] ) ] . this interaction mixes the states @xmath116 and @xmath117 with the mixing angle @xmath322)$ ] . since the single - qubit splittings @xmath323 are given by the josephson energy ( @xmath324 in ref . ) , @xmath325 and the interqubit coupling may be approximated by @xmath326 . therefore , capacitively coupled qubits interacting with a cavity may be mapped onto eq . ( [ eq : gen - ham ] ) , wherein @xmath327 and @xmath92 . for @xmath328 and characteristic parameters for cooper pair boxes in a resonator,@xcite we obtain for the coupling energy @xmath329 . we have studied two directly coupled qubits which interact perturbatively with a single off - resonant cavity mode . based on the hamiltonian eq . ( [ eq : gen - ham ] ) we have provided a diagonalization by means of a schrieffer - wolff transformation for various cases in order to obtain an effective hamiltonian describing the perturbative interaction of the cavity with the two - qubit system . for identical qubits , the effective hamiltonian is given by eq . ( [ eq : gen - ham - transf ] ) , while for the more general case of non - identical qubits the effective hamiltonian is given by eqs . ( [ eq : gen - ham - transf2 ] ) ( [ eq : gen - ham - transf2c ] ) . beyond the rwa for the optical interaction , the effective hamiltonian for non - identical qubits has been obtained as eqs . ( [ eq : gen - ham - transf3 ] ) ( [ eq : gen - ham - transf3c ] ) . based on these results , we have shown that the state of the coupled qubits can be read out from the photon dispersion , the coupled qubit state being projected onto a singlet - triplet basis . further , we have investigated the effect of the direct qubit interaction on a cavity - mediated @xmath89 gate and have shown that a two - qubit gate can also be realized with the total qubit - qubit interaction for a finite residual direct inter - qubit coupling which might be present for , e.g. , cooper - pair boxes in a resonator . for asymmetric coupling of the qubits to the cavity , we have discussed the control of the direct qubit interaction via the ac stark effect . finally , we have derived explicit expressions for the energy scales of the hamiltonian for three different qubit systems , namely quantum dots , quantum shells , and cooper - pair boxes , and we have calculated the microscopic coupling constants @xmath51 and @xmath52 of the direct qubit interaction . we thank r. hanson and w. h. lau for discussions and acknowledge support from darpa spins , darpa quist , cnid , aro , onr , nccr nanoscience , and the swiss nsf . in order to clarify the physical processes that correspond to @xmath146 in eq . ( [ eq : gen - ham - transf2c ] ) , we consider the case of two qubits with identical level spacing , @xmath35 , but with strongly asymmetric qubit - cavity mode coupling , @xmath163 , @xmath330 . as will be discussed in more detail below , @xmath146 then describes the @xmath331 between the direct coupling and the cavity - induced stark and lamb shift . for strongly asymmetric coupling , only qubit @xmath171 will experience a stark and lamb shift and hence will be shifted out of resonance with qubit @xmath214 . in particular , if the stark shift of qubit @xmath171 is large compared to @xmath16 , the qubits will become effectively decoupled . in order to quantify our argument , we evaluate the terms proportional to @xmath332 in eqs . ( [ eq : gen - ham - transf2a ] ) and ( [ eq : gen - ham - transf2c ] ) in the limit of weak direct inter - qubit coupling , @xmath333 . then the denominators in the expressions for @xmath135 [ eq . ( [ eq : swtrafo5 ] ) ] can be replaced by @xmath334 and by @xmath335 . then , @xmath336 which represents the stark and lamb shift of qubit @xmath171 . in particular , the last two terms in eq . ( [ eq : asym - exp1 ] ) represent the relative energy shift of @xmath337 and @xmath338 induced by the cavity . as discussed in sec . [ sec : disp - control ] , this energy shift can be utilized to tune the qubits into and out of resonance by controlling the photon number in the cavity mode . for the coupling of the two - qubit system to the cavity via linearly polarized transitions , the full hamiltonian reads in general @xmath339 \label{eq : gen - ham - full } \\ & & + \hbar \omega \hat{a}^\dagger \hat{a } + \frac{\hbar j_\perp}{2 } \left ( \hat{s}_1^+ \hat{s}_2 ^ - + \hat{s}_1 ^ - \hat{s}_2^+ \right ) + \hbar j_z \hat{s}_{1,z } \hat{s}_{2,z}. \nonumber\end{aligned}\ ] ] the energy non - conserving terms are usually neglected because of their smallness , leading to the hamiltonian eq . ( [ eq : gen - ham ] ) . in this appendix we analyze the additional contribution of the energy non - conserving terms to the coupled - qubit dynamics . as shown in section [ sec : sw - general ] , the eigenstates of the coupled qubits are given by eq . ( [ eq : gen - es ] ) for vanishing qubit - cavity coupling . in this basis , @xmath340 \label{eq : gen - ham2full},\end{aligned}\ ] ] with the coupling constants @xmath132 given by eqs . ( [ eq : gen - coupling - const ] ) and ( [ eq : gen - coupling - const2 ] ) . to first order in @xmath132 , the hamiltonian @xmath341 is diagonalized by the schrieffer - wolff transformation @xmath342 where @xmath343 is defined by eq . ( [ eq : swtrafo4 ] ) and @xmath344 with the coefficients @xmath345 clearly , @xmath346 for all @xmath4 and @xmath347 . yet , @xmath348 for @xmath349 , and @xmath350 for @xmath351 , where @xmath352 and @xmath353 . - \gamma_4 ( \tilde{\gamma}_4 + \tilde{\gamma}_4^+ ) \right ] |\psi_a \rangle \langle \psi_a|\right . \nonumber \\ & & \left.+ \left[\gamma_3(\tilde{\gamma}_3 + \tilde{\gamma}_3^+ ) + \gamma_4 ( \tilde{\gamma}_4 + \tilde{\gamma}_4^+ ) \right ] |t_+ \rangle \langle t_+|-\left[\gamma_1 ( \tilde{\gamma}_1 + \tilde{\gamma}_1^+ ) + \gamma_2 ( \tilde{\gamma}_2 + \tilde{\gamma}_2^+ ) \right ] |t_- \rangle \langle t_-| \right\}\nonumber\\ & & + \hbar\left[\gamma_3\tilde{\gamma}_3 |\psi_s \rangle \langle \psi_s| + \gamma_4\tilde{\gamma}_4 |\psi_a \rangle \langle \psi_a| + \left(\gamma_1\tilde{\gamma}_1 + \gamma_2\tilde{\gamma}_2\right ) in contrast to the result using the rwa , the additional terms containing @xmath357 modify the stark shift , see fig . [ figstark ] , and also the lamb shift . in fig . [ figstark ] we have assumed a photon fock state in the cavity . further , the two - photon transition term is given by @xmath360 ( \hat{a}^\dagger\hat{a } + 1 ) ( |\psi_s\rangle \langle \psi_a| + |\psi_a\rangle \langle \psi_s| ) \label{eq : gen - ham - transf3c}\\ & & + \left(\gamma_1\tilde{\gamma}_2^+ - \gamma_2\tilde{\gamma}_1^+ + \gamma_3\tilde{\gamma}_4 + \gamma_4\tilde{\gamma}_3\right ) & & + \left[\gamma_1(\tilde{\gamma}_3 + \tilde{\gamma}_3^+ ) + \gamma_2(\tilde{\gamma}_4 + \tilde{\gamma}_4^+ ) - \gamma_3 ( \tilde{\gamma}_1 + \tilde{\gamma}_1^+ ) - \gamma_4 ( \tilde{\gamma}_2 + \tilde{\gamma}_2^+ ) \right ] ( \hat{a}^\dagger\hat{a } + 1 ) ( |t_+\rangle \langle t_-| + |t_-\rangle \langle t_+| ) \nonumber\\ & & + \left(\gamma_3\tilde{\gamma}_1 + \gamma_4\tilde{\gamma}_2 - \gamma_1\tilde{\gamma}_3^+ - \gamma_2\tilde{\gamma}_4^+\right ) contains @xmath361 and new terms that couple @xmath64 and @xmath65 in addition to @xmath143 and @xmath144 . in contrast to eq . ( [ eq : gen - ham - transf2c ] ) , the above term induces mixing of @xmath64 and @xmath65 even for identical qubits .

we study a model for a pair of qubits which interact with a single off - resonant cavity mode and , in addition , exhibit a direct inter - qubit coupling . possible realizations for such a system include coupled superconducting qubits in a line resonator as well as exciton states or electron spin states of quantum dots in a cavity . the emergent dynamical phenomena are strongly dependent on the relative energy scales of the inter - qubit coupling strength , the coupling strength between qubits and cavity mode , and the cavity mode detuning . we show that the cavity mode dispersion enables a measurement of the state of the coupled - qubit system in the perturbative regime . we discuss the effect of the direct inter - qubit interaction on a cavity - mediated two - qubit gate . further , we show that for asymmetric coupling of the two qubits to the cavity , the direct inter - qubit coupling can be controlled optically via the ac stark effect .

Combination picture of new graphic cigarette packages, released by the U.S. Food and Drug Administration June 21, 2011, shows a varied collection of a man on a ventilator, diseased lungs and dead bodies were among the graphic images for revamped U.S. tobacco labels, unveiled by health officials who hope the warnings will help smokers quit. Proposed in November under a law that put the multibillion-dollar tobacco industry under the control of the U.S. Food and Drug Administration, the new labels must be on cigarette packages and in advertisements no later than September 2012. They represent the first change in cigarette warnings in 25 years. WASHINGTON (Reuters) - A U.S. judge sided with tobacco companies on Wednesday, ruling that regulations requiring large graphic health warnings on cigarette packaging and advertising violate free-speech rights under the U.S. Constitution. Cigarette makers challenged the U.S. Food and Drug Administration's rule requiring companies to label tobacco products with images of rotting teeth, diseased lungs and other images intended to illustrate the dangers of smoking. "The government has failed to carry both its burden of demonstrating a compelling interest and its burden of demonstrating that the rule is narrowly tailored to achieve a constitutionally permissible form of compelled commercial speech," U.S. District Judge Richard Leon said in the ruling. The judge granted a preliminary injunction last year blocking the new label requirement from taking effect in 2012, a decision the Obama administration has already taken to the U.S. Court of Appeals for the District of Columbia Circuit. The government is also likely to appeal the new ruling. While educating the public about the dangers of smoking "might be compelling, an interest in simply advocating that the public not purchase a legal product is not," Leon wrote in a 19-page ruling. Further, Leon noted the warning labels were too big to pass constitutional muster and that the government has numerous other tools at its disposal to deter smoking such as raising cigarette taxes or including simple factual information on the labels rather than gruesome images. Congress passed a law in 2009 ordering the FDA to adopt the label regulation, which requires color warning labels big enough to cover the top 50 percent of a cigarette pack's front and back panels, and the top 20 percent of print advertisements. The FDA released nine new warnings in June to go into effect in September 2012, the first change in U.S. cigarette warning labels in 25 years. Cigarette packs already carry text warnings from the U.S. Surgeon General. Tobacco companies, including Reynolds American Inc's R.J. Reynolds unit, Lorillard Inc, Liggett Group LLC, Commonwealth Brands Inc, which is owned by Britain's Imperial Tobacco Group Plc, and Santa Fe Natural Tobacco Co Inc challenged the rule, arguing it would force them to engage in anti-smoking advocacy against their own legal products. "Unfortunately, because Congress did not consider the First Amendment implications of this legislation, it did not concern itself with how the regulations could be narrowly tailored to avoid unintentionally compelling commercial speech," Leon wrote. A spokesman for the Justice Department, which represented the FDA in the case, had no comment. Representatives for the tobacco companies involved in the litigation were not immediately available for comment. Tobacco companies have said it would cost them millions of dollars to comply and also argued the graphics offer no information that could not be accomplished through messages similar to warnings already on cigarette packages and ads. The Centers for Disease Control and Prevention estimates some 45 million adults smoke cigarettes, which are the leading cause of preventable deaths in the United States. The ruling "ignores decades of First Amendment precedent that support the right of the government to require strong warning labels to protect the public health," Matthew Myers, president of the Campaign for Tobacco-Free Kids said in a statement. The case is R.J. Reynolds Tobacco Co et al v. FDA, U.S. District Court for the District of Columbia, No. 11-1482. (Reporting By Jeremy Pelofsky; editing by Matthew Lewis and Andre Grenon) ||||| Bloomberg News The U.S. Food and Drug Administration was blocked by a federal judge from requiring tobacco companies to put graphic health warnings on cigarette packaging. U.S. District Judge Richard Leon in Washington said the government’s rule violates the tobacco companies’ rights to free speech. “These mandatory graphic images violate the First Amendment by unconstitutionally compelling speech,” Leon wrote in today’s decision. Under direction from Congress, which wanted tobacco companies to use color graphics depicting the negative health consequences of smoking, the FDA selected nine images, including ones of a corpse and cancerous lungs. The FDA wanted to require tobacco companies beginning Sept. 22 to put one of the labels on each pack of cigarettes, pairing the images with text such as “Smoking can kill you.” The graphics were supposed to cover the top half of the front and back of cigarette packages and 20 percent of print advertisements. The FDA estimated the visual warnings would help lower the smoking rate by about 0.212 percentage points, Leon wrote in his opinion. Lorillard, Reynolds Units of Lorillard Inc. (LO) and Reynolds American Inc. (RAI), along with Commonwealth Brands Inc. and Liggett Group LLC, sued the FDA in August, claiming the mandates for cigarette packages, cartons and advertising would violate the First Amendment. The companies said in court papers that it would cost them a combined total of about $20 million to meet the 2012 deadline. “The opinion is a straightforward and clear affirmation that compelled speech by the government is not only rarely constitutional but plainly unconstitutional in this case,” Floyd Abrams, a lawyer for Lorillard, said in a phone interview. Michelle Bolek, an FDA spokeswoman, said in an e-mail that the agency doesn’t comment on litigation as a matter of policy. Christopher Hansen, president of the American Cancer Society Cancer Action Network, said the ruling “is bad for public health” and a “victory for big tobacco.” “Larger, graphic warning labels have the potential to encourage adults to quit smoking cigarettes and deter children from starting in the first place,” Hansen said in an e-mailed statement. U.S. cigarette packs and ads now carry one of four text warnings under a federal law enacted in 1984. The messages include “Cigarette Smoke Contains Carbon Monoxide” and “Smoking Causes Lung Cancer, Heart Disease, Emphysema and May Complicate Pregnancy.” They aren’t paired with images. ‘Toxic Qualities’ Representative Henry Waxman, a California Democrat, said in a statement that Congress considered First Amendment issues when it enacted the graphic warnings law in 2009. “These provisions were informed by scientific evidence showing that current warning labels have run their course and that labels with graphic warnings would be more effective in protecting the public’s health from tobacco’s addictive and toxic qualities,” Waxman said. Canada, the U.K. and Brazil are among countries that require graphic cigarette warnings. One in five Canadian smokers reported smoking less as a result of graphic labels in a 2004 study of more than 600 people. The case is R.J. Reynolds Tobacco Co. v. U.S. Food and Drug Administration, 11-cv-01482, U.S. District Court, District of Columbia (Washington). To contact the reporter on this story: Sara Forden in Washington at sforden@bloomberg.net To contact the editor responsible for this story: Michael Hytha at mhytha@bloomberg.net

– Tobacco companies can't be forced to put ultra-graphic images on cigarette packages and advertising to scare away smokers, a federal judge ruled today. The FDA requirement, which was supposed to go into effect later this year, violates the companies' free-speech rights, declared US District Judge Richard Leon in Washington, reports BusinessWeek. The feds are expected to appeal, adds Reuters. “These mandatory graphic images violate the First Amendment by unconstitutionally compelling speech,” said Leon. "While the line between the constitutionally permissible dissemination of factual information and the impermissible expropriation of a company's advertising space for government advocacy can be frustratingly blurry, here the line seems quite clear."

cerebral shunts are indicated for hydrocephalus to drain the csf into a cavity to prevent the increase in intracranial pressure . hydrocephalus could be congenital or due to a tumor , aqueductal stenosis , craniosynostosis , dandy - walker syndrome or idiopathic intracranial hypertension . a commonly used route for the shunt is the ventriculoperitoneal ( vp ) shunt , which drains csf into the peritoneal cavity . the other routes that are used are ventriculo - atrial , ventriculo - pleural , and lumbar - peritoneal . the complications that can occur with a shunt are infection , blockage , and overdrainage . there are various shunts , all of which have a unidirectional valve system in place to prevent the retrograde infection or increase in pressure . advances in surgeries of cerebral shunts and the increased life span associated with them , has made the incidence of patients with vp shunts presenting with an indication for laparoscopy higher . a few questions that arise : whether the pneumoperitoneum created during a laparoscopy procedure will cause retrograde diffusion of gases into the ventricles causing increased intracranial pressure and associated complications?whether the shunt can get infected and cause meningitis?the effect of co2 on the brain as the shunt connects two cavities?what pre - operative counseling is required for such patients ? whether the pneumoperitoneum created during a laparoscopy procedure will cause retrograde diffusion of gases into the ventricles causing increased intracranial pressure and associated complications ? whether the shunt can get infected and cause meningitis ? a 32-year lady came with complaints of bleeding p.v . following 1 months of amenorrhea and pain in the left lower abdomen since 2 days and an ultrasound examination revealed a 4.5 cm left ectopic tubal pregnancy with no intrauterine gestation and with free fluid in the pod . she was operated 10 years back for a vp shunt in view of a normal pressure hydrocephalus . she has 3 children , first two delivered vaginally and her last child birth was by cesarean section 6 years back . routine pre - operative evaluation was carried out and specifically to note whether the shunt was functional , we ruled out any neurological symptoms like headache or visual symptoms . under general anesthesia , the laparoscopic port was inserted , pelvic evaluation was carried out and a left isthmic ectopic gestation was noted with minimal blood in the pod . the vp shunt catheter was seen in the peritoneum [ figure 13 ] and 30 trendelenburg 's position was given . the average insufflation pressure was maintained below 12 mm hg with a set flow rate of 12 l / min . intraoperative vitals were monitored for pulse , bp , oxygenation , etco2 and electrocardiogram leads . there was no evidence of intraoperative bradycardia , hypertension or desatutarion . the ectopic was treated by a left salpingectomy and the surgery was uneventful . during the procedure , the operative time was 25 min from the time of skin incision to closure of the ports . post - operative , her vitals were monitored and examined for any neurological symptoms and signs such as headache , neck stiffness , and fever . with an uneventful post - operative recovery , she was discharged after 24 h. patient followed - up after a week without any neurological signs or symptoms ventriculo - peritoneal shunt there is still controversy regarding the safety of performing laparoscopic surgery in patients with vp shunt and potentially decreased cerebral compliance . in previous studies using minimal monitoring of csf shunt function limited to clinical observation , laparoscopic procedures were reported as safe and efficient in patients with csf shunts . however , animal studies have demonstrated that increased intra - abdominal pressure with gas insufflation and trendelenburg position could induce a linear increase in icp reaching 150% over control values with intra - abdominal pressures above 16 mm hg . the main advocated mechanisms for increased icp in the presence of pneumoperitoneum , were increased intra - thoracic pressure , and impaired venous drainage of the lumbar venous plexus , rather than increased arterial carbon dioxide because of systemic carbon dioxide diffusion . jackman et al . observed 19 laparoscopic surgeries in patients with vp shunts with a mean insufflation pressure of 16 mm hg and an average operative time of 3 h. they did not find clinically significant increased intracranial pressure in patients . routine anesthetic monitoring should remain the standard of care in the absence of clear evidence to the contrary . fraser et al . found no episodes of air embolism one shunt infection in a study conducted over 51 laparoscopy procedures in patients with vp shunts . neale et al . studied an in vitro model with nine shunts subjected to increased back pressure and none of the valves showed any signs of leak associated with the increased back pressure . the risk of retrograde failure of the valve system has been shown to be minimal even with intra - abdominal pressures as high as 80 mm hg . the presence of a vp shunt does not appear to have any significant risk in patients undergoing laparoscopic procedures . the risk of retrograde failure of the valve , air embolism , and infection is minimal . the insufflation pressure must be the minimum required and at all - time less than 16 mm hg . the operative time allowed for such patients would require further evaluation , but around 3 h has proven to be safe .

there has been an increasing trend in laparoscopic surgeries . there is also a higher incidence of patients with ventriculoperitoneal ( vp ) shunts due to the advances in the techniques of cerebral shunts . surgeons may come across patients of vp shunts presenting with an indication for laparoscopic surgery . although there is no absolute contraindication for laparoscopy in vp shunts , there is always a risk of raised intracranial pressure . we describe a case of vp shunt presenting with an ectopic pregnancy and undergoing laparoscopic salpingectomy . patient withstood the procedure well and had an uneventful recovery . reviewing the literature , we found that laparoscopy is safe in vp shunts . however , there should always be accompanied by good monitoring facilities .

the anomaly phenomenon is , as well as the renormalization , one of important aspects of the quantum field theories . it is a local quantum effect originating from regularization of the continuous space - time . we may say it is the problem of how to define the space - time as the continuum . generally the symmetry , imposed at the classical level , does not hold at the quantum level due to the anomaly . as for the chiral anomaly , which is the anomaly concerned with the @xmath1-symmetry(chiral symmetry ) , the general form is well - established in arbitrary even dimensions @xcite . it is fixed , except for an overall coefficient , by its cohomology structure and is given in a beautiful form in terms of the differential form : @xmath2 . the topological nature due to the @xmath1-projection is the origin of its simplicity . on the other hand , as for the weyl anomaly , the general form in higher dimensions is not so simple . this is the anomaly concerned with local scale transformations . cohomology analysis restricts the weyl anomaly to some extent , but there generally remains numerous candidate terms in higher dimensions@xcite . the undetermined coefficients of those terms must be fixed in some way . the situation originates from the `` rich '' structure of the functional space on which the scale transformation acts . in the development of the string theory or m - theory , it becomes more and more necessary to investigate the weyl anomaly in higher dimensional field theories@xcite . at this circumstance we present a new formalism for it . the weyl anomaly itself is not harmful to the construction of physical theories because we know the realistic theories have some dimensional parameters , such as the mass or the cosmological constant , and they break the weyl symmetry . however when we try to understand the origin of those massive parameters , the weyl anomaly is so important because it triggers the symmetry breaking of the conformal invariant vacuum . in this sense the weyl anomaly can be regarded as a `` softer '' anomaly than the chiral one . the latter threatens the consistency of the theory whereas the former does not . the nonrenormalization theorem is valid for the latter , whereas generally not for the former . in supersymmetric theories , however , it is also known that both anomalies make a super multiplet together with the super current@xcite . under the supersymmetric treatment both anomalies are intimately related . in this connection there has been a lot of work . because our interest here is to establish a general algorithm to treat the weyl anomaly of the higher dimensional theories , we do not consider supersymmetry here . we suppose , using the present result , we can investigate how the weyl anomaly is constrained by the supersymmetry . we analyze the weyl anomaly in the heat - kernel regularization . the content is essentially the same as , or overlaps with , topics with other names such as the effective action analysis , the background field method , the schwinger - de witt technique , seeley series , etc . they all treat some background functional which represents ( 1-loop ) quantum effects . it has a long history since schwinger@xcite , dewitt@xcite and seeley@xcite . especially the first author , in 1951 , treated quantum matter theories in external gauge fields keeping the gauge invariance of the effective action . he introduced an additional `` coordinate '' into the ordinary space(-time ) coordinates , called `` proper time '' or `` temperature '' in a natural way . it was exploited by alvarez - gaum and witten @xcite in the modern problem of the chiral anomaly of the gravitational theories . later it was generalized to the weyl anomaly by a suny group @xcite . the effective action has been analyzed in various ways . its divergent part was systematically and algorithmically analyzed by thooft@xcite in 1973 and with veltman@xcite in 1974 using dimensional regularization . as will be shown later , the weyl anomaly is obtained from the `` heat - kernel '' , which is the 1-loop effective action with the proper time as the ultraviolet regularization . the evaluation of the heat - kernel has been well - developed by many people @xcite . each of them has their own characteristic formalisms . generally they start with expressing a differential operator by some general background quantities . most of them put emphasis on the covariance in the formulae in the intermediate stages . as originally done by thooft@xcite , the `` intermediate covariance '' is powerful as far as the lower - order calculations , such as the heat - kernel on 2 and 4 dimensions , are concerned . however , at higher - order ( this means higher dimensions too ) , it hinders one from performing explicit calculations because many more `` intermediate invariants '' appear than those appearing in the final explicit answer . the important thing is not the formulae at intermediate stages , but the final explicit result . aiming at the treatment of the weyl anomaly in higher dimensions , we present a new algorithm which is based on a simple weak - field expansion . of course , we assume the invariance of the general coordinate and gauge symmetries at the final result , because it is guaranteed by the background ( effective action ) formalism @xcite . the following are new points of the present approach : 1 . we take a formalism in the regularized coordinate space , that is the space with the ordinary space(-time ) coordinates and the proper time@xcite . the feynman rules in the coordinate space are given for the anomaly ( effective action ) calculation@xcite . the ultra - violet regularization is done with the schwinger s parameter ( proper time ) . the regularization lets us properly evaluate both chiral and weyl anomalies@xcite.@xcite the feynman rules help us to investigate the weyl anomaly in higher dimensional theories . the graphical representation is taken at all stages . the familiar procedures in the ordinary perturbative treatment , such as the propagator rule and the vertex rule , are all graphically represented in coordinate space . the expanded terms themselves are also graphically represented . especially we introduce `` graphical calculation '' . this makes the higher - order calculation transparent and the weyl anomaly calculation in the higher dimensions tractable . we have not introduced any covariant quantities in intermediate stages . it is based on the weak - field perturbation . although loosing manifest general covariance in intermediate stages , the expanded elements have the simplest symmetry ( w.r.t . the suffix permutation ) and are preferable for the computer algorithm . we focus only on a special type of term : @xmath3 , in the @xmath4 dimensional space . these are the lowest order of the product of @xmath4 riemann tensors . we demonstrate they can determine the weyl anomaly up to `` trivial terms '' . in sec.2 we briefly give the present formalism of the weyl anomaly . the anomaly is given by the trace of the heat - kernel . in sec.3 we present the feynman rules to compute the heat - kernel _ to any higher order_. they are naturally expressed in the _ regularized _ coordinate space , that is , the space of n - dim ordinary space - coordinates plus the the proper time . as always in perturbative approaches , a graphical representation helps to systematically compute the heat - kernel at the higher order . the taylor expansion , with respect to the `` regularization '' parameter @xmath5 , is explained in sec.4 . the more the number of the space dimensions , the more expansion is necessary . we apply the general algorithm to the 6 dim scalar - gravity theory in sec.5 . we focus on four special graphs and introduce a new graphical calculation . the final result of the weyl anomaly for the model is obtained in sec.6 . we conclude in sec.7 . four appendices are provided to supplement the text . the propagator rules are given in app.a . some supplementary calculation , relegated by sec.5 of the text , is done in app.b . weak field expansion of the 6 dim scalar - gravity is graphically given in app.c . the table of coefficients , when some general invariants are weak - field expanded , is given in app.d . let us explain the present formulation of anomalies taking a simple example : n - dim euclidean gravity - scalar coupled system . ( see ref.@xcite ) @xmath6={\sqrt{g}}{\phi}(- { { \frac{1}{2 } } } { \nabla}^2 + { { \frac{1}{2 } } } q r){\phi}\equiv { { \frac{1}{2 } } } { { \tilde \phi}}{{\vec d}}{{\tilde \phi}}{{\quad , } } { \nonumber}\\ q=-\frac{n-2}{4(n-1)}{{\quad , } } { \quad}{{{\vec d}}}_x\equiv { \sqrt[4]{g}}(-{\nabla}_x^2-\frac{n-2}{4(n-1)}r(x)){\frac{1}{\sqrt[4]{g}}}{{\quad , } } \label{f.1}\end{aligned}\ ] ] where @xmath7 and @xmath8 are the metric field and the scalar field respectively . we have introduced @xmath9{g}}~{\phi}$ ] for the measure @xmath10 to be general coordinate ( brs ) invariant @xcite . this lagrangian is invariant under the local weyl transformation : @xmath11 where @xmath12 is the parameter of the local weyl transformation . even if the lagrangian is weyl invariant , the quantum theory is generally not ( weyl anomaly ) . the effective action @xmath13 $ ] defined by @xmath14}=\int{{\cal d}}{{\tilde \phi}}~ exp\{~-\int d^nx{{\cal l}}[g_{{\mu\nu}},{\phi}]~\}{{\quad , } } \label{f.3}\end{aligned}\ ] ] changes as @xmath15}=\int{{\cal d}}{{\tilde \phi}}'exp\{~-\int d^nx~{{\cal l}}[g_{{\mu\nu}}',{\phi}']~\}{\nonumber}\\ = \int { { \cal d}}{{\tilde \phi}}(x)~det\frac{{\partial}{{\tilde \phi}}'(y)}{{\partial}{{\tilde \phi}}(x ) } exp\{~-\int d^nx{{\cal l}}[g_{{\mu\nu}},{\phi}]~\}{{\quad .}}\label{f.4}\end{aligned}\ ] ] the weyl anomaly is given by the jacobian@xcite . @xmath16 = \exp \left ( -{{\rm tr\,}}{\alpha}(x){\delta}^n(x - y)+o({\alpha}^2 ) \right ) { { \quad .}}\label{f.4b}\end{aligned}\ ] ] taking the heat - kernel regularization , we obtain the expression for the weyl anomaly as @xmath17+o({\alpha}^2)){{\quad , } } { \nonumber}\\ \mbox{weyl anomaly } = \left.\frac{{\delta}{\gamma}}{{\delta}{\alpha}(x)}\right|_{{\alpha}=0 } = -\left.\frac{{\delta}\ln j}{{\delta}{\alpha}(x)}\right|_{{\alpha}=0 } = -2g^{{\mu\nu}}<t_{{\mu\nu}}>=\lim_{t{\rightarrow}+0}{{\rm tr\,}}g(x , y;t){{\quad , } } \label{f.5}\end{aligned}\ ] ] where @xmath18 is the heat - kernel defined by @xmath19 where @xmath20 means it operates on the left . the parameter @xmath5 is regarded here as a regularization parameter and is called schwinger s _ proper time _ @xcite . the last equation expresses the regularization of the delta function @xmath21 @xcite . @xmath18 can be symbolically written as @xmath22 we note here the physical dimension of the space coordinate @xmath23 and the proper - time @xmath5 are @xmath24=l{{\quad , } } { \quad}[t]=l^2{{\quad , } } \label{f.7}\end{aligned}\ ] ] where @xmath25 is some length . for other ( conformally invariant ) theories , the weyl anomaly is obtained by replacing the operator @xmath26 above . see ref.@xcite for detail . let us solve eq.([f.7e ] ) in weak - field perturbation theory . for a general theory with the derivative couplings up to the second order , the operator @xmath27 can be always divided into the field - independent ( free ) part and the field - dependent ( perturbation ) one . @xmath28 where @xmath29 are external fields ( background coefficient fields ) and the field suffixes ( such as a fermion suffix and a vector suffix ) @xmath30 are introduced for the general use . in the present example ( [ f.1 ] ) , the above quantities are explicitly written as ( @xmath31 ) @xmath32{g}}({\nabla}^\mu{\nabla}_{\mu}-qr){\frac{1}{\sqrt[4]{g}}}-{\delta}_{{\mu\nu}}{\partial}_{\mu}{\partial}_{\nu}{{\quad , } } { \nonumber}\\ w_{{\mu\nu}}&= & g^{{\mu\nu}}-{\delta}_{{\mu\nu}}=-h_{{\mu\nu}}+h_{{\mu}{\lambda}}h_{{\lambda}{\nu}}+o(h^3){{\quad , } } \label{f.10b}\\ n_{\lambda}&= & -g^{{\mu\nu}}{\gamma}^{\lambda}_{{\mu\nu}}-g^{{\lambda}{\mu}}{\gamma}_{{\mu\nu}}^{\nu}=-{\partial}_{\mu}h_{{\lambda}{\mu}}+o(h^2){{\quad , } } { \nonumber}\\ m & = & -qr+{\frac{1}{4 } } g^{{\mu\nu}}\{{\gamma}_{{\mu}{\lambda}}^{\lambda}{\gamma}_{{\nu}{\sigma}}^{\sigma}+2{\gamma}_{{{\mu\nu}}}^{\lambda}{\gamma}_{{\lambda}{\sigma}}^{\sigma}-2{\partial}_{\nu}{\gamma}_{{\mu}{\lambda}}^{\lambda}\}{\nonumber}\\ & = & -q({\partial}^2h-{\partial}_{\alpha}{\partial}_{\beta}h_{{\alpha\beta}})-{\frac{1}{4 } } { \partial}^2h+o(h^2){{\quad , } } { \nonumber}\end{aligned}\ ] ] where @xmath33 . the graphical representation of @xmath34 and @xmath35 above is given , up to @xmath36-order , for the n=6 dim case in app.c : fig.16 for @xmath37 and @xmath38 , fig.17 - 21 for @xmath35 . the usage of general coefficients @xmath39 and @xmath40 , instead of their concrete contents , makes it possible to do the general treatment valid for many theories @xcite . all equations below are valid for all theories so far as they have no higher - derivative interactions . let us solve the differential equation ( [ f.7e ] ) perturbatively for the case of weak external fields ( @xmath41 ) . ( in the present example , this corresponds to perturbation around _ flat _ space . ) the differential equation ( [ f.7e ] ) becomes @xmath42 in the following we suppress the field suffixes @xmath43 and take the matrix notation . this equation ( [ f.11 ] ) is the n - dim heat equation with the small perturbation @xmath44 . we give two important quantities in order to obtain the solution . ( this approach is popular in the perturbative quantum field theory under the name _ propagator approach_@xcite . in @xcite the momentum representation is taken , which is to be compared with the coordinate one of the present approach . the weyl anomaly in the string theory was analyzed in this approach by alvarez@xcite . ) i ) heat equation the heat equation : @xmath45 has the solution @xmath46 where @xmath47 is the identity matrix of the size @xmath48 . @xmath49 satisfies the initial condition : @xmath50 . we define @xmath51 ii ) heat propagator the heat equation with the delta - function source defines the heat propagator . @xmath52 @xmath53 is the _ step function _ defined by : @xmath54 . @xmath55 satisfies the initial condition : @xmath56 and @xmath57 . now the formal solution of ( [ f.11 ] ) with the initial condition ( [ f.7e ] ) is given by @xmath58 @xmath18 appears in both sides above . we can iteratively solve ( [ f.15 ] ) as@xcite @xmath59 expressions for higher - order terms are similarly obtained . as in the ordinary field theory , it is illuminating to represent this perturbative solution in graphs . we do it in the ( n+1 ) dimensional space , which is composed of the space of the ordinary n - dim ( euclidean ) space plus 1-dim positive proper time . in the above solution , @xmath60 plays the role of `` propagator '' . it is represented by a directed@xcite straight line as in fig.1 . fig.1 graph of @xmath60 @xmath61 plays the role of `` vertex '' , which acts on the system , during the process of `` propagation of particles '' , some times according to the perturbation order . the situation up to the 3-rd order is represented in fig.2 - 4 . we can easily write down the expression of any higher order , @xmath62 , with the help of this graphical representation . fig.2 graph of @xmath63 fig.3 graph of @xmath64 fig.4 graph of @xmath65 generally , in n - dim , the terms up to @xmath66 are sufficient for the anomaly calculation@xcite . in this sense , the present expansion looks like that with respect to the space(-time ) dimension . because of the presence of the positive regularization parameter @xmath5 , we can safely ( without singularity ) take the trace - part , @xmath67 , in the above equations . @xmath68 as shown in ( [ f.5 ] ) , the @xmath69-part of @xmath70 is the weyl anomaly . in order to see their @xmath5-dependence , it is best to replace the dimensional coordinate variables such as ( z , s ) in ( [ f.16 ] ) by the dimensionless ones ( w , r ) . @xmath71 where the relation ( [ a.2 ] ) is used . in the same way , we obtain @xmath72 the above quantities of @xmath73 are depicted in fig.5 - 8 with the dimensionless quantities . we can easily write down higher - order terms with the help of graphs . fig.5 graph of @xmath74 fig.6 graph of @xmath75 fig.7 graph of @xmath76 fig.8 graph of @xmath77 the vertex operator @xmath78 in the expression @xmath79 has differentials @xmath80 and acts only on the `` adjacently right '' @xmath49 in eqs.([f.17b1])-([f.17b3 ] ) . here we have the following _ vertex rule_. @xmath81 where @xmath82 does _ not _ have differentials . especially taking @xmath83 in the above and dropping primes ( @xmath84 ) , we obtain a relation . @xmath85 making use of the above rule , we can evaluate @xmath75 of eq.([f.17b1 ] ) as @xmath86 where the relation : @xmath87 , which is derived from a _ propagator rule _ 4 ( [ a.6z ] ) , is used in order to reduce the number of @xmath49 s by one . in appendix a , we list the propagator rules ( [ a.5]-[a.6z ] ) , and their graphical ( `` geometrical '' ) expressions in the coordinate space : fig.10 - 13 . @xmath76 of eq.([f.17b2 ] ) is written , in terms of @xmath82 , as @xmath88 by changing the integration variable @xmath89 to a new one @xmath90 defined below , we can make all @xmath49 s have space - variables independent of each other . using the following relations , @xmath91 which are obtained from rule 2 , ( [ a.6x ] ) , and rule 3 , ( [ a.6z ] ) , respectively , we can finally evaluate eq.([ver.5 ] ) as @xmath92 where the integration variable @xmath89 is changed to @xmath90 ( @xmath93 ) . we note the following things in the above evaluation . 1 . the number of propagators , @xmath49 s , decreases by one and becomes the same as that of the space integration variables . all `` gaussian '' coordinates in @xmath49 s ( @xmath90 and @xmath94 in the present case ) can be taken independent 3 . in the above reduction , we have applied the propagator rules on @xmath49 s from `` left '' to `` right '' . there are some other choices ( for example , from `` right '' to `` left '' ) which give expressions different from ( [ ver.7 ] ) in appearance . these properties are valid for any order of @xmath79 . similarly we can evaluate @xmath95 as @xmath96 where the integration variables @xmath97 and @xmath89 are changed to @xmath98 and @xmath90 ( @xmath99 ) . as in @xmath100 , there are some different expressions depending on how we apply the propagator rules in @xmath49 s . because of the integration formulae ( [ a.3 ] ) of app.a , the space integrations in ( [ ver.4]),([ver.7 ] ) and ( [ ver.8 ] ) give a product of kronecker s deltas times some rational function of dimensionless parameters . from above results we can write down @xmath79 for any higher @xmath101 . @xmath79 has @xmath101-fold parameter integrals . let us evaluate @xmath103 . we consider @xmath104 dim space . we focus on the @xmath105-type terms , because that part has the sufficient information to determine the weyl anomaly in 6 dim . taking the taylor - expansion of @xmath106 and @xmath107 around @xmath108 , @xmath109 can be expanded as @xmath110 where @xmath111 are irrelevant parts because they all have odd - time derivatives of @xmath112 s : @xmath113 . @xmath114 is also irrelevant because it has no derivatives of @xmath115s.@xcite @xmath116 are given by @xmath117 the taylor - expansion of @xmath118 , for the case of the 6 dim scalar - gravity theory , is graphically shown in app.c : ( [ graphexp.1 ] ) for @xmath119 , ( [ graphexp.2 ] ) for @xmath120 and ( [ graphexp.3 ] ) for @xmath121 . now we pick up the @xmath69-part@xcite and focus on the @xmath105-terms in the final form . for @xmath75 @xmath122 { { \quad , } } { \nonumber}\\ \left[\frac{1}{t^{2}}v('')\right]|_{t^0}=v_2(x , w;w , r){{\quad .}}\label{g1}\end{aligned}\ ] ] we notice the @xmath123 parts give , after the @xmath94-integration , different products of kronecker s deltas times powers of @xmath124 . see ( [ a.3 ] ) . as for @xmath76,from ( [ ver.7 ] ) , @xmath125\ , { \nonumber}\\ \left [ \frac{1}{t}v('')v ( ' '' ) \right]|_{t^0 } = v_1(x , w';w'-w , r'-r)v_0(x , w;w , r)+v_0(x , w';w'-w , r'-r)v_1(x , w;w , r ) { \nonumber}\\ + \mbox{irrel . terms}{{\quad , } } { \nonumber}\\ w'= { { \bar w}}+r_1w{{\quad , } } { \quad}w'-w= { { \bar w}}-s_1w{{\quad , } } { \nonumber}\\ r_1\equiv\frac{1-r'}{1-r}\equiv r(r , r'){{\quad , } } { \quad}s_1\equiv\frac{r'-r}{1-r}\equiv s(r , r'){{\quad , } } { \quad}r_1>0{{\quad , } } { \quad}s_1>0{{\quad , } } { \quad}r_1+s_1=1{{\quad .}}\label{g2}\end{aligned}\ ] ] the functions @xmath126 and @xmath127 will be used in ( [ g3.1 ] ) . the irrelevant terms ( `` irrel . terms '' ) are such ones as @xmath128 , etc . as for @xmath77 , from ( [ ver.8 ] ) , @xmath129{{\quad , } } { \nonumber}\\ \left[v('')v(''')v('''')\right]|_{t^0 } = v_0(x , w'';w''-w',r''-r')v_0(x , w';w'-w , r'-r)v_0(x , w;w , r ) { \nonumber}\\ + \mbox{irrel . terms}{{\quad , } } \label{g3}\end{aligned}\ ] ] where `` irrel . terms '' above are such ones as @xmath130 , etc . in the above , the coordinate variables in the integrand are written by the integration variables @xmath131 and @xmath94 as @xmath132 where @xmath126 and @xmath127 was introduced in the previous order ( [ g2 ] ) , and @xmath133 is a new function . @xmath134 and @xmath135 have the following relations . @xmath136 here we finish treating the weyl anomaly @xmath103 in terms of the general ones : @xmath137 and their derivatives . their explicit forms depend on each model . the content of app.c comes from the 6 dim scalar - gravity theory ( [ f.10b ] ) . in the following two sections , we explain how we obtain the explicit form of the weyl anomaly using the obtained formulae . in the 6 dim space , there are four `` important general invariants '' as the weyl anomaly terms , which will be explained in the next section . in order to obtain the four coefficients of those terms , let us determine the coefficients of the following four @xmath105-terms which appear in @xmath103 . @xmath138 here we introduce a useful graphical representation to express so(n ) invariants like given above . ( see ref.@xcite for detail . ) we graphically express the basic ingredient @xmath139 as @xmath140 the contraction of suffixes is expressed by gluing the corresponding suffix - lines . then the above four terms ( [ coef.0 ] ) are graphically shown in fig.9 . the advantage of this representation is that the way suffixes are contracted can be read by the topology of the graph . we need not bother about the dummy contracted suffixes . for later use , we introduce the following usage too . @xmath141 the choice of those graphs ( [ coef.0 ] ) is an important step of this algorithm . as will be explained in sec.6 , it is done by looking the table of app.d and the content of the `` important invariants '' . in the evaluation , we exploit the topology of graphs in order to efficiently select relevant terms . , , , fig.9 four graphs of 3,67,1 and 2 . see the ( [ graph.1 ] ) for the definition of the graph . all four graphs above come only from @xmath142 . it is graphically seen by the following common features : * there is no . * no tadpoles ( , ) . and the structure of @xmath143 and @xmath100 : @xmath144 where @xmath145 and @xmath119 are graphically shown in app.c.2 . both @xmath146 and @xmath147 contain , at least , one of two graph - ingredients itemized above . for simplicity we focus , in this section , only on graphs3 and 67 . graph1 and 2 are evaluated in app.b . because of the following common features of graph3 and 67 , * no tadpoles . * there is no . we can reduce the expression of @xmath142 , ( [ g3 ] ) with @xmath119 given by ( [ c2.2 ] ) and ( [ graphexp.1 ] ) , to the following form as the relevant part . @xmath148{c } \mbox { { \epsfysize=30mm\epsfbox{s5d.eps } } } \end{array } { \nonumber}\\ + \mbox{irrelevant terms}{{\quad , } } \label{coef.1}\end{aligned}\ ] ] where the relations @xmath149 are used ( see ( [ g3.2 ] ) ) . furthermore , again by the common features of the graphs3 and 67 , we see no contribution comes from @xmath150- and @xmath151-terms.@xcite @xmath152{c } \mbox { { \epsfysize=30mm\epsfbox{s5e.eps } } } \end{array } { \nonumber}\\ = \begin{array}{c } \mbox { { \epsfysize=30mm\epsfbox{s5f.eps } } } \end{array } { \nonumber}\\ \times \ { ( r_1)^6(s_1)^2 w^{{\alpha}_1}w^{{\alpha}_2}w^{{\mu}}w^{{\nu}}w^{{\beta}_1}w^{{\beta}_2}w^{{\lambda}}w^{{\sigma}}{\nonumber}\\ + ( r_1)^6 w^{{\alpha}_1}w^{{\alpha}_2}w^{{\mu}}w^{{\nu}}w^{{\beta}_1}w^{{\beta}_2 } { { \bar w}}^{{\lambda}}{{\bar w}}^{{\sigma}}{\nonumber}\\ -(r_1)^5 s_1 ( w^{{\alpha}_1}w^{{\alpha}_2}w^{{\mu}}w^{{\nu}}w^{{\beta}_1}{{\bar w}}^{{\beta}_2}+\mbox{}_6c_1 ) { { \bar w}}^{{\lambda}}w^{{\sigma}}\times 2{\nonumber}\\ + ( r_1)^4 ( s_1)^2 ( w^{{\alpha}_1}w^{{\alpha}_2}w^{{\mu}}w^{{\nu}}{{\bar w}}^{{\beta}_1}{{\bar w}}^{{\beta}_2}+\mbox{}_6c_2 ) w^{{\lambda}}w^{{\sigma}}{\nonumber}\\ + ( r_1)^2 ( s_1)^2 ( { { \bar w}}^{{\alpha}_1}{{\bar w}}^{{\alpha}_2}{{\bar w}}^{{\mu}}{{\bar w}}^{{\nu}}w^{{\beta}_1}w^{{\beta}_2 } + \mbox{}_6c_4 ) w^{{\lambda}}w^{{\sigma}}{\nonumber}\\ -(r_1)^3 ( s_1 ) ( { { \bar w}}^{{\alpha}_1}{{\bar w}}^{{\alpha}_2}{{\bar w}}^{{\mu}}w^{{\nu}}w^{{\beta}_1}w^{{\beta}_2 } + \mbox{}_6c_3 ) { { \bar w}}^{{\lambda}}w^{{\sigma}}\times 2{\nonumber}\\ + ( r_1)^4 ( { { \bar w}}^{{\alpha}_1}{{\bar w}}^{{\alpha}_2}w^{{\mu}}w^{{\nu}}w^{{\beta}_1}w^{{\beta}_2 } + \mbox{}_6c_2 ) { { \bar w}}^{{\lambda}}{{\bar w}}^{{\sigma } } \}{\nonumber}\\ + o({{\bar w}}^6)+o({{\bar w}}^8){{\quad , } } \label{coef.2}\end{aligned}\ ] ] where @xmath153 means `` other choices of @xmath154 @xmath90 s among @xmath155 suffixes appearing in the first term within the brackets '' . the @xmath156-integrations are three independent gaussian integrations , and they give the product of two parts for each term . one part is a rational function of the parameters and the other is a symmetrized product of the kronecker s deltas . in terms of a `` components '' notation : @xmath157 the final result is evaluated as @xmath158 { \nonumber}\\ + \mbox{other graph - terms}{\nonumber}\\ = \frac{1}{(4\pi)^{3}}<\frac{4}{27\times 105},-\frac{1}{36\times 63 } > + \mbox{other graph - terms}{{\quad .}}\label{coef.4}\end{aligned}\ ] ] the above numbers @xmath159 are obtained by a computer calculation@xcite . the numbers @xmath160 and @xmath161 show the `` weights '' when a symmetrized product of kronecker s deltas are multiplied to a @xmath105-tensor . for example the first one of ( [ coef.4 ] ) , @xmath162 , says @xmath163{\nonumber}\\ = 64\mbox{(graph3)}+16\mbox{(graph67)}+\mbox{other graph - terms } { { \quad , } } \label{coef.4b}\end{aligned}\ ] ] where the notation @xmath164 $ ] is the symmetrized product of kronecker s deltas and is defined in ( [ a.4 ] ) of app.a . note that in the expression just before the parameter integral , poles at @xmath165 cancel out and there remain no divergences of the parameter integrals . this occurs also in the calculation in app.b . adding the result for graph1 and 2 explained in app.b , we obtain finally the total contribution of @xmath103 to the four graphs as @xmath166 the general structure of the weyl anomaly has been analyzed by refs.@xcite . they claim that the weyl anomaly is composed of three types of term : a ) the euler term ; b ) conformal invariants ; c ) trivial terms . trivial terms are those which can be absorbed by local counter - terms made of the metric . this statement is checked by the cohomology analysis up to 6 dimensions@xcite . we called , in sec.5 , the a and b terms `` important invariants '' . therefore we may write , for the present 6 dim case , @xmath167 where @xmath168 is the weyl tensor , @xmath169 and @xmath170 are three independent conformal invariants , and @xmath171 is the euler term . @xmath172 , and @xmath94 are some constants to be determined . it is well - established that all possible independent invariants ( parity even ) with mass - dimension 6 are , in the 6 and higher space - dimensions , given by the following 17 terms@xcite . @xmath173 in terms of above 17 `` basis '' , we can rewrite ( [ inv.1 ] ) as follows . @xmath174 where `` other invariants '' means other than @xmath175 and @xmath176 . now we see how nicely we have chosen the four graphs in sec.5 . we note that the trivial terms are written in the total derivative form , therefore they do not contain any one of @xmath175 and @xmath176.now we know , from app.d , @xmath177 where `` other @xmath105-terms '' means `` other terms than graph1,2,3 and 67''.@xcite we also note , again from app.d , graphs1,2,3 and 67 do not come from other invariants than ( @xmath178 ) . these properties are due to the chosen four graphs . then we can rewrite ( [ inv.3 ] ) as @xmath179 comparing the result of sec.5 , we finally obtain @xmath180 the trivial terms can be similarly obtained , but they do change by introducing the local counterterms in the action and seem to be unimportant . this result ( [ inv.6 ] ) is similar to that of ref.@xcite . we have presented a new algorithm to obtain the weyl anomaly in the higher - dimensions . the feynman rules in coordinate space are presented . the graphical representation is exploited at all stages . especially the graphical calculation is taken to efficiently compute the coefficients of the four graphs given in sec.5 . explicit result of the weyl anomaly for the 6 dim scalar - gravity is obtained . as the space - time dimension increases , the number of suffixes to deal with increases because we must treat higher products of riemann tensors . the aid of the computer is indispensable in this algebraic calculation . as mentioned at some places in the text and the appendices , the weight calculation in the contraction of multi - suffixed quantities relies on a computer ( a c - program@xcite ) . although we do not touch on the computer algorithm in the present paper , it helps to obtain the concrete results . in the recent rapid development of string theory , the low - energy effective actions play an important role . they are field theories ( supergravities ) on various ( higher ) dimensions . the chiral anomalies of gravitational and gauge symmetries were well analyzed for those low - energy effective actions . the famous one is the pioneering work by green and schwarz@xcite where they found the so(32 ) and @xmath181 gauge group from the analysis of the chiral anomaly structure of 10 dim n=1 supergravity . clearly the analysis from the weyl anomaly side is lacking . from the present standpoint , we stress the importance of examining the string from the structure of the weyl anomaly in the low - energy effective theories.@xcite one reason is we know some important models often have vanishing weyl anomaly due to conformal symmetry . another is that the supersymmetry surely relates the weyl anomaly to the chiral one . we can examine the role of supersymmetry from this point . ref.@xcite recently analyzed the weyl anomaly of conformal field theories using the ads / cft correspondence conjectured by @xcite . weyl anomalies are explicitly obtained for some theories in 2 , 4 and 6 dimensions . we hope the present result will become useful when we go over the quantum field theory through the string theory . we have most experience with quantization only in 0 to 4 dim field theories . higher dimensional quantum field theories have not been so thoroughly examined ( at least systematically ) so far , because they are unrenormalizable except for free theories . in the text we consider free theories on curved space . it is meaningful if we ignore the trivial terms and the the divergent massive terms , which should be explained by the quantum gravitational mode . it might be possible to find a clue to make meaningful the higher dimensional field theories through the present analysis . although the non - perturbative aspect is recently stressed in string theory , the perturbative analysis is still important because it is one of few reliable approaches to analyze dynamical aspects systematically . we suppose the analysis will become important to understand how the quantum field theory is generalized in the coming new era of planck physics . finally we point out that the graphs shown in fig.10 and fig.11 are expected to become some of the `` important graphs '' in the weyl anomaly calculation in 8 dim and 10 dim respectively . the authors thank prof . m. creutz for reading the manuscript carefully . one of the authors ( s.i . ) thanks the hospitality at physics department , brookhaven national laboratory where this work is finished . @xmath184 is the solution of the heat equation eq.([f.12 ] ) and is given by @xmath185 where @xmath47 is the @xmath48 unit matrix and @xmath186 is the n - dim euclidean space coordinates . it has the basic properties : @xmath187 the integral formula is given by @xmath188(2t)^s~i_n{{\quad , } } \label{a.3}\end{aligned}\ ] ] where @xmath189 $ ] is the totally symmetric sum of products of kronecker s deltas and is concretely defined by @xmath190&\equiv&{\delta}^{{\mu\nu}}{{\quad , } } { \nonumber}\\ { [ } { { \mu\nu}}{{\lambda\sigma}}]&\equiv&{\delta}^{{\mu\nu}}{\delta}^{{\lambda\sigma}}+{\delta}^{{\mu}{\sigma}}{\delta}^{{\nu}{\lambda } } + { \delta}^{{\mu}{\lambda}}{\delta}^{{\nu}{\sigma}}{{\quad , } } { \nonumber}\\ { [ } { \mu}_1\cdots{\mu}_6]&\equiv&{\delta}^{\mu_1\mu_2}[\mu_3\cdots\mu_6 ] + { \delta}^{\mu_1\mu_3}[\cdots]+\cdots+{\delta}^{\mu_1\mu_6}[\cdots]{{\quad , } } { \nonumber}\\ & \cdots&{\nonumber}\\ & \cdots&{\nonumber}\\ { [ } { \mu}_1\cdots{\mu}_{2s } ] & \equiv&{\delta}^{\mu_1\mu_2}[\mu_3\cdots\mu_{2s } ] + { \delta}^{\mu_1\mu_3}[\cdots]+\cdots+{\delta}^{\mu_1\mu_{2s}}[\cdots]{{\quad .}}\label{a.4}\end{aligned}\ ] ] @xmath191 has the `` convolution '' property . @xmath192 this relation is geometrically expressed in the coordinate space as in fig.12 . in sec.5 of the text , we have evaluated @xmath103 focusing on 4 special @xmath105-terms(graphs ) in order to fix 4 coefficients of the main weyl anomaly terms given in ( [ inv.1 ] ) . among the four graphs , graph3 and 67 only are explained for simplicity . we evaluate the remaining graphs , graph1 and 2 to supplement sec.5 . from ( [ g3 ] ) , @xmath194 where @xmath195 and @xmath135 are defined in ( [ g3.1 ] ) . because graph1 and 2 do not have tadpoles and subgraph , we can reduce @xmath119 of ( [ c2.2 ] ) with ( [ graphexp.1 ] ) to the following relevant form . @xmath196 the first @xmath119 in ( [ b2.1 ] ) is evaluated as @xmath197 the above @xmath119 , with the @xmath98-integration , gives @xmath198 where @xmath98 is integrated out and the relations @xmath199 are used . therefore the @xmath200-part of ( [ b2.1 ] ) , with the @xmath98-integration , can be written as @xmath201 now we can further evaluate ( [ b2.1 ] ) by picking up relevant powers of @xmath90 in ( [ b2.5 ] ) in the same way as sec.5 . after integration of the remaining coordinates @xmath202 and the parameters @xmath203 , the final result is @xmath204 in the text , we have taken 6 dim scalar - gravity theory ( [ f.1 ] ) as an higher - dimensional model . the expressions for the general theories are expressed in terms of @xmath205 and @xmath35 ( [ f.10 ] ) . in this appendix we graphically express those general expressions for the case of the explicit model . for the 6 dim scalar - gravity theory , @xmath205 and @xmath35 are given by ( [ f.10b ] ) . their weak - field expansions ( @xmath206 ) up to @xmath207 are given in fig.16 for @xmath37 and @xmath38 , and in fig.17 - 21 for @xmath35 . especially they are classified by the number of closed suffix - loops . in sec.4 of the text , we have taylor - expanded @xmath210 and @xmath35 , which are the background - functional appearing in the differential operator @xmath26 . @xmath211 we focus on those terms which have only @xmath212-type ones . they are sufficient to determine the weyl anomaly , and are used in the text . @xmath218{c } \mbox { \epsfysize=3cm\epsfbox{figc2i2l.eps } } \end{array } { \nonumber}\\ \begin{array}[t]{c } \mbox { \epsfysize=6cm\epsfbox{figc2i1l.eps } } \end{array } { \nonumber}\\ \begin{array}[t]{c } \mbox { \epsfysize=3cm\epsfbox{figc2i0l.eps } } \end{array } { \nonumber}\\ + \mbox{irrel . terms}{{\quad .}}\label{graphexp.3}\end{aligned}\ ] ] in 6 dim space , there are totally 17 independent general invariants given in ( [ inv.2 ] ) . in this appendix , we list the coefficients of @xmath105-terms when the invariants are weak - field- expanded ( @xmath206 ) . they are obtained by a computer using a c - program@xcite . among 17 ones , @xmath220 terms do not have @xmath105-terms . as shown in the first column of the table , there are 90 independent @xmath105-terms . some terms ( g3,g67,g1,g2 ) are given , in the ordinary literal form , in ( [ coef.0 ] ) and graphically in fig.9 . their complete list is graphically given in @xcite . for example the @xmath221 column says @xmath222 the content of the table is fully used in sec.5 and 6 of the text . especially the choice of the four graphs of fig.9 relies on the table . @xmath223 & @xmath224 & @xmath225 & @xmath176 & @xmath226 & @xmath221 & @xmath227 & @xmath135 & @xmath228 & @xmath229 & @xmath230 & @xmath231 + @xmath232 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath235 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath237 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath239 & @xmath233 & @xmath233 & @xmath233 & @xmath240 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath241 & @xmath242 + @xmath243 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath241 + @xmath245 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 + @xmath246 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath247 & @xmath233 & @xmath233 & @xmath248 & @xmath233 & @xmath233 + @xmath249 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 + @xmath250 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath251 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath252 + @xmath253 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath254 + @xmath255 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath247 & @xmath233 & @xmath233 & @xmath256 & @xmath233 & @xmath252 + @xmath257 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath258 & @xmath240 & @xmath233 & @xmath233 & @xmath241 & @xmath233 & @xmath242 + + + + @xmath223 & @xmath224 & @xmath225 & @xmath176 & @xmath226 & @xmath221 & @xmath227 & @xmath135 & @xmath228 & @xmath229 & @xmath230 & @xmath231 + @xmath259 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath261 + @xmath262 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath263 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 + @xmath264 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath241 & @xmath242 + @xmath265 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath254 + @xmath267 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath240 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath242 + @xmath268 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath247 & @xmath269 + @xmath270 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath240 & @xmath233 & @xmath233 & @xmath241 & @xmath233 & @xmath256 + @xmath271 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath272 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath273 & @xmath233 & @xmath233 & @xmath241 & @xmath233 & @xmath233 + @xmath274 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath241 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath275 & @xmath233 & @xmath233 & @xmath248 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath276 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath277 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath278 & @xmath233 & @xmath233 & @xmath233 & @xmath279 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath248 + @xmath280 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath260 + @xmath281 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath282 & @xmath233 & @xmath233 & @xmath283 + @xmath284 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath283 + @xmath285 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 + @xmath286 & @xmath233 & @xmath233 & @xmath233 & @xmath287 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath248 + @xmath288 & @xmath233 & @xmath233 & @xmath233 & @xmath279 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath248 + @xmath289 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 + @xmath290 & @xmath233 & @xmath233 & @xmath233 & @xmath279 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath242 + @xmath291 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath244 & @xmath233 & @xmath241 + @xmath292 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath252 + @xmath293 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath242 + @xmath294 & @xmath233 & @xmath233 & @xmath233 & @xmath279 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath260 & @xmath241 + @xmath295 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath244 & @xmath238 + @xmath296 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 + @xmath297 & @xmath233 & @xmath233 & @xmath233 & @xmath287 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 + + + + @xmath223 & @xmath224 & @xmath225 & @xmath176 & @xmath226 & @xmath221 & @xmath227 & @xmath135 & @xmath228 & @xmath229 & @xmath230 & @xmath231 + @xmath298 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath241 + @xmath299 & @xmath233 & @xmath233 & @xmath233 & @xmath240 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath252 + @xmath300 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath266 & @xmath233 & @xmath301 + @xmath302 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath240 & @xmath303 + @xmath304 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath283 + @xmath305 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath260 & @xmath248 + @xmath306 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath287 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath307 + @xmath308 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath247 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath309 & @xmath233 & @xmath233 & @xmath233 & @xmath240 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath307 + @xmath310 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath307 + @xmath311 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath248 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath312 & @xmath233 & @xmath233 & @xmath241 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath313 & @xmath233 & @xmath233 & @xmath233 & @xmath240 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath238 & @xmath248 + @xmath314 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath315 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath266 & @xmath240 & @xmath316 + @xmath317 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath307 + @xmath318 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 + @xmath319 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath260 & @xmath241 + @xmath320 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath241 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath321 & @xmath233 & @xmath233 & @xmath233 & @xmath240 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath273 & @xmath258 + @xmath322 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 + @xmath323 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath324 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath260 & @xmath248 + @xmath325 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath248 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath326 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath327 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath328 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + + + + @xmath223 & @xmath224 & @xmath225 & @xmath176 & @xmath226 & @xmath221 & @xmath227 & @xmath135 & @xmath228 & @xmath229 & @xmath230 & @xmath231 + @xmath329 & @xmath233 & @xmath233 & @xmath233 & @xmath330 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath307 + @xmath331 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath332 & @xmath233 & @xmath266 & @xmath241 + @xmath333 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath273 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath334 & @xmath233 & @xmath233 & @xmath233 & @xmath279 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath307 + @xmath335 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath248 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath336 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath266 & @xmath263 + @xmath337 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath338 & @xmath233 & @xmath233 & @xmath233 & @xmath330 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath236 & @xmath244 + @xmath339 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath330 & @xmath233 & @xmath266 & @xmath238 + @xmath340 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath341 & @xmath233 & @xmath233 & @xmath233 & @xmath279 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath236 & @xmath266 + @xmath342 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath241 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath343 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath234 & @xmath233 & @xmath266 & @xmath260 + @xmath344 & @xmath233 & @xmath266 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath345 & @xmath233 & @xmath233 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath346 & @xmath263 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath347 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath348 & @xmath233 & @xmath236 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath349 & @xmath258 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath350 & @xmath233 & @xmath244 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath238 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + @xmath351 & @xmath260 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 & @xmath233 + + + + 99 l.alvarez-gaum and e.witten,nucl.phys.*b234*,269(1983 ) . l.bonora,p.pasti and m.bregola,class.quantum.grav.*3*,635(1986 ) . t.arakelyan,d.r.karakhanyan,r.p.manvelyan and r.l.mkrtchyan , phys.lett.*b353*,52(1995 ) . d.r.karakhanyan,r.p.manvelyan and r.l.mkrtchyan , mod.phys.lett.*a11*,409(1996 ) s.ichinose and s.d.odintsov,preprint of univ . of shizuoka , us-98 - 01,hep - th/9802043 , to be published in nucl.phys.b , `` conformal anomaly in 4d gravity - matter theories non - minimally coupled with dilaton '' . s. deser , uniqueness of d=11 supergravity , hep - th/9712064,lecture at quantum mechanics of fundamental systems vi,santiago , chile , august 1997 . s.ferrara and b.zumino,nucl.phys.*b87*,207(1975 ) . j.schwinger,phys.rev.*82*,664(1951 ) . b.dewitt,dynamical theory of groups and fields , gordon and breach , new york,1965 . r.t.seeley,proc.symp.pure math.*10*,amer.math.soc.,(1967)288 . f.bastianelli,nucl.phys.*b376*,113(1992 ) . f.bastianelli and p. van nieuwenhuizen , nucl.phys.*b389*,53(1993 ) . boer , b.peeters , k.skenderis and p. van nieuwenhuizen , nucl.phys.*b446*,211(1995 ) . boer , b.peeters , k.skenderis and p. van nieuwenhuizen , nucl.phys.*b459*,631(1996 ) . g.thooft,nucl.phys.*b62*,444(1973 ) . g. thooft and m. veltman , _ ann.inst.h.poincar _ * 20 * ( 1974 ) 69 . p.b.gilkey,j.diff.geom.*10*,601(1975 ) . i.g.avramidi , the covariant methods for calculation of the effective action in quantum field theory and the investigation of higher derivative quantum gravity , phd thesis , moscow state univ.,moscow,1986 ; hep - th/9510140 i.g.avramidi,nucl.phys.*b355*,712(1991 ) . a.o.barvinsky and g.a.vilkovisky,phys.rep.*c119*,1(1985 ) . s.yajima,class.quantum grav.*14*,2853(1997 ) . i.l.buchbinder,s.d.odintsov and i.l.shapiro,effective action in quantum gravity , iop pub.,1992 . other examples of the coordinate space approach are the operator product expansion method and the lattice field theory . the former was exploited in the 2 dim conformal field theory . traditionally the coordinate space has been used for the analysis of conformally invariant or covariant green functions . for example , see a recent progress of @xcite . j. pachos and r. schiappa , mit - ctp#2760 , hep - th/9807128 , to be published in phys.rev.d , `` conformal symmetry and the three point function for the gravitational axial anomaly '' . the heat - kernel is formulated in the coordinate space , using the quatum - mechanical non - linear sigma model , and the feynman rules are given in @xcite . s.ichinose and n.ikeda,phys.rev.*d53*,5932(1996 ) . it must be compared with the dimensional regularization . k.fujikawa,nucl.phys.*b226*,437(1983 ) . k.fujikawa,phys.rev.lett.*42*,1195(1979);*44*,1733(1980 ) ; phys.rev.*d21*,2848(1980);*d22*,1499(e)(1980 ) . k.fujikawa,lecture in quantum gravity and cosmology , kyoto summer inst.1985,ed.by sato and inami , world scientific : 106 ( 1985 ) ; this is the good review of the series of works by fujikawa . e.abdalla , m.c.b.abdalla and k.d.rothe,_non-perturbative methods in 2 dimensional quantum field theory_(world scientific , singapore , 1991 ) . e.dhoker,_tasi lectures on critical string theory _ , ucla/92/tep/30(1992 ) . s.ichinose and n.ikeda,damtp/96-87 , hep - th/9610136 , `` gauge symmetry of the heat kernel and anomaly formulae '' . the case of special @xmath352 ( riemann geometry ) was done by gilkey@xcite , where he analyzed using the normal coordinates in order to keep the general covariance manifestly . j.d.bjorken and s.d.drell,_relativistic quantum mechanics _ ( mcgraw - hill , new york,1964 ) . o.alvarez,nucl.phys.*b216*,125(1983 ) . the condition @xmath353 in @xmath60 requires the directedness . these properties come only from the physical dimensions of @xmath354 and @xmath35 , not the speciality of the present model . the relevant - part selection in this section is valid for general theories . the divergent parts @xmath355 are considered to be canceled by the divergent counter - terms . they generally correspond to power - divergences ( not log - divergence ) and the counter - terms are those operators which have massive couplings : ex . the cosmological term , the einstein term . the @xmath150-term gives disconnected graphs , and @xmath151-terms give graphs which conflict with the second one of the common features of graph3 and 67 . s.ichinose , int.j.mod.phys.*c9*,243(1998),hep-th/9609014 m.j.duff,nucl.phys.*b125*(1977)334 s.deser and a.schwimmer,phys.lett.*b309*(1993)279 . s.ichinose , us-97 - 08 , hep - th/9801056 , `` general structure of conformal anomaly and 4 dimensional photon - dilaton gravity '' . s.a.fulling , r.c.king , b.g.wybourne and c.j.cummins , class.quantum.grav.,*9*,1151(1992 ) s.ichinose,class.quantum grav.*12*,1021(1995 ) . the total independent @xmath105-terms are given by 90 terms shown in the first column of the table in app.d . m.b.green and j.h.schwarz,phys.lett.*149b*,117(1984 ) . m.j.duff,class.quantum grav.*11*,1387(1994 ) . m.henningson and k.skenderis,j.high energy phys.*9807*,023(1998),hep - th/0806087 . j.m.maldacena,adv.theor.math.phys.*2*,231(1998),hep-th/9711200 . s.ichinose and n.ikeda,j.math.phys.*38*,6475(1997 ) . * fig.1 graph of @xmath60 * fig.2 graph of @xmath63 * fig.3 graph of @xmath64 * fig.4 graph of @xmath65 * fig.5 graph of @xmath74 * fig.6 graph of @xmath75 * fig.7 graph of @xmath76 * fig.8 graph of @xmath77 * fig.9 four graphs of 3,67,1 and 2 . see the ( [ graph.1 ] ) for the definition of the graph . * fig.10 two important @xmath182-graphs in 8 dim . * fig.11 two important @xmath183-graphs in 10 dim . * fig.12 propagator rule 1 , eq.([a.5 ] ) . * fig.13 propagator rule 2 , eq.([a.6x ] ) . * fig.14 propagator rule 3 , eq.([a.6y ] ) . * fig.15 propagator rule 4 , eq.([a.6z ] ) . * fig.16 @xmath208 and @xmath38 . * fig.17 @xmath35 , order of @xmath112 . * fig.18 @xmath35 , order of @xmath209 . * fig.19 @xmath35 , order of @xmath36 and loop no=2 . * fig.20 @xmath35 , order of @xmath36 and loop no=1 . * fig.21 @xmath35 , order of @xmath36 and loop no=0 .

an algorithm to obtain the weyl anomaly in higher dimensions is presented . it is based on the heat - kernel method . feynman rules , such as the vertex rule and the propagator rule , are given in ( regularized ) coordinate space . graphical calculation is introduced . the 6 dimensional scalar - gravity theory is taken as an example , and its explicit result is obtained . pacs no : 02.70.-c , 04.60.-m , 11.15.bt , 11.25.db , 11.30.-jkeywords : weyl anomaly , higher dimensional field theories , heat kernel , feynman rule , graphical representation = cmr5 # 1#1^^ # 1 us-98 - 07 + october,1998 + hep - th/9810256 * weyl anomaly in higher dimensions and + feynman rules in coordinate space * shoichi ichinose and noriaki ikeda@xmath0 + physics department , brookhaven national laboratory , + upton , ny 11973 , usa + and + @xmath0research institute for mathematical sciences + kyoto university , kyoto 606 - 01 , japan

the runt domain ( rd ) is the dna - binding domain of p53 type transcription factors known as core binding factor ( cbf ) subunits . the cbfs are expressed by the three related genes runx1 , runx2 and runx3 ( 1 ) . the three runx genes are important for developmental processes ; runx1 is important for hematopoiesis , runx2 is essential for skeletal development ( osteogenesis ) and runx3 is required for the development of gastric epithelium ( 24 ) . runx1 and runx2 also have been shown to be important for vascular development or angiogenesis and their activity is augmented by angiogenic growth factors ( 5,6 ) . mutation of the runx1 gene is associated with human leukemias , whereas mutation of the runx3 gene is involved with the development and progression of gastric cancers and testicular yolk sac tumor ( 1,7,8 ) . mutation of the runx2 gene is associated with the inherited human skeletal disorder known as cleidocranial dysplasia ( 9 ) . a related protein , known as cbf , binds to the rd of the cbfs and enhances the dna - binding affinity of the rd . the rd is the site of both dna binding and heterodimerization with cbf. because of the involvement of cbfs in many developmental processes and cancerous diseases , understanding rd dna and rd cbf interactions may shed light on the control of these processes . in addition , the involvement of runx genes with angiogenesis also makes the rd a potential target in the development and treatment of many types of cancers . the 3d structures of the rd in the free state , bound to dna , cbf and both dna and cbf have been determined using nuclear magnetic resonance ( nmr ) spectroscopy and/or x - ray crystallography ( 1014 ) . biochemical and biophysical studies have been performed characterizing the binding of rd to dna in the presence and absence of cbf ( 15,16 ) . in the presence of cbf , the dissociation constant ( kd ) for rd dna decreases 6- to 10-fold ( 16 ) . several studies have identified rd residues important for both dna and cbf binding via mutational analysis ( 1719 ) . the mutational analysis usually involved mutations to alanine and analysis of its effect on rd dna and rd cbf-binding activities , as determined using yeast hybrid assay analysis . in addition , a recent nmr - based study has identified a variety of residues involved in the cooperativity associated with cbf binding to rd ( 20 ) . while these important studies have given insights into the role of individual residues to rd dna and rd cbf interactions , the interpretation of the mutational analysis may be complicated by the influence of the mutation on protein stability , protein folding and other localized changes , especially at protein protein interfaces , while structural and dynamic information from nmr and x - ray studies can not yield energetic information at an atomic level of detail . computational approaches can yield important details about the interaction of rd with dna and cbf ( 21 ) . for example , the energetic contribution of individual residues to both dna and cbf binding can be determined . by doing such analysis in systems with all wild - type residues present , the risk of mutation induced conformational change , including changes in protein stability , is avoided . computational analysis can also account for the contribution of all atoms in a given residue , including the backbone atoms , whereas mutational analysis can only detect the importance of side chain atoms . thus , computational analysis can fill gaps in understanding the rd dna , rd cbf and cbfrd dna ternary complex interactions . in the present work , the rd was subjected to molecular dynamic ( md ) simulations in the free state and in several complexes . complexes include the binary rd dna and rd cbf complexes , and the cbfrd dna ternary complex . in addition , two dna simulations and a cbf monomer simulation were performed . from the md simulations , in combination with free energy component analysis ( 2224 ) based on the generalized - born model ( 25,26 ) , overall binding energies , desolvation effects and detailed interaction energies these results , along with previous structural analysis and observations , were used to interpret a variety of experimental data involving rd dna and rd cbf interactions ( 1619,27 ) . md simulations and all calculations were performed using the program charmm ( 28 ) . the all - hydrogen charmm22 protein ( 29 ) and charmm27 nucleic acid ( 30,31 ) , the tip3p water model ( 32 ) , along with published sodium and chloride parameters were used ( 33 ) . coordinates from the cbfrd dna ternary complex x - ray crystal structure ( pdb accession code 1h9d ) ( 13 ) were used as starting structures of the seven simulation systems ( supplementary table s1 ) . the only exception was the second dna simulation , which was initiated with the dna in the canonical b form ( 34 ) , as obtained from the program quanta ( accelrys inc . ) . in the crystal structure terminal residues 5053 and 179183 in rd are not observed experimentally as are residues 7179 of cbf. accordingly , in the simulations these residues were omitted . omission of residues 7179 of cbf , which are spatially removed from the rd in the experimental structure ( figure 1 ) , was performed by creating a peptide bond between residues 70 and 80 and relaxing the structure during the minimization and md simulation protocols described below . root - mean - square ( rms ) difference analysis of the residues adjacent to the deleted residues in cbf ( i.e. residues 6670 and 8084 ) showed significant structural changes to occur only in the one or two residues directly adjacent to the deleted residues ( supplementary table s2 ) . the dimensions of each complex ( solute ) were determined , and a box of solvent was prepared to overlay the solute . the edge of the solvent was extended to a minimum of 8 beyond the solute in each dimension . then each solute was overlaid with the solvent water box that also contained either sodium or chloride ions , depending on the total charge of the solute . all water molecules whose oxygen atom was within 2.5 of any solute non - hydrogen atom were then deleted and excess ions were deleted to make the systems electrically neutral . all subsequent calculations were performed using periodic boundary conditions , with images generated using the crystal module of charmm . equilibration of each simulation system was carried out by performing 500 steps of steepest descent energy minimization followed by a 10 ps md nvt simulation with harmonic restraints of 5 kcal/(mol ) on the solute non - hydrogen atoms . additional minimization using the adopted basis newton raphson ( abnr ) algorithm was performed for 100 steps without any restraints . the systems were then subjected to a 5 ns md simulation in the npt ensemble at 300 k with the leap frog integrator , and a time step of 0.002 ps . particle mesh ewald ( pme ) was used to treat long - range electrostatic interactions ( 37 ) . pme calculations were carried out using real space electrostatic and lennard jones interaction cutoffs at 10 , with utilization of heuristic non - bond list update out to 12 and smoothing of the lj interactions from 8 to 10 using the force switch method ( 38 ) . coordinates were saved every 5 ps , and by the end of the 4.5 ns production md simulation , 900 sets of structural coordinates were available for analysis . structural figures were generated using the program vmd ( 39 ) and rendered by raster3d ( 40 ) . calculation of binding free energies via free energy component analysis : binding free energies , gbind , were calculated as follows : 1gbind = gcomplexgpartneragpartnerb , where the overall free energy of each complex was described using ( 24 ) 2g = emm+gsolvationtsmm . in equation 2 emm describes the molecular mechanical energy of the system consisting of all components in the charmm potential energy function , as shown in the following equation 3 : 3emm = ebond+eangle+eurey - bradley+edihedral+eimproper+evdw+eelec . for complexes , emm , can be separated into interaction energy , eie and strain , estrain components : 4emm , complex = eie+estrain , where eie is the sum of the vdw and electrostatic interaction energy between individual molecules in a complex and estrain is the sum of emm terms for each molecule in the complex ( i.e. all mm energy contributions for each species ignoring contributions from the other molecules in the complex ) . the gsolvation term describes the solvation free energy of a system and includes both electrostatic , gelec and non - polar , gnp , components . the electrostatic portion of the solvation free energy was calculated using the generalized - born molecular volume ( gbmv ) method ( 25,26 ) . the non - polar portion of the solvation energy ( i.e. due to cavity formation and hydrophobicity ) was calculated using the still equation , enp = sa , where is an empirical atomic solvation parameter , 7.2 cal / , and sa is the solvent accessible surface area calculated with a solvent probe radius of 1.4 ( 25,41 ) . the final term in equation 2 , tsmm , describes the entropic part of the energy as a sum of translational , rotational and vibrational entropy terms calculated via the harmonic approximation ( 42 ) for the temperature 300 k. vibrational analysis was performed on the solute molecules extracted out of the solvent box . the solute structure was minimized using the conjugate - gradient method to an rms gradient of 10 kcal/(mol ) with a distance - dependent dielectric of 4r applied to approximate the screening of electrostatic interactions by solvent , where r is the distance between two atoms , as performed previously ( 22 ) . to better understand the contributions of the various energetic terms to complex formation this typically involved calculation of the difference between a selected term for the complex and those of the individual molecules comprising the complex . in the case of the interaction energies their contribution was simply the sum of the contribution between the individual molecules in each complex ( i.e. for the cbfrd dimer the eie between cbf and rd was included ) . however , in the case of the trimer formation via dimer + monomer complexation the eie contribution includes those between the monomer being added and the two molecules in the original dimer along with the change in the interaction energy between the molecules in the original dimer upon going to a trimer . for example , eie , cbf-rd + dna = eie , cbf-dna + eie , rd - dna eie , cbf-rd(dimer to trimer ) . this term accounts for gains or losses in the interaction energy of the molecules in a dimer when the third molecule binds to form a trimer . interaction energies , einter , and strain energies , estrain , were calculated for each individual species using an infinite cutoff in order to mimic the long - range electrostatic interactions treated via pme in the md simulations . energy calculations were performed on the 900 structures from each simulation system with statistical analysis performed by dividing each 4.5 ns simulation into nine 500 ps time blocks . statistical analysis was performed by obtaining the averages from each time block , with those averages treated as independent data points , allowing calculation of the overall averages , and standard errors as described previously ( 43 ) . the entropy calculations were performed on 30 structures extracted from the simulation trajectories at 150 ps time intervals , with the statistical analysis derived by dividing the 30 observations into ten 450 ps independent time blocks from which the averages and the standard errors were obtained . overall rms differences of all simulated structures versus the crystallographic structure of the trimer are shown in supplementary table s3 . md simulation studies were undertaken on the rd to understand the nature of interactions with the dna and with the binding partner , cbf. average rms differences for all non - hydrogen atoms with respect to the crystallographic ternary complex structures were 1.62 0.04 , 3.56 0.10 , 2.15 0.04 , 3.23 0.16 , 3.63 0.11 and 2.81 0.05 for the dna , rd , cbf , rd dna , rd cbf and cbfrd dna structures , respectively , indicating that the overall structures were maintained in the simulations . the structure of the trimer after a 4.5 ns simulation is illustrated in figure 1 . analysis focused on the overall binding as calculated using equation 1 followed by investigation of the contributions of different components to the overall binding ( equations 2 and 4 ) . this was followed by identifying contributions of different regions of the proteins and dna to binding , ultimately analyzing the role of individual amino acids . emphasis was placed on using the present results to interpret the body of experimental data available on rd . free energies of complex formation for the dimers and the trimer were calculated using equation 1 based on the data presented in supplementary table s4 . the resulting free energies of binding for the various complexes are presented in table 1 and are included in the thermodynamic cycle shown in figure 2 . two free energies of binding are reported , gbind and gbind , ts , that exclude and include the configuration entropy , tsmm , respectively . for gbind the calculated energies are all favorable , although the interactions involving addition of cbf are extremely exothermic . in contrast , upon inclusion of the entropy the events that involve dna binding become unfavorable . in addition , the calculations predict that rd cbf binding is more favorable than rd dna binding , in contrast to experimental observations ( 16 ) . the presence of these discrepancies is not surprising due to a variety of assumptions in the calculations , including the omission of energetic contributions , such as the solvation and entropic contributions of the added counterions ( 23 ) , limitations in the potential energy function and the force field ( 44 ) along with possible limitations in the sampling of conformational space . dna interaction energies in the force field by < 4% would account for the prediction that binding of rd to cbf is more favorable than rd binding to dna . with respect to the tsmm , the use of gas phase minimized structures may be problematic , especially in the case of the polyanionic dna where the electrostatic screening due to the 4r dielectric is expected to be insufficient when compared with the proteins . however , when the two types of binding free energy are compared , the trends are similar . moreover , in both scenarios , the binding of dna to the rd cbf dimer to form the trimer is more favorable than the binding of rd and dna to form the rd thus , it appears that the present results , although not in quantitative agreement with experiment due to assumptions and limitations in the theoretical models , are representative of the experimental regimen , allowing for atomic details of events driving binding to be elucidated . in addition , the emphasis in this work on differences in energies and structures between the systems rather than absolute energies should allow for increased confidence in the observations and the conclusions based on those observations . concerning the convergence of the present results , the energies calculated from the two independent dna simulations are within the estimated errors ( supplementary table s4 ) , suggesting that the present calculations have adequately converged . analysis of the thermodynamic cycle in figure 2 predicts that binding of both cbf and dna are cooperative . these results are consistent with previous studies showing the binding of dna to rd to be enhanced by the binding of cbf as well as the binding of cbf to rd to be enhanced by dna based on electrophoretic mobility shift assay ( 10,16,18 ) . as discussed , such cooperativity may be important for maintaining binding of rd to dna via stabilization of the ternary complex to insure adequate transcriptional activation . tighter protein protein interactions due to dna binding have been observed in other types of transcription factors ( 45 ) . contributions from solvation , strain and interaction energies to the calculated binding energies are shown in table 1 . as expected , the solvation energies are all unfavorable upon binding , with the unfavorable contributions being significantly larger for the interactions involving the highly solvated polyanionic dna . the strain energies are all also unfavorable with the exception of formation of the cbfrd dimer . typically , it would be expected that the protein protein or protein dna interactions would lead to an unfavorable strain contribution upon binding ( 23 ) . ongoing studies in our laboratory are investigating the unusual behavior in the cbfrd dimer interaction . countering the unfavorable solvation and clearly , the free energies of binding are driven by the large , opposing forces of solvation and , typically , strain energies versus interaction energies between the macromolecules in the complexes . data at the bottom of table 1 addresses the contributions to the calculated gain in binding energy associated with cooperativity upon going from the dimers to the trimer . contributing to the cooperativity is a decrease in the unfavorable solvation that occurs upon binding , evidenced by the trimer the more favorable change in interaction energy occurred with both the rd dna and the rd cbf interactions in the trimer ( table 1 ) ; details of the contributions of different regions of the proteins to this will be discussed below . countering these contributions are unfavorable increases in the strain energy , consistent with gains in interaction energies , as discussed above . thus , the cooperativity of dna and cbf binding to rd is predicted to be dominated by gains in the favorable interactions between the macromolecules and with lowering of the solvation penalty to complex formation . a more detailed understanding of the atomic determinants of cooperativity associated with rd binding to cbf and dna was obtained via interaction energy partitioning analysis between different regions of the rd and both cbf and dna . this was facilitated by partitioning rd into a variety of segments as specified in table 2 and shown in figure 1 . several regions of the protein have been previously indicated to contribute to either rd dna or rd cbf interactions ( 13 ) . residues adjacent to the respective binding partner but not included in a defined segment are referred to as other - dna and other - cbf and all residues not previously defined are referred to as non - interacting - cbf , allowing for the quantification of their contributions to binding . of note are the wing residues , which are primarily important for dna binding , while residues in wing1 are proximal to the wing residues , contacting both cbf and the wing residues . for all these segments of rd , interaction energies were calculated between the respective monomers in the dimers as well as in the trimer . as discussed above , cooperativity exists between both dna and cbf with respect to their binding to rd . dna interaction energies in both the trimer and the dimer complexes along with the change in interaction energy upon going from the rd dna dimer to the trimer , with those contributions broken down into the segments presented in table 2 . upon trimer formation the total rd dna interaction energy becomes more favorable , with three of the segments contributing significantly to the more favorable interaction energy in the trimer . these include wing , a loop and other - dna segments . the largest contribution is from the wing segment , consistent with its location in the vicinity of both the dna and the cbf. this location allows for interactions of cbf to be communicated to wing via wing1 ( see below for additional details ) , as discussed previously ( 13 ) . interestingly , the other - dna region makes a significant contribution to cooperativity by its unfavorable contribution in the rd such a change indicates that the binding of cbf leads to a conformational change in the core region of rd that favors interactions with the dna and , due to the other - dna region not being in direct contact with the dna , suggests that long - range interactions contribute to binding cooperativity . to better understand the role of the wing segment in facilitation of dna binding upon trimer formation , the contribution of this region was broken down into a per residue basis ( table 4 ) . overall , the majority of the favorable interactions are made by arg139 , arg142 and lys144 , as expected due to their positive charge and the polyanionic nature of dna . with all three residues in addition , more favorable interactions occur with ser140 , gly143 and ser145 , with the contribution of gly143 being relatively large . thus , specific residues in the wing contribute to more favorable interactions with the dna upon formation of the ternary complex . details of the role of cbf and the wing1 segment to these contributions will be discussed below . similar to rd dna binding , the rd to cbf interaction energy is increased upon trimer formation . the overall cooperativity gain of 60 kcal / mol is due to the wing1 and n - terminal segments . the contribution of the wing segment to cbf binding becomes less favorable whereas the contribution of this segment becomes more favorable to dna binding upon trimerization ( table 3 ) . such a scenario suggests a subtle balance between interactions of the wing and wing1 segments that contribute to the cooperative binding . interestingly , as with the other - dna segment discussed above for rd dna binding , the n - terminal segment makes a favorable contribution to the cooperativity of rd cbf binding although it is spatially remote from the dna in the ternary complex . this indicates that binding of dna to form the trimer leads to global conformational changes in rd that favor rd cbf interactions , further indicating the contribution of long - range interactions to cooperativity . residue breakdown of the interaction energy contributions of the wing1 and n - terminal regions to cbfrd interactions is presented in table 6 . the energetic contribution of a number of the residues changes significantly upon going from the cbfrd dimer to the trimer , with both favorable and unfavorable contributions occurring . the most significant contributions , both favorable , occur with glu116 in wing1 and asp66 in the n - terminal segment . the importance of glu116 for the binding of cbf has not previously been described , although perturbed chemical shifts of glu116 have been observed in nmr studies in the presence of either cbf or dna ( 13,17,46 ) and a significant decrease in the order parameter of glu116 has been observed upon going from the rd the interaction energies between rd glu116 and cbf in the binary and ternary complexes are 20 8 and 67 9 kcal / mol , respectively . in the present study , it was found that rd glu116 interacts with cbf residue arg33 . interestingly , the experimental change in kd was not accounted for in terms of any residue(s ) in the rd . to understand this omission , distances between the two residues in the binary and ternary complexes as a function of time were obtained ( supplementary figure s1 ) . it is observed that in the ternary complex during the md simulation , the sidechains of rd glu116 and cbf arg33 move to within 23 , in contrast to the oe2-nh2 distance being 9.4 in the crystallographic structure of the ternary complex ( 13 ) . in contrast , in the binary complex crystal structure the oe2-nh2 distance is 12 ; this distance initially decreases to shorter values during the md simulation , but upon further simulation time assumes a stable conformation with a distance of 12 between the oe2-nh2 atoms . to better understand the significant changes in the rd glu116 and cbf arg33 distances for the different systems the experimental structure along with final time frames from the 4.5 ns rd cbf binary and ternary simulations were obtained ( figure 3 ) . in the rd cbf dimer , rd glu116 and cbf arg33 are relatively far apart ( figure 3a ) . upon going to the ternary complex in the md simulation it is clear that a salt bridge forms between glu116 and arg33 ( figure 3b ) . the formation of this salt bridge is associated with a shift in the position of the arg33 sidechain towards the rd , which is suggested to be associated with the electrostatic field due to the presence of dna in the ternary complex as evidenced by the favorable interactions between the cbf arg33 and the dna ( 252.2 6.1 kcal / mol ) . in addition , energy partitioning analysis shows that arg33 of cbf overall disfavors rd cbf binding in the trimer with this effect significantly increased in the rd cbf dimer by 40 kcal / mol [ arg33-rd(trimer ) = 11.0 4.9 and arg33-rd(dimer ) = 50.3 3.3 ] , further disfavoring the rd glu116 to cbf arg33 interaction in the dimer . however , the question remains why is the rd glu116 and cbf arg33 interaction not observed in the ternary complex crystal structure ( figure 3c ) . although speculative , it may be due to the presence of higher salt concentrations in the experimental study ( 200 mm nacl ) ( 13 ) , which may partially screen the arg33dna interactions . this screening combined with competing interactions involving other residues , such as the rd tyr113 to cbf arg33 interaction that occurs in the crystal and rd cbf dimer md structures , may lead to the subtle difference between the two systems . supporting this possibility is the nmr observed decrease in the glu116 order parameter in the ternary complex ( 20 ) , suggesting that in solution and at lower salt concentration the proposed salt bridge may be present . other experimental results indicate a 5-fold increase in the dissociation constant upon formation of the ternary complex from the rd dna dimer ( 18 ) , which may be related to tyr113 properly orienting arg33 for the actual binding event . regardless , the rd glu116 to cbf arg33 salt bridge along with the additional interactions leads to the more favorable interaction energy between cbf and rd in the ternary versus the binary complex ( table 3 ) . thus , it is predicted that glu116 of rd has a significant impact on the binding of cbf to rd as well as on the cooperativity of rd binding to dna and cbf. notably , binding of cbf to the rd dna dimer has been shown via nmr to decrease the conformational variability of glu116 ( 20 ) , supporting the impact of rd interactions with its binding partners on this residue . the interaction energies for met106 , ala107 , asn109 , asn112 , tyr113 and ser114 ( table 6 ) are consistent with the experimental mutation data . mutation of these residues decreases rd cbf binding in the experimental study ( 17,18 ) , consistent with the favorable interaction energies of these residues with cbf. however , mutation of asn109 to alanine decreased the rd cbf binding by 60-fold while the calculated interaction energy is relatively small . this discrepancy may be due to mutation induced structural perturbations of the rd ( i.e. partial unfolding ) , leading to the experimentally observed decrease in binding ( 18 ) . recently , it has been shown that polar residues at protein protein interfaces provide structural rigidity so as to maintain specificity and to reduce the entropic cost upon binding ( 47 ) . thus , asn109 may play an important role in maintenance of the structural integrity of rd with a modest contribution to affinity associated with direct interactions with cbf. the n - terminal segment makes a significant , favorable gain in interaction energy with cbf upon going from the rd cbf binary to the ternary complex ( table 5 ) . as shown in table 6 , the contribution was dominated by asp66 . however , experimental mutation of asp66 to alanine only moderately affected the rd cbf binding strength ( 19 ) . visual inspection of the binary md , ternary md and crystal structures ( figure 4 ) , along with energy partitioning analysis shows asp66 to interact favorably , via its backbone carbonyl , with lys11 of cbf , with this interaction becoming a salt bridge involving the sidechains in the trimer . cbf dimer md and crystal structures and the trimer md structure appears to be due to a competitive interaction between asp66 with his163 in rd ( figure 4a and c , respectively ) . consistent with the results discussed above , this suggests that the electrostatic field imposed by the polyanionic dna in the ternary simulations disrupts the asp66-his163 interaction seen in the dimer and helps in orienting asp66 toward lys11 ( figure 4c ) , with the presence of 200 mm nacl in the experimental structure potentially damping this interaction . his163 was treated as neutral in the md simulations ; hypothetically , a different result might be obtained if his163 was treated as being protonated . presumably this would create a stronger interaction between rd asp66 and his163 , such that this interaction would dominate in both the ternary and the binary md simulations , with the asp66 backbone carbonyl oxygen interacting with the lys11 sidechain amino group in both cases . such a scenario where the interaction of asp66 with lys11 involves the formers backbone atoms could explain why a significant contribution of this residue to binding was not observed experimentally . area2 residues make favorable contributions to the interaction energy between rd and cbf ( table 5 ) . although this region does not contribute to the cooperativity , as evidenced by the similar contribution in the binary and the ternary complexes , the large favorable interaction energy contribution makes it of interest to investigate the role of individual residues in this region to binding ( table 6 ) . the importance of thr161 is thought to be due to its interaction with asn104 of cbf. indeed , visual inspection of the rd cbf binary md , ternary md and crystal structures shows two hydrogen bonds between these residues [ asn(nh2)-thr(og1 ) and asn(od1-thr(hn ) ] ( figure 5 ) . however , calculation of the residue residue interaction energy between rd thr161 and cbf asn104 yields a value of 4.9 0.4 kcal / mol , including the contribution from the thr hn atom , which does not correlate well with the change in dissociation constant in the t161a mutation . alternatively , calculation of the contribution of thr161 to the strain energy of rd yields values of 21.0 1.8 and 26.5 0.2 kcal / mol in the rd monomer and rd cbf dimer , respectively . interestingly , it has been reported that the mutation of thr161 to alanine leads to decreased exchange broadening in rd alone in nmr experiments , indicating a decrease in the conformational flexibility of residue 161 and surrounding residues ( 18 ) . this observation combined with the present energetic results suggests that thr161 may play a role in maintaining the conformation of the local region of rd , thereby impacting binding , rather than contributing directly to protein protein interactions . such a role of thr161 is consistent with the idea that conserved polar residues at protein protein binding sites provide structural rigidity ( 47 ) . the role of such conserved residues is primarily structural rather than functional . as discussed previously ( 13 ) and as emphasized above , the region of rd that includes the segments wing and wing1 appears to be of central importance for binding cooperativity . presented in table 7 are the interaction energies between wing and wing1 , including a breakdown of the interaction of wing residues with all wing1 residues and vice versa . upon going from rd to the rd wing1 total interaction energy becomes significantly more favorable , even though favorable intermolecular interactions occur between wing1 and cbf in the rd this suggests that the binding of cbf to rd , while forming a favorable interaction of cbf with wing1 also induces a conformational change in wing1 that favors the wing wing1 interaction . indeed , figure 6 shows that two salt bridges , arg142-glu111 and lys144-asp110 , are present in the rd cbf dimer ( figure 6b ) ; this represents a gain in interaction energy over the hydrogen bonds between lys144 and asp110 and glu111 in rd alone ( figure 6a ) . indeed , these favorable interactions contribute to the gain in favorable strain energy upon formation of the rd cbf dimer discussed above ( table 1 ) . moreover , nmr experiments indicate all four of these residues to undergo changes in mobility upon going from the rd thus , these intramolecular interactions make a significant contribution to the binding of rd to cbf. in contrast to the rd cbf interaction , upon going from rd alone to the rd this is consistent with the significantly favorable interaction energy between rd and dna in the binary complex , such that when the wing residues interact with the dna , the wing wing1 interactions are diminished ( table 7 ) . similarly , the wing wing1 interaction energy in the trimer is not significantly different as that in rd alone . visual analysis of the rd structure in the monomer ( figure 6a ) , the rd dna complex ( figure 6c ) and the ternary complex ( figure 6d ) , reveals the spatial relationships of residues asp110 , glu111 , arg142 and lys144 to be similar , consistent with the interaction energy contributions in these systems ( table 7 ) . in the rd dna binary and ternary complexes , it is evident that the negatively charged dna attracts arg142 away from the wing1 residues , contributing to the less favorable interactions . in the rd monomer , the lack of salt bridges between arg142 and asp110 or glu111 may be related to repulsion between the two positively charged residues , arg142 and lys144 , such that the system gains more stabilization by orienting arg142 toward the solvent . the balance of attraction and repulsion taking place between closely situated positively and negatively charged residues suggests a subtle balance of interactions , such that their relative orientations are sensitive to the influence of solvent and the presence of dna and cbf. as stated above , formation of the ternary complex leads to a wing energy partitioning analysis ( table 7 ) shows significantly less favorable interaction energies involving arg142 , asp110 and glu111 as compared with the cbfrd binary complex . the less favorable interactions of asp110 and glu111 are consistent with the loss of salt bridges with arg142 , although more favorable interactions with lys144 occur ( figure 6d ) . thus , a subtle balance of intramolecular and intermolecular interactions appear to contribute to the observed cooperativity . interaction of rd with dna leads to favorable intermolecular interactions ( table 3 ) with a simultaneous loss of wing however , upon formation of the ternary complex , the binding of cbf leads to the favorable wing interestingly , the majority of residues predicted to make the largest contributions to cooperativity are charged ( i.e. rd residues asp66 , asp110 , glu111 , glu116 , arg139 , arg142 and lys144 ) . consequently , the long - range character of electrostatic interactions may be an important factor in the observed cooperativity . for example , asp to glu mutations , or vice versa , of the acidic residues suggested to be important for cooperativity may alter the subtle balance of intermolecular and intramolecular interactions contributing to the cooperativity . in addition , mutation of any of the charged residues discussed above to neutral species would be expected to impact cooperativity . asp110 and glu111 may be the most interesting as their impact on cbf binding would be expected to be minimal while their impact on cooperativity should be large . md simulations of rd along with its binding partners cbf and dna , as well as the cbfrd and rd dna binary complexes and the cbfrd dna ternary complex have been performed to better understand the cooperative nature of the binding of these residues . in accordance with the experiment , the simulation data show cooperative binding of dna in the presence of cbf as well as predict that binding of dna to rd facilitates rd cbf binding , indicating cooperativity for this interaction . these observations are consistent with the experimental data ( 16,18 ) , supporting that ability of the applied simulation models to represent the experimental regimen . energetic and structural analysis allow for contributions to the binding and cooperativity to be understood in terms of different regions of the rd protein as well as the contribution of individual residues . of note these interactions are , to a large extent , dominated by charged residues suggesting that long - range interactions may contribute to cooperativity . from these results a number of residues of interest for mutational analysis are suggested . ribbon image of the cbfrd dna after 4.5 ns dynamics simulation including coloring of the rd segments used for analysis ( table 2 ) . dna ( green ) , cbf ( tan ) and residues surrounding omitted residues 7179 in cbf ( red ) . overall binding pathways rd dna , rd cbf and rd cbfdna . free energies before and after the / represent gbind and gbind , ts , as reported in table 1 . cbf interactions involving rd residues tyr113 , glu116 , arg118 and arg139 , and cbf residues arg33 and arg35 . images from snapshots at 4.5 ns from the ( a ) rd cbf binary and ( b ) ternary md simulations and ( c ) from the x - ray crystal structure . images from snapshots at 4.5 ns from the ( a ) rd cbf binary and ( b ) ternary md simulations and ( c ) from the x - ray crystal structure . rd cbf interactions involving rd residue thr161 and cbf residue asn104 . images from snapshots at 4.5 ns from the ( a ) rd cbf binary and ( b ) ternary md simulations and ( c ) from the x - ray crystal structure . wing1 interaction in the md simulation structures at 4.5 ns for ( a ) rd , ( b ) rd cbf , ( c ) rd dna and calculated binding energies and component contributions energies in kcal / mol calculated using equations 14 from the data reported in supplementary table s4 . free energy of binding based on the differences in the free energy of each monomer or complex , g , in supplementary table s4 . it should be noted that the sum of the terms gsolvation , estrain and eie are not exactly equivalent to gbind due to rounding errors . based on the sums , free energies of binding of 1.3 , 81.4 , 86.5 , 6.4 , 87.8 and 5.2 kcal / mol were obtained for the rd + dna , cbf + rd , rd dna + cbf , rd cbf + dna , trimer total and trimer definitions of regions of the rd interacting with dna or cbf color as shown in figure 1 . dna interaction energy energies in kcal / mol as mean se , ie = cbfrd dna rd dna . interaction energy of rd wing residues with dna energies in kcal / mol as mean se , ie = cbfrd dna rd dna . cbf interaction energy energies in kcal / mol as mean se , ie = cbfrd dna cbfrd . interaction energy of selected rd residues with cbf energies in kcal / mol as mean se , ie = cbfrd dna cbfrd . interaction energies between individual wing and wing1 residues in rd alone and in the three complexes energies in kcal / mol .

the runt domain ( rd ) is the dna - binding region of the runx genes . a related protein , known as core binding factor ( cbf ) also binds to the rd to enhance rd dna interaction by 6- to 10-fold . here , we report results from molecular dynamics ( md ) simulations of rd alone , as a dimer in complexes with dna and cbf and in a ternary complex with dna and cbf. consistent with the experimental findings , in the presence of cbf the estimated free energy of binding of rd to the dna is more favorable , which is shown to be due to more favorable intermolecular interactions and desolvation contributions . also contributing to the enhanced binding are favorable intramolecular interactions between the wing residues ( rd residues 139145 ) and the wing1 residues ( rd residues 104116 ) . the simulation studies also indicate that the rd cbf binding is more favorable in the presence of dna due to a more favorable rd cbf interaction energy . in addition , it is predicted that long - range interactions involving ionic residues contribute to binding cooperativity . results from the md calculations are used to interpret a variety of experimental mutagenesis data . a novel role for rd glu116 to the rd cbf interaction is predicted .

let @xmath0 be a discrete subset . in @xcite , to study the teichmller space of the punctured plane @xmath1 , the author gave some criteria for @xmath2 to be quasiconformally equivalent to @xmath1 ( that is , there exists a quasiconformal mapping @xmath3 such that @xmath4 ) . in this paper , furthermore , we investigate the correspondences between @xmath5 and @xmath6 which are the restrictions of global quasiconformal mappings @xmath3 such that @xmath4 . a motivation of this attempt is to study the teichmller modular group of @xmath1 and its action . let @xmath7 be a homeomorphism and @xmath8 be an @xmath9quasisymmetric embedding from a subset @xmath10 into @xmath11 . the theory of the quasisymmetry and its quasiconformal extension originated from the well known study for @xmath12 and @xmath13 by beurling ahlfors @xcite . they proved that a homeomorphism @xmath14 admits a quasiconformal extension @xmath15 if and only if @xmath16 is quasisymmetric . this result enables us to treat the universal teichmller space , the teichmller space of the unit disk , as the space of all orientation preserving quasisymmetric homeomorphisms of the unit circle which fix given three points . later , visl posed the following question in ( * ? ? ? * question 8) which is still open ; can @xmath16 be extended to a @xmath17quasiconformal mapping @xmath18 with a constant @xmath19 which depends only on @xmath20 and @xmath21 ? for example , alestalo visl showed that if @xmath8 is @xmath22 bilipschitz , then there always exists a @xmath23 bilipschitz extension @xmath24 of @xmath16 ( see ( * ? ? ? * theorem 5.5 ) ) . on the other hand , for quasisymmetric embeddings , there is an obstacle ; trotsenko visl proved in ( * ? ? ? * theorem 6.6 ) that if @xmath10 is not relatively connected , then there exists a quasisymmetric embedding @xmath8 which can not be extended to a quasisymmetric embedding @xmath25 for any @xmath26 . since global quasiconformal mappings @xmath24 are also quasisymmetric ( see ( * ? ? ? * theorem 11.14 ) ) , this fact implies that the visl problem can not be solved affirmatively for general subsets @xmath27 even if @xmath13 . according to the recent study by vellis @xcite , he showed that if @xmath28 is @xmath22relatively connected , then every @xmath9quasisymmetric embedding @xmath8 can be extended to an @xmath29quasisymmetric embedding @xmath30 , where @xmath31 depends only on @xmath21 and @xmath32 , and @xmath33 depends only on @xmath20 , @xmath21 , and @xmath32 . considering the one dimensional case of the visl problem , it is interesting to find out whether we can choose @xmath34 uniformly when @xmath13 in the vellis s result . + let us consider the case of @xmath35 and @xmath13 . in this paper , we would like to give detailed observations on quasisymmetric embeddings @xmath36 , as an example of a relatively connected set for which the visl problem can be solved affirmatively ; ( extensibility of quasisymmetric embeddings of @xmath6 ) [ t5.1 ] + every @xmath9quasisymmetric embedding @xmath37 admits a @xmath38 @xmath39quasiconformal extension @xmath3 where @xmath38 is a constant depending only on @xmath21 . compared to the beurling ahlfors extension theorem , the difficulty in our case is that @xmath16 can change the magnitude relation . to prove theorem [ t5.1 ] , first , we will observe the extensibility of quasisymmetric automorphisms @xmath40 in section [ automorphism ] and [ prooft1 ] . ( extensibility of quasisymmetric automorphisms of @xmath6 ) [ t3.2 ] for a bijection @xmath40 , the following conditions are quantitatively equivalent ; 1 . @xmath16 is @xmath9quasisymmetric . 2 . @xmath41 satisfies the @xmath42three point condition . @xmath16 admits a @xmath17quasiconformal extension @xmath43 . we say that a sequence @xmath44 satisfies the @xmath42three point condition for @xmath45 if @xmath46 holds for any integers @xmath47 . thus theorem [ t3.2 ] does not only state every quasisymmetric automorphism of @xmath6 is quasiconformally extensible , but also characterizes the quasisymmetry by a simple geometric condition . further , an analogous theorem holds for quasisymmetric automorphisms of @xmath48 ( see theorem [ t3.3 ] ) . next , we will observe a subset of @xmath49 which is an image of a quasisymmetric embedding @xmath50 in section [ images ] , to complete the proof of theorem [ t5.1 ] . in this case , such subsets can also be characterized by a simple geometric condition as follows ; ( characterizetion of quasisymmetric images ) [ t4.1 ] for a subset @xmath51 , the following conditions are quantitatively equivalent ; 1 . there exists an @xmath9quasisymmetric bijection @xmath52 . @xmath5 can be written as a monotone increasing sequence @xmath53 with @xmath54 , and there exists a constant @xmath55 such that the following inequality holds for all @xmath56 and @xmath57 ; @xmath58 3 . there exists a @xmath17quasiconformal mapping @xmath59 , such that @xmath60 . first , let @xmath7 be a homeomorphism and @xmath61 be a subset . an injection @xmath62 is said to be @xmath9quasisymmetric if the following inequality holds for any three points @xmath63 ; @xmath64 if @xmath65 , replacing @xmath66 and @xmath67 , the following lower estimate holds ; @xmath68 notice that if there exists at least one @xmath9quasisymmetric mapping ( and @xmath27 contains at least two elements ) , applying ( [ qs ] ) to @xmath69 , it turns out that @xmath21 must satisfy @xmath70 . next , let @xmath71 and @xmath72 be a domain . an orientation preserving homeomorphism @xmath73 into @xmath74 is said to be @xmath17quasiconformal if its distributional derivatives @xmath75 and @xmath76 are in the locally integrable class , and @xmath77 @xmath78 is called the maximal dilatation of @xmath16 . these two concepts are closely related by the so - called egg - yolk principle ( see ( * ? ? ? * theorem 11.14 ) ) . in particular , for orientation preserving homeomorphisms from @xmath74 onto itself , the quasiconformality and the quasisymmetry are quantitatively equivalent . we would like to start from a simple observation which is trivial for ones who are familiar with quasiconformal mappings . however , this observation will play a central role in the construction of quasiconformal extensions in later sections . + let us consider a rectangle @xmath79 , we set @xmath80 then @xmath16 defines a quasiconformal homeomorphism of @xmath74 ( see figure [ obs1 ] ) . in particuler @xmath81 on @xmath82 , @xmath83 , and its maximal dilatation depends only on @xmath84 and @xmath85 . by using this flexible deformation , we have the following preliminary lemma . [ l1 ] let @xmath86 and @xmath87 $ ] , and let @xmath88 then , for any bijection @xmath89 , there exists a @xmath90quasiconformal extension @xmath91 of f , such that @xmath92 on @xmath93 , where @xmath94 is a constant depending only on @xmath20 and @xmath95 . we prove the claim by induction with respect to @xmath86 . clearly , the claim holds for @xmath13 . we assume the claim holds for @xmath96 . let @xmath97 be a bijection , and let @xmath98 . by the preceding observation , we can easily construct a quasiconformal mapping @xmath99 which maps @xmath100 , fixes the other integers , and is identity on @xmath101 ( see figure [ obs2 ] ) . similarly we construct global quasiconformal mappings @xmath102 which maps @xmath103 , and @xmath104 which maps @xmath105 . then @xmath106 is a quasiconformal mapping which permutes @xmath20 and @xmath107 , fixes the other integers , and is identity on @xmath108 . since the possible values of @xmath107 are only @xmath109kinds , the maximal dilatation of @xmath110 is bounded by a constant depending only on @xmath20 and @xmath95 . .,width=491 ] by the construction , @xmath111 fixes @xmath20 . thus @xmath112 defines a permutation of the set @xmath113 . from the assumption , @xmath112 extends to a global quasiconformal mapping which satisfies the conditions of the claim . thus , we have a desired extension @xmath114 . each bijection @xmath40 can be regarded as a permutation of countably many elements . on the other hand , lemma [ l1 ] guarantees that any permutation of @xmath115 , a finite set , can be represented by a quasiconformal homeomorphism of @xmath74 which deforms only a small neighborhood @xmath116 of @xmath117 . the aim of this section is to prove theorem [ t3.2 ] . for this purpose , it is useful to consider bijections @xmath40 as sequences . we say that a sequence @xmath118 is _ bijective _ if the correspondence @xmath119 is bijective . for two integers @xmath120 , we use the following notations ; @xmath121_{\mathbb{z}}&:=&[k,\ell]\cap \mathbb{z}=\{k , k+1,\cdots , \ell-1,\ell \},\\ \bigl| [ k,\ell]_{\mathbb{z}}\bigr|&:=&\ # [ k,\ell]_{\mathbb{z}}\ \ = \ \ell - k+1.\end{aligned}\ ] ] remark that we allow the case of @xmath122 in the above notations , and in this case , @xmath123_{\mathbb{z}}=\{k\}$ ] and @xmath124_{\mathbb{z}}\bigr|=1 $ ] . [ d3.1 ] let @xmath125 be bijective . we say that an interval @xmath126_{\mathbb{z}}$ ] splits @xmath127 if @xmath128 holds for all @xmath129 , and @xmath130 holds for all @xmath131 . further , we say that @xmath127 is @xmath132splittable for a constant @xmath133 if there exists a strictly monotone increasing sequence @xmath134 which satisfies the following conditions for all @xmath56 ; * the interval @xmath135_{\mathbb{z}}$ ] splits @xmath127 , * @xmath136 . by the definition , the following is immediately confirmed . [ l2 ] if an interval @xmath126_{\mathbb{z}}$ ] splits a bijective sequence @xmath137 , then @xmath138 is an interval @xmath139_{\mathbb{z}}$ ] with @xmath140 . further @xmath141 , and @xmath142_{\mathbb{z } } = \{k'-1,k'-2,\cdots\}$ ] . let @xmath143 and @xmath144 . by the definition , we have @xmath145_{\mathbb{z}}$ ] , @xmath146 , and @xmath147_{\mathbb{z}}$ ] . since @xmath148 is bijective , the above implications must be equalities . further @xmath149 . note that if an interval @xmath150 splits a bijective sequence @xmath151 , then @xmath152 as @xmath153 . define a bijective sequence @xmath154 by @xmath155 then @xmath152 as @xmath153 , but there is no interval which splits @xmath127 . in figure [ sbs1 ] , each arrow represents the orbit of the sequence @xmath148 , that is , each arrow starts from @xmath156 and gets to @xmath157 for some @xmath158 . such diagrams as figure [ sbs1 ] are useful for our argument , and will be used frequently in later sections . [ l3 ] let @xmath118 be a bijective sequence , @xmath133 , and @xmath87 $ ] . if @xmath127 is @xmath132splittable , then there exists a @xmath159quasiconformal mapping @xmath160 which satisfies the following conditions ; * @xmath161 for all @xmath56 , * @xmath92 on @xmath162 , where @xmath163 is a constant depending only on @xmath164 and @xmath95 . since @xmath127 is @xmath132splittable , there is a strictly monotone increasing sequence @xmath165 such that each interval @xmath135_{\mathbb{z}}$ ] splits @xmath127 , and satisfies @xmath166 . since translation @xmath167 is conformal for any @xmath168 , we may assume @xmath169_{\mathbb{z}}=i_n$ ] for all @xmath158 . namely , the correspondence @xmath170 splits into permutations @xmath171 . by lemma [ l1 ] , for each @xmath56 , there exists a @xmath159quasiconformal mapping @xmath172 such that * @xmath173 for all @xmath174 , * @xmath175 on @xmath176 . let @xmath177 if @xmath178 then , clearly @xmath179 defines a homeomorphism of @xmath74 . since domains @xmath180 are disjoint , the maximal dilatation of @xmath179 is also @xmath181 . thus @xmath179 is a desired mapping . let @xmath125 be a bijective sequence , and let @xmath45 . we say that @xmath127 satisfies the @xmath42three point condition if for any integers @xmath47 , it holds that @xmath182 suppose @xmath127 satisfies the @xmath42three point condition . then for any integers @xmath47 , it holds from the triangle inequality that @xmath183 thus , we have a symmetric condition ; @xmath184 [ remark1 ] we would like to emphasise that the condition ( [ 3pc ] ) holds even if @xmath185 , and the condition ( [ 3pc ] ) holds even if @xmath186 . this makes our arguments concise . the conditions ( [ 3pc ] ) and ( [ 3pc ] ) have a simple geometrical meaning ; suppose the orbit starts from a certain point @xmath156 and goes far away , say @xmath187 , then the orbit @xmath188 can not return to a point near to @xmath156 above a certain rate ( see figure [ 3pc1 ] ) . three point condition , width=377 ] [ p1 ] if a bijective sequence @xmath125 satisfies the @xmath42three point condition for some @xmath45 , then @xmath189 or @xmath190 holds . first , we prove @xmath191 or @xmath192 as @xmath193 . to obtain a contradiction , we assume @xmath194 as @xmath193 . further , we suppose @xmath195 for simplicity . by the assumption , @xmath196 is unbounded from above and below . thus there is an integer @xmath197 such that @xmath198 holds , and @xmath199 or @xmath200 holds . indeed if such an integer does not exist , @xmath196 must contain @xmath201 . this can not occur since @xmath202 is an infinite subset . let @xmath203 be an integer which satisfies @xmath204 or @xmath205 . then , by the three point condition , we have a contradiction ; @xmath206 similarly , we can show @xmath191 or @xmath192 as @xmath207 . obviously , if @xmath208 , then @xmath209 . thus we have the claim . the following theorem will be proved in section [ prooft1 ] . [ t1 ] let @xmath125 be bijective , @xmath45 , and @xmath210 $ ] . if @xmath127 satisfies the @xmath42three point condition and @xmath211 , then there exists a @xmath212quasiconformal mapping @xmath91 such that * @xmath92 on @xmath213 , * @xmath214 is @xmath215splittable , where @xmath216 is a constant depending only on @xmath217 and @xmath95 . as a direct corollary of theorem [ t1 ] , we have the following ; ( extensibility of quasisymmetric automorphisms of @xmath6 ) [ t3.2 ] for a bijection @xmath40 , the following conditions are quantitatively equivalent ; 1 . @xmath16 is @xmath9quasisymmetric . 2 . @xmath41 satisfies the @xmath42three point condition . @xmath16 admits a @xmath17quasiconformal extension @xmath218 . first , @xmath219 is clear . indeed , for any integers @xmath47 , we have @xmath220 next , @xmath221 is also clear , since @xmath17quasiconformal self - homeomorphisms of @xmath74 are @xmath9quasisymmetric with an @xmath21 depending only on @xmath181 ( thus the restrictions to @xmath6 are also @xmath9quasisymmetric with the same @xmath21 ) . last , we prove that @xmath222 . by proposition [ p1 ] , @xmath223 or @xmath224 holds . since @xmath225 is conformal , we may assume the former case holds . then we can apply theorem [ t1 ] , that is , there exists a @xmath226quasiconformal mapping @xmath227 such that @xmath228 is @xmath215splittable . further , applying lemma [ l3 ] , we have @xmath229quasiconformal mapping @xmath230 such that @xmath231 . therefore we obtain a desired extension @xmath232 . next , we consider quasisymmetric automorphisms of @xmath233 . in this case , we analogously obtain the following theorem ; [ t3.3 ] for a bijection @xmath234 , the following conditions are quantitatively equivalent ; 1 . @xmath16 is @xmath9quasisymmetric . 2 . @xmath235 as @xmath207 , and @xmath236 satisfies the @xmath42three point condition , that is , for any integers @xmath47 it holds that @xmath237 3 . @xmath16 admits a @xmath17quasiconformal extension @xmath238 . assume @xmath239 is @xmath9quasisymmetric . since quasisymmetric mappings map cauchy sequences to cauchy sequences , we have @xmath240 . further , for any integers @xmath47 @xmath241 thus @xmath219 is valid , and @xmath242 is clear for the same reason as the preceding proof . in the condition @xmath243 , @xmath240 is necessary . more precisely , the @xmath42three point condition does not imply this property . in fact , for @xmath244 , the sequence @xmath245 satisfies the @xmath246three point condition , but @xmath247 . thus we only need to show @xmath222 . to prove this , we prepare some lemmas . let us assume @xmath239 satisfies the condition @xmath243 . + let @xmath248 ( then @xmath249 holds ) . since @xmath250 , we have @xmath251 . note that @xmath252 is a bijective sequence . [ l3.4 ] there exists a constant @xmath253 depending only on @xmath217 , such that @xmath254 holds if @xmath255 and @xmath256 . assume that integers @xmath257 satisfy @xmath255 and @xmath256 . since @xmath258 , there exists an integer @xmath259 such that @xmath260 . thus , by the three point condition , @xmath261 since @xmath262 , we have @xmath263 . therefore @xmath264 . [ l3.5 ] @xmath44 satisfies the @xmath265three point condition , where @xmath266 is a constant in lemma [ l3.4 ] . let @xmath47 . if @xmath267 , then @xmath268 . thus we consider the case of @xmath269 . first , if @xmath270 , then we have @xmath271 in this estimation , remark that @xmath156 and @xmath272 are distinct integers , that is , @xmath273 holds . next , if @xmath274 , by @xmath275 it holds @xmath276 thus , by lemma [ l3.4 ] we have @xmath277 and @xmath278 [ p3.2 ] @xmath279 in theorem [ t3.3 ] holds . by lemma [ l3.5 ] and proposition [ p1 ] , the sequence @xmath280 satisfies the @xmath265three point condition and @xmath281 . thus by theorem [ t1 ] and lemma [ l3 ] , there exists a @xmath282quasiconformal mapping @xmath283 such that * @xmath284 , * @xmath285 on @xmath286 . define a homeomorphism @xmath287 by @xmath288 for @xmath158 , and @xmath289 . clearly , @xmath290 is @xmath282quasiconformal and @xmath291 . thus , the projection of @xmath290 with respect to the universal covering @xmath292 , that is , the mapping @xmath293 defined by @xmath294 gives a @xmath17quasiconformal extension of @xmath16 . since @xmath295 , we obtain a desired extension by the removable singularity theorem for quasiconformal mappings . by the construction of @xmath296 , it turns out that we can choose the quasiconformal extension in theorem [ t3.3 ] so that it is identity on the negative real axis . we devote this section to the proof of theorem [ t1 ] . the statement of theorem [ t1 ] is the following ; let @xmath125 be bijective , @xmath45 , and @xmath210 $ ] . if @xmath127 satisfies the @xmath42three point condition and @xmath211 , then there exists a @xmath212quasiconformal mapping @xmath91 such that * @xmath92 on @xmath213 , * @xmath214 is @xmath215splittable , where @xmath216 is a constant depending only on @xmath217 and @xmath95 . we would like to start proving this claim . throughout this section , we assume @xmath151 satisfies the @xmath42three point condition @xmath297 and @xmath298 . further , let @xmath210 $ ] . by translation , we may assume @xmath195 . since @xmath298 , there uniquely exist integers @xmath299 and @xmath300 such that @xmath301 remark that since @xmath195 , it holds that @xmath302 . , width=453 ] let @xmath303_{\mathbb{z}}$ ] , and let @xmath304 satisfy @xmath305 , and @xmath306 ( see figure [ pt11 ] ) . further , let @xmath307 . [ claim1 ] @xmath308 and @xmath309 hold . by the three point condition , the following hold for any integers @xmath310 ( see remark [ remark1 ] ) ; @xmath311 let @xmath312 be an integer such that @xmath313 . then by the condition ( [ a ] ) , we have @xmath314 . thus , @xmath315 since @xmath316 and @xmath317 , we have @xmath318 . similarly , we can show @xmath319 . further , we have @xmath320 . next , we sort the interval @xmath321_{\mathbb{z}}$ ] appropriately by a global quasiconformal mapping . let @xmath322 be the unique sequence such that @xmath323 that is , @xmath322 is the ascending sort of @xmath324 normalized by @xmath325 . remark that @xmath326 and @xmath327 are also uniquely determined by the above conditions . similarly , let @xmath328 and @xmath329 be the unique sequences such that @xmath330_{\mathbb{z}}\setminus \{a_n\}_{n\in i_0},\vspace{1ex}\\ d_{p_0}<d_{p_0 + 1}<\cdots < d_{-1}<0<d_{1}<\cdots < d_{p_1}. \end{array } \right.\ ] ] @xmath331 and @xmath332 are also uniquely determined by the conditions @xmath333 and @xmath334 . ( if @xmath335 or @xmath336 , then we assume the corresponding sequences are empty . ) by lemma [ l1 ] and claim [ claim1 ] , there exists a @xmath212quasiconformal mapping @xmath337 such that 1 . @xmath338 on @xmath339 , 2 . @xmath340 , + @xmath341 , + @xmath342 . using this mapping , we set @xmath343 ( see figure [ pt12 ] ) . then @xmath344_{\mathbb{z}}$ ] splits @xmath345 and @xmath346 . , width=491 ] by lemma [ l2 ] , @xmath347_{\mathbb{z}}$ ] and @xmath348 . let @xmath349 be the maximum integer which satisfies @xmath350_{\mathbb{z}}$ ] , and let @xmath351_{\mathbb{z}}$ ] . further we let @xmath352 be the integer such that @xmath353 . remark that since @xmath338 on @xmath354 , it holds @xmath355 if @xmath356 . in particular , @xmath357 . [ claim2 ] @xmath358 , and @xmath359 hold . let @xmath360 satisfy @xmath361 . then @xmath362 . further by the preceding remark , it holds @xmath363 . by the definition of @xmath364 , we have @xmath365 . therefore , @xmath366 moreover by claim [ claim1 ] , we have @xmath367_{\mathbb{z}}|&= & a_{\ell_1}-m_1\\ & \leq & a_{\ell_1}-(a_{\ell_0}+1)+a_{\ell_0}+1 \leq 2\lambda ' + 1 . \end{aligned}\ ] ] similarly to step1 , we sort the interval @xmath368_{\mathbb{z}}$ ] appropriately by a global quasiconformal mapping . let @xmath369 be the unique sequence such that @xmath370_{\mathbb{z } } \cap \{a_n^0\}_{n\in i_1},\vspace{1ex}\\ a_{\ell_0}+1=c_{a_{\ell_0}+1}^1<c_{a_{\ell_0}+2}^1<\cdots < c_{m_2 - 1}^1 < c_{m_2}^1=a_{\ell_1 } , \end{array } \right.\ ] ] and let @xmath371 be the unique sequence such that @xmath372_{\mathbb{z } } \setminus \{a_n^0\}_{n\in i_1},\vspace{1ex}\\ d_1 ^ 1<d_2 ^ 1<\cdots < d_{p_2}^1 . \end{array } \right.\ ] ] again , we remark that @xmath373 is automatically determined by the equation @xmath374 , and if @xmath375 , we assume @xmath371 is empty . by lemma [ l1 ] and claim [ claim2 ] , there exists a @xmath17quasiconformal mapping @xmath376 which satisfies 1 . @xmath377 on @xmath378 , 2 . @xmath379 , + @xmath380 , where @xmath181 is the same constant appeared in the construction of @xmath364 . , width=415 ] let @xmath381 . then intervals @xmath344_{\mathbb{z}}$ ] and @xmath382_{\mathbb{z}}$ ] split @xmath383 , and @xmath384 hold . furthermore , since @xmath364 and @xmath385 deform disjoint domains , the maximal dilatation of @xmath386 does not increase . namely , @xmath386 is also @xmath17quasiconformal ( see figure [ pt13 ] ) . applying step2 repeatedly , for each @xmath387 , we can construct an interval @xmath388_{\mathbb{z}}$ ] , a @xmath17quasiconformal mapping @xmath389 , and a sequence @xmath390 such that * intervals @xmath391 split @xmath392 , * @xmath393 , * @xmath394 are identity on @xmath395 . furthermore , by the construction of @xmath394 , the mappings @xmath396 deform disjoint domains . thus @xmath397 converges to a @xmath17quasiconformal mapping uniformly on each compact subset of @xmath74 as @xmath398 . further , we can apply the same argument to the negative direction of @xmath399 . consequently we have a desired @xmath17quasiconformal mapping @xmath400 . @xmath401 in this section , we characterize subsets @xmath51 which are images of some quasisymmetric embeddings @xmath50 . on the other hand , the author have characterized images of quasiconformal mappings as follows ; [ oldthm ] ( f. 2015 ( * ? ? ? * theorem a ) ) for a subset @xmath51 , the following conditions are quantitatively equivalent . 1 . there exists a @xmath17quasiconformal mapping @xmath59 , such that @xmath60 . @xmath5 can be written as a monotone increasing sequence @xmath53 with @xmath54 , and there exists a constant @xmath55 such that the following inequality holds for all @xmath56 and @xmath57 ; @xmath58 further , if @xmath5 satisfies the second condition , there exists a quasiconformal mapping @xmath59 such that @xmath402 for all @xmath56 . we will see that the above conditions are desired characterizations . to see this , we can use almost the same proof as ( * ? ? ? * theorem a ) . however , we would like to give proofs here for completeness and convenience . first , we prepare some preliminary lemmas . if @xmath51 is an image of a quasisymmetric mapping @xmath403 , since quasisymmetric mappings take cauchy sequences to cauchy sequences , @xmath5 must be closed and discrete in @xmath49 . [ l4.1 ] let @xmath50 be an @xmath9quasisymmetric mapping , and let @xmath404 . then @xmath405 and @xmath406 . to obtain a contradiction , we assume @xmath407 . since @xmath5 is closed and discrete , we have @xmath405 . thus @xmath5 can be written as a monotone increasing sequence @xmath408 with @xmath191 as @xmath193 . let @xmath409 . by translation , we may assume @xmath410 . further , note that @xmath110 is @xmath29quasisymmetric where @xmath411 . let @xmath412 and consider the set @xmath413 since @xmath414 is bijective , @xmath415 consists of infinitely many elements . we number @xmath416 in ascending order . then the sequence @xmath417 is monotone increasing . on the other hand , there exist infinitely many @xmath86 with @xmath418 . thus we can find @xmath419 such that @xmath420 and @xmath421 . moreover since @xmath422 for all @xmath423 , if @xmath424 then @xmath425 . consequently we confirmed that there exists @xmath426 and exist @xmath427 such that * @xmath428 , * @xmath421 and @xmath429 ( see figure [ img1 ] ) . therefore , we have a contradiction ; @xmath430 [ l4.2 ] let @xmath431 be a monotone increasing sequence with @xmath152 as @xmath153 . if @xmath414 is an @xmath29quasisymmetric bijection , then there exists a constant @xmath432 depending only on @xmath433 which satisfies the following inequality for all @xmath158 and @xmath57 ; @xmath434 to prove lemma [ l4.2 ] , first , we prove the following estimation ; [ subclaim1 ] for any @xmath158 , it holds @xmath435 . since @xmath436 , it suffices to consider the case that @xmath437 . then we may assume @xmath438 since the same argument mentioned below can be applied to the case @xmath439 . letting @xmath440 satisfy @xmath441 and @xmath442 satisfy @xmath443 ( then @xmath444 by the construction ) , we can construct @xmath445 which satisfy the following conditions ( see figure [ img2 ] ) ; 1 . @xmath446 and @xmath447 , 2 . @xmath448 . first , suppose @xmath449 . then @xmath450 are distinct and @xmath451 thus we have @xmath452 . next , suppose @xmath453 . then @xmath454 holds . since @xmath455 , @xmath456 that is , @xmath457 . therefore @xmath458 are distinct . similarly we have @xmath452 . [ subclaim2 ] for any @xmath56 and @xmath459 , the following inequality holds ; @xmath460 ( _ upper bound _ ) by the triangle inequality , it immediately follows from claim [ subclaim1 ] that @xmath461 . + ( _ lower bound _ ) suppose @xmath462 . since the open interval @xmath463 contains at most @xmath464 integer points , there exists an integer @xmath465 such that @xmath466 by the quasisymmetry , we obtain @xmath467 that is , @xmath468 . [ subclaim3 ] lemma [ l4.2 ] holds . if @xmath462 , it immediately follows from claim [ subclaim2 ] that @xmath469 for @xmath470 . moreover , even if @xmath471 , it follows from claim [ subclaim1 ] @xmath472 by the above lemmas , we obtain the following ; [ t4.1 ] for a subset @xmath51 , the following conditions are quantitatively equivalent ; 1 . there exists an @xmath9quasisymmetric bijection @xmath52 . @xmath5 can be written as a monotone increasing sequence @xmath53 with @xmath54 , and there exists a constant @xmath55 such that the following inequality holds for all @xmath56 and @xmath57 ; @xmath58 3 . there exists a @xmath17quasiconformal mapping @xmath59 , such that @xmath60 . the equivalence @xmath473 is already confirmed by theorem [ oldthm ] ( see ( * ? ? ? * theorem a ) ) . further , for the same reason as the proof of theorem [ t1 ] , @xmath221 follows . thus it suffices to show @xmath219 . let us assume that there exists an @xmath9quasisymmetric bijection @xmath52 . by lemma [ l4.1 ] , @xmath5 can be written as a monotone increasing sequence @xmath474 with @xmath152 as @xmath475 ( recall @xmath5 must be closed and discrete in @xmath49 ) . let @xmath476 . then @xmath110 is @xmath29quasisymmetric where @xmath411 . by lemma [ l4.2 ] , there exists a constant @xmath432 depending only on @xmath477 which satisfies the following inequality for any @xmath158 and @xmath478 ; @xmath479 therefore we obtain @xmath480 and @xmath481 we would like to complete this paper , proving the following theorem ; let @xmath50 be an @xmath9quasisymmetric embedding , and let @xmath404 . then , by theorem [ t4.1 ] , there exists a @xmath483quasiconformal mapping @xmath484 such that @xmath60 , where @xmath485 depends only on @xmath21 . since compositions of quasisymmetric mappings are also quasisymmetric , @xmath486 becomes an @xmath29quasisymmetric automorphism where @xmath31 depends only on @xmath21 . by theorem [ t3.2 ] , @xmath487 admits a @xmath488quasiconformal extension @xmath489 , where @xmath490 depends only on @xmath21 . therefore , we obtain a @xmath491quasiconformal extension @xmath492 of @xmath16 . the proof is completed .

we prove that an injection from the integer set into the real line admits a quasiconformal extension to the complex plane if and only if it is quasisymmetric .

deep inelastic diffractive lepton nucleon scattering was observed at the electron proton collider hera some years ago @xcite . this process is measured in detail by now @xcite and the structure function @xmath2 was extracted has not yet been possible . for the dis structure function cf . @xcite . ] the diffractive events are characterized by a rapidity gap between the final state nucleon and the set of the diffractively produced hadrons due to a color neutral exchange . the ( semi - inclusive ) structure functions emerging in the diffractive scattering cross section show the same scaling violations as the structure functions in deep inelastic scattering within the current experimental resolution @xcite . this is a remarkable fact , which should also be understood with the help of field theoretic methods within quantum chromodynamics ( qcd ) . in the description of diffractive @xmath3 scattering one has to clearly distinguish @xcite the case of hard scattering , i.e. large @xmath4 , from that of softer hadronic interactions , cf . also @xcite . a perturbative description of the scaling violations can only by hoped for in the former case , to which we limit our considerations in this paper . there is a vast amount of varying descriptions of the underlying dynamics of the diffractive scattering process , ranging from intuitive phenomenological models @xcite to non - perturbative semi - classical descriptions @xcite , being able to describe and to parameterize @xcite the existing data differentially . in this paper we describe the process of inclusive deep inelastic diffractive scattering , being a non forward process , at large space like momentum transfer using the general light cone expansion for the non forward case , cf . [ 1214 ] . as will be shown , the scaling violations of the diffractive structure functions can be described perturbatively in this region . we show that the diffractive parton densities can be derived as a special projection of two variable distribution functions @xmath5 , where @xmath6 and @xmath7 are light cone momentum fractions ; for other projections in similar cases related to different observables see e.g. [ 1315 ] . in particular we have _ no need _ to refer to the specific mechanism of the non perturbative color singlet exchange between the proton and the set of diffractively produced hadrons and consider instead the expectation values of operators of a given twist and their anomalous dimensions . in this way we can generalize the analysis to operators of higher twist . this formulation is very appropriate for potential later studies of the corresponding operator matrix elements with the help of lattice techniques similar to the case of deep inelastic scattering @xcite calculating their mellin moments . the paper is organized as follows . in section 2 we consider the lorentz structure of the differential cross section for inclusive deep inelastic diffractive scattering . the short distance structure of the matrix element is derived in section 3 using the ( non local ) light cone expansion in the generalized bjorken region . in section 4 we derive the anomalous dimensions for the case of twist2 , discuss the implications for higher twist operators and compare the case of diffractive scattering to that of deep inelastic scattering , and section 5 contains the conclusions . [ sec-2 ] the process of deep inelastic diffractive scattering is described by the diagram figure 1 . the differential scattering cross section for single photon exchange is given by @xmath8 here @xmath9 is the cms energy of the process squared and @xmath10 denotes the nucleon mass . ( -50,100)(0,0 ) ( -150,100)(-100,100 ) ( -100,100)(-50,120 ) ( -100,100)(-70,70)55(-30,30)(0,0 ) ( -100,0)(-70,30 ) ( -30,70)(0,100 ) ( -50,50)26blackyellow ( -160,110)[]@xmath11 ( -40,130)[]@xmath12 ( -90,75)[]@xmath13 ( -110,-10)[]@xmath14 ( 10,-10)[]@xmath15 ( 10,110)[]@xmath16 figure 1 : the virtual photon - hadron amplitude for diffractive @xmath3 scattering the phase space @xmath17 depends on five variables since one final state mass varies . they can be chosen as bjorken @xmath18 , the photon virtuality @xmath19 , @xmath20 , a variable describing the non forwardness w.r.t . the incoming proton direction , @xmath21 demanding @xmath22 and where @xmath23~,\ ] ] and @xmath24 the angle between the lepton plane @xmath25 and the hadron plane @xmath26 , @xmath27 @xmath28 and @xmath29 denote the hadronic mass squared and the square of the diffractive mass , respectively . since the leptonic tensor @xmath30 is symmetric for unpolarized scattering and the electromagnetic current is conserved the hadronic tensor , which is generally composed out of the tensors @xmath31 , consist out of four structure functions only @xmath32 \frac{w_5}{m^2}~,\end{aligned}\ ] ] with @xmath33 the size of the rapidity gap @xcite is of the order @xmath34 and large in the kinematic domain of hera . if target masses can be neglected , @xmath35 , and @xmath36 is considered to be very small compared to all other invariants the in and outgoing proton four momenta become proportional , @xmath37 . the variable @xmath38 is then related to @xmath39 and @xmath40 by @xmath41 in this limit the hadronic tensor is described by two structure functions @xmath42 with @xmath43 due to the dependence on @xmath39 or @xmath40 , eq . ( [ eqv1 ] ) , the process is _ non forward _ although the algebraic structure of the hadronic tensor is the same as in the forward case . finally the generalized bjorken limit is carried out , @xmath44 which leads to @xmath45 and @xmath46 . note that @xmath47 always holds in this region . in the limit @xmath48 and @xmath49 the @xmath50integral becomes trivial . the scattering cross section reads @xmath51~,\end{aligned}\ ] ] with @xmath52 . the renormalized and time ordered product of two electromagnetic currents is given by @xmath53 \nonumber\\ & = & -e^2 \frac{\tilde x^\lambda}{2 \pi^2 ( x^2-i\epsilon)^2 } rt \left [ \overline{\psi } \left(\frac{\tilde x}{2}\right ) \gamma^\mu \gamma^\lambda \gamma^\nu \psi \left(-\frac{\tilde x}{2}\right ) - \overline{\psi } \left(-\frac{\tilde x}{2}\right ) \gamma^\mu \gamma^\lambda \gamma^\nu \psi \left(\frac{\tilde x}{2}\right ) \right ] s\end{aligned}\ ] ] @xmath54 denotes a light like vector corresponding to @xmath55 , @xmath56~,\end{aligned}\ ] ] and @xmath57 is a subsidiary vector . following refs . @xcite the operator @xmath58 can be expressed in terms of a vector and an axial vector operator by @xmath59~,\end{aligned}\ ] ] where @xmath60 the bilocal light ray operators are @xmath61s~ , \\ \label{oo5 } o^{\alpha}_5\left(\frac{\tilde x}{2},-\frac{\tilde x}{2}\right ) & = & \frac{i}{2 } rt \left[\overline{\psi}\left(\frac{\tilde x}{2}\right ) \gamma_5\gamma^\alpha\psi\left(-\frac{\tilde x}{2}\right ) + \overline{\psi}\left(-\frac{\tilde x}{2}\right ) \gamma_5\gamma^\alpha\psi\left(\frac{\tilde x}{2}\right)\right]s~.\end{aligned}\ ] ] the general operator @xmath58 is now to be related to the diffractive scattering cross section . this is possible upon applying mueller s generalized optical theorem @xcite ( figure 2 ) , which moves the final state proton into an initial state anti - proton . ( 200,100)(0,0 ) ( -107,102)(-107,-2 ) ( 7,102)(7,-2 ) ( -100,100)(-70,70)55 ( -30,30)(0,0 ) ( -100,0)(-70,30 ) ( -30,70)(0,100 ) ( -50,50)26blackyellow ( 15,107)[]@xmath62 ( 50,50)[]@xmath63 ( -105,115)[]@xmath13 ( -105,-15)[]@xmath14 ( 5,-15)[]@xmath15 ( 75,115)[]@xmath13 ( 75,-15)[]@xmath14 ( 95,-15)[]@xmath15 ( 60,35)[]@xmath64 ( 175,20)[]@xmath64 ( 275,115)[]@xmath13 ( 275,-15)[]@xmath14 ( 255,-15)[]@xmath15 ( 80,100)(110,70)55 ( 80,0)(110,30 ) ( 130,30)(100,0 ) ( 150,50)(200,50 ) ( 150,45)(200,45 ) ( 150,55)(200,55 ) ( 150,40)(200,40 ) ( 150,60)(200,60 ) ( 240,30)(270,0 ) ( 250,0)(220,30 ) ( 130,50)26blackyellow ( 220,50)26blackyellow ( 240,70)(270,100)55 figure 2 : a. mueller s optical theorem . consequently , the compton amplitude is obtained as the expectation value @xmath65 which is forward w.r.t . to the direction defined by @xmath66 . the quantity @xmath66 , in the strict sense , is not a _ single _ physical state of the hilbert - space of states , since this would imply @xmath67 . the analytic continuation is such , that @xmath36 is kept space like , which is necessary for the non perturbative behavior of the matrix element . the twist2 contributions to the expectation values of the operators ( [ oo],[oo5 ] ) are obtained @xmath68 the corresponding scalar and pseudo - scalar operators . the index @xmath69 labels the quark or gluon operators , cf . @xcite . in the unpolarized case only the vector operators contribute . the scalar twist2 quark operator matrix element has the representation due to the overall symmetry in @xmath55 @xmath70 and is independent of @xmath71 . here we assume that all the trace terms have been subtracted , see @xcite . the action of @xmath66 onto the scalar operator yield projections onto two directions @xmath72 and @xmath73 . @xmath74 and @xmath75 denote the corresponding scalar two variable distribution amplitudes and the measure @xmath76 is @xmath77 here , we decomposed the vector @xmath78 as @xmath79 with @xmath80 momentum fractions along @xmath81 and @xmath82 , @xmath83 and @xmath84 note that , @xmath85 . in the approximation @xmath86 , in which we work from now on , the vector @xmath87 vanishes . in this limit only the first term contributes to the matrix element eq . ( [ eqscam ] ) . the fourier transform of the compton amplitude is given by @xcite @xmath88 f(z_+,z_-)~,\end{aligned}\ ] ] with @xmath89 . the function @xmath90 is related to the distribution function @xmath91 by @xmath92 the denominators take the form @xmath93 where @xmath94 the conservation of the electromagnetic current is easily seen @xmath95 since the symmetry relation , @xcite , @xmath96 holds . subsequently we will use the distribution @xmath97 the distribution function @xmath98 is related to @xmath91 by @xmath99 with @xmath100 . the diffractive quark and anti quark densities are given by @xmath121 we finally can express the diffractive parton densities in terms of the distribution function @xmath91 directly @xmath122 the evolution equation of the scalar twist2 quark and gluon operator eq . ( [ eqsca ] ) read , cf . @xcite , . ] @xmath123 with @xmath124 and the measure @xmath125 we consider the non forward evolution equations to trace an eventual @xmath40dependence . here @xmath126 is the general non forward twist2 singlet evolution matrix . the same evolution equation applies to the matrix elements @xmath127 , which may be related to the distribution functions @xmath128 by with @xmath129 which is possible after the bjorken limit is taken . ] @xmath130 where @xmath131 and @xmath132 . ( [ eqfou ] ) and the inverse fourier transform @xmath133 are used to obtain evolution equations for @xmath134 . to perform the @xmath135integral the dependence on this variable has to be made explicit in the anomalous dimensions @xmath136 to all orders . the scalar operator matrix elements , eq . ( [ eqscam ] ) , do not depend on the light cone mark @xmath71 due to translation invariance on the light cone , which therefore can be set to zero in eq . ( [ eqan1 ] ) . furthermore , the anomalous dimension @xmath136 obeys the re - scaling relation , cf . @xcite , @xmath137 with @xmath138 . the anomalous dimension transforms to @xmath139 with @xmath140/2=\xi(1-u ) , \alpha_2=[1-(\kappa_+'-\kappa_-')/\kappa_-]/2=(1-\xi)(1-u)$ ] . the @xmath135integral yields @xmath141 the following evolution equations for the distribution functions @xmath128 are obtained : @xmath142 the functions @xmath143 are the _ forward _ splitting functions , which are independent of @xmath40 resp . @xmath39 , leading to @xmath144 they act on the momentum fraction @xmath102 of the diffractive parton densities . note that the range of @xmath145 is yet different from that of the corresponding quantity for deep inelastic scattering . after identifying @xmath146 taking the absorptive part , however , one arrives at the twist2 evolution equation @xmath147 in the case of deep inelastic scattering the corresponding identification for the momentum fraction is @xmath148 . the dependence of the diffractive parton densities w.r.t . @xmath40 , or @xmath39 , is _ entirely _ parametric and not changed under the evolution , which affects @xmath116 . in the case of the twist2 contributions factorization proofs were given @xcite theory in @xmath149 dimensions @xcite . ] , leading to the same evolution equations , ( [ eqev4 ] ) , which are confirmed by the present derivation . for phenomenological applications to next - to - leading order , see e.g. @xcite . we expressed the compton amplitude with the help of the light cone expansion at short distances and applied this representation to the process of deep inelastic diffractive scattering using mueller s generalized optical theorem . this representation is _ not _ limited to leading twist operators but can be extended to all higher twist operators synonymously . the corresponding evolution equations for the higher twist hadronic matrix elements , which depend on more momentum fractions @xmath150 than one , transform analogously to the case of twist2 being outlined above . a central parameter @xmath151 may be set to zero , and analogous re scaling relations apply . by virtue of this also here forward evolution equations are derived . however , the connection of the momentum fractions @xmath150 to the outer kinematic parameters is less trivial than in the case of twist2 due to the structure of the corresponding wilson coefficients . this is the case also for deep inelastic scattering , cf . e.g. @xcite . the differential cross section of unpolarized deep inelastic @xmath3diffractive scattering is described by four structure functions for pure photon exchange , which depend on the four kinematic variables , @xmath152 and @xmath36 . in the limit of vanishing target masses and @xmath153 only two structure functions contribute . in the case of hard diffractive scattering the scaling violations of these structure functions can be described perturbatively . this is possible in transforming the non forward amplitude of the process via mueller s optical theorem , by rotating the final state proton into an initial state anti proton . the compton amplitude is calculated for the hadronic two particle state @xmath66 and w.r.t . this state in the forward direction . the diffractive parton densities are associated to the general two variable distribution functions , which describe the hadronic matrix element . the scaling variable of the diffractive parton densities , which directly compares to the bjorken variable @xmath55 in the deep inelastic case , is @xmath154 . however , the callan gross relation takes the usual form @xmath155 . due to the transformation of the problem , which is made possible applying mueller s optical theorem , the anomalous dimensions are the same as for forward scattering . we demonstrated this by an explicit calculation in the case of the twist2 operators , however , the same mechanism applies also for higher twist operators using the light cone expansion . in the case of the twist2 contributions the effective momentum fraction , @xmath156 may be identified with the variable @xmath157 for diffractive scattering . the dependence of the parton densities on @xmath39 is not affected by qcd evolution , which acts on the variable @xmath116 . 999 m. derrick et al . , zeus collaboration , phys . * b315 * ( 1993 ) 481 ; 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a quantum field theoretic treatment of inclusive deep inelastic diffractive scattering is given . the process can be described in the general framework of non forward scattering processes using the light cone expansion in the generalized bjorken region . evolution equations of the diffractive hadronic matrix elements are derived at the level of the twist2 contributions and are compared to those of inclusive deep inelastic forward scattering ( dis ) . the diffractive parton densities are obtained as projections of two variable parton distributions . we also comment on the higher twist contributions in the light cone expansion . desy 01072 + may 2001 * on the scaling violations of diffractive * johannes blmlein@xmath0 and dieter robaschik@xmath1 + + + _ pf 101344 , d03013 cottbus , germany _ +

A handcycle is a type of human-powered land vehicle powered by the arms rather than the legs, as on a bicycle. Most handcycles are tricycle in form, with two coasting rear wheels and one steerable powered front wheel. Despite usually having three wheels, they are also known as handbikes. Description [ edit ] Hand trike Many manufacturers have designed and released hand-powered recumbent trikes, or handcycles. Handcycles are a regular sight at HPV meets and are beginning to be seen on the streets. They commonly follow a delta design with front wheels driven by standard derailleur gearing powered by hand cranks. Brake levers are usually mounted on the handholds which are usually mounted in phase, unlike pedal cranks, which are usually 180° out of phase. This allows the rider to more easily use their torso to help propel the cycle. The entire crank assembly and the front wheel turn together, allowing the rider to steer and crank simultaneously. Some designs use two front wheels and a single rear wheel, while others use lean-steer designs. A handcycle is not a wheelchair, handcycle has a crank and gears, while a wheelchair has push-rims directly on the main wheels.[1][2] Styles [ edit ] Handcycles come in a variety of styles, making them accessible to people with a wide variety of disabilities. There are also hybrids between a handcycle, a recumbent bike and a tricycle.[3] Fork steer [ edit ] Fork steer handcycles represent the majority of handcycles sold. They work well for both low and high-level spinal injuries, and most have adjustable footrests, seat angle, and come with a variety of gearing, wheel and tire configurations depending on intended use: racing, recreation, or touring. Manufacturers of this type of handcycle include Invacare (Top End), Intrepid Equipment, Varna, Schmicking and Sunrise Medical (Quickie). Lean steer [ edit ] Riders turn lean steer handcycles by leaning into the turn. There is a longer learning curve with lean steer handcycles and they are significantly less stable at high speed. The lean steer system feels similar to mono skiing: using your whole body to steer the handcycle. Lean steer handcycles can work well for lower-level injuries; although, some athletes with high-level disability use them as well. Manufacturers of this type of handcycle include Lighting Handcycles and Brike International Ltd. (Freedom Ryder). Another type of lean steer hand trike has two steering rear wheels and one non-steerable, powered front wheel with handholds offset at 180°, similar to pedal cranks, that can be operated with only one hand, thus making it easy to ride on an up-hill[citation needed], and it can be ridden in a tighter curve with the automatic rear wheels steering system.[citation needed] An "off road" handcycle, designed in the Netherlands Off road [ edit ] The off road is different from other handcycles in that there are two wheels in front and one behind, and it has a lower gear ratio range. This gives the cycle the ability to tackle steep slopes and permits handcycle mountain biking. The addition of a wider tire with suitable tread makes some mountain biking possible on standard road bikes. Touring [ edit ] Handcycles have also been used for touring, and to better accommodate this interest, some manufacturers incorporate mudguards and pannier cargo racks. As handcycles have evolved they have become progressively lighter, and they have better gearing for long climbs and long distance touring. See also [ edit ] ||||| The New 2018 Experience It all began in San Diego in 1998 and for over 20 years, the Rock ‘n’ Roll Marathon Series has made running fun by infusing each course with live bands, cheer teams and more. In 2018, we are bringing our best to the Synchrony Rock ‘n’ Roll San Diego Marathon & 1/2 with more music, runner support, and community engagement every step of the way. This event has always been our Epic Summer Run, and this year we made it better than ever! Register Finisher Zone presented by Synchrony Check out your Finisher Zone presented by Synchrony! View race times, collect finisher badges, and share your achievement. Please note, for participants who were impacted by the race stoppage on Sunday, June 3, you should have received additional communication in your Congrats email sent Friday, June 8. This information is also available here. View Results ||||| The last thing Anna Hackenberg remembers about walking along the beach at Torrey Pines State Natural Reserve in San Diego last spring was looking out at the Pacific and feeling a “Zen-like” oneness with the water, sun and sand. A week later, she woke up in the intensive care unit at Scripps Memorial Hospital La Jolla, paralyzed from the chest down. Doctors said she’d never be able to walk again. Get push notifications with news, features and more. The urgent care physician and avid runner had been crushed by a boulder that had tumbled down the rugged bluff that golden April morning. Anna and two friends on the beach with her didn’t hear the rock break away. In fact, it was only when they turned their heads to talk to talk to her, that they saw Anna lying unconscious on the beach, surrounded by debris and sharp pieces of broken stone. Courtesy of Anna Hackenberg Anna, 31, was devastated to learn about her spinal cord injury, but grateful to be alive. And within weeks, she decided that she would participate in the half marathon at San Diego’s Rock ‘n’ Roll Marathon Series in 2018 — this time as a handcyclist. Anna Hackenberg on a hike with her dog, Max, in 2016 Courtesy of Anna Hackenberg Anna Hackenberg on a hike with her dog, Max, in 2016 Anna Hackenberg with her sister Daphne Hackenberg in 2012, training for a marathon Courtesy of Anna Hackenberg “Exercise has always been a big part of my life, so there was never any question that I needed to do it,” Anna, who will be competing as a Toyota-sponsored athlete on June 3rd, tells PEOPLE. “Coming back and getting myself into shape for this was the hardest thing I’ve ever gone through, but also the most rewarding. It’s really made a difference in my life — I know that things could be much worse.” Now living with her sister, Daphne Hackenberg, 24, Anna has returned to her job at the Sharp Rees-Stealy Urgent Care Center and has spent most of her spare time the past year re-learning how to complete basic tasks such as rolling over in bed, getting into a wheelchair, walking a dog and bathing, along with training on a handcycle donated to her by the Challenged Athletes Foundation. “Anna’s positive attitude and willingness to try new things and accept help have been the catalyst to her finding a new path in life,” says Kristine Entwistle, the foundation’s associate executive director. “We’re thrilled to support her as she trains for her first competition after her accident — no doubt, the first of many.” Anna Hackenberg on her first day back to work Courtesy of Anna Hackenberg “When she was injured, I was worried that my sister would have new limits — she could have let her injury define her,” Daphne tells PEOPLE of her sister, “but she continues to surpass them each day with the mindset of an athlete. Anna’s body doesn’t define her — her mind does. She is limitless.” At the half marathon, more than 30 members of “Team Anna” will be on hand to cheer her toward the finish line, says Anna, who is thankful to them all for “not giving up on me and helping me to make the most of every moment.” Mike Badami “I used to throw on my running shoes and head out the door,” she tells PEOPLE, “and now, it’s much more complicated than that. I don’t know where I’d be without everybody’s help. Although it was devastating to learn that I was paralyzed, I’ve had a support system to help me figure out new ways of caring for myself and living my life. Nobody ever let me feel that there was anything to be sad about. For that, I’m truly grateful.”

– One San Diego physician knows more about rehabilitation and recovery than any medical course could have taught her, as People reports. Anna Hackenberg was walking along the beach at Torrey Pines State Natural Reserve in San Diego with two friends one day last April. A week later, the 31-year-old urgent care doctor woke up in intensive care at Scripps Memorial Hospital in La Jolla, paralyzed from the chest down. She would later find out from her friends that she had been hit by a falling boulder, a freak accident on an otherwise calm day. The avid runner spent the better part of the next year re-learning how to perform everyday tasks and manage a wheelchair. But it took her just weeks to decide she would complete the Rock ‘n’ Roll Half-Marathon in San Diego as a handcyclist. The Challenged Athletes Foundation says Anna fell in love with handcycling at one of its clinics just months after her accident. It gave her a handcycle soon after that; in a December Facebook post, she is pictured using it—and thanking the foundation for allowing her to "feel the ocean breeze in my hair again." After months of training, she will compete in the half-marathon as a Toyota-sponsored athlete on Sunday. She will have more than 30 friends there cheering her on, and her strongest emotion is gratitude for what she has learned and the support she’s received. “Nobody ever let me feel that there was anything to be sad about,” she tells People. “For that, I’m truly grateful.” Her sister notes that Anna "could have let her injury define her." Instead, she says, “Anna’s body doesn’t define her—her mind does. She is limitless.” (A paralyzed groom walked down the aisle at his wedding.)

BEIJING/SHANGHAI (Reuters) - President Donald Trump can return to the United States claiming to have snagged over $250 billion in deals from his maiden trip to Beijing. Whether those deals live up to the lofty price tag is another question altogether. FILE PHOTO: Boeing's logo is seen during Japan Aerospace 2016 air show in Tokyo, Japan, October 12, 2016. REUTERS/Kim Kyung-Hoon/File Photo Watched by Trump and China’s President Xi Jinping at a signing ceremony in Beijing, U.S. planemaker Boeing Co, General Electric Co and chip giant Qualcomm Inc sealed lucrative multi-billion dollar deals. “This is truly a miracle,” China’s Commerce Minister Zhong Shan said at a briefing in Beijing. The quarter of a trillion dollar haul underscores how Trump is keen to be seen to address a trade deficit with the world’s second-largest economy that he has long railed against and called “shockingly high” on Thursday. But U.S. businesses still have many long-standing concerns to complain about, including unfettered access to the China market, cybersecurity and the growing presence of China’s ruling Communist Party inside foreign firms. William Zarit, chairman of the American Chamber of Commerce in China, said the deals pointed to “a strong, vibrant bilateral economic relationship” between the two countries. “Yet we still need to focus on leveling the playing field, because U.S. companies continue to be disadvantaged doing business in China.” U.S. tech companies like Facebook Inc and Google are mostly blocked in China. Automakers Ford Motor Co and General Motors must operate through joint ventures, while Hollywood movies face a strict quota system. “(These deals) allow Trump to portray himself as a master dealmaker, while distracting from a lack of progress on structural reforms to the bilateral trade relationship,” Hugo Brennan, Asia analyst at risk consultancy Verisk Maplecroft, said in a note. PUMP IT UP Some huge deals were announced. Among them is a 20-year $83.7 billion investment by China Energy Investment Corp in shale gas developments and chemical manufacturing projects in West Virginia, a major energy producing state that voted heavily for Trump in the 2016 election. [ “The massive size of this energy undertaking and level of collaboration between our two countries is unprecedented,” West Virginia Secretary of Commerce H. Wood Thrasher said in a statement. It marks the first major overseas investment for the newly founded China Energy, which formed from the merger of China Shenhua Group, the country’s largest coal producer and China Guodian Corp, one of China’s top five utilities. However, as is often the case during state visits, many of the deals were packaged as “non-binding” agreements, gave scant details or rolled over existing tie-ups, helping pump up the headline figure. “I am somewhat skeptical of such a large number,” Alex Wolf, senior emerging markets economist at Aberdeen Standard Investments, told the Reuters Global Markets Forum, adding that the overall tone of the visit so far had been “positive”. “I suspect they might be primarily MOUs (memorandum of understandings) instead of actual contracts and the actual contract amount may be substantially less.” Qualcomm signed non-binding agreements worth $12 billion with Xiaomi, OPPO and Vivo, three Chinese handset makers that the firm said it had “longstanding relationships” with. Qualcomm already earns more than half of its revenues in China. Boeing announced a deal with state-run China Aviation Suppliers Holding Co to sell 300 Boeing jets with a valuation of $37 billion at list prices, though analysts said it was unclear how many of these were new orders. “Interesting to see how many of those are past agreements/purchase orders repackaged. Beijing is a master of selling the same agreement 10 times,” former Mexican ambassador to China Jorge Guajardo posted on Twitter. XI VOWS TRANSPARENCY Speaking alongside Trump in Beijing as they announced the deals, Xi said the Chinese economy would become increasingly open and transparent to foreign firms, including those from the United States, and welcomed U.S. companies to participate in his ambitious “Belt and Road” infrastructure-led initiative. Trump made clear he blamed his predecessors, not China, for allowing the U.s. trade deficit to get “out of kilter”, and repeatedly praised Xi, calling him “a very special man”. “But we will make it fair and it will be tremendous for both of us,” Trump said. Xi smiled widely when Trump said he does not blame China for the deficit. Slideshow (4 Images) Asked whether the big package of deals would go some way towards helping fix American trade concerns in China, executives were cautiously optimistic. “Generally the sense was that this is all a good thing, and that’s great,” said Gentry Sayad, a Shanghai-based lawyer who attended the trade delegation event in Beijing. “Now let’s see what really happens and whether or not the agreements signed during this trip can become a basis for a better bilateral trade relationship going forward.” ||||| Tweet with a location You can add location information to your Tweets, such as your city or precise location, from the web and via third-party applications. You always have the option to delete your Tweet location history. Learn more ||||| BEIJING — President Trump lavished praise on Chinese leader Xi Jinping here Thursday, touting “great chemistry” between them while refusing to criticize his counterpart for the trade imbalance that Trump railed against during his campaign. Speaking at a joint appearance with Xi in front of business leaders, Trump said the U.S. trade relationship with China is “a very one-sided and unfair one.” But, he quickly added: “I don’t blame China. Who can blame a country that is able to take advantage of another country for the benefit of its citizens? I give China great credit.” During the presidential campaign, Trump accused China of “raping” the U.S. economy and threatened to label the country a “currency manipulator” — even though economic analysts have said Beijing has not artificially suppressed the value of the renminbi for years, a tactic designed to make exports cheaper. In his remarks here, Trump reiterated that the United States must “change its policies,” but he offered no details about actions his administration will pursue. “We’ve gotten so far behind on trade with China and frankly many other countries,” Trump said ahead of a bilateral meeting with Xi, before adding he has “great respect” for Xi for “representing China.” Trump blamed past U.S. administrations “for having allowed it to get so far out of kilter. We’ll make it fair, and it’ll be tremendous for both of us. My feeling toward you is incredibly warm. We have great chemistry. I think we’ll do tremendous things, China and the U.S.” Trump echoed those points in a series of tweets Friday morning before leaving Beijing, including one in which he said, “I blame the incompetence of past Admins for allowing China to take advantage of the U.S. on trade leading up to a point where the U.S. is losing $100's of billions. How can you blame China for taking advantage of people that had no clue?” Trump's comments drew quick criticism Thursday from Senate Minority Leader Charles E. Schumer (D-N.Y.). “The president may not blame China, but I do, and so do millions of Americans who voted for him and others who have lost their jobs at the hands of China’s rapacious trade policies,” he said in a statement. “After campaigning like a lion against China’s trade practices, the president is governing like a lamb. Rather than treating China with kid gloves, the president should be much tougher with China — as he promised he would be on the campaign trail.” Their high-stakes, two-day summit is being closely watched for signs of how the leaders of the world’s two biggest economies will be able to cooperate on issues from North Korea to trade to cybersecurity amid mounting challenges in the Asia-Pacific. Trump is hoping to win concessions from Xi, but the Chinese leader is in a strong position after having consolidated power at a Communist Party congress last month. The two countries announced memorandums of understanding to increase trade by $253 billion, which the leaders said was a sign of greater cooperation. In contrast to Trump’s effusive praise, Xi appeared reserved and spoke in carefully scripted language about “win-win” cooperation and a “new starting point” for the bilateral relationship — language Beijing has employed in a bid to get the United States to agree to allow China to operate in its “sphere of influence” in Asia without meddling. Xi did not talk in personal terms about Trump. The United States and China had clashed on issues from cybersecurity to trade in the final years of the Obama administration, although they had struck a landmark climate deal during Barack Obama’s 2014 visit to Beijing that served as a prelude to the Paris climate accord. Trump has announced intentions to withdraw the United States from that agreement, but Xi has pledged to make China a leader on reducing carbon emissions. Xi vowed to work together in the “spirit of mutual respect and mutual benefit.” During a joint statement with Xi in front of reporters, Trump reiterated his harsh criticism of North Korea and said he and Xi discussed their shared goal of pursuing the “complete denuclearization” of the Korean Peninsula. “We call on all responsible nations to join together to stop arming and financing and even trading with the murderous North Korean regime,” Trump said. But the two leaders did not take questions from reporters, a win for Xi, who oversees an authoritarian system that has sought to sharply limit free speech and press freedoms. Secretary of State Rex Tillerson, briefing reporters after the meetings, said the U.S. delegation was “quite pleased” because there was “no disagreement” on North Korea. Trump pressed Xi to fully implement the economic sanctions on Pyongyang authorized by the United Nations Security Council, Tillerson said, and Xi outlined additional steps his government is taking to crack down on banks doing business with the North. “There was no space between both of our objectives,” Tillerson said. But he cautioned that Xi also emphasized that “it will take time” for the new sanctions to create stress on the North. On trade, Tillerson called the deals struck at the summit relatively “small in the grand scheme of things,” given a trade deficit of more than $300 billion a year. “In terms of really getting at some of the fundamental imbalance that exists, we have a lot more work to do,” Tillerson said. Asked about Trump’s change in tone on trade from the campaign, Tillerson said the remarks were intended as “a little bit tongue in cheek.” But he added that the imbalance has stretched for decades and was fanned by the “benign neglect” from past U.S. administrations. “His characterization is that you cannot not blame a large developing country for doing what they have to do,” Tillerson said. Chinese state media appeared pleased with the summit. The Global Times, a newspaper known for its nationalist rhetoric, declared that Trump “respects our head of state and has repeatedly praised President Xi Jinping in public.” Tao Wenzhao, a researcher at the Chinese Academy of Social Science’s Institute for American Studies, said in an interview that Trump’s decision not to blame China “shows that he understands the complex reasons behind the trade imbalance. The trade imbalance cannot be corrected overnight.” On Trump’s first full day in China — the third stop on a five-country, 12-day trip through Asia — Xi greeted him with a lavish reception at the Great Hall of the People, a display that included three horn players in red uniforms, a military band and ceremonial cannon fire. Trump, who has suggested he would like to stage a military parade in Washington over the July 4 weekend, seemed impressed. He called the parade “magnificent.” “I already had people calling from all parts of the world,” he added. “They were watching. Nothing you can see is so beautiful.” The Chinese have described Trump’s trip to the country as a “state visit plus” and so far have lavished him with special treatment. He arrived Wednesday afternoon for a sunset tour of the Forbidden City, the ornate Chinese imperial palace stretching from the Ming to Qing dynasties, before taking in a performance of the Peking opera. Trump effusively thanked Xi for hosting him and first lady Melania Trump at a dinner after his arrival a night earlier, saying their meal was scheduled to last less than half an hour because Trump was tired after a long day of traveling from Seoul. Instead, Trump said, it went on for more than two hours. “I enjoyed every minute of it,” Trump said. At another point, Trump told Xi: “You are a very special man.” Trump arrived in China while being dogged with political problems back home and facing the lowest approval numbers of his presidency. And despite the pageantry surrounding the visit and an eagerness of the Chinese to reset their relationship with the United States, Xi — now arguably his nation’s most powerful leader since Mao Zedong — appeared emboldened to demand concessions from the United States. Asked if Trump had been too deferential to Xi on the Chinese leader’s home turf, Tillerson replied: “I didn’t detect that at all.” Emily Rauhala in Beijing and John Wagner in Washington contributed to this report.

– President Trump has previously expressed being "disappointed" at China for "taking advantage" of the US with "one-sided" trade, as well as called the country a "currency manipulator." But speaking in Beijing on Thursday, he appeared to admire any clever exploitation of the US. "I don't blame China," he said in a speech to business leaders after a two-hour sit-down with President Xi Jinping. "After all, who can blame a country for being able to take advantage of another country for benefit of their citizens? I give China great credit." Instead of pointing the finger at his host nation, Trump blamed his own predecessors "for allowing this trade deficit to take place and to grow." Trump also touted the "great chemistry" he says he shares with Xi and said he thinks the two countries will do "tremendous things," per the Washington Post. Trump said he mentioned the "chronic imbalance" of the nations' trade status to Xi, and the leaders announced they'd worked out $250 billion in various trade deals, which China's commerce minister called a "miracle," per Reuters. Details weren't offered, and CNN notes that many agreements were already in progress when Trump took office. Xi, for his part, was more "reserved," per the Post, simply talking about a "new starting point" for the two nations and a "win-win" relationship while avoiding discussing his personal relationship with Trump. Trump and Xi didn't field questions during their joint appearance; CNN notes that Trump's three immediate predecessors in the White House had all convinced Chinese leaders on their own first state visits there to take questions. "It was at the Chinese insistence there were no questions today," press secretary Sarah Huckabee Sanders said.

the x - ray sky as seen by satellite observations over the past 40 years , shows a substantially different picture than for example the optical band . while the visual night sky is dominated by main sequence stars , galactic binary systems and super nova remnants form the brightest objects x - rays . common to both regimes is the dominance of active galactic nuclei ( agn ) toward lower fluxes . in the x - ray range itself , one observes a slightly different population of agn at soft and at hard x - rays . below 5 kev the x - ray sky is dominated by agn of the seyfert 1 type ; above 5 kev the absorbed seyfert 2 objects appear to become more numerous . these type 2 agn are also believed to be the main contributors to the cosmic x - ray background above 5 kev ( setti & woltjer 1989 ; comastri et al . 1995 ; gilli et al . 2001 ) , although only @xmath4 of the xrb above @xmath5 can be resolved ( worsley et al . 2005 ) . the hard x - ray energy range is not currently accessible to x - ray telescopes using grazing incidence mirror systems . instead detectors without spatial resolution like the pds on _ bepposax _ and osse on _ cgro _ have been applied . a synopsis of these previous results is as follows : the 2 10 kev seyfert 1 continua are approximated by a @xmath6 powerlaw form ( zdziarski et al . . a flattening above @xmath7 has been noted , and is commonly attributed to compton reflection ( george & fabian 1991 ) . there is a great deal of additional detail in this spectral domain - `` warm '' absorption , multiple - velocity component outflows , and relativistic line broadening - which are beyond the scope of this paper . the seyfert 2 objects are more poorly categorized here , but the general belief is that they are intrinsically equivalent to the seyfert 1s , but viewed through much larger absorption columns . above 20 kev the empirical picture is less clear . the @xmath8 continuum shape of both seyfert types is consistent with a thermal comptonization spectral form , although in all but a few cases the data are not sufficiently constraining to rule out a pure powerlaw form . nonetheless , the non - thermal scenarios with pure powerlaw continua extending to @xmath9 energies reported in the pre-_cgro _ era are no longer widely believed , and are likely a result of background systematics . however , a detailed picture of the comptonizing plasma - its spatial , dynamical , and thermo - dynamic structure - is not known . among the critical determinations which _ integral _ or future hard x - ray instruments will hopefully provide are the plasma temperature and optical depth ( or compton `` y '' parameter ) for a large sample of objects . the other major class of gamma - ray emitting agn - the blazars ( fsrqs and bl lac objects ) are even more poorly constrained in the _ integral _ spectral domain ( for early _ integral _ results see for example pian et al . critical to each of these issues is the need to obtain improved continuum measurements over the hard x - ray to soft gamma - ray range for as large a sample of objects as possible . _ integral _ , since its launch in october 2002 , offers unprecedented @xmath10 collecting area and state of the art detector electronics and background rejection capabilities . thus it offers hope of substantial gains in our knowledge of the agn phenomenon and in particular of the cosmic hard x - ray background . the first _ integral _ agn catalogue offers the possibility to address these questions and to compare the results with previous missions . our _ integral _ agn sample consists of 42 extragalactic objects , detected in the @xmath11 energy band with the imager ibis / isgri . spectra have been extracted from ibis / isgri , the spectrometer spi , and the x - ray monitor jem - x in order to cover the energy range from @xmath12 . the list of sources with their redshift , the optical counterpart type , the flux in the 20 40 kev band as measured by isgri , the luminosity in the 20 100 kev band , and the intrinsic absorption as measured at soft x - rays is given in table [ tab : sample ] . details on the analysis and on individual spectra can be found in beckmann et al . the distribution of sources in the sky is shown in figure [ fig : agnmap ] . the seyfert type agn found in the sample are preferentially low redshift objects . figure [ fig : zhisto ] shows the distribution of redshifts in the sample . the blazars all show higher redshifts ( @xmath13 ) and are not included in the histogram . the one object on the right is pg 1416129 ( @xmath14 ) and is an anomalous radio quiet quasar with similar spectroscopic properties as radio - loud sources ( sulentic et al . 2000 ) . in order to investigate the agn subtypes , we have derived averaged spectra of the seyfert 1 and 2 types , as well as for the intermediate seyferts and the blazars . the average seyfert 1 spectrum was constructed using the weighted mean of 10 isgri spectra , the seyfert 2 composite spectrum includes 15 sources , and 8 objects form the intermediate seyfert 1.5 group . the two brightest sources , cen a and ngc 4151 , have been excluded from the analysis as their high signal - to - noise ratio would dominate the averaged spectra . the average spectra have been constructed by computing the weighted mean of all fit results on the individual sources . in order to do so , all spectra had been fit by an absorbed single powerlaw model . when computing the weighted average of the various sub - classes , the seyfert 2 objects show flatter hard x - ray spectra ( @xmath15 ) than the seyfert 1.5 ( @xmath16 ) , and seyfert 1 appear to have the steepest spectra ( @xmath17 ) together with the blazars ( @xmath18 ) . the seyfert type classification of the objects is based on optical observations . an approach to classifying sources according to their properties in the x - rays can be done by separating the sources with high intrinsic absorption ( @xmath19 ) from those objects which do not show significant absorption . the distribution of absorption at soft x - rays for the agn sample is shown in figure [ fig : nh_histogram ] . the black part of the histogram represents the seyfert 2 agn ( including the seyfert 1.8 and seyfert 1.9 subtypes ) . it has to be pointed out that not all objects which show high intrinsic absorption in the x - rays are classified as seyfert 2 galaxies in the optical , and the same applies for the other agn sub - types . nevertheless a similar trend in the spectral slopes can be seen : the 21 absorbed agn show a flatter hard x - ray spectrum ( @xmath20 ) than the 13 unabsorbed sources ( @xmath21 ) . the blazars have again been excluded from these samples . among the seyfert 2 galaxies we find 4 objects with low absorption ( @xmath22 ) , 7 with intermediate absorption ( @xmath23 ) , and four compton thick agn ( @xmath24 ) . although the _ integral _ agn sample discussed here is not a complete flux limited one , the number counts give a first impression regarding the flux distribution within the sample ( fig . [ fig : lognlogs ] ) . excluding the two brightest objects ( cen a and ngc 4151 ) and the objects with @xmath25 ( where the number counts shows a turnover ) , the number counts relation shows a gradient of @xmath26 , and is consistent with the value of 1.5 expected for eucledian geometry and no evolution in the local universe . figure [ fig : loglx_nh ] shows the intrinsic absorption of the objects , as measured in the soft x - rays , versus the luminosity in the 20 100 kev energy band as measured by _ integral_. there is no discernable correlation between those values . the optically classified seyfert 2 objects naturally populate the area with higher intrinsic absorption . the typical _ integral _ spectrum can be described by a simple powerlaw model with average photon indices ranging from @xmath27 for obscured agn to @xmath28 for unabsorbed sources . the simple model does not give reasonable results in high signal - to - noise cases , where an appropriate fit requires additional features such as a cut - off and a reflection component ( soldi et al . 2005 , beckmann et al . 2005 ) . the results presented here show slightly steeper spectra than previous investigations of agn in comparable energy ranges . the same trend is seen in the comparison of crab observations , where the _ integral_/isgri spectra also appear to be slightly steeper than in previous observations , and in comparison of _ rxte _ and _ integral_/isgri spectra of cen a ( rothschild et al . this trend might be based on improper calibration and/or background subtraction . the average properties , like spectral slope , redshift , luminosity , are rather similar compared to previous studies ( e.g. zdziarski et al . 1995 , gondek et al . 1996 ) . comparing the ratio @xmath29 of obscured ( @xmath19 ) to unobscured agn we find in the _ integral _ data that @xmath30 . the ratios change slightly when taking into account only those objects which belong to the complete sample with an isgri significance of @xmath31 or higher ( beckmann et al . this sub - sample includes 32 agn , with 18 obscured and 10 unobscured objects ( absorption information is missing for the remaining four objects ) . using only the complete sample gives a similar ratio of @xmath32 . splitting this result up into objects near the galactic plane ( @xmath33 ) and off the plane shows for all objects a ratio of @xmath34 and @xmath35 , respectively . this trend shows that the harder spectra of those objects , where the absorption in the line of sight through the galaxy is low compared to the intrinsic absorption , are more likely to shine through the galactic plane . risaliti et al . ( 1999 ) studied a large sample of seyfert 2 galaxies focusing especially on the intrinsic absorption measured at soft x - rays . they also find a fraction of 75% of seyfert 2 with an intrinsic absorption @xmath36 , but a 50% fraction of compton - thick objects with @xmath24 , where the _ integral _ sample only finds 4 objects ( 27 % ) . optical studies in the local universe find evidence that type 2 agn are about a factor of four more numerous than type 1 agn ( setti & woltjer 1989 ; comastri et al . in x - rays the situation is similar , although not all seyfert 1 objects show low intrinsic absorption and vice versa ( see fig . [ fig : loglx_nh ] ) . recent studies have shown that the fraction of absorbed sources depends both on luminosity and redshift in a way that the fraction of type 2 agn increases towards higher redshifts and lower luminosity ( e.g. gilli et al . 2001 ; ueda et al . 2003 ; la franca et al . 2005 ) . ueda et al . ( 2003 ) sudied 247 agns in the 2 10 kev band with luminosities in the range @xmath37 , similar to the luminosity range of the _ integral _ agn but extending to higher redshifts ( @xmath38 ) and to fainter fluxes ( @xmath39 ) . they find that the number of agn decreases with the intrinsic x - ray luminosity of the agn and therefore favour a luminosity dependend density evolution ( ldde ) to explain the luminosity function in the @xmath40 band . la franca et al . ( 2005 ) used an even larger sample and confirmed the necessity of a ldde model , where low luminosity agn peak at @xmath41 , while high luminosity agn peak at @xmath42 . in addition , they find evidence that the fraction of absorbed ( @xmath43 ) agn decreases with the intrinsic luminosity in the @xmath40 energy range . consistent with our study , la franca et al . also find a ratio of @xmath44 at @xmath45 . all these results based on the 2 10 kev band are consistent with the findings of the _ integral _ agn sample at higher energies ( @xmath11 ) . it is surprising though that different from the findings of risaliti et al . ( 1999 ) we do not detect a large fraction of compton - thick agn . these agn , if exisiting , could explain the peak in the hard x - ray background around 30 kev ( e.g. maiolino et al . 2003 ) . in view of recent results this lack of compton - thick objects is explainable by the type of agn detected so far by _ integral_. all objects are local agn , with a mean redshift of @xmath2 ( fig . [ fig : zhisto ] ) . the objects are bright ( @xmath46 ; fig . [ fig : lognlogs ] ) , but have low luminosities ( @xmath1 ) . this still leaves room in the parameter space of agn to locate compton - thick agn . those objects could have lower fluxes and therefore even lower luminosities in the local universe than the objects studied by _ this possibility is supported by the unified model for agn as described by treister & urry ( 2005 ) . they predict a strong correlation of the fraction of broad line agn with luminosity , and expect up to a factor of 10 more absorbed than un - absorbed agn at very low luminosities ( @xmath47 ) . this trend can be seen also in the _ integral _ agn sample . when considering only the 14 objects with @xmath48 the ratio of obscured to unobscured objects increases to @xmath49 . studying the population of sources at lower limiting fluxes should also reveal further highly absorbed sources at high redshifts , because these have been missed so far and with increasing redshift an increase of absorbed agn fraction is expected ( la franca et al . 2005 ) . the energy range in the 15 200 kev is now also accessible through the bat instrument aboard _ swift _ ( gehrels et al . 2005 ) . a study by markwardt et al . ( 2005 ) used data from the first three months of the _ swift _ mission for studying the extragalactic sky and reached a flux limit of @xmath50 . the source population is similar to the _ integral _ one , with an average redshift of @xmath51 , and a ratio of @xmath52 between obscured and unobscured agn , fully consistent with _ integral_. although the _ swift_/bat survey covers different areas of the sky , the energy band is similar to the _ integral_/isgri range and the type of agn detectable should be the same . within their sample of 44 agn they detect 5 compton - thick agn , the same ratio as in the _ integral _ sample . the only difference appears in the relation between luminosity and absorption . while in the _ integral _ sample no correlation is detectable ( fig . [ fig : loglx_nh ] ) , markwardt et al . find in their sample evidence for an anti - correlation of luminosity and absorption . the _ integral _ agn sample opens the window to the hard x - ray sky above 20 kev for population studies . with the 42 extragalactic objects discussed here , a fraction of about @xmath53 shows absorption above @xmath54 , but only four objects are actually compton - thick ( @xmath24 ) . this shows that the source population above 20 kev , at least at the high flux end , is very similar to the one observed in the @xmath40 energy region . the results are consistent with observations by the _ swift_/bat instrument , although we can not confirm a correlation of x - ray luminosity with instrinsic absorption . further investigations are necessary and with the ongoing _ integral _ and _ swift _ mission it will be revealed in the near future , if there is a significant compton - thick agn population to explain the peak in the extragalactic x - ray background around 30 kev . these objects would have to have lower fluxes than the objects studied here ( i.e. @xmath55 ) and might therefore be low - redshift , low - luminosity ( @xmath56 ) seyfert galaxies , or higher redshift ( @xmath57 ) objects . lllccc name & z & type & @xmath58 & @xmath59 & @xmath60 + & & & @xmath61 $ ] & @xmath62 $ ] & @xmath63 $ ] + ngc 788 & 0.0136 & sy 1/2 & @xmath64 & 43.52 & @xmath65 + ngc 1068 & 0.0038 & sy 2 & @xmath66 & 41.92 & @xmath67 + ngc 1275 & 0.0176 & sy 2 & @xmath68 & 43.47 & 3.75 + 3c 111 & 0.0485 & sy 1 & @xmath69 & 44.90 & 0.634 + mcg + 81111 & 0.0205 & sy 1.5 & @xmath70 & 44.06 & @xmath65 + mrk 3 & 0.0135 & sy 2 & @xmath71 & 43.53 & 110 + mrk 6 & 0.0188 & sy 1.5 & @xmath72 & 43.57 & 10 + ngc 4051 & 0.0023 & sy 1.5 & @xmath73 & 41.60 & @xmath74 + ngc 4151 & 0.0033 & sy 1.5 & @xmath75 & 43.15 & 4.9 + ngc 4253 & 0.0129 & sy 1.5 & @xmath76 & 42.93 & 0.8 + ngc 4388 & 0.0084 & sy 2 & @xmath77 & 43.55 & 27 + ngc 4395 & 0.0011 & sy 1.8 & @xmath78 & 40.64 & 0.15 + ngc 4507 & 0.0118 & sy 2 & @xmath79 & 43.68 & 29 + ngc 4593 & 0.0090 & sy 1 & @xmath80 & 43.08 & 0.02 + coma cluster & 0.0231 & gclstr . & @xmath81 & 43.40 & @xmath74 + ngc 4945 & 0.0019 & sy 2 & @xmath82 & 42.30 & 400 + eso 323g077 & 0.0150 & sy 2 & @xmath83 & 43.21 & 55 + ngc 5033 & 0.0029 & sy 1.9 & @xmath84 & 41.55 & 2.9 + cen a & 0.0018 & sy 2 & @xmath85 & 42.75 & 12.5 + mcg0630015 & 0.0077 & sy 1 & @xmath86 & 42.93 & 17.7 + 4u 134460 & 0.043 & ? & @xmath87 & 44.36 & 2.19 + ic 4329a & 0.0161 & sy 1.2 & @xmath88 & 44.04 & 0.42 + circinus gal . & 0.0014 & sy 2 & @xmath89 & 41.97 & 360 + ngc 5506 & 0.0062 & sy 1.9 & @xmath90 & 42.83 & 3.4 + pg 1416129 & 0.1293 & sy 1 & @xmath91 & 45.78 & 0.09 + ic 4518 & 0.0157 & sy 2 & @xmath92 & 42.92 & ? + ngc 6221 & 0.0050 & sy 1/2 & @xmath93 & 42.39 & 1 + ngc 6300 & 0.0037 & sy 2 & @xmath94 & 42.36 & 22 + grs 1734292 & 0.0214 & sy 1 & @xmath95 & 43.88 & 3.7 + igr j180271455 & 0.0350 & sy 1 & @xmath96 & 44.03 & 19.0 + eso 103g35 & 0.0133 & sy 2 & @xmath97 & 43.51 & 13 16 + 1h 1934063 & 0.0106 & sy 1 & @xmath98 & 42.51 & ? + ngc 6814 & 0.0052 & sy 1.5 & @xmath99 & 42.52 & @xmath100 + cygnus a & 0.0561 & sy 2 & @xmath101 & 44.71 & 20 + mrk 509 & 0.0344 & sy 1 & @xmath102 & 44.42 & @xmath103 + igr j21247 + 5058 & 0.020 & radio gal . ? & @xmath104 & 44.00 & ? + mr 2251178 & 0.0634 & sy 1 & @xmath105 & 44.40 & 0.02 0.19 + mcg 0258022 & 0.0469 & sy 1.5 & @xmath106 & 44.18 & @xmath107 + s5 0716 + 714 & 0.3@xmath108 & bl lac & @xmath109 & 45.21@xmath108 & @xmath74 + s5 0836 + 710 & 2.172 & fsrq & @xmath110 & 47.87 & @xmath111 + 3c 273 & 0.1583 & blazar & @xmath112 & 45.92 & @xmath113 + 3c 279 & 0.5362 & blazar & @xmath114 & 46.37 & @xmath115 + pks 1830211 & 2.507 & blazar & @xmath116 & 48.09 & @xmath117 + + @xmath108 tentative redshift + [ tab : sample ] beckmann v. , shrader c. r. , gehrels n. , et al . 2005 , apj in press , astro - ph/0508327

we present results based on the first _ integral _ agn catalogue . the catalogue includes 42 agn , of which 10 are seyfert 1 , 17 are seyfert 2 , and 9 are intermediate seyfert 1.5 . the fraction of blazars is rather small with 5 detected objects , and only one galaxy cluster and no star - burst galaxies have been detected so far . the sample consists of bright ( @xmath0 ) , low luminosity ( @xmath1 ) , local ( @xmath2 ) agn . although the sample is not flux limited , we find a ratio of obscured to unobscured agn of @xmath3 , consistent with luminosity dependent unified models for agn . only four compton - thick agn are found in the sample . this implies that the missing compton - thick agn needed to explain the cosmic hard x - ray background would have to have lower fluxes than discovered by _ integral _ so far .

embryos were prepared for ec ( early chick ) cultures and then electroporated and/or ablated followed by culture on the microscope stage for time - lapse recordings . rusty landford ( caltech ) . a monoclonal antibody to avian fibronectin , b3d6 ( developmental studies hybridoma bank , university of iowa , iowa city , ia ) was directly coupled to a fluorochrome alexa-555 ( molecular probes , eugene , or ) and microinjected into the psm and lateral mesoderm 1 h before the start of a time - lapse experiment . time - lapse microscopy and image treatment were accomplished as described and in the supplementary methods . a fragment corresponding to the xenopus fgfrdn ( xfd ) ( gift from dr patrick lemaire as described ) was cloned into pbi - egfp ( clontech ) . for the inducible constructs , pbi - egfp or pbi - fgfrdn was coelectroporated with pcirx - rtta - advanced ( gift from dr tadahiro iimura ) . a version of the pbi vectors devoid of gfp and rtta - advanced without red fluorescent protein was also used in order to facilitate tracking of co - electroporated h2b - gfp or fibronectin antibody . full methods and any associated references are available in the online version of this paper at www.nature.com/nature . embryos were prepared for ec ( early chick ) cultures and then electroporated and/or ablated followed by culture on the microscope stage for time - lapse recordings . rusty landford ( caltech ) . a monoclonal antibody to avian fibronectin , b3d6 ( developmental studies hybridoma bank , university of iowa , iowa city , ia ) was directly coupled to a fluorochrome alexa-555 ( molecular probes , eugene , or ) and microinjected into the psm and lateral mesoderm 1 h before the start of a time - lapse experiment . time - lapse microscopy and image treatment were accomplished as described and in the supplementary methods . a fragment corresponding to the xenopus fgfrdn ( xfd ) ( gift from dr patrick lemaire as described ) was cloned into pbi - egfp ( clontech ) . for the inducible constructs , pbi - egfp or pbi - fgfrdn was coelectroporated with pcirx - rtta - advanced ( gift from dr tadahiro iimura ) . a version of the pbi vectors devoid of gfp and rtta - advanced without red fluorescent protein was also used in order to facilitate tracking of co - electroporated h2b - gfp or fibronectin antibody . full methods and any associated references are available in the online version of this paper at www.nature.com/nature .

vertebrate embryos are characterized by an elongated antero - posterior ( ap ) body axis , which forms by progressive cell deposition from a posterior growth zone in the embryo . here , we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm ( psm ) plays a key role in axis elongation . using time - lapse microscopy , we analysed the movements of fluorescently labelled cells in the psm during embryo elongation which revealed a clear posterior - to - anterior gradient of cell motility and directionality in the psm . we tracked the movement of the psm extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells . after subtraction , cell motility remained graded but lacked directionality , indicating that the posterior cell movements associated with axis elongation in the psm are not intrinsic but reflect tissue deformation . the gradient of cell motion along the psm parallels the fibroblast growth factor ( fgf)/mitogen - activated protein kinase ( mapk ) gradient 1 , which has been implicated in the control of cell motility in this tissue2 . both fgf signalling gain- and loss - of - function experiments lead to disruption of the motility gradient and a slowing down of axis elongation . furthermore , embryos treated with cell movement inhibitors ( blebbistatin or rhok inhibitor ) , but not cell cycle inhibitors , show a slower axis elongation rate . we propose that the gradient of random cell motility downstream of fgf signalling in the psm controls posterior elongation in the amniote embryo . our data suggest that tissue elongation is an emergent property that arises from the collective regulation of graded , random cell motion rather than by the regulation of directionality of individual cellular movements .

Tweet with a location You can add location information to your Tweets, such as your city or precise location, from the web and via third-party applications. You always have the option to delete your Tweet location history. Learn more ||||| Gal Gadot is currently filming the highly anticipated Wonder Woman 1984 around parts of Virginia and in downtown Washington D.C., as the nation’s capital police traffic Twitter account slyly confirmed last month. Filming the sequel to the popular superhero movie is obviously being kept tightly under wraps. But on Friday, Gadot took a break from her hectic film schedule to brighten the lives of some ailing kids at the Inova Children’s Hospital in Falls Church, Virginia And naturally, Gadot—a mother of two herself—surprised the kids in her full Wonder Woman garb, as you can see from the social media posts chronicling the visit. Thank you �?�@GalGadot�?� for visiting us �?�@InovaHealth�?� Children’s Hospital. You are a true Wonder Woman. The kids loved it…and so did the staff 😉 #wonderwoman84 pic.twitter.com/EFDLM02rpf — Dr. Lucas Collazo (@DrCollazo) July 6, 2018 Dear @GalGadot– Thank you SO MUCH for visiting my patients and colleagues at #InovaChildrensHospital! Next time, can you align your visit with my call schedule? Love, #SuperFan pic.twitter.com/kmE7CoFRvE — Patty Seo-Mayer (@PSeoMayer) July 7, 2018 This is yet another example of Gadot continuing to be a hero onscreen and off. Last November, in the wake of accusations lobbed against Brett Ratner, whose production company RatPac-Dune Entertainment helped finance Wonder Woman—and who profited greatly from the film—Gadot said that would not participate in a sequel if the film producer was involved. In total, six women, including Olivia Munn and Ellen Page, came forward as part of the #MeToo movement to allege that Ratner had sexually abused or harassed them. As a result, Warner Bros. has ended its co-financing deal with Ratner’s production company and kicked him to the curb, much to the relief of Gadot. “Everyone knew what was the right thing to do,�? she said at the time. Gadot has also kept busy by calling out Ryan Reynolds for pilfering Wonder Woman’s signature move and by advocating for the immigrant families who have been separated at the border to be reunited once again. Wonder Woman 1984 is scheduled to be released in November 2019. READ MORE: H/T WTOP

– Gal Gadot may not have actual superpowers but she definitely has a big heart. The Wonder Woman star, who is filming sequel Wonder Woman 1984 in Washington, DC, and northern Virginia, surprised kids at a Virginia children's hospital by turning up in costume, the Daily Dot reports. "The kids loved it ... and so did the staff," tweeted Dr. Lucas Collazo at the Inova Children's Hospital in Falls Church, sharing a photo of the Israeli star posing with staff members. "You are a true Wonder Woman," he wrote. The hotly anticipated sequel, which also brings back co-star Chris Pine, is due out on Nov. 1 next year, the Hollywood Reporter notes.

Former House Speaker Newt Gingrich said Sunday that he was self-funding his Republican presidential presidential bid "a little bit." "A little bit, but not dramatically," Gingrich said on "Fox News Sunday" in response to a question from host Brit Hume on whether he was contributing to his own campaign out of pocket. On the question of the campaign's debt, Gingrich said ""We owe much more than we wanted to. Florida got to be a real brawl. Unfortunately, our guys tried to match Romney." "We're operating on a shoestring," Gingrich said. Read more about: Newt Gingrich ||||| The seed for this crawl was a list of every host in the Wayback Machine This crawl was run at a level 1 (URLs including their embeds, plus the URLs of all outbound links including their embeds) The WARC files associated with this crawl are not currently available to the general public.

– He was hoping for a bounce in the polls, but the only thing bouncing in Utah was Newt Gingrich's $500 application fee to get on the primary ballot, reports the Salt Lake City Tribune. Worse—when Utah officials tried to get in touch with Gingrich's local office, there was no response from the phone numbers or email addresses provided on the application. Gingrich has until April 20 to sort things out if he wants to get on the ballot there. Gingrich has largely run a tight campaign (save for those multimillion dollar donations from Sheldon Adelson), and he Sunday admitted to using "a little bit" of his own money to offset the campaign's $4.5 million in debt, reports Politico. Other signs of Gingrich money problems include his health care think tank filing for Chapter 7 bankruptcy last week. But there's always Jimmy Kimmel's suggestion to pay Gingrich to just go away.

it is widely accepted that a complete infertility workup should include an evaluation of the uterine cavity . uterine abnormalities , congenital or acquired , are implicated as one of the causes of infertility . in fact , infertility related to uterine cavity abnormalities has been estimated to be the causal factor in as many as 10% to 15% of couples seeking treatment . moreover , today , hysteroscopy is considered the gold standard for evaluating the uterine cavity , and due to improved endoscopic developments , can be performed reliably and safely as an office procedure . direct view of the uterine cavity offers a significant advantage over other blind or indirect diagnostic methods . although fayez reported hysterosalpingography ( hsg ) to be as accurate as hysteroscopy in the diagnosis of normal and abnormal cavities , the nature of the intrauterine filling defects is more accurately revealed by hysteroscopy . later studies have shown a correlation of only 65% between findings diagnosed with hsg compared with those diagnosed with hysteroscopy . the role of hysteroscopy in infertility investigation is to detect possible intrauterine changes that could interfere with implantation or growth , or both , of the conceptus , and to evaluate the benefit of different treatment modalities in restoring a normal endometrial environment . oliveira reported detection of significant , unsuspected intrauterine abnormalities , found only with hysteroscopy , in 25% of patients with repeated failed in vitro fertilization and embryo transfer ( ivf - et ) cycles . more importantly , relevant therapeutic interventions significantly improved the clinical pregnancy rate in those with abnormal uterine cavity at hysteroscopy . hysteroscopy can diagnose much more precisely , compared with hsg and even transvaginal ultrasonography , small intrauterine lesions that might affect fertility . in view of all of the above , it is clear why many authors believe that uterine and endometrial integrity should be evaluated primarily by hysteroscopy in the infertile / ivf treated population . still , many consider hysteroscopy as only a complementary procedure in case of abnormal findings detected by other methods ( primarily hysterosalpingography and ultrasound ) . the aim of this study was to examine the role of diagnostic hysteroscopy in a basic infertility workup and to compare its use in primary versus secondary infertility . included in this retrospective study were 221 women who had undergone hysteroscopy as part of their infertility workup in our outpatient clinic between october 1997 and june 2000 . of these a detailed explanation of the procedure was given by the operating physician and a nurse , and all women signed an informed consent before undergoing the procedure . diagnostic hysteroscopy was performed as an office procedure , using a 2.3-mm diameter continuous - flow endoscope ( mr - pc , circon acmi ) . the procedure was considered complete only when the entire uterine cavity and both tubal ostia were visualized . uterine anomalies were diagnosed according to the american society of reproductive medicine classification within the limits of hysteroscopy . in particular , we could not differentiate between bicornuate and septate uterus . arcuate uterus was diagnosed when fundal protrusion was less than one fifth of the uterine cavity . at the end of the hysteroscopy , under direct vision , included in this retrospective study were 221 women who had undergone hysteroscopy as part of their infertility workup in our outpatient clinic between october 1997 and june 2000 . of these a detailed explanation of the procedure was given by the operating physician and a nurse , and all women signed an informed consent before undergoing the procedure . diagnostic hysteroscopy was performed as an office procedure , using a 2.3-mm diameter continuous - flow endoscope ( mr - pc , circon acmi ) . the procedure was considered complete only when the entire uterine cavity and both tubal ostia were visualized . uterine anomalies were diagnosed according to the american society of reproductive medicine classification within the limits of hysteroscopy . in particular , we could not differentiate between bicornuate and septate uterus . arcuate uterus was diagnosed when fundal protrusion was less than one fifth of the uterine cavity . at the end of the hysteroscopy , under direct vision hysteroscopy was performed in 221infertile women : 106 ( 48% ) were diagnosed with primary infertility and 115 ( 52% ) with secondary infertility . the median age was 30 years ( range , 18 to 52 ) and 34 years ( range , 20 to 50 ) , respectively . in the group with secondary infertility , the parity ranged from 1 to 5 , the spontaneous abortions ranged from 0 to 7 , and induced abortions ranged from 0 to 5 . the most common indication for diagnostic hysteroscopy was as a part of an early infertility workup . other indications included cases being part of a continuous workup either before ivf treatment or after a number of failed ivf cycles ( table 1 ) . hysteroscopy revealed a normal uterine cavity in 156 ( 70% ) women ( table 2 ) . indications for hysteroscopy in 221 infertile women hysteroscopic findings in 219 infertile women among women with primary infertility , intrauterine pathologies were diagnosed in 28 ( 26% ) . these pathologies were divided into acquired findings diagnosed in 15 women ( 14% ) and congenital malformations found in 13 women ( 12% ) . considering the group with secondary infertility , intrauterine pathologies were diagnosed in 36 women ( 31% ) . of these , 23 ( 20% ) had acquired findings , and 13 ( 11% ) were diagnosed with congenital uterine malformations ( table 2 ) . a significantly higher rate of patients with submucous fibroids and a significantly higher rate of patients with arcuate uterus were found in the group with secondary infertility ( p<0.04 and p<0.02 , respectively ) . besides that , no statistically significant difference was found in other uterine findings while comparing the 2 groups ( table 2 ) . one of the basic steps of an infertility workup is to evaluate the shape and regularity of the uterine cavity . acquired uterine lesions , such as uterine fibroids , endometrial polyps , intrauterine adhesions , or all of these , may cause infertility by interfering with proper embryo implantation and growth . hysteroscopy has been proved to be the definite method for evaluation of the uterine cavity and diagnosis of associated abnormalities . several studies have demonstrated that once the uterine cavity has to be investigated as part of the infertility workup , hysteroscopy is much more accurate than other diagnostic methods , mainly hsg . in the current study , this also was the main indication for performing diagnostic hysteroscopy . based on the results of the previous studies , it appears that more than 1/3 of the patients interpreted as normal following hsg are found to have a uterine abnormality after diagnostic hysteroscopy , which might be a significant cause of reproductive failure . these women may be wrongly treated , or unnecessarily investigated , while their intrauterine lesion has been missed . in the current study , 30% of women , undergoing infertility evaluation , had abnormal uterine findings on hysteros - copy . these results are comparable to those of the other studies reporting that only 43% to 69% of infertile patients have a normal uterine cavity . no significant differencein the rate of uterine pathology was found between women with primary and secondary infertility ( 26% and 31% , respectively ) . yet , more cases of arcuate uterus ( p<0.02 ) and submucous fibroid ( p<0.04 ) occurred in the group of women with secondary infertility . while the relationship between congenital uterine malformations and impaired pregnancy outcome ( such as recurrent pregnancy loss , late abortions , preterm deliveries , and malpresentations ) is quite established , the issue of these malformations as a cause of infertility is still debatable . the incidence of uterine malformations in other series of infertile patients varies between 1% and 26% , with a mean incidence of 3.4% . in concordance with other reports , septate / bicornuate uterus was the most common anomaly found . the reported incidence of myomas in infertile women without any obvious cause of infertility is estimated to be between 1% and 2.4% . in the current study , donnez and jadoul tried to address the issue of whether myomas influence fertility , by reviewing 106 relevant articles . they concluded that they do influence fertility , mainly based on the favorable pregnancy rates obtained after myomectomy . furthermore , they concluded that submucous and intramural myomas distort the cavity , impairing implantation and pregnancy rates in women undergoing ivf . several theories have been proposed regarding this issue , including alteration of uterine contractility or induction of inflammatory and vascular changes leading to a less receptive implantation site . hysteroscopy can not only diagnose these pathologies accurately , but also enables optimal assessment for possible myomectomy . endometrial polyps were diagnosed in both primary and secondary infertility groups with no statistically significant difference ( 7.6% vs 4.3% , ns ) . the true incidence of endometrial polyps in the general population is difficult to determine , because many of them are clinically asymptomatic . nevertheless , shokeir found such lesions to be more frequent in the unexplained infertility population compared with fertile women . the possible role of these polyps in infertility is yet unclear , although follow - up on these women revealed improved reproductive outcomes after polypectomy . he concluded , in view of his results , that it seems logical to propose surgical treatment of all endometrial polyps among eumenorrheic infertile women , since even if small , they are likely to impair fertility . no significant difference was found in the rate of intrauterine adhesions comparing the patients with primary versus secondary infertility , in spite of the known relationship between secondary infertility and the existence of adhesions , being mostly the result of uterine curettage for postpartum or postabortion residua . oliveira also found intrauterine adhesions in 10% of patients with repeated failed ivf cycles of whom none had undergone previous abortions or other uterine manipulation . while debating the need for routine diagnostic hysteroscopy in the evaluation of the infertile woman , one must keep in mind that this procedure today is no longer a complicated in - patient - general - anesthesia one , but rather a simple , fast , outpatient procedure , requiring short training with high success rates . diagnostic hysteroscopy allows complete , accurate identification of intrauterine abnormalities that might negatively affect endometrial receptivity and implantation . the information derived from hysteroscopy helps the physician to institute appropriate therapy , and by doing so improve conception rates over shorter intervals . our results show that the incidence of uterine pathologies ( congenital and acquired ) in women with primary or secondary infertility approximates 30% , thus , justifying , in our opinion , the use of diagnostic hysteroscopy in the primary routine investigation of infertile women . because no significant difference was found regarding the intrauterine findings between women with primary and secondary infertility , we believe that diagnostic hysteroscopy has a similar importance in the evaluation of patients with both primary and secondary infertility .

objective : to assess the value of diagnostic hysteroscopy in a primary workup of infertility.methods:we performed a retrospective analysis ( canadian task force classification ii-2 ) of 221 infertile patients referred to the outpatient center for uterine cavity evaluation and the tel - aviv university affiliated assaf harofe medical center for evaluation of the uterine cavity . patients underwent a diagnostic office hysteroscopy.results:hysteroscopy revealed an abnormal uterine cavity in 30% of women evaluated for either primary or secondary infertility . no significance was found regarding the total number of intrauterine pathologies when comparing the groups of primary versus secondary infertility.conclusion:routine diagnostic hysteroscopy should be part of an infertility workup in primary and secondary infertility .

prior studies reported an association between ambient air concentrations of total suspended particles and so2 during pregnancy and adverse pregnancy outcomes . we examined the possible impact of particulate matter up to 10 microm ( pm10 ) and up to 2.5 microm ( pm2 . 5 ) in size on intrauterine growth retardation ( iugr ) risk in a highly polluted area of northern bohemia ( teplice district ) . the study group includes all singleton full - term births of european origin over a 2-year period in the teplice district . information on reproductive history , health , and lifestyle was obtained from maternal questionnaires . the mean concentrations of pollutants for each month of gestation were calculated using continuous monitoring data . three intervals ( low , medium , and high ) were constructed for each pollutant ( tertiles ) . odds ratios ( ors ) for iugr for pm10 and pm2.5 levels were generated using logistic regression for each month of gestation after adjustment for potential confounding factors . adjusted ors for iugr related to ambient pm10 levels in the first gestational month increased along the concentration intervals : medium 1.62 [ 95% confidence interval ( ci ) , 1.07 - 2.46 ] , high 2.64 ( ci , 1.48 - 4.71 ) . ors for pm2.5 were 1.26 ( ci , 0.81 - 1.95 ) and 2.11 ( ci , 1 . 20 - 3.70 ) , respectively . no other associations of iugr risk with particulate matter were found . influence of particles or other associated air pollutants on fetal growth in early gestation is one of several possible explanations of these results . timing of this effect is compatible with a current hypothesis of iugr pathogenesis . seasonal factors , one of the other possible explanations , is less probable . more investigation is required to examine these findings and alternative explanations.imagesfigure 1

Yo is a simple, strangely addictive app: You download it and add some friends, and then it lets you say “Yo” to them. Yep, that’s it. Yo became wildly popular seemingly out of the blue this week. After news reports of Yo receiving $1 million in venture capital funding were widely mocked as a sign we’re all living in another tech bubble, curious people starting downloading it to see what it was all about. By Thursday, Yo was everywhere — including the Top Free App list in Apple’s App Store and this writer’s iPhone. On Friday, Yo was hacked. Some nefarious types have been able to crack into Yo — which makes users verify their phone numbers and activate push notifications before the app can set about on its singular purpose — to send unwanted push notifications and grab users’ digits. One of the app’s creators, Or Arbel, told TechCrunch that Yo is having “security issues” and “we are taking this very seriously.” But Yo was a golden opportunity for troublemakers and hackers: An app that everybody’s downloading, which requires users to enter in their phone numbers and turn on push notifications, and one that certainly doesn’t have anything resembling an effective internal security team. If you’re somebody who goes around looking for ways to make trouble on people’s phones, Yo was a prime target. It’s really no wonder it was hit. The lesson here, Yo? The next time an app falls from the heavens and lands on everybody’s phones, maybe we should think twice before installing it. Just because all your friends are doing it, doesn’t mean you should, too. ||||| "Rick Roll" redirects here. It is not to be confused with Richard Roll Rickrolling, alternatively rick-rolling, is a prank and an Internet meme involving an unexpected appearance of the music video for the 1987 Rick Astley song "Never Gonna Give You Up". The meme is a type of bait and switch using a disguised hyperlink that leads to the music video. The victims, believing that they are accessing some unrelated material, are said to have been rickrolled.[1] The trend has extended to disruptive or humorous appearances of the song in other situations, such as a live appearance of Astley himself in the 2008 Macy's Thanksgiving Day Parade in New York.[2] History Astley recorded "Never Gonna Give You Up" on his 1987 album Whenever You Need Somebody.[3] The song, his solo debut single, was a number-one hit on several international charts, including the Billboard Hot 100, Hot Adult Contemporary Tracks and UK Singles Chart. As a means of promoting the song, it was also made into Astley's first music video, which features him performing the song while dancing.[4] The song's eventual internet popularity may be traced back to a 2005 episode of It's Always Sunny In Philadelphia, ""Charlie Has Cancer", in which the song is used quite prominently. Rickrolling was reported to have begun as a variant of an earlier prank from the imageboard 4chan known as duckrolling. The director of the site, who went by the name "moot", started replacing occurrences of the word "egg" on the site with the word "duck". When the word "eggroll" was turned into "duckroll", other users started changing innocent looking links going somewhere (such as to a specific picture or news item) to redirect readers to a thread or site containing an edited picture of a duck with wheels. The user at that point is said to have been "duckrolled".[1][5] The first known instance of a rickroll occurred in May 2007 on /v/, 4chan's video game board, where a link to the Rick Astley video was claimed to be a mirror of the first trailer for Grand Theft Auto IV (which was unavailable due to heavy traffic). The joke was confined to 4chan for a very brief period.[1] By May 2008, the practice had spread beyond 4chan and became an Internet phenomenon,[7] eventually attracting coverage in the mainstream media.[8] An April 2008 poll by SurveyUSA estimated that at least 18 million American adults had been rickrolled.[9] In September 2009, Wired magazine published a guide to modern hoaxes which listed rickrolling as one of the better known beginner-level hoaxes, alongside the fake e-mail chain letter.[10] The term has been extended to simple hidden use of the song's lyrics.[11] Cover versions of "Never Gonna Give You Up" have also been used as part of rickrolling; in advance of the 2018 premier of Season 2 of Westworld, the show's creators released a video that purported to be a spoiler guide for the entire season in advance, but instead featured lead actress Evan Rachel Wood singing the song while accompanied by a pianist.[12] The original video[13] on YouTube from 2007 used for rickrolling was removed for terms-of-use violations in February 2010[14] but the takedown was revoked within a day.[15] It was taken down again on 18 July 2014.[16] It has since been unblocked again and has gained over 78 million views as of November 2018.[13] The 's channel on YouTube uploaded another version[17] on 24 October 2009 which has had over 500 million views as of November 2018. Effects on Astley and reaction In a March 2008 interview, Astley said that he found the rickrolling of Scientology to be "hilarious"; he also said that he will not try to capitalise on the rickroll phenomenon with a new recording or remix of his own, but that he would be happy to have other artists remix it. Overall, Astley is not troubled by the phenomenon, stating that he finds it "bizarre and funny" and that his only concern is that his "daughter doesn't get embarrassed about it."[18] A spokesperson for Astley's record label released a comment which showed that Astley's interest with the phenomenon had faded, as they stated, "I'm sorry, but he's done talking about Rickrolling".[5] In November 2008, Rick Astley was nominated for "Best Act Ever" at the MTV Europe Music Awards after the online nomination form was flooded with votes.[19] The push to make Astley the winner of the award, as well as efforts to encourage MTV to personally invite Astley to the awards ceremony, continued after the announcement.[20] On 10 October, Astley's website confirmed that an invitation to the awards had been received. On 6 November 2008, just hours before the ceremony was due to air, it was reported that MTV Europe did not want to give Astley the award at the ceremony, instead wanting to present it at a later date. Many fans who voted for Astley felt the awards ceremony failed to acknowledge him as a legitimate artist. Astley stated in an interview that he felt the award was "daft", but noted that he thought that "MTV were thoroughly rickrolled", and went on to thank everyone who voted for him.[21] In 2009, Astley wrote about 4chan founder moot for Time magazine's annual Time 100 issue, and thanked moot for the rickrolling phenomenon.[22] According to The Register, as of 2010 , Astley had only directly received $12 in performance royalties from YouTube. Although by that time the song had been played 39 million times, Astley did not compose the song and received only a performer's share of the sound recording copyright.[23] Its meme status led to the song’s usage in the post-credits scene for Walt Disney Animation Studios’s 2018 film Ralph Breaks the Internet, the sequel to 2012’s Wreck-It Ralph. The film Bumblebee was also rickrolled on its teaser trailer.[24] See also References

– Well that was fast: Yo has been hacked. The app that lets you send messages that say "yo" (yes, that's all it does) was virtually unknown a week ago, but then it got a $1 million cash injection, prompting a flood of mostly incredulous news stories—and a lot of curious downloads. By yesterday it was on Apple's Top Free Apps list, and now three Georgia Tech students have hacked it, TechCrunch reports. The hack, which Yo has confirmed, allows the students to collect any user's phone number, spam users with "Yo"s—or any other push notification—and much more. Another so far unconfirmed hack appears to allow Yo to Rickroll people. "The lesson here, Yo? The next time an app falls from the heavens and lands on everybody’s phones, maybe we should think twice before installing it," writes Alex Fitzpatrick at Time. Yo, developed in all of eight hours and suddenly instantly popular, "certainly doesn't have anything resembling an effective internal security team," and was a "prime target." Meanwhile, over at the Atlantic, Ian Bogost takes a more thoughtful look at the app, and while he thinks there's some honesty in its grand-yet-stupid ambition to formalize meta-communication, he also finds it kind of "gross," both because "yo" is "a dudebro's term" that's "stocky and aggressive," and because the app tries to "contain all human activity within the logics of tech startups. The need to expect something from every idea, even the stupid ones." His whole column is worth a read.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Armed Forces Suicide Prevention Act of 2011''. SEC. 2. ENHANCEMENT OF SUICIDE PREVENTION PROGRAM OF THE DEPARTMENT OF DEFENSE. (a) Enhancement.--The Secretary of Defense shall take appropriate actions to enhance the suicide prevention program of the Department of Defense through the provision of suicide prevention information and resources to members of the Armed Forces from their initial enlistment or appointment through their final retirement or separation. (b) Cooperative Effort.--The Secretary of Defense shall develop suicide prevention information and resources in consultation with-- (1) the Secretary of Veterans Affairs, the National Institute of Mental Health, and the Substance Abuse and Mental Health Services Administration of the Department of Health and Human Services; and (2) to the extent appropriate, institutions of higher education and other public and private entities, including international entities, with expertise regarding suicide prevention. SEC. 3. SUICIDE PREVENTION TRAINING COMPONENT DURING RECRUIT BASIC TRAINING. (a) Army.-- (1) Training required.--Chapter 401 of title 10, United States Code, is amended by inserting after section 4320 the following new section: ``Sec. 4320a. Recruit basic training: availability of suicide prevention resources ``(a) Availability.--As part of the initial entry training program of the Army that constitutes the basic training of new recruits, the Secretary of the Army shall include a training component on suicide prevention. ``(b) Elements.--The suicide prevention training component shall include the following: ``(1) Methods for recognizing risk factors for suicide. ``(2) Protocols for responding to crisis situations involving members who may be at high risk for suicide. ``(3) Information about suicide prevention services available to members, including toll-free hotlines and Internet resources. ``(4) Information on best practices for suicide prevention.''. (2) Clerical amendment.--The table of sections at the beginning of such chapter is amended by inserting after the item relating to section 4320 the following new item: ``4320a. Recruit basic training: availability of suicide prevention resources.''. (b) Navy and Marine Corps.-- (1) Training required.--Chapter 602 of such title is amended by adding at the end the following new section: ``Sec. 6933. Recruit basic training: availability of suicide prevention resources ``(a) Availability.--As part of the initial entry training program of the Navy and the Marine Corps that constitutes the basic training of new recruits, the Secretary of the Navy shall include a training component on suicide prevention. ``(b) Elements.--The suicide prevention training component shall include the following: ``(1) Methods for recognizing risk factors for suicide. ``(2) Protocols for responding to crisis situations involving members who may be at high risk for suicide. ``(3) Information about suicide prevention services available to members, including toll-free hotlines and Internet resources. ``(4) Information on best practices for suicide prevention.''. (2) Clerical amendment.--The table of sections at the beginning of such chapter is amended by adding at the end the following new item: ``602. Recruit basic training: availability of suicide prevention resources.''. (c) Air Force.-- (1) Training required.--Chapter 901 of such title is amended by inserting after section 9320 the following new section: ``Sec. 9320a. Recruit basic training: availability of suicide prevention resources ``(a) Availability.--As part of the initial entry training program of the Air Force that constitutes the basic training of new recruits, the Secretary of the Air Force shall include a training component on suicide prevention. ``(b) Elements.--The suicide prevention training component shall include the following: ``(1) Methods for recognizing risk factors for suicide. ``(2) Protocols for responding to crisis situations involving members who may be at high risk for suicide. ``(3) Information about suicide prevention services available to members, including toll-free hotlines and Internet resources. ``(4) Information on best practices for suicide prevention.''. (2) Clerical amendment.--The table of sections at the beginning of such chapter is amended by inserting after the item relating to section 4320 the following new item: ``4320a. Recruit basic training: availability of suicide prevention resources.''. SEC. 4. NOTICE OF AVAILABILITY OF AND ACCESS TO SUICIDE PREVENTION RESOURCES DURING PRESEPARATION COUNSELING. Section 1142(b)(8) of title 10, United States Code, is amended by inserting before the period the following: ``and the availability to the member and the member's family of the suicide prevention resources described in section 1177(d) of this title''. SEC. 5. NOTICE OF AVAILABILITY OF AND ACCESS TO SUICIDE PREVENTION RESOURCES DURING MEDICAL EXAMINATION TO EVALUATE A DIAGNOSIS OF POST-TRAUMATIC STRESS DISORDER OR TRAUMATIC BRAIN INJURY. Section 1177 of title 10, United States Code, is amended by adding at the end the following new subsection: ``(d) Availability of Suicide Prevention Resources.--(1) The medical examination required by subsection (a) shall include the provision of information to the member regarding the availability of the suicide prevention resources described in paragraph (2) and the right of the member to access such resources. ``(2) The suicide prevention resources available under paragraph (1) shall include the following: ``(A) Methods for recognizing risk factors for suicide. ``(B) Protocols for responding to crisis situations involving members who may be at high risk for suicide. ``(C) Information about suicide prevention services available to members, including toll-free hotlines and Internet resources. ``(D) Information on best practices for suicide prevention.''.

Armed Forces Suicide Prevention Act of 2011 - Directs the Secretary of Defense to enhance the suicide prevention program of the Department of Defense (DOD) through the provision of suicide prevention information and resources to members of the Armed Forces from their initial enlistment or appointment through their final retirement or separation. Requires the Secretary of each military department (Secretary concerned) to include a training component on suicide prevention, which shall include: (1) methods for recognizing suicide risk factors; (2) protocols for responding to crisis situations involving members who may be at high risk for suicide; and (3) information about available suicide prevention services and best practices for suicide prevention. Directs the Secretary concerned to notify members of the the availability of and access to suicide prevention services during their preseparation counseling. Requires medical evaluations for the diagnosis of post-traumatic stress disorder or traumatic brain injury in members who were deployed overseas in support of a contingency operation to also include the provision of information on the availability of suicide prevention services and the member's right of access to such services.

Please visit our new campaign to continue supporting the fight for children with Sanfilippo Syndrome. The campaign on this page is no longer accepting donations due to GoFundMe changing payment processors. Please visit the new page at www.SavingEliza.com Every single dollar raised here has, and continues to go to Cure Sanfilippo Foundation, a 501c3 nonprofit (tax ID: 46-4322131). Donations are tax deductible. Cure Sanfilippo has a mission to advocate and fund research directed toward a cure or treatment options for children with Sanfilippo Syndrome. In short, we fund research to save children via treatments & clinical trials. No dollars ever go to or for any particular family or child. We tell individual stories, for the greater cause and mission....which is to cure this terrible fatal brain disease in little children, often referred to as a Childhood Alzheimer's. Our deepest and humble thanks for visiting this page and considering support. You are our hero! Glenn O'Neill (Dad, Donor and President of Cure Sanfilippo Foundation) curesff@gmail.com (anytime) --------------------------------------------------------------------------------------------------------------------------------------------- Our Story It all started back in 2014, with this 3 minute video: Now, we truly believe we are witnessing a miracle. What else can explain more than 36,000 people already donating more than $2 million dollars, over the past 2 years, to fund a chance at life for our daughter Eliza and other children. Diagnosed 3 years ago with Sanfilippo Syndrome —a terminal disease sometimes called “Childhood Alzheimer's”— Eliza has now become the first child in the world to have been given this new treatment! The second child has also been treated and in the coming months & through next year, a few handful more children around the world will be part of this groundbreaking gene therapy clinical trial that is already showing promising results. The WORLD decided to rally around our little girl for this greater cause, and she’s become the face of this disease…a symbol for Sanfilippo parents everywhere not to give up HOPE. And we’re not giving up on them either. Many more children are still fighting, and we won’t stop until every last one of them is afforded a chance at life. There are more children that need this treatment than there are available spots in clinical trials, and these precious little ones can’t wait. Given the rapidly degenerative nature of Sanfilippo Syndrome, not receiving a treatment, and soon, is a death sentence. Can you imagine being one of these parents? Since treatment, we see a new light in Eliza’s eyes— she is connecting with us in a way we thought was gone forever. She is working to regain the skills the disease stripped away in the 6 and half years it tore through her body. She is a fighter! Other Sanfilippo children deserve this chance too. At this stage, funding is one of the only things that will accelerate research to give these children a chance. Money doesn’t make the world go round, but it does bring medical treatments faster to children who are dying. Our goal is to reach $4M here to help make this happen. Please donate TODAY to give these beautiful Sanfilippo children a rightful chance at life. Please share so the world can hear their collective voices. Our hearts are forever thankful for giving our daughter Eliza and others a chance at life. We are reminded of one quote from a special supporter that has helped us through the hard days: “Keep the faith, and the faith will keep you”. We believe! Glenn, Cara, Beckham and Eliza (The O’Neill Family) Learn more about Sanfilippo Syndrome here www.CureSFF.org/about-sanfilippo Meet just some of the Sanfilippo families here: www.CureSFF.org/meet-the-families Baby Sadie Paisleigh and the Butler Family Rowen and the Fernandez Family Izzy and the Jurado Family Keira and the Esposito Family Parker and the Talbert Family Abby Grace and the Ferguson family All funds go toward the mission of our non-profit 501c3 Cure Sanfilippo Foundation (Tax ID: 46-4322131), which is to advocate for and fund research directed toward a cure or treatment options for children with Sanfilippo Syndrome. We are out to end this disease and help ensure treatments for as many children as possible along the way. We must reach our goal and mission before it is too late for these beautiful children. With a donation and a share, you can make the difference! Action saves lives. Action brings miracles. Our daughter Eliza is proof of that. Donations are tax-deductible. Other donation options: -- www.CureSFF.org (click Donate) --By check: Cure Sanfilippo Foundation, PO Box 6901, Columbia, SC 29260 Follow the latest at www.facebook.com/ElizaOStory Special thanks to the artists, who worked free of charge to help us: Video by the amazing Benjamin Von Wong Photograpy by the talented Anna Tenne Photography ||||| Life in Quarantine: Parents of Girl with Rare Disorder Live in Self-Imposed Isolation Life in Isolation A 'Virtual' Reality Want more stories like this? Sign up for our newsletter and other special offers: sign me up Thank you for signing up! While Americans debate whether a handful of Ebola cases here should lead to stricter quarantine rules , a family in Columbia, South Carolina, have been living in self-imposed quarantine for nearly five months – all to protect their daughter.Eliza O'Neill, 4, suffers from a rare, ultimately fatal genetic disorder called Sanfilippo syndrome , type A.Since she was diagnosed in 2013, the usually energetic and fearless Eliza has been slowly losing her ability to speak. Over time, doctors tell her family, she will lose the ability to walk, eat and ultimately breathe.Her parents, Glenn, 42, and Cara, 39, are racing to raise $2.5 million they need for a clinical trial that is their only chance to find a possible treatment to save Eliza and help other children who suffer from the disorder.As tough as that mission has been with their end-of-the-year deadline soon approaching , they have made another tough decision: To self-quarantine their family of four so as not to expose Eliza to potential illnesses in her vulnerable state."For Eliza to be a great candidate for the trial we don't want her to come down with any sickness or virus at all," Glenn tells PEOPLE. "We have heard stories from families of older kids with Sanfilippo where a sickness at this stage started the downward slide even faster and they never fully recovered."The O'Neills believe that the only way to ensure she doesn't catch anything is for the entire family to avoid contact with the outside world."It's beyond hard, but this is what you do for someone you love," says Glenn, a consultant at Symantec ; the company has allowed him to work from home.Cara had to quit her job as a pediatrician and the couple now try to homeschool Eliza and her big brother, Beckham, 7. They get their groceries delivered to the front door and clean every door handle, countertop and package with antibacterial wipes.They haven't had friends or family over for five months. They are now 150 days into their self-imposed isolation and plan to continue it until the clinical trial's hoped-for start date early next year."Sometimes we drive around in the car, and now I consciously avoid the roads that take us by playgrounds, parks and schools with kids playing outside. It's not just hard for her, it's also torture for me knowing she wants to be out there," Cara writes in a blog post about their experience If they have to stop for gas, only Cara and Glenn will get out of the car."We wear masks and gloves and we don't go inside any stores," says Glenn. "I know we look crazy, but we are just trying to save our daughter's life."They don't have the diversion of television because her parents believe Eliza communicates better without it around."With our decision to not go out, we are in essence, taking experiences away from her. We're doing all of this in hopes that we will actually be giving her the best chance at a full future, but it is still very hard to reconcile in our minds," Cara writes. "Our lives have become completely 'virtual.' "Eliza and Beckham won't see friends on their birthdays that are coming up, they won't trick-or-treat on Halloween, and there will be no visit to Santa at the mall this Christmas.As young as he is, Cara and Glenn have explained the restrictions to Beckham – and he seems to understand. "It's not worth it to go out where people are," he writes on the blog. "I wouldn't take the risk."At times, Glenn says, the family goes a bit stir crazy being stuck inside. But they never forget why they are doing this."The first few weeks were very hard, but it has become the new normal," Glenn writes. "[One hundred and fifty days] is a long time, but we will go to any lengths. We'll do this as long as it takes." ||||| Sanfilippo syndrome is an inherited condition, which means it is passed down through families. If both parents carry a nonworking copy of a gene related to this condition, each of their children has a 25% (1 in 4) chance of developing the disease. This is called an autosomal recessive trait. Sanfilippo syndrome occurs when the substances (enzymes) needed to break down the heparan sulfate sugar chain are missing or defective. There are 4 main types of Sanfilippo syndrome, also called MPS III. The type a person has depends on which enzyme is affected. ||||| Courtesy Glenn O’Neill The O’Neill family in Colombia, S.C., have placed themselves on self-quarantine for the past 160 days to protect sickly little girl Eliza. A South Carolina family has lived the past 160 days under self-quarantine and would know better than anyone the challenges facing Ebola medical workers under mandated quarantines. But Glenn O'Neill told the Daily News his family's situation was much different than the health care professionals returning home from West Africa, because the O'Neills can decide to leave their house whenever they want. Instead, they choose to stay away from other people as a precaution to protect the health of Glenn's 4-year-old daughter, Eliza, who has Sanfilippo syndrome. Children with the extremely rare disease typically start developing deficiencies in muscle growth, speech and brain functions by age 5. Many of the victims are confined to a wheelchair as the disease starts to spread. Mandated Quarantines States including New York, New Jersey and Illinois established policies madating that workers who treated Ebola patients in West Africa must put themselves on 21-day quarantines. People placed under the mandates have resisted the protocols and medical experts have decried the regulations as unnecessary — though politicians say they're in the public's best interest. Courtesy of Glenn O’Neill Eliza O’Neill performs her speech therapy over Skype. The VonWong via YouTube The O’Neills have enjoyed their unprecedented family time. Courtesy Glenn O’Neill The kids have had a lot of time to draw pictures that now adorn their kitchen wall. Courtesy Glenn O’Neill The family thoroughly cleans any item that enters their home. Previous Next Enlarge Doctors Without Borders nurse Kaci Hickox was placed in a tent outside a New Jersey hospital with no shower, no TV and only a portable toilet after returning from Sierra Leone on Friday. She remained under supervision, despite testing negative for the disease, until Monday night, when she was allowed to serve her 21-day quarantine at her home in Maine. The O'Neills say their situation is less intense than a government-issued quarantine. They do leave their house once every other week, but only to places they are sure there will not be any other people, such as a deserted beach or an open field. And the only time Glenn O'Neill has gone somewhere with people, he might have gotten arrested. He needed to go to a bank to sign a form for the family's Saving Eliza Foundation. The 42-year-old was as cautious as he could be, informing the bank members ahead of time he that would walk in, sign the papers and leave without touching anything. As he pulled into the parking lot, he started to put on his protective mask and gloves — and scared a fellow motorist who spotted him. People say we're being overprotective, but when it comes to protecting your daughter how can you use that word? "He pulled back real slowly and had a look on his face like, 'what the heck?'" O'Neill said. "He thought I was going to rob the place. I called the bank and said 'I'm coming in with gloves and a mask. Just making sure there won't be any trouble.'" Making the Decision In May the children, Eliza and her brother, Beckham, 7, were pulled out of school and Glenn's wife, Cara, left her job as a pediatrician for special needs children. Glenn now works from home as a purchasing consultant. "People say we're being overprotective, but when it comes to protecting your daughter, how can you use that word?" he said. Eliza, who turns 5 next month, is at a crucial stage at which simple colds and illnesses could accelerate her deterioration. The measure has worked. Eliza has not gotten sick and is doing as well as could reasonably be expected for the time being, Glenn said. Steven J. Hyman Kaci Hickox, 33, the first person snared by the 21-day mandatory quarantine announced by New Jersey Gov. Chris Christie, sits in a quarantine tent outside Universlity Hospital in Newark, N.J. Uncredited/AP Hickox, who did not test positive for the disease, was allowed to serve her quarantine time at her home in Maine. Previous Next Enlarge The family is raising money to fund a clinical trial that will hopefully cure the disease. The plan is to continue the quarantine until the procedure is available, possibly by early next year, Glenn said. Family's Adjustment The family does not have a TV and spendsa limited amount of time on the computer because Eliza's condition lends to more addictive characteristics. If she is in front of a screen it will affect her speaking ability. Cara said they appreciated the time they could spend with their kids. "You don't have that rush of a typical life where you say we have to stop reading right now because we have something to do," she said. "We're OK. We do what we can do. Sometimes we get overwhelmed, but it's just life. We have bad moments and good ones." The family doesn't get visitors, but they will Skype their relatives and Eliza's speech therapist. Glenn jokes the house has felt smaller over time. "My wife says after this we're going to get a bigger house," he said. "I said, 'Sounds good to me.'" jlandau@nydailynews.com Follow on Twitter @joelzlandau

– Talk these days of quarantines revolves around Ebola, but one South Carolina family has voluntarily blocked themselves off from the outside world—not to protect others, but to protect their 4-year-old daughter, Eliza, who suffers from the most severe form of a rare genetic disorder called Sanfilippo syndrome. The metabolic disorder, diagnosed in 2013, is already slowing Eliza's ability to talk, reports People, and will eventually rob her of the ability to walk, eat, and finally, to breathe. Most people with the syndrome die by their teen years, so while the isolation—now in its fifth month—is taking its toll, the family says it's worth it. "We'll do this as long as it takes," says dad Glenn O'Neill. Their aim is to keep her healthy so she can take part in a clinical trial, likely early next year, they hope will lead to a cure. "We have heard stories from families of older kids with Sanfilippo where a sickness at this stage started the downward slide even faster and they never fully recovered," says Glenn O'Neill. Because even fairly benign viruses like the common cold can exacerbate Eliza's symptoms and speed the progression of the disorder, mom Cara O'Neill has quit her job as a pediatrician and Glenn O'Neill now works from home, while Eliza and her 7-year-old brother, Beckham, are home-schooled. Though the family does go out on a rare occasion to, say, a deserted beach or field, reports the New York Daily News, they have groceries delivered to their doorstep and wipe all incoming packages with antibacterial wipes. So far it's worked; Eliza hasn't gotten sick. The O'Neills' fundraising website is here. (Another sufferer of a rare genetic disorder was able to give birth.)

dimension reduction is ubiquitous in many areas ranging from pattern recognition , clustering , classification , to fast numerical simulation of complicated physical phenomena . the fundamental question to address is how to approximate a @xmath4-dimensional space by a @xmath5-dimensional one with @xmath6 . specifically , we are given a set of high - dimensional data @xmath7 \in { \mathbb r}^{m \times n},\ ] ] and the goal is to find its low - dimensional approximation @xmath8 \in { \mathbb r}^{m \times d}\ ] ] with reasonable accuracy . there are two types of dimension reduction methods . the first category consists of `` projective '' ones . these are the linear methods that are _ global _ in nature , and that explicitly transform the data matrix @xmath0 into a low - dimensional one by @xmath9 . the leading examples are the principal component analysis ( pca ) and its variants . the methods in the second category act locally and are inherently nonlinear . for each sample in the high - dimensional space ( e.g. each column of @xmath0 ) , they directly find their low - dimensional approximations by preserving certain locality or affinity between nearby points . in this paper , inspired by the reduced basis method ( rbm ) , we propose a linear method called `` reduced basis decomposition ( rbd ) '' . it is much faster than pca / svd - based techniques . moreover , its low - dimensional vectors are equipped with error estimator indicating how close they are approximating the high - dimensional data . rbm is a relative recent approach to speed up the numerical simulation of parametric partial differential equations ( pdes ) @xcite . it utilizes an offline online computational decomposition strategy to produce surrogate solution ( of dimension @xmath10 ) in a time that is of orders of magnitude shorter than what is needed by the underlying numerical solver of dimension @xmath11 ( called _ truth _ solver hereafter ) . the rbm relies on a projection onto a low dimensional space spanned by truth approximations at an optimally sampled set of parameter values @xcite . this low - dimensional manifold is generated by a greedy algorithm making use of a rigorous _ a posteriori _ error bounds for the field variable and associated functional outputs of interest which also guarantees the fidelity of the surrogate solution in approximating the truth approximation . the rbd method acts in a similar fashion . given the data matrix @xmath0 as in , it iteratively builds up @xmath2 whose column space approximates that of @xmath0 . it starts with a randomly selected column of @xmath0 ( or a user input if existent ) . at each step where we have @xmath12 vectors @xmath13 , the next vector @xmath14 is found by scanning the columns of @xmath0 and locating the one whose error of projection into the current space @xmath15 is the largest . this process is continued until the maximum projection / compression error is small enough or until the limit on the size of the reduced space is reached . an important feature is an offline - online decomposition that allows the computation of the compression error , and thus the cost of locating @xmath14 , to be independent of ( the potentially large ) @xmath16 . this paper is organized as follows . in section [ sec : background ] , we review the background material , mainly the rbm . section [ sec : rbc ] describes the reduced basis decomposition algorithm and discuss its properties . numerical validations are presented in section [ sec : numerical ] , and finally some concluding remarks are offered in section [ sec : conclusion ] . the reduced basis method was developed for use with finite element methods to numerically solve pdes . we assume , for simplicity , that the problems ( usually parametric partial differential equations ( pde ) ) to simulate are written in the weak form : find @xmath17 in an hilbert space @xmath0 such that @xmath18 where @xmath19 is an input parameter . these simulations need to be performed for many values of @xmath19 chosen in a given parameter set @xmath20 . in this problem @xmath21 and @xmath22 are bilinear and linear forms , respectively , associated to the pde ( with @xmath23 and @xmath24 denoting their numerical counterparts ) . we assume that there is a numerical method to solve this problem and the solution @xmath25 , called the `` truth approximation '' or `` snapshot '' , is accurate enough for all @xmath26 . the fundamental observation utilized by rbm is that the parameter dependent solution @xmath27 is not simply an arbitrary member of the infinite - dimensional space associated with the pde . instead , the solution manifold @xmath28 can typically be well approximated by a low - dimensional vector space . the idea is then to propose an approximation of @xmath29 by @xmath30 where , @xmath31 are @xmath10 @xmath32 pre - computed truth approximations corresponding to the parameters @xmath33 judiciously selected according to a sampling strategy @xcite . for a given @xmath19 , we now solve in @xmath34 for the reduced solution @xmath35 . the online computation is @xmath36-independent , thanks to the assumption that the ( bi)linear forms are affine @xmath37 and the fact that they can be approximated by affine ( bi)linear forms when they are nonaffine @xcite . hence , the online part is very efficient . in order to be able to `` optimally '' find the @xmath10 parameters and to assure the fidelity of the reduced basis solution @xmath35 to approximate the truth solution @xmath27 , we need an _ a posteriori _ error estimator @xmath38 which involves the residual @xmath39 and stability information of the bilinear form @xcite . with this estimator , we can describe briefly the classical * greedy algorithm * used to find the @xmath10 parameters @xmath40 and the space @xmath34 . we first randomly select one parameter value and compute the associated truth approximation . next , we scan the entire ( discrete ) parameter space and for each parameter in this space compute its rb approximation @xmath41 and the error estimator @xmath42 . the next parameter value we select , @xmath43 , is the one corresponding to the largest error estimator . we then compute the truth approximation and thus have a new basis set consisting of two elements . this process is repeated until the maximum of the error estimators is sufficiently small . the reduced basis method typically has exponential convergence with respect to the number of pre - computed solutions @xcite . this means that the number of pre - computed solutions can be small , thus the computational cost reduced significantly , for the reduced basis solution to approximate the finite element solution reasonably well . the author and his collaborators showed @xcite that it works well even for a complicated geometric electromagnetic scattering problem that efficiently reveals a very sensitive angle dependence ( the object being stealthy with a particular configuration ) . in this section , we detail our proposed methodology by stating the algorithm , studying the error evaluation , and pinpointing the computational cost . set @xmath44 , @xmath45 , and @xmath46 a random integer between @xmath47 and @xmath4 . at the heart of the method stated in algorithm [ alg : c_greedy ] is a greedy algorithm similar to that used by rbm . it builds the reduced space dimension - by - dimension . at each step , the _ greedy _ decision for the best next dimension to pursue in the space corresponding to the data is made by examining an error indicator quantifying the discrepancy between the uncompressed data and the one compressed into the current ( reduced ) space . in the context of the rbm , we view each column ( or row if we are compressing the row space ) of the matrix as the fine solution of certain ( virtual ) parametric pde with the ( imaginary ) parameter taking a particular value . since this solution is _ explicitly _ given already by the data , the fact that the pde and the parameter are absent does not matter . once this _ common mechanism _ satisfied by each column ( or row ) is identified , the greedy algorithm still relies on an accurate and efficient estimate quantifying the error between the original data and the compressed one . this will be the topic of the next subsection . to state the algorithm , we assume that we are given a data matrix @xmath48 , the largest dimension @xmath49 that the practitioner wants to retain , and a tolerance @xmath50 capping the discrepancy between the original and the compressed data . the output is the set of bases for the compressed data ( a low - dimensional approximation of the original data ) @xmath51 and the transformation matrix @xmath52 . here , @xmath53 is the actual dimension of the compressed data . with this output , we can * compress . * : : we represent any data entry @xmath54 , the @xmath55 column of @xmath56 , by the @xmath55 column of @xmath3 , @xmath57 , with usually @xmath58 . * uncompress . * : : an _ approximation _ of the data is reconstructed by @xmath59 * evaluate the compression of out - of - sample data . * : : given any @xmath60 that is not equal to any column of @xmath0 , its compressed representation in @xmath61 is @xmath62 a critical part to facilitate the greedy algorithm and make the algorithm realistic is an efficient mechanism measuring ( or estimating ) the error @xmath63 under certain norm , @xmath64 , in step @xmath65 of the algorithm . in this work , we are using the @xmath66norm defined as follows . for a given symmetric and positive definite matrix @xmath67 , the @xmath66norm of a vector @xmath60 is defined by @xmath68 for @xmath69 being any column of the data matrix @xmath0 and @xmath70 its low - dimensional approximation @xmath71 , it is easy to see that @xmath72 the choice of @xmath73 reflects the criteria of the data compression . typical examples are : * * identity : * equal weights are assigned to each component of the data entry . this makes the quality of compression uniform . in this case , the evaluation of is greatly simplified and the algorithm is the fastest as shown below by the numerical results . * * general diagonal matrix : * this setting can be used if part of each data entry needs to be preserved better and other parts can afford less fidelity . * * general spd matrix : * this most general case can be helpful if the goal is to preserve data across different entries anisotropiclly . the goal is then to evaluate the error through as efficiently as possible for any given @xmath74 . this is achieved by employing an offline - online decomposition strategy where the @xmath74-independent parts are evaluated beforehand ( offline ) enabling a quick turnaround time for any given @xmath74 encountered online . the specifics are given in the next subsection . the offline - online decomposition of the computations and their complexities are as follows . here , we use @xmath75 to denote the number of nonzero entries of a sparse matrix @xmath73 . * offline * : : the total cost is of order @xmath76 + * offline mgs * ; ; every basis needs to orthogonalized against the current set of bases . the total cost is of order @xmath77 . * offline calculation of errors * ; ; the next basis is located by comparing each column with its compressed version into the current space . to enable that , we encounter the following computational cost : + * pre - computation * : : of @xmath78 ( for @xmath79 in ) and @xmath80 ( for @xmath81 in ) . the cost is of order @xmath82 . * expansion * : : of @xmath83 and @xmath84 . the former takes time of order @xmath85 , and the latter of order @xmath86 . * offline searching * ; ; after these calculations , the comparison between the original and compressed data is then only dependent on the size of @xmath74 ( which is also the number of columns for @xmath2 ) . the complexity is of order @xmath87 . it will be repeated for up to @xmath4 times in the searching process of step 2.3 of the algorithm for each of the up to @xmath88 basis elements . the total cost is at the level of @xmath89 . * online * : : given any ( possibly out - of - sample ) data @xmath60 , its coefficients in the compressed space is obtained by evaluating @xmath90 . the cost is of order @xmath91 . the decoding ( @xmath92 ) can be done with the same cost . the online computation has complexity of order @xmath93 we remark that , if the actual practice does not requires forming @xmath70 ( e.g. clustering and classification etc ) and so we only work with the coordinates @xmath74 of @xmath69 in the compressed space , then the online cost will be independent of @xmath16 and thus much smaller . in this section , we test the reduced basis decomposition on image compression , and data compression . lastly , we devise a simple face recognition algorithm based on rbd and test it on a database of @xmath94 images while comparing rbd with @xmath95 other face recognition algorithms . the computation is done , and thus the speedup numbers reported herein should be understood as , in matlab 2014a on a 2011 imac with a @xmath96 ghz intel core i7 processor . [ sec : numerical ] we first test it on compressing two standard images lena and mandrill in figure [ fig : original ] . they both have an original resolution of @xmath97 . we take @xmath98 and test the algorithm . for each component of every image , we run the algorithm with @xmath99 which implies a compression ratio of @xmath100 , @xmath101 , and @xmath102 respectively . the resulting images ( formed by multiplying the corresponding @xmath2 and @xmath3 together ) are shown on the @xmath103 and @xmath104 row of figures [ fig : lenaresult ] . as a comparison , we run svd and obtain the reconstructed matrices with the first @xmath88 singular values accordingly . the resulting images are on the second and last row . clearly , svd provides the best quality pictures among all possible algorithms ( and thus better than what rbd provides ) . however , we see that the rbd pictures are only slightly blurrier . moreover , it takes much less time . in fact , we show the comparison in time between svd and rbd in table [ tab : lenatime ] . we see that , when @xmath105 , rbd is three times faster than svd and seven times faster when @xmath106 . here the svd time is the shorter between those taken by ` vd } and { \verb ` vds commands in matlab . from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] + from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] + from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] + from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] from left to right . the first and third row are from reduced basis decomposition , and the second and fourth are from singular value decomposition.,title="fig:",scaledwidth=32.0% ] .relative computational time for image compression . [ cols="^,^,^",options="header " , ] we use the umist database @xcite that is publicly available on roweis web page . table [ tab : datasetinfo ] summarizes its characteristics : it contains @xmath107 people under different poses . the number of different views per subject varies from @xmath108 to @xmath109 . we use the cropped version whose snapshot is shown in figure [ fig : umist ] . as in @xcite , we randomly choose @xmath110 views from each class to form a training set . the rest of the samples ( @xmath111 of them ) are used as testing images . we show the average classification error rates in figure [ fig : fr_result ] left . these averages are computed over @xmath112 random formations of the training and test sets . shown in the middle are the results of six traditional dimension reduction techniques taken from @xcite . clearly , our method has similar performance as the pca method , and outperforms three of the other five methods . however , rbd is much faster than pca and other methods since they all involves solving eigenproblems @xcite . a speedup factor as a function of the number of bases is plotted in figure [ fig : fr_result ] right which demonstrates a speedup factor of larger than two for this particular test when we reach the asymptotic region ( around when the number of basis vectors is @xmath113 ) . this paper presents and tests an extremely efficient dimension reduction algorithm for data processing . it is multiple times faster than the svd / pca - based algorithms . what makes this possible is a greedy algorithm that iteratively builds up the reduced space of basis vectors . each time , the next dimension is located by exploring the errors of compression into the current space for all data entries . thanks to an offline - online decomposition mechanism , this searching is independent of the size of each entry . numerical results including one concerning a real world face recognition problem confirm these findings . m. barrault , n. c. nguyen , y. maday , and a. t. patera , _ an `` empirical interpolation '' method : application to efficient reduced - basis discretization of partial differential equations _ , c. r. acad . paris , srie i * 339 * ( 2004 ) , 667672 . a. buffa , y. maday , a. t. patera , c. prudhomme , and g. turinici , _ a priori convergence of the greedy algorithm for the parametrized reduced basis _ , esaim - math . model . ( 2011 ) , special issue in honor of david gottlieb . j. p. fink and w. c. rheinboldt , _ on the error behavior of the reduced basis technique for nonlinear finite element approximations _ , z. angew . * 63 * ( 1983 ) , no . 1 , 2128 . mr mr701832 ( 85e:73047 ) d. b graham and n. m allinson , _ characterizing virtual eigensignatures for general purpose face recognition _ , face recognition : from theory to applications ( h. wechsler , p. j. phillips , v. bruce , f. fogelman - soulie , and t. s. huang , eds . ) , nato asi series f , computer and systems sciences , vol . 163 , 1998 , pp . 446456 . m. a. grepl , y. maday , n. c. nguyen , and a. t. patera , _ efficient reduced - basis treatment of nonaffine and nonlinear partial differential equations _ , mathematical modelling and numerical analysis * 41 * ( 2007 ) , no . 3 , 575605 . l. machiels , y. maday , i. b. oliveira , a. t. patera , and d. v. rovas , _ output bounds for reduced - basis approximations of symmetric positive definite eigenvalue problems _ , c. r. acad . * 331 * ( 2000 ) , no . 2 , 153158 . mr mr1781533 ( 2001d:65148 ) y. maday , _ reduced basis method for the rapid and reliable solution of partial differential equations _ , international congress of mathematicians . vol . iii , eur . soc . , zrich , 2006 , pp . mr 2275727 ( 2007m:65099 ) y. maday , a. t. patera , and d. v. rovas , _ a blackbox reduced - basis output bound method for noncoercive linear problems _ , nonlinear partial differential equations and their applications . collge de france seminar , vol . xiv ( paris , 1997/1998 ) , stud . 31 , north - holland , amsterdam , 2002 , pp . mr mr1936009 ( 2003j:65120 ) y. maday , a. t. patera , and g. turinici , _ a priori convergence theory for reduced - basis approximations of single - parameter elliptic partial differential equations _ * 17 * ( 2002 ) , 437446 . nguyen , k. veroy , and a. t. patera , _ certified real - time solution of parametrized partial differential equations _ , handbook of materials modeling ( sidney yip , ed . ) , springer netherlands , 2005 , pp . 15291564 ( english ) . c. prudhomme , d. rovas , k. veroy , y. maday , a. t. patera , and g. turinici , _ reliable real - time solution of parametrized partial differential equations : reduced - basis output bound methods _ , journal of fluids engineering * 124 * ( 2002 ) , no . 1 , 7080 . g. rozza , d.b.p . huynh , and a.t . patera , _ reduced basis approximation and a posteriori error estimation for affinely parametrized elliptic coercive partial differential equations : application to transport and continuum mechanics _ , arch comput methods eng * 15 * ( 2008 ) , no . 3 , 229275 . s. sen , k. veroy , d.b.p . huynh , s. deparis , n.c . nguyen , and a.t . `` natural norm '' a posteriori error estimators for reduced basis approximations _ , j. comput . * 217 * ( 2006 ) , no . 1 , 37 62 .

dimension reduction is often needed in the area of data mining . the goal of these methods is to map the given high - dimensional data into a low - dimensional space preserving certain properties of the initial data . there are two kinds of techniques for this purpose . the first , projective methods , builds an explicit linear projection from the high - dimensional space to the low - dimensional one . on the other hand , the nonlinear methods utilizes nonlinear and implicit mapping between the two spaces . in both cases , the methods considered in literature have usually relied on computationally very intensive matrix factorizations , frequently the singular value decomposition ( svd ) . the computational burden of svd quickly renders these dimension reduction methods infeasible thanks to the ever - increasing sizes of the practical datasets . in this paper , we present a new decomposition strategy , reduced basis decomposition ( rbd ) , which is inspired by the reduced basis method ( rbm ) . given @xmath0 the high - dimensional data , the method approximates it by @xmath1 with @xmath2 being the low - dimensional surrogate and @xmath3 the transformation matrix . @xmath2 is obtained through a greedy algorithm thus extremely efficient . in fact , it is significantly faster than svd with comparable accuracy . @xmath3 can be computed on the fly . moreover , unlike many compression algorithms , it easily finds the mapping for an arbitrary `` out - of - sample '' vector and it comes with an `` error indicator '' certifying the accuracy of the compression . numerical results are shown validating these claims . data mining , lossy compression , reduced basis method , singular value decomposition , greedy algorithm

in the united states , foodborne pathogens cause 76 million illnesses , 325,000 hospitalizations , and 5,000 deaths annually . some of the main pathogens behind these sicknesses are gram - negative bacteria such as salmonella , escherichia , and campylobacter . infections with gram - negative bacteria may lead to endotoxemia caused by lipopolysaccharides ( lps ) which is a complex of glycolipids made up of two distinct regions . these are hydrophilic polysaccharide region ( composed of o antigen and core oligosaccharide ) and hydrophobic regions known as lipid a . lipid a is responsible for most of the lps induced biological effects . since lipid a is the innermost component of lps , it is closely adherent to the inner cell wall of bacteria and is generally not released ( and therefore not toxic ) until the death of the bacterial cell . lps is heat stable and not strongly immunogenic , so it can not be converted to a toxoid . histone modification is the central point for the control of cardiac growth and gene expression in response to acute and chronic stress stimuli . in the prevention and treatment of cardiac disease , histone modification and the signaling pathways manipulation is a major therapeutic step . histone acetyltransferases ( hats ) mediate acetylation of histone tails , loosening the interaction between dna and histones . acetylation of histones reduces their overall positive charge , thus decreasing their tight interactions with negatively charged dna . histone deacetylases ( hdacs ) can remove the acetyl groups on amino - terminus of histones , restore tight interactions between dna and histones , and deactivate the transcriptional pathway . therefore , hats ( histone acetyltransferases ) and hdacs ( histone deacetylases ) activity determines the transcriptional activation or repression . hat activity in cardiac muscle is determined by p300 that causes modification of chromatin and associated transcription factors and gene expression . studies done by yanazume et al . , 2003 , showed that agonist - induced cardiac hypertrophy accentuates p300 transcriptional activity and that this agonist - mediated cardiac hypertrophy is reversed by the blocking of p300-hat activity . curcumin is an inhibitor of p300-hat but very little is known about whether this regulatory effect is related to a protective role in cardiac dysfunction . curcumin which is derived from turmeric ( curcuma longa plant ) is a tropical plant that is native to southern and southeastern tropical asia . it is a perennial herb within the ginger family and is known for its yellow - orange color and for numerous therapeutic applications . curcumin is a polyphenolic compound and has been used in the treatment of many conditions , including cardiovascular diseases . this study was designed to determine the potential for curcumin to attenuate lps induced cardiac hypertrophy in rodents . curcumin c3 complex ( r ) was a kind gift from sabinsa corporation , hyderabad , india . the patented c3 complex ( r ) contains curcumin and its derivates demethoxycurcumin and bisdemethoxycurcumin , also known as curcuminoids . lps sc-3535 was obtained from santa cruz biotechnology as a white to yellow lyophilized powder . for the live and dead experiment , lps was used as 1.5 mg / mice ( dissolved in distilled water ) , and in curcumin attenuation of lps induced cardiac hypertrophy , lps was used as 60 mg / kg body weight dose ( dissolved in distilled water ) . histone h3 ( n-20 ) , was produced against a peptide mapping at the n - terminus of histone h3 of human origin . histone h4 ( n-18 ) , purified goat polyclonal antibody , was produced against a peptide mapping at the n - terminus of histone h4 of human origin . p300 ( c-20 ) was obtained from santa cruz biotechnology , santa cruz , ca . p300 ( c-20 ) , affinity purified rabbit polyclonal antibody , was raised against a peptide mapping at the c - terminus of p300 of human origin . acetyl - histone h3 ( lys9 ) antibody was obtained from cell signaling technology , danvers , ma . endogenous levels of histone h3 were detected by acetyl - histone h3 ( lys9 ) antibody only when acetylated at lysine 9 . acetyl - histone h4 ( lys12 ) antibody was obtained from cell signaling technology , danvers , ma . endogenous levels of histone h4 were detected by acetyl - histone h4 ( lys12 ) antibody only when acetylated at lys12 . acetyl - cbp ( lys1535)/p300 ( lys1499 ) antibody was obtained from cell signaling technology , danvers , ma . acetyl - cbp ( lys1535)/p300 ( lys1499 ) antibody detects endogenous levels of cbp or p300 only when acetylated at lysine 1535 or lysine 1499 , respectively . the animal care and use committee of tuskegee university approved the experimental protocol ( protocol number r0804 - 12 - 1 ) . eight breeding pairs of mice ( mus musculus ) strain 129s6/sveev , il-10 , were received from the gnotobiotic unit of the mutant mouse resource center , university of north carolina , chapel hill , nc ( iacuc approval number r076 - 10 - 2 ) . the mice were housed under specific pathogen - free ( spf ) conditions in the comparative medicine resource center ( cmrc ) , tuskegee university , and bred via brother : sister mating to produce the mice used in this study . subsequently , 48 of the resulting mice were randomly assigned to one of four treatment groups . the adult 129svev mice ( 68 weeks old ) used in the current study were assigned to 4 groups ( 3 males and 3 females in each group ) : ( a ) control , ( b ) curcumin : 100 g / kg of body weight , ( c ) lps : 60 mg / kg , and ( d ) lps ( 60 mg / kg ) + curcumin ( 100 g / kg of body weight ) . then , following a 24 acclimation period , curcumin and curcumin + lps treated groups received intraperitoneal ( i.p . ) injections of curcumin ( 100 g / kg of body weight ) . one day after the pretreatment with 100 g / kg curcumin , the lps and curcumin + lps groups received lps : 60 mg / kg i.p . all mice in the 12 hrs subgroups were sacrificed with co2 12 hrs after lps injection . all mice in the 24 hrs subgroups were sacrificed with co2 , 24 hrs after lps injection . hearts and lungs of the sacrificed mice were dissected and weighed to compare heart weight / brain weight ( mg / g ) and lung weight / brain weight ( mg / g ) ratios in lps and curcumin treated mice . the collected organs were then preserved in 10% regular formalin in 50 ml tubes . immunohistochemistry is the process of detecting antigens in cells of a tissue section by exploiting the principle of antigen - antibody binding specificity . the sections of murine tissue were placed on the heated water bath and picked up , placed on the slides , and placed in a rack . after all slides had been cut and placed in a rack they were put into a 60 degrees celsius oven over night . the slides were deparaffinized by going through 3 changes of xylene 2 minutes each , followed by 3 changes of 100% alcohol at 1 minute and one change of 95% alcohol at 1 minute . slides were washed in running tap water for 1 minute and stored in distilled water slides . each group was normally distributed , and the variances were equal in the two groups . the test statistic , ts , was calculated using a formula that has the difference between the means in the numerator . the denominator was the standard error of the difference in the means , which got smaller as the sample variances decrease or the sample sizes increase . thus ts got larger as the means got farther apart , the variances got smaller , or the sample sizes increased . mice in the lps treated group showed significant cardiac hypertrophy as measured by heart weight / brain weight ( hw / bw ) ratio . figure 1 illustrates that the lps treated group showed significant cardiomegaly . in 12 hrs subgroup , the p = .04 denotes a significant difference between the control and lps , and in the 24 hrs subgroup , the p = .0026 denotes a significant difference between the control and lps treated groups . mice , in the lps + curcumin treated group , showed attenuation of cardiac hypertrophy as measured by heart weight / brain weight ( hw / bw ) ratio ( figure 1 ) . in 12 hrs subgroup , the p = .005 denotes a significant difference between the lps and lps + curcumin , and in 24 hrs subgroup , the p = .04 denotes a significant difference between the lps and lps + curcumin treated groups . no significant changes were observed in the mice treated with either curcumin or control group ( figure 1 ) . in figure 2 , the heart collected from lps treated mice group showed significant cardiomegaly . dna wound around eight core histone proteins ( two each of h2a , h2b , h3 , and h4 ) form the nucleosome which is the primary building block of chromatin . the amino - terminal tails of core histones pass through various posttranslational modifications , including acetylation , phosphorylation , methylation , and ubiquitination . these modifications happen in response to various stimuli and serve to open the transcriptional machinery , increase the accessibility of chromatin to transcription factors , and ultimately result gene expression . acetylation of h3 has a central role in histone deposition and chromatin assembly in some organisms . hats acetylate histone proteins , relax chromatin , and expose prohypertrophic genes for activation by cardiogenic transcription factors . inhibition of histone acetylation has a central role for the antihypertrophic activity of curcumin . in order to evaluate the mechanism of action of curcumin against lps induced cardiac hypertrophy , we determined the condition of histone h3 acetylation by using acetylation specific antibodies . in this study , curcumin repressed the lps induced acetylation of histone-3 in mice ( figure 4 ) . as a control , the paraffin blocks were exposed to histone h3 antibody , and endogenous levels of histone h3 were detected by h3 antibody ( figure 3 ) . as expected , lps induced a significant increase in histone acetylation that was blocked and sustained by curcumin ( figure 4 ) . histone proteins were detected by histone h3 antibody in control ( figure 3(a ) ) , curcumin ( figure 3(b ) ) , lps ( figure 3(c ) ) , and curcumin + lps ( figure 3(d ) ) groups . but the cardiac cells in the lps treated group showed more staining in the cytoplasm indicating hypertrophy . figure 4 illustrates the degree of histone acetylation in cardiac tissue occurring in each treatment group . as can be seen in figure 4(c ) , lps induced a significant increase in histone acetylation as indicated by the intense staining . the histone proteins were mainly acetylated in the n - terminal end of the histone protein on lysine residues . in the curcumin + lps treatment group ( figure 4(d ) ) , there was a much lesser degree of nuclear staining with staining being similar to the control group , indicating that curcumin inhibited the histone acetylation activity of lps . these findings indicate that acetylation of histone tails by histone specific antibodies , mediated by histone acetyltransferases , is involved in activation of gene expression in the myocardium . conversely , repression of gene expression can be induced by histone deacetylation , which is mediated by histone deacetylases ( hdacs ) . modulation of chromatin structure has a central role in the regulation of transcription in eukaryotes . in eukaryotes , histone h4 acetylation at the position of lysine 16 ( h4-k16ac ) is a reversible posttranslational chromatin modification . the incorporation of this modified histone into the nucleosome inhibits the formation of compact 30 fibers and inhibits the ability of chromatin to form cross - fiber interactions . acetylation of histone tails , mediated by histone acetyltransferases , is involved in activation of gene expression in the myocardium . conversely , repression of gene expression can be induced by histone deacetylation , which is mediated by histone deacetylases ( hdacs ) . histone h4 acetylation at the position of lysine 16 ( h4-k16ac ) is a posttranslational chromatin modification . in addition to histone h3 we also measured histone h4 acetylation by measuring the [ h ] acetate incorporation into histones using h4 acetylation specific antibody . figure 5 illustrates the level of histone proteins as detected by histone h4 antibody in cardiac tissue from control ( figure 5(a ) ) , curcumin ( figure 5(b ) ) , lps ( figure 5(c ) ) , and curcumin + lps ( figure 5(d ) ) treatment groups . as can be seen in the figure , there was little variation in histone h4 basal expression levels among any of the treatment groups . as can be seen in figure 6(c ) , the lps treated group showed a significant increase in histone [ h ] acetylation . control and curcumin alone treatment groups , figures 6(a ) and 6(b ) , respectively , showed little difference in the staining of the acetylated histone h4 . similar to histone h3 acetylation , lps induced h4 acetylation was also blocked by curcumin treatment ( figure 6(d ) ) . this data strongly indicates that curcumin inhibits the acetylation of histones induced by lps . hats ( histone acetyl - transferase ) acetylate histone proteins , relax chromatin , and expose genes for activation by cardiogenic transcription factors . two highly related and widely expressed molecules , camp regulated enhancer binding protein ( cbp ) and p300 , have emerged as important cofactors for a broad number of transcription factors . cbp was originally discovered based on its ability and to interact with the camp response element binding protein , whereas p300 was isolated as a cellular target of the adenoviral oncoprotein e1a . sequence analysis of cbp and p300 has shown substantial homology that these proteins are transcriptional coactivators . p300 , high molecular weight transcriptional factor , has three cysteine and histidine - rich regions . p300 knockout mice showed the defects of cardiac muscle differentiation and trabeculation , indicating the importance of p300 for early cardiac morphogenesis and heart development . curcumin ( diferuloylmethane ) , a major curcumanoid in the spice turmeric , is a specific inhibitor of the p300/creb - binding protein ( cbp ) . to further check the mechanism of action of curcumin , we analyzed p300 protein acetylation levels . curcumin inhibited the lipopolysaccharide - induced acetylation resulting in an increase in the binding of p300 to the gene promoter ( figure 7(c ) ) . as was seen with histone acetylation , p300 acetylation was also inhibited by curcumin ( figure 7(d ) ) . the results of the present study indicate that inhibition of histone acetylation is a key mechanism for the anti - cardiac hypertrophy activity of curcumin and that p300-hat serves as its molecular target . p300 may maintain basal function in the normal heart but it also promotes cardiac hypertrophy under lps infusion . we can conclude from our study that curcumin attenuated lps induced cardiac hypertrophy in vivo . curcumin plays its anti - cardiac hypertrophy role by the involvement of chromatin remodeling , especially histone acetylation . acetylation of lysine residues upon a single histone tail ( hyperacetylation ) would produce a stronger effect . histone acetyltransferases have a critical role to acetylate histone proteins , relax chromatin , and expose cardiac hypertrophy genes for activation by cardiogenic transcription factors . hat activity in muscle is determined by p300 that causes modification of chromatin and associated transcription factors and gene expression . lps induced cardiac hypertrophy accentuates p300 transcriptional activity , and lps mediated cardiac hypertrophy is reversed by blocking of p300-hat activity . therefore , blocking p300-hat activity may be a viable method for the treatment or prevention of myocardial hypertrophy . the results showed that curcumin attenuated lps induced cardiac hypertrophy in rodents and that the most probable mechanism of action involves inhibiting the p300-hat activity .

to study the ameliorating effects of curcumin in lipopolysaccharide ( lps ) induced cardiac hypertrophy , mice were assigned to 4 groups ( 3 males and 3 females in each group ) : ( a ) control , ( b ) curcumin : 100 g / kg of body weight by intraperitoneal route ( ip ) , ( c ) lps : 60 mg / kg ( ip ) , and ( d ) lps + curcumin : both at previously stated concentrations by ip route . all mice were sacrificed as 12 hr and 24 hrs groups accordingly after lps injection . the hearts were collected , photographed for cardiomegaly , and weighed to compare heart weight / brain weight ( hw / bw ) in mg / mg . for immunohistochemistry , the tissue sections were exposed to histone h3 , h4 and acetylated histone h3 , h4 antibody . lps induced a significant increase in histone acetylation as shown by intense staining . in curcumin + lps treated mice nuclear staining was similar to the control group indicating that curcumin traversed the histone acetylation activity of the lps . to further check the mechanism of action of curcumin , p300 protein acetylation levels were analyzed . this study suggests that the probable mechanism of action of curcumin is via the reduction of p300 hat activity .

The alleged mastermind of the Sept. 11 terror attacks wrote former President Barack Obama in a long suppressed letter that America brought the 9/11 attacks on itself for years of foreign policy that killed innocent people across the world. “It was not we who started the war against you in 9/11. It was you and your dictators in our land,” Khalid Sheik Mohammed, 51, writes in the 18-page letter to Obama, who he addressed as “the head of the snake” and president of “the country of oppression and tyranny.” It is dated January 2015 but didn’t reach the White House until a military judge ordered Guantánamo prison to deliver it days before Obama left office. Allah helped us to defend ourselves and attack your most significant military and commercial targets in your land for your crimes in our lands. Khalid Sheik Mohammed, accused Sept. 11 attacks mastermind In it, the man on trial for his life at Guantánamo as the alleged architect of the hijackings that killed nearly 3,000 people in New York, the Pentagon and a Pennsylvania field adds that he neither fears a death sentence nor life in a prison cell. He also appends a 50-page manuscript he wrote, “The Truth About Death,” illustrated with a picture of a noose. $20 for 365 Days of Unlimited Digital Access Last chance to take advantage of our best offer of the year! Act now! An excerpt from Khalid Sheik Mohammed's letter to former President Barack Obama. “I will be happy to be alone in my cell to worship Allah the rest of my life and repent to Him all my sins and misdeeds,” he says in the letter that he wrote at the U.S. Navy base in Guantánamo Bay, Cuba. “And if your court sentences me to death, I will be even happier to meet Allah and the prophets and see my best friends whom you killed unjustly all around the world and to see sheik Osama bin Laden.” The Herald obtained the document from Mohammed’s lawyers after a judicially ordered 30-day review period expired. The Kuwait-born Pakistani citizen of Baluch ethnic background, lists a long litany of U.S. overseas interventions — from Iraq and Iran to Vietnam and Hiroshima — to justify the worst terror attack on U.S. soil. But he is particularly focused on the cause of the Palestinians, highlights civilian suffering and accuses Obama of being beholden to special interests, notably Israel and “the occupier Jews.” Israel gets 39 mentions while Osama bin Laden gets a dozen, including once to excoriate Obama for the mission that hunted down and killed the founder of the al-Qaida movement for the 9/11 attacks. An excerpt from Khalid Sheik Mohammed's letter to former President Barack Obama. Mohammed ridicules Obama — “a smart attorney, well acquainted with human rights” — who “can kill his enemy without trial and throw his dead body into the sea instead of giving him to his family or respecting him enough as a human being to bury him.” The former al-Qaida operations chief wrote the letter “in the context of violence in Gaza and the occupied territories,” said Mohammed’s death-penalty defense attorney, David Nevin. He called it “the primary motive for the drafting of the letter” and declined to say whether the client or his legal staff typed it up. Mohammed began drafting the letter during 2014 when Israel had an offensive in the Gaza Strip that claimed civilian lives, according to his military attorney, Marine Maj. Derek Poteet. “He’s upset at U.S. foreign policy and he plainly perceives that the United States has signed a blank check to Israel,” Poteet said. In the opening paragraph Mohammed tells Obama: “Your hands are still wet with the blood of our brothers and sisters and children who were killed in Gaza.” SHARE COPY LINK In an Aug. 14, 2014 news conference at the U.S. Navy base at Guantánamo Bay, Cuba, Khalid Sheik Mohammed's attorney, David Nevin, discusses the letter that Mohammed sent to President Obama. Mohammed is one of five men in pretrial hearings at the Guantánamo war court that accuses them of engineering the Sept. 11, 2001 hijackings, and seeks their execution if convicted. The man was hidden for 3 1/2 years in the CIA’s secret prison network, where he was waterboarded 183 times and subjected to other brutal interrogation techniques. “I will never ask you, or your court for mercy,” he writes. “Do what you wish to do, my freedom, my captivity and my death is a curse on all evil doers and tyrants.” Mohammed spent about three years in North Carolina in the 1980s. He attended Chowan College in Murfreesboro for one semester and then transferred to North Carolina A&T in Greensboro, where he earned an engineering degree in 1986. An excerpt from Khalid Sheik Mohammed's letter to former President Barack Obama. Prison officials refused to deliver the letter, a position backed by prosecutors who said it should be suppressed as propaganda. His Pentagon-paid defense attorneys asked the judge to intervene in September 2015, arguing Mohammed’s First Amendment right to petition the president. The Army judge in charge of the trial, Col James L. Pohl, eventually ruled that the commander in chief could receive it, virtually as the Obamas were packing out of the White House — and the public could see it a month later, once President Donald J. Trump moved in. “What’s so troubling to me is it took so long to get approval, even to get this litigated,” Nevin said, reminding that the defense team started out asking the military, “How do we provide this to the president of the United States?” Link to the Herald guide to Guantánamo’s Sept. 11 trial here In the letter Mohammed also: ▪ Endorses Al-Jazeera. “Don’t let Fox, CNN, BBC, or American and pro-Israeli channels cover your eyes ... Their main task is brainwashing. They are experts at lying and distorting the facts to achieve their masters’ ends.” ▪ Invokes “the blood of the innocents your drone attacks killed in Waziristan, Yemen, Iraq, Libya, Afghanistan, Somalia, and elsewhere around the globe.” ▪ Singles out “the CIA, the FBI, the Jewish community of Brooklyn, the merchants of AIPAC, the war profiteers, to pro-Israeli militias and the Christian-Zionist Lords” for condemnation, as well as “the Christian right wing and the followers of Jerry Falwall, Gary Bauer, Pat Robertson and John Hague.” ▪ Says “Allah aided us in conducting 9/11, destroying the Capitalist economy, catching you with your pants down, and exposing all the hypocrisy of your long-held claim to democracy and freedom.” The theme is not new. In October 2012, when he was first allowed to wear a hunting vest to the war court he scolded the judge with this: “Your blood is not made of gold and ours is made out of water. We are all human beings.” The Herald obtained the document from Mohammed’s lawyers after a judicially ordered 30-day review period expired. Pohl ruled on Jan. 6 that there was no “legal basis for continued sealing of the letter’s contents” but gave the prison an extra month to scrub it of sensitive information before releasing it on the Pentagon war court website whose motto is “Fairness * Transparency * Justice.” A spokesman at the Pentagon could not explain Wednesday why the document was not yet posted on the website. The Herald asked Obama’s office on Tuesday whether the former president had read the letter. It has yet to respond. ||||| The alleged mastermind behind 9/11 told President Obama that the U.S. brought the 2001 terrorist attack on itself, according to a letter obtained and published Wednesday by The Miami Herald. The 18-page letter is dated January 2015, but wasn’t sent to the White House until a military judge ordered for it to be delivered just days before Obama left office last month. Officials at the prison at Guantanamo Bay, where he’s a detainee, had refused to deliver the letter because it could be considered propaganda. “It was not we who started the war against you in 9/11. It was you and your dictators in our land,” Khalid Sheik Mohammed, 51, wrote in the letter. The letter was addressed to Obama and described him as “the head of the snake” and president of “the country of oppression and tyranny,” the report said. One section said, “Why did 9/11 happen? And Why May it Happen Again?” “The war crimes perpetrated in Palestine since 1948, and those taking place in Gaza today, are the clearest indication of why 9/11 happened, and why it may happen against in the future,” he wrote as an answer in the letter. Mohammed has been held at the prison at Guantanamo Bay since 2006 after being captured in Pakistan in 2003. During an interrogation in 2007, he confessed to being the mastermind of the 9/11 attacks. Mohammed was subjected to the CIA’s harshest interrogation methods, including waterboarding. “I will be happy to be alone in my cell to worship Allah the rest of my life and repent to Him all my sins and misdeeds,” he wrote in the letter to Obama. “And if your court sentences me to death, I will be even happier to meet Allah and the prophets and see my best friends whom you killed unjustly all around the world and to see sheik Osama bin Laden.” The letter also listed a number of U.S. interventions overseas including in Hiroshima, Vietnam, Iran and Iraq to justify the 9/11 attacks, the report said, and condemned Obama for the operation that resulted in the death of Osama bin Laden. He called Obama “a smart attorney, well acquainted with human rights” who “can kill his enemy without trial and throw his dead body into the sea instead of giving him to his family or respecting him enough as a human being to bury him,” the report said. Mohammad, meanwhile, is awaiting his death-penalty trial at Guantanamo Bay.

– The man who allegedly spearheaded 9/11 blames America for the terrorist attack in a letter written to Barack Obama and delivered in the final days of his presidency. A copy of the letter, which was finished in 2015 but held up by officials at Guantanamo, was obtained from Khalid Sheik Mohammed's lawyers by the Miami Herald. In the letter's 18 pages (it came along with a 50-page manuscript), Mohammed says America had 9/11 coming after years of killing innocent people around the world, including in Vietnam, Hiroshima, and Iraq. He was particularly concerned with Palestinian deaths in the Gaza Strip, telling Obama: “Your hands are still wet with the blood of our brothers and sisters and children who were killed in Gaza." Elsewhere in the letter, Mohammed says he's fine with a life in prison, but he'll "be even happier" if the US sentences him to death because he'll be able to see Allah and Osama bin Laden. On the topic of bin Laden, Mohammed blames Obama—"the head of the snake"—for throwing the former al Qaeda leader's body into the ocean instead of burying it or returning it to his family. Mohammed also attacks drone strikes, CNN, Fox, "the Jewish community of Brooklyn," the CIA, the FBI, "the followers of Jerry Falwell," and more. Mohammed was captured in Pakistan in 2003 and is currently being held at Guantanamo, CBS News reports. He confessed to plotting 9/11 while under interrogation in 2007.

Cher is headed for Lifetime. The iconic singer-actress has been tapped to star in Flint, a TV movie based on the Flint, Mich., water crisis, The Hollywood Reporter has confirmed. Craig Zadan, Neil Meron and Katie Couric will executive produce, alongside Cher. Bruce Beresford will direct the movie from Sony Pictures Television. Barbara Stepansky will pen the script. Cher will portray a Flint resident whose family is impacted by the water crisis. The drama is based on events in Flint about the poor management that led to water poisoning as well as the human elements of the residents who suffered — and whose voices were ignored. The movie was inspired by a February 2016 cover story in Time magazine called "The Toxic Tap," by Josh Sanburn. Zadan and Meron's Sony Pictures TV-based Storyline Entertainment optioned the rights to the story. This is Cher's second TV movie role, following HBO's 1996 If These Walls Could Talk, for which she scored a Golden Globe nomination. She has been actively involved in helping Flint residents, including donating thousands of bottles of water. "This is a tragedy of staggering proportion and shocking that it's happening in the middle of our country," the Oscar winner said at the time. ||||| Behind the Story: TIME’s Flint Water Crisis Cover Piece Gabriella Schwarz / January 23, 2016 Story: “The Toxic Tap“ Outlet: TIME Reporter: Josh Sanburn TIME reporter Josh Sanburn experienced the anger felt by Flint water residents following the water crisis as he reported from the Michigan city for TIME’s cover story. Sanburn said residents are angry at politicians and bureaucrats who failed to stop the nearly two-year long crisis of contaminated water flowing from their faucets, but he said many residents believe Flint will rebound and that the crisis has brought the community together. Read more about what Sanburn experienced on the ground and what’s next for the city. Can you describe the emotions felt by the Flint residents with whom you spoke? Flint residents, by and large, are angry. Angry at their governor. Angry at city officials who told them the water was safe to drink despite reports to the contrary. Angry at the series of emergency managers who were appointed by the state to clean up Flint’s financial woes but put dollars ahead of the safety of city residents. Much of that anger comes from parents who simply turned on the tap and unwittingly served their children what amounted to poison. Lead exposure in kids age six and under can be devastating. If a Flint resident’s son or daughter appears to be doing poorly in school in a few years, has problems focusing, is showing signs of learning disabilities, those parents will always wonder: Maybe it was the water. What most surprised you about the reality on the ground? Two things. There are extremely high levels of poverty in Flint, and seeing it up close is a visceral reminder of the severity of this crisis. I visited one home where a family was barely getting by on the bottled water that had been donated to them. Many residents not only have incredibly high water bills—even as the water remains unsafe to drink—but they then can’t afford to regularly buy enough water to bathe in, cook with, and drink. Some of them only bathe their children once a week. The other surprising thing: There is a sizable portion of Flint residents who still believe in their city and believe that Flint will rebound even after the water crisis. A number of Flint residents told me that the recent problems have brought residents together in ways they’ve never seen before. How did the situation get to this point? How Flint’s water became poisoned is a tangle of events, but the basic story is this: A few years ago, Flint made the decision to stop purchasing water from Detroit and join a pipeline project called the Karegnondi Water Authority. The problem was that the pipeline wasn’t finished, so Flint needed a temporary water source and turned to the Flint River. When the city started pumping the river water into people’s homes, there was no corrosion control in place, meaning the city was not effectively treating the water. As the water flowed through the city’s lead service pipes, it ate away at them, carrying extremely high levels of lead into residences. State officials denied this was happening for months even though there were internal reports showing elevated lead levels in several Flint homes. It took outside researchers—notably Marc Edwards at Virginia Tech University and Mona Hanna-Attisha, a pediatrician at Hurley Medical Center in Flint—to eventually prod officials to acknowledge that, yes, there is lead in the water and it is not safe to drink. Are the residents receiving the help and aid they need now? They’re receiving some help, but it’s not enough. A number of residents I spoke to said that most of the water they were receiving was coming from donations, often from everyday people just trying to help. When the National Guard was first deployed, only seven members were sent to help a city of 100,000, and I only saw one of them when I was there. The White House has now pledged $80 million for Flint while the governor is asking the state legislature to approve $28 million. But that money will take a while to get to residents who are still struggling to pay the costs of constantly stocking up on safe water. You write about the history of Flint and decline of manufacturing and the auto industry. Is the current situation a repercussion of that decline in some way(s)? If so, how? Flint has been in decline for decades. It now has half the population it did in 1960, and much of that is due to General Motors packing up and leaving town. GM employed roughly 80,000 people in the Flint area in the 1950s. Today, it’s just a few thousand, and nothing has come in to fill that void. So the declining tax base means the city hasn’t been able to invest in the kinds of infrastructure or development projects that might help the city grow. That has led to budget deficits which led to emergency managers which led to decisions being made—like switching from Detroit water and not investing in corrosion control—purely to save money. I know every tragedy is different, but did this situation remind you of another event in recent memory or in our history? More than a decade ago, thousands of children were exposed to lead in Washington, D.C., which led to a Congressional investigation and, as it turns out, was discovered by Marc Edwards, the same corrosion expert who shed light on Flint’s water problems. There were the groundwater contamination issues in Hinkley, Calif., uncovered by activist Erin Brockovich. And then there are other instances of corporations polluting water sources, like the story of Dupont dumping toxic waste into a creek. The seriousness of the problems in Flint certainly rank up there with the most serious breaches involving water sources in the U.S. Are the residents united to push for change? If so, what is the change they’re seeking? By most accounts, they are. Many of them certainly want to see the governor resign because they believe he knew more about the situation than he’s letting on. The real change may have to come through a long-term, systematic investment in the city’s aging infrastructure, most notably the corroded lead service lines that connect residents’ homes to the main city water pipes. What will the short and long-term repercussions be—in the city, state, nationally or in the minds and lives of those most hurt? The long-term consequences are most importantly the developmental issues that many children potentially face from lead exposure. And it will take years for those effects to make themselves known. But there is also the problem of trust. It will be extraordinarily difficult for most residents to ever believe what their government tells them. Lee-Anne Walters, who was instrumental in hounding officials about lead showing up in her home, has since moved part-time to Virginia. She’s now hundreds of miles from Flint, and she still doesn’t drink water from the tap. Learn more about how to help the Flint residents through several charities in this piece on Time.com. See more photos from the ground here and follow the Flint topic to keep up with the latest on the crisis. ~GabyS is reading the water topic GET FLIPBOARD ON: iOS / ANDROID / WINDOWS / WEB FOLLOW US ON: FLIPBOARD / TWITTER / INSTAGRAM / FACEBOOK / GOOGLE+ / TUMBLR / YOUTUBE / SOUNDCLOUD / PINTEREST / MEDIUM

– The Flint, Mich., water crisis will be turned into a Lifetime movie starring ... Cher. The singer will star as a resident of the city whose family struggles with the water poisoning, according to the Hollywood Reporter. The casting move is perhaps not as unexpected as it might seem; a year ago, Cher gave Flint 180,000 bottles of water. The movie, based on Josh Sanburn's Feb. 2016 Time cover story "The Toxic Tap," will be produced by Cher, Craig Zadan, Neil Meron, and Katie Couric; it will be directed by Bruce Beresford. It's not Cher's first TV role: She notched a Golden Globe nom for her turn in HBO's 1996 If These Walls Could Talk.

cornual pregnancy is a rare form of ectopic pregnancy where implantation occurs in the cavity of a rudimentary horn of the uterus , which may or may not be communicating with the uterine cavity . cornual pregnancy represents 24% of all tubal pregnancies and occurs once in every 25005000 live births . the increased difficulties associated with the diagnosis and management of cornual gestations have resulted in this being the most hazardous of ectopic pregnancies . as a result , uterine rupture may occur in up to 20% of the cases that progress beyond 12 weeks of amenorrhea , resulting in massive hemorrhage due to high vascularity in this region through the branches of the uterine and ovarian arteries , leading to a higher mortality rate . in very rare circumstances this case is presented because of its rarity where cornual pregnancy was continued to a late gestation without rupture and was diagnosed at the time of cesarean section with a successful conservation of uterus . a 24-year - old , unbooked primigravida presented to labor room with the complaint of decreased fetal movement at 37 weeks of gestational age . there was no history of pelvic inflammatory disease ( pid ) , previous pelvic surgery or assisted reproductive technique ( art ) procedures . she belonged to a tribal community without proper antenatal care with history of two antenatal checks up in a peripheral hospital . she had two previous ultrasound scan reports done in second and third trimester showing single live intrauterine fetus with anterior low lying placenta at 24 weeks and 34 weeks of gestation respectively . ultrasonography revealed a single live intrauterine fetus in cephalic presentation with anterior low lying placenta and severe oligohydramnios ( amniotic fluid index = 1.8 cm ) . there was severe bleeding from the placental bed and intraoperative blood loss was around 1500 ml . intraoperatively it was diagnosed that pregnancy occurred in the right horn noncommunicating horn of uterus . uterus , left adnexa and bilateral ovaries found normal [ figures 1 and 2 ] . she had an uneventful postoperative period and she was discharged on day 7 in good condition . right noncommunicating horn of the uterus with placenta percreta and normal left fallopian tube and ovary right horn of uterus with placenta percreta with healthy right ovary cornual resection with repair in cornual pregnancy , the rudimentary horn does not always communicate with the rest of the uterine cavity in which case it must be assumed that spermatozoa ascend through the other horn and tube and fertilize an ovum in the peritoneal cavity . an important feature of cornual pregnancy is that the sac is surrounded by myometrium and even though it is poorly developed , it can contain the pregnancy for a longer period than tube or ovary . in some respects cornual pregnancy resembles the interstitial type of tubal pregnancy and they can be confused at the time of operation . a distinguishing feature is the insertion of the round ligament , which is always lateral to the cornual pregnancy . the risk factors for cornual and interstitial pregnancy are similar to those for ectopic pregnancy in general , including pelvic pid , previous pelvic surgery and the use of art . in our case the possible mechanism in art procedures that have been proposed to explain this include hydrostatic forces delivering the embryo into the cornual or tubal area , the tip of the catheter directing transfer towards the tubal ostia , or reflux of uterine secretions leading to retrograde tubal implantation . early diagnosis of cornual pregnancy can be done with transvaginal ultrasound . in our case , two abdominal ultrasound scans done one in second and one in third trimester each which failed to diagnose the condition . tulandi and al - jaroudi reviewed the management of 32 reported cases of cornual pregnancy . ultrasound revealed an ectopic cornual gestational sac in 40.6% of women and a hyperechoic mass in the cornual region in another 25% . the diagnosis was established in 71.4% of 32 women with a sensitivity of 80% and specificity of 99% . uterine rupture may occur in up to 20% of the cases of cornual pregnancy that progress beyond 12 weeks of amenorrhea , resulting in massive hemorrhage . in very rare circumstances , the pregnancy was continued to a late gestation resulting a viable fetus as reported by hill et al . where the interstitial pregnancy was not ruptured at the time of cesarean delivery and uterus was conserved successfully . traditionally , the treatment of cornual pregnancy has been hysterectomy or cornual resection at laparotomy . conservative techniques such as laparoscopic cornual resection , laparoscopic cornuostomy or hysteroscopic removal of interstitial ectopic tissue , unilateral uterine artery ligation have been tried . medical methods such as systemic methotrexate , ultrasound - guided methotrexate , laparoscopic - guided methotrexate ( or potassium chloride ) or systemic methotrexate , followed by selective uterine artery embolization are safe and highly effective treatment for cornual pregnancy and hence that surgery can be avoided . our patient presented in relatively late gestation , and the diagnosis was done at the time of caesarean section . cornual pregnancy can cause significant maternal mortality and morbidity , hence early diagnosis aided by ultrasound or laparoscopy may help to contribute toward effective conservative management .

cornual pregnancy is uncommon among ectopic pregnancies . a diagnosis of cornual pregnancy remains challenging , and rupture of a cornual pregnancy causes catastrophic consequence due to massive bleeding . in very rare circumstances , cornual pregnancies can result in a viable fetus . we report a case of a 24-year - old primigravida who presented to us with complaints of decrease fetal movements at 37 + 5 weeks . ultrasound revealed a single live intrauterine fetus with anterior low lying placenta with severe oligohydramnios ( amniotic fluid index = 1.8 ) . emergency cesarean section was done and intraoperatively it was diagnosed as a case of placenta percreta with pregnancy in right noncommunicating horn of uterus . right cornual resection with right salpingectomy done . uterus , left fallopian tube and bilateral ovary were healthy . postoperative period was uneventful .

high - energy spin physics has been going through a period of great popularity and rapid developments ever since the measurement of the proton s spin - dependent deep - inelastic structure function @xmath3 by the emc @xcite more than a decade ago . as a result of combined experimental and theoretical efforts , we have gained some fairly precise information concerning , for example , the total quark spin contribution to the nucleon spin . yet , many other interesting and important questions , most of which came up in the wake of the emc measurement , remain unanswered so far , the most prominent `` unknown '' being the nucleon s spin - dependent gluon density , @xmath4 . also , polarized _ inclusive _ deep - inelastic scattering ( dis ) data do not provide enough information for a complete separation of the distributions for the different quark and anti - quark flavors @xmath5 , and @xmath6 . here in particular a possible flavor asymmetry in the nucleon s light sea , @xmath7 , has attracted quite some interest , and several models have been proposed recently @xcite . current and future dedicated spin experiments are expected to vastly broaden our understanding of the nucleon spin structure by studying reactions that give further access to its spin - dependent parton distributions , among them @xmath4 and @xmath8 , @xmath9 . in addition to lepton - nucleon scattering , there will also be for the first time information coming from very inelastic polarized @xmath0 collisions at the bnl relativistic heavy - ion collider rhic @xcite . having available at some point in the near future spin data on various different reactions , one needs to tackle the question of how to determine the polarized parton densities from the data . of course , this problem is not at all new : in the unpolarized case , several groups perform such `` global analyses '' of the plethora of data available there @xcite . the strategy is in principle clear : an ansatz for the parton distributions at some initial scale @xmath10 , given in terms of appropriate functional forms with a set of free parameters , is evolved to a scale @xmath11 relevant for a certain data point for a certain cross section . then the parton densities at scale @xmath11 are used to compute the theoretical prediction for the cross section , and a @xmath12 value is assigned that represents the quality of the comparison to the experimental point . this is done for all data points to be included in the analysis , and subsequently the parameters in the ansatz for the parton distribution functions are varied , until eventually a minimum in @xmath12 is reached . in practice , this approach is not fully viable if the partonic scattering is treated beyond the lowest order of perturbation theory . the numerical evaluation of the hadronic cross section at higher orders is usually a rather time - consuming procedure as it often requires several tedious numerical integrations , not only for the convolutions with the parton densities , but also for the phase space integrations in the partonic cross section . the fitting procedure outlined above , on the other hand , usually requires thousands of computations of the cross section for any given data point , and so the computing time required for a fit easily becomes excessive even on modern workstations . we note that for practically all reactions of interest in the unpolarized and polarized cases the first - order qcd corrections to the respective partonic cross sections are known by now . they are generally indispensable in order to arrive at a firmer theoretical prediction for hadronic cross sections ; for instance the dependence on the unphysical factorization and renormalization scales is reduced when going to higher orders in the perturbative expansion . only then can one reliably extract information on the parton distribution functions . in the unpolarized case , a way to get around this problem is based on the fact that the parton densities are already known here rather accurately @xcite . their gross features are basically determined by the wealth of very precise dis data which cover a wide kinematical range in the momentum fraction @xmath13 and the scale @xmath14 . as a consequence , the theory answer for a certain cross section is expected to change in a very predictable way when going from the lowest - order born level to the first - order approximation . it is then possible to pre - calculate a set of correction factors @xmath15 ( @xmath16 running over the data points ) , and to simply multiply them in each step of the fitting procedure to the _ lowest - order _ approximation for the cross section , the latter being usually much faster to evaluate than that involving higher order terms . the @xmath15 usually hardly change at all from one set of parton distributions to another , and in any case one may update them if necessary at certain stages of the fitting procedure . it should be noted , however , that this way of treating next - to - leading order ( nlo ) corrections in a fit is not necessarily adequate in all cases of interest . in particular if one is interested in extracting information about the gluon density at large values of @xmath13 , where it is only rather poorly constrained at the moment , the correction factors @xmath15 can not be reliably pre - calculated , and they may vary considerably during the fitting procedure . it is therefore desirable to incorporate nlo cross sections without any approximations in future analyses of parton densities . in the polarized case it is in general not at all clear whether a strategy based on correction factors @xmath15 will work . here , the parton densities are known with _ much _ less accuracy so far . it is therefore not possible to pre - calculate higher - order correction factors that one would be able to keep fixed throughout the fit , while using `` fast '' lowest - order expressions for the partonic cross sections . for instance , even though it is well known that for a sizable @xmath4 the @xmath17 compton subprocess is the dominant contributor to the transverse momentum distribution of a `` prompt '' photon in the kinematical region of interest , this is by no means the case if @xmath4 happens to be small , in which case all other channels , even genuine nlo ones , may become equally important . in addition , the spin - dependent parton distributions , as well as the polarized partonic cross sections , may have zeros in the kinematical regions of interest , near which the predictions at lowest order and the next order will show marked differences . therefore , even if the correction factors are updated at times during the fitting procedure , the convergence of the fit is not warranted . conversely , if one updates the @xmath15 frequently , the fit will become too slow again . clearly , in the polarized case , the goal _ must _ be to find a way of implementing efficiently , and without approximations , the _ exact _ nlo expression for any hadronic cross section such as the prompt photon cross section into the fitting procedure . as will be shown in the next section , this can be achieved in a very simple and straightforward way by going to mellin-@xmath18 moment space . a technique of this sort was first used for the case of jet production in dis as a means of extracting information about the unpolarized gluon density @xcite . the relevant generalization to hadron - hadron scattering , which is more involved and requires a `` double mellin transform '' was recently provided in @xcite . however , @xcite focuses on the formalism and the technical aspects of the mellin transformation , rather than on its actual practicability , and the usefulness in a global qcd analysis has never been demonstrated . before we demonstrate in some detail the potential of the mellin technique in praxis for two examples relevant for future global analyses of polarized parton densities , which is the main thrust of this paper , we start off in the next section by rederiving the required formalism in an easy and transparent way . in section 3 we will consider first the semi - inclusive production of hadrons in polarized dis as the simplest application of the mellin technique . the @xmath18 moments of the partonic cross sections can be taken analytically in this case . due to the subsequent fragmentation of a final state parton into the observed hadron , semi - inclusive dis ( sidis ) is sensitive to different flavor combinations than inclusive dis data . it has also the advantage that we have already data at our disposal @xcite which can be analysed in terms of a possible flavor asymmetry @xmath19 of the light sea . as a second example we study the production of a prompt photon at high transverse momentum @xmath20 in @xmath0 collisions at rhic in section 4 . its sensitivity to the gluon distribution via the lo compton subprocess , which , along with the cleanliness of the prompt photon signal , is the reason why this process will be the flagship measurement of @xmath4 at rhic @xcite . as a first case study for future global analyses we also carry out a `` toy '' analysis of dis _ and _ projected prompt photon data to highlight the power of future rhic @xmath0 data to pin down @xmath4 . we briefly summarize the main results in section 5 . the factorization theorem @xcite ensures that in the presence of a hard scale in a reaction the corresponding ( spin - dependent ) hadronic cross section can be written as a sum over `` convolutions '' of parton densities with partonic hard - scattering cross sections . the latter are perturbatively calculable and are specific to the reaction under consideration . the parton distributions , which for spin - dependent interactions contain the desired information on the nucleon s spin structure , depend on long - distance phenomena . however , they are universal : a single set of distributions for ( anti-)quarks @xmath21 and gluons @xmath22 , predicts all data sets simultaneously . to be specific , for a general spin - dependent cross section in longitudinally polarized @xmath0 collisions , differential in a certain observable @xmath23 and integrated over experimental bins in other kinematical variables @xmath24 , one has @xmath25 \\[2 mm ] % & = & % \sum_{a , b , c}\ , \int_{\mathrm exp - bin } dt\ , \int_{x_a^{\mathrm min}}^1 dx_a \int_{x_b^{\mathrm min}}^1 dx_b \int_{z_c^{\mathrm min}}^1 dz_c \,\ , \delta f_a ( x_a,\mu_f ) \,\delta f_b ( x_b,\mu_f ) d_c^h(z_c,\mu_f ' ) \ , \nonumber \\ [ 2 mm ] % & & % \times \,\frac{d\delta \hat{\sigma}_{ab}^{c}}{do dt } ( x_ap_a , x_bp_b , p_h / z_c , t , \mu_r , \mu_f , \mu_f ' ) \ ; , \nonumber\end{aligned}\ ] ] where the arguments @xmath26 and @xmath27 in the first line of eq . ( [ eq1 ] ) refer to the helicities of the incoming hadrons @xmath28 and @xmath29 . the @xmath30 are the spin - dependent parton distributions , defined as @xmath31 where @xmath32 ( @xmath33 ) denotes the number density of a parton - type @xmath34 with helicity ` + ' ( ` @xmath35 ' ) in a proton with positive helicity , carrying the fraction @xmath13 of the proton s momentum . the @xmath36 represent the unpolarized fragmentation functions . they parameterize the probability that a parton @xmath37 fragments into the observed final state @xmath38 , e.g. , a charged pion , with momentum @xmath39 . for some observables , such as ( di-)jets , there is no need for a fragmentation function in eq . ( [ eq1 ] ) . the scales @xmath11 and @xmath40 are the factorization scales for initial and final state collinear singularities , respectively , and reflect the certain amount of arbitrariness in the separation of short - distance and long - distance physics embodied in eq . ( [ eq1 ] ) . even though the parton densities ( fragmentation functions ) can not presently be derived from first principles , their dependence on @xmath11 ( @xmath40 ) is calculable perturbatively in terms of the `` dglap '' evolution equations @xcite , allowing to relate their values at one scale to their values at any other @xmath11 ( @xmath40 ) . the other scale , @xmath41 , in eq . ( [ eq1 ] ) is the renormalization scale , introduced in the procedure of renormalizing the strong coupling constant . finally , the sum in eq . ( [ eq1 ] ) is over all contributing partonic channels @xmath42 , with @xmath43 the associated partonic cross section , defined in complete analogy with the first line of eq . ( [ eq1 ] ) , the helicities now referring to partonic ones : @xmath44 \ ; .\ ] ] as mentioned earlier , the @xmath43 are perturbative , that is , they have the expansion @xmath45 it should be noted that lepton - hadron reactions are also included in eq . ( [ eq1 ] ) by simply setting @xmath46 . we will consider this example in some detail in section 3 as it is the simplest application of the mellin moment technique which we are going to advocate in the following as a straightforward tool to extract information about parton densities from a global qcd analysis . for the polarized parton distribution functions , the mellin moments are defined as f_i^n ( ) _ 0 ^ 1 dx x^n-1 f_i(x , ) . it is well known @xcite that the evolution equations for the the parton densities become particularly simple in mellin-@xmath18 space , since the convolutions occuring in the @xmath13-space equations factorize into simple products under moments . this allows for a straightforward analytic solution of the differential evolution equations , see , e.g. , @xcite . in fact , several of the nlo evolution codes used for parton density analyses in the unpolarized and polarized cases are set up in mellin-@xmath18 space . after evolving from one scale to another in moment space , the evolved parton distributions in bjorken-@xmath13 space are recovered by an inverse mellin transform , given by [ eq6 ] f_i(x , ) = _ c_n dn x^-n f_i^n ( ) , where @xmath47 denotes a contour in the complex @xmath18 plane that has an imaginary part ranging from @xmath48 to @xmath49 and that intersects the real axis to the right of the rightmost poles of the @xmath50 . the evolution of the time - like fragmentation functions can be treated in a very similar way in mellin space as well . the crucial , but simple , step in applying moment techniques to eq . ( [ eq1 ] ) is to express the @xmath51 by their mellin inverses in eq . ( [ eq6 ] ) @xcite . one subsequently interchanges integrations and arrives at @xmath52 % & & % \times \ , \int_{\mathrm{exp - bin } } dt\ , \int_{x_a^{\mathrm min}}^1 dx_a \int_{x_b^{\mathrm min}}^1 dx_b \int_{z_c^{\mathrm min}}^1 dz_c\,\ , x_a^{-n } x_b^{-m}\ ; d_c^h(z_c,\mu_f ' ) \nonumber \\[2 mm ] % & & % \times \ , \frac{d\delta \hat{\sigma}_{ab}^{c}}{dodt } ( x_ap_a,\ , x_bp_b\ , , p_h / z_c , t,\,\mu_r,\mu_f,\mu_f ' ) \\[2 mm ] % & \equiv & % \sum_{a , b } \ , \int_{{\cal c}_n } dn \ ; \int_{{\cal c}_m } dm\;\delta f_a^n(\mu_f)\,\delta f_b^m(\mu_f ) \ ; \delta \tilde{\sigma}_{ab}^{h } ( n , m , o,\mu_r,\mu_f ) \ ; .\label{eq8}\end{aligned}\ ] ] one can now pre - calculate the quantities @xmath53 , which do not depend at all on the parton distribution functions , _ prior _ to the fit for a specific set of the two mellin variables @xmath18 and @xmath54 , for each contributing subprocess and in each experimental bin . effectively , one has to compute the cross sections with complex `` dummy '' parton distribution functions @xmath55 . we emphasize that all the tedious and time - consuming integrations are already dealt with in the calculation of the @xmath53 . we have included the integration over the fragmentation function @xmath56 and the summation over the final state parton @xmath37 in the definition of the pre - calculated quantities @xmath57 . this also implies that @xmath57 does not depend anymore on the choice for @xmath40 apart from some residual dependence which is of higher order in @xmath58 . usually the fragmentation functions are taken from `` elsewhere '' , i.e. , @xmath59 data , rather than being fitted simultaneously with the parton densities . we note , however , that one can also replace @xmath56 by their mellin inverse according to eq . ( [ eq6 ] ) . in that case the pre - calculated quantities would depend on three mellin variables . the double inverse mellin transformation which finally links the parton distributions with the pre - calculated @xmath53 of course still needs to be performed _ in each step _ of the fitting procedure . however , the integrations over @xmath18 and @xmath54 in eq . ( [ eq8 ] ) are extremely fast to perform by choosing the values for @xmath60 in @xmath53 on the contours @xmath47 , @xmath61 simply as the supports for a gaussian integration . the point here is that the integrand in @xmath18 and @xmath54 falls off very rapidly as @xmath62 and @xmath63 increase along the contour , for two reasons : first , each parton distribution function is expected to fall off at least as a power @xmath64 at large @xmath13 , which in moment space converts into a fall - off of @xmath65 or higher . secondly , we may choose contours in moment space that are bent by an angle @xmath66 with respect to the vertical direction ; a possible choice is shown in fig . then , for large @xmath62 and @xmath63 , @xmath18 and @xmath54 will acquire large negative real parts , so that @xmath67 and @xmath68 decrease exponentially along the respective contours . this helps for the numerical convergence of the calculation of the @xmath53 and also gives them a rapid fall - off at large arguments . we note that no new poles in @xmath18 and @xmath54 , beyond those already present in the moments of the parton distribution functions , are introduced by the @xmath53 @xcite . we note that if one wishes to integrate also over an experimental bin in @xmath23 in eq . ( [ eq7 ] ) , a potential complication arises if the hard scale @xmath11 in the parton distribution functions depends explicitly on @xmath23 . this makes it impossible to straightforwardly include the @xmath23 integration in the pre - calculation of the @xmath57 . a typical example for @xmath23 , which often appears in practice , is the transverse momentum @xmath20 of an observed jet , hadron , or prompt photon . in this case , the @xmath23 dependence of @xmath11 is , however , not a serious limitation @xcite : the logarithmic dependence of the parton densities on @xmath11 is much weaker than the overall @xmath20 dependence of the cross section . therefore , it is always possible to choose a bin - average of @xmath20 as the scale in the parton densities . alternatively , one could choose not to include the @xmath20 integration in the @xmath69 and to construct grids of somewhat larger size , taken at a small number of support points for a simple gaussian integration over the @xmath20 bin . a further possibility @xcite is to absorb also the evolution of the parton densities from their initial scale @xmath10 to @xmath11 into the @xmath57 , which in moment space simply enters in the form of exponentials involving the anomalous dimensions , see , e.g. , @xcite . this procedure , which is somewhat more involved , would eliminate any complication related to @xmath70 . anyway , the experiments will usually quote results for the @xmath20-_differential _ cross section at the @xmath20-average over the bin , which of course is exactly what we have considered in eqs . ( [ eq7 ] ) , ( [ eq8 ] ) . in the latter case it is also easily possible to organize the grids in such a way that the renormalization and/or factorization scales can be varied during the fit , by simply taking the ( logarithmic ) dependence on @xmath71 and the strong coupling @xmath72 out of the partonic cross sections beforehand . as a technical sidestep , we give an explicit expression for the double inverse transform in eq . ( [ eq8 ] ) for the contours depicted in fig . [ fig1 ] . to this end , we parameterize the various segments in fig . [ fig1 ] by @xmath73 where @xmath74 $ ] and the sign of @xmath75 has to be chosen appropriately for the branches of the contours . we then find [ eq10 ] & = & - _ a , b re , where the asterisk denotes the complex conjugate , and where we have made use of @xmath76 , since the @xmath77 are real functions . this identity also implies that there is no need to separately compute the moments of the parton densities at the complex conjugate values @xmath78 , which has a further positive effect on the computing time required for performing the mellin inverses . in addition , there is no need to provide separate grids for @xmath79 and @xmath80 . before proceeding , we reemphasize that the idea outlined above of reverting to mellin moment space in the implementation of any higher - order cross section into parton density fits is not entirely new , but was first developed in refs . the example considered in @xcite was jet production in dis , which offers the simplification of being only linear in the parton distribution functions . there is a difference between our approach and that of ref . @xcite in practical terms : in the language of our example in eq . ( [ eq7 ] ) , ref . @xcite would insert a factor @xmath81 in the integrands for the @xmath82 and @xmath83 integrations , while undoing this operation through a factor @xmath84 in the @xmath18 and @xmath54 integrands . even though obviously equivalent mathematically , the disadvantage of this procedure is that the resulting factors @xmath85 , @xmath86 in the @xmath82 , @xmath83 integrands will now _ grow _ exponentially along the contours in mellin space , making it numerically much more cumbersome @xcite to perform the @xmath82 and @xmath83 integrations yielding the @xmath87 . as a matter of fact , the actual extension of the method of ref . @xcite to the case of hadronic collisions involving bilinear combinations of parton distributions appears difficult . the generalization of @xcite to hadron - hadron scattering , without the shortcomings mentioned above , was first provided in @xcite . the difference between our organization of the expression in eq . ( [ eq8 ] ) and ref . @xcite is the choice of the contour . reference @xcite fully exploits the freedom in deforming the contours for the inverse mellin transform and constructs a `` surface of steepest descent '' which in principle has the best numerical convergence properties but is difficult to parameterize . instead we stick to the simple contours in fig . [ fig1 ] which , as we will show below , turn out to be sufficient to obtain numerical agreement between eqs . ( [ eq1 ] ) and ( [ eq8 ] ) of far better than 1% for all applications we are going to consider . we should also note that in @xcite the usefulness of the mellin transform method was not demonstrated in practice . as a first application for the mellin transform technique outlined in the previous section we consider the semi - inclusive production of a hadron @xmath38 in dis . sidis starts at the born level with the lo reaction @xmath88 . the nlo @xmath89 corrections also comprise the processes @xmath90 and @xmath91 and have been calculated in the spin - dependent case in the @xmath92 scheme in @xcite . in each case one of the final state partons subsequently fragments into the observed hadron @xmath38 . as in the fully inclusive case , the expression for the cross section is given by a single structure function @xmath93 : @xmath94 to nlo in @xmath58 , @xmath95 can be written as @xcite @xmath96 % \nonumber & & \delta q \left(\frac{x}{\hat{x}},\mu_f\right ) \delta c_{qq}^{(1)}(\hat{x},\hat{z},\frac{\mu_f}{q},\frac{\mu_f'}{q } ) d_{q}^h\left(\frac{z}{\hat{z}},\mu_f'\right)+ \nonumber \\[2 mm ] % & & % \delta q \left(\frac{x}{\hat{x}},\mu_f\right ) \delta c_{gq}^{(1 ) } ( \hat{x},\hat{z } , \frac{\mu_f}{q},\frac{\mu_f'}{q } ) d_{g}^h\left(\frac{z}{\hat{z}},\mu_f'\right ) + \nonumber\\ [ 2 mm ] % & & % \delta { g } \left(\frac{x}{\hat{x}},\mu_f\right ) \delta c_{qg}^{(1 ) } ( \hat{x},\hat{z},\frac{\mu_f}{q},\frac{\mu_f'}{q } ) d_{q}^h\left(\frac{z}{\hat{z}},\mu_f'\right)\bigg\}\bigg ] % \end{aligned}\ ] ] with @xmath13 and @xmath97 denoting the usual dis scaling variables ( @xmath98 ) , and where @xcite @xmath99 . ( [ eq : polsidis ] ) and the variable @xmath100 only apply to hadron production in the current fragmentation region characterized by positive values for the feynman variable @xmath101 . all nlo @xmath92 partonic coefficient functions @xmath102 are collected in app . c of @xcite . they are non - trivial functions of @xmath13 _ and _ @xmath100 such that the @xmath13 and @xmath100 dependences of the cross section do not factorize into separate functions . therefore the inclusion of the nlo corrections seems to be indispensable for a reliable extraction of parton densities from sidis . due to the double convolutions appearing in eq . ( [ eq : polsidis ] ) and the fact that the coefficient functions contain mathematical distributions as @xmath103 and/or @xmath104 , the direct use of eq . ( [ eq : polsidis ] ) in a global analysis of parton densities is rather time consuming and awkward , though not impossible @xcite since the partonic coefficient functions are still fairly simple . sidis has the advantage , however , that the mellin moments in @xmath13 and @xmath100 can be taken completely analytically for the partonic coefficient functions in eq . ( [ eq : polsidis ] ) . in doing so , the double convolutions in eq . ( [ eq : polsidis ] ) reduce to simple multiplications @xmath105 and all distributions become ordinary functions of the moment variables . the @xmath106 , defined by @xmath107 are straightforwardly determined from the expressions for the corresponding @xmath108 in app . c of @xcite and read : @xmath109 % & & % - s_2(n ) + \left [ s_1(m ) + s_1(n ) \right ] \left\ { s_1(m ) + s_1(n ) -\frac{1}{m(m+1)}-\frac{1}{n(n+1)}\right\ } \nonumber \\ [ 1.5 mm ] % & & + \left[\frac{2}{n(n+1)}+3 - 4 s_1(n)\right ] \ln\left(\frac{q}{\mu_f}\right ) \nonumber \\ [ 1.5 mm ] & & + \left[\frac{2}{m(m+1)}+3 - 4 s_1(m)\right ] \ln\left(\frac{q}{\mu_f'}\right ) \bigg ] \ ; , \\ [ 2 mm ] \label{cgq } % \delta c_{gq}^{(1),nm } ( \frac{\mu_f}{q},\frac{\mu_f'}{q } ) % \!&=&\ ! % c_f \bigg [ \frac{2 - 2 m-9 m^2+m^3-m^4+m^5}{m^2 ( m-1)^2(m+1)^2}+ \frac{2m}{n ( m+1)(m-1 ) } \nonumber \\ [ 1.5 mm ] % & & % -\frac{2-m+m^2}{m ( m+1)(m-1)(n+1)}- \frac{2+m+m^2}{m ( m+1)(m-1 ) } \left [ s_1(m ) + s_1(n ) \right ] \nonumber \\ [ 1.5 mm ] % & & % - \frac{2}{(m+1)n ( n+1 ) } + 2 \frac{2+m+m^2}{m(m+1)(m-1 ) } \ln\left(\frac{q}{\mu_f'}\right ) \bigg ] \ ; , \\ [ 2 mm ] \label{cqg } % \delta c_{qg}^{(1),nm } ( \frac{\mu_f}{q},\frac{\mu_f'}{q } ) % \!&=&\ ! % t_r \frac{n-1}{n(n+1 ) } \bigg[\frac{1}{m-1}-\frac{1}{m}+\frac{1}{n}-s_1(m ) - s_1(n ) + 2 \ln\left(\frac{q}{\mu_f}\right ) \bigg ] \ ; , % \end{aligned}\ ] ] where @xmath110 , @xmath111 , and @xmath112 for completeness we give also the mellin moments for the corresponding unpolarized coefficient functions @xmath113 and @xmath114 relevant for the structure functions @xmath115 and @xmath116 , respectively . using again eq . ( [ eq : cmellin ] ) and the @xmath117 space expressions in app . c in @xcite one finds @xmath118 % c_{1,gq}^{(1),nm } ( \frac{\mu_f}{q},\frac{\mu_f'}{q } ) % & = & % \delta c_{gq}^{(1),nm } ( \frac{\mu_f}{q},\frac{\mu_f'}{q } ) + c_f \frac{2}{(m+1)n(n+1)}\;\ ; , \\ [ 1.5 mm ] % c_{1,qg}^{(1),nm } ( \frac{\mu_f}{q},\frac{\mu_f'}{q } ) % & = & % \nonumber t_r \bigg[\frac{2+n+n^2}{n(n+1)(n+2 ) } \bigg ( \frac{1}{m-1}-\frac{1}{m}-s_1(m)-s_1(n)+2 \ln\left(\frac{q}{\mu_f}\right ) \bigg ) \\ [ 1.5 mm ] % & & \hspace*{6mm}+\frac{1}{n^2 } \bigg]\;\ ; , % \end{aligned}\ ] ] and @xmath119 % c_{l , gq}^{(1),nm } & = & c_f \frac{4}{m(m+1)(n+1)}\;\ ; , \\ [ 1.5 mm ] % c_{l , qg}^{(1),nm } & = & t_r \frac{8}{(n+1)(n+2)}\;\;. % \end{aligned}\ ] ] we note that the usefulness of taking double mellin moments for unpolarized sidis was first pointed out , though not further pursued , in @xcite . in the polarized case mellin-@xmath18 moments of the semi - inclusive cross section at fixed @xmath100 have been recently considered in @xcite . having available the coefficient functions in mellin moment space one can evaluate the desired sidis structure function @xmath120 in a fast way by a double inverse mellin transform as discussed in section 3 . one further ingredient required is the evolution of the moments of the fragmentation functions @xmath121 which proceeds along very similar lines as for the parton densities . below we will use the recent nlo analysis of @xcite which can be applied down to the @xmath122 values required for the available spin - dependent sidis fixed - target data @xcite . it should be noted that the mellin approach allows in principle a simultaneous fit of parton densities and fragmentation functions in sidis at no extra `` costs '' . the experimentally relevant quantity is the so - called spin asymmetry , defined as the ratio of the polarized and unpolarized sidis structure functions , @xmath123 and @xmath124 , respectively , @xmath125 due to limited statistics all presently available results for eq . ( [ eq : a1sidis ] ) are integrated over the entire @xmath100 range accessible experimentally ( @xmath126 ) @xcite . to facilitate the comparison with these data it is more convenient to define an `` effective '' coefficient function @xmath127 rather than using the double moments and integrating afterwards over @xmath100 . the @xmath127 already incorporate the @xmath100 integration and can be easily pre - calculated _ once _ prior to the fit . they are defined by @xmath128 ( in lo one has @xmath129 ) and can be used in a similar way as the usual fully inclusive dis coefficient functions . this makes the numerical evaluation extremely fast : 100 calculations of the sidis cross section in nlo take only about 1 second on a standard workstation . clearly , sidis data can be as easily incorporated in a global qcd analysis as dis data . in fig . [ fig : sidis ] we compare the result of a nlo fit to all available data for dis _ and _ sidis spin asymmetries with data for @xmath130 for positively or negatively charged hadrons @xmath131 and different targets @xmath132 @xcite . regarding the details of the analysis , we stay in the framework of the `` standard '' fit of @xcite , but allow for an su(2 ) breaking of the light sea by introducing a function @xmath133 , @xmath134 \delta d'(x,\mu_0 ) = \delta d(x,\mu_0 ) + f_{\mathrm{su(2)}}(x,\mu_0)\;\ ; & , & \;\ ; \delta \bar{d}'(x,\mu_0 ) = \delta \bar{d}(x,\mu_0 ) - f_{\mathrm{su(2)}}(x,\mu_0)\;\;,\end{aligned}\ ] ] such that all quark combinations measured in inclusive dis remain unchanged , @xmath135 , but @xmath136 . we choose a `` minimal '' ansatz for @xmath133 with 3 additional parameters @xmath137 where @xmath138 is the initial scale for the evolution in @xcite . we choose the renormalization and factorization scales @xmath139 . the resulting asymmetry of the light sea at the input scale @xmath10 is shown in fig . [ fig : su2 ] . for comparison we also show model predictions for @xmath19 from @xcite and @xcite . it turns out that the flavor asymmetry obtained in our analysis is much less pronounced than predicted in most models . it has to be stressed , however , that the change in the total @xmath12 for all sidis data is _ less than one unit _ if one chooses an su(3 ) symmetric sea , the model calculations @xcite or our fit result . thus one has to conclude that present sidis data are not precise enough to distinguish between different results for @xmath19 and that one has to wait for new sidis data from hermes and , in particular , for results on @xmath140 boson production at rhic @xcite . similar conclusions have been reached in the analysis of @xcite . to give an example for the mellin technique in hadron - hadron collisions , we study the production of a prompt photon in @xmath0 collisions at rhic . in this case @xmath141 in eq . ( [ eq4 ] ) starts at lo with the reactions @xmath142 and @xmath17 , the latter channel being sensitive to the polarized gluon distribution . the nlo corrections , @xmath143 , are also available @xcite . the nlo @xmath13-space expressions are rather lengthy and complicated , and mellin moments can not be taken analytically anymore . nevertheless , as we shall see below , it is in the analysis of hadron - hadron collision data where the mellin moment technique exhibits its full potential and usefulness . to be specific , the transverse momentum ( @xmath20 ) distribution of a prompt photon in @xmath0 collisions at a center - of - mass energy @xmath144 , integrated over a certain experimental bin in pseudorapidity @xmath145 [ i.e. , `` @xmath146 '' and `` @xmath147 '' in eq . ( [ eq1 ] ) ] , is given by @xmath148 % & & % \times \,\frac{d\delta \hat{\sigma}_{ab}^{\gamma}}{dp_t d\eta } ( x_ap_a,\ , x_bp_b\ , , p_t,\eta,\,\mu_r,\mu_f ) \ ; , \end{aligned}\ ] ] where @xmath149 and @xmath150 with @xmath151 . for our case study , we analyse the polarized prompt photon cross section in eq . ( [ eq : pp ] ) at nlo . the associated spin - asymmetry , defined as the ratio of the polarized and the unpolarized cross sections , @xmath152 will soon be measured at rhic in collisions of longitudinally polarized protons and , as mentioned above , will be a key process for measuring @xmath4 . we use @xmath153 gev and look at the cross section as a function of the photon s transverse momentum @xmath20 for five values of @xmath20 which will be experimentally accessible at rhic , @xmath154 $ ] gev . we average over @xmath155 in pseudorapidity . as in experiment @xcite , we impose an isolation cut on the photon , for which we choose the isolation proposed in @xcite with parameters @xmath156 , @xmath157 . a positive feature of this isolation criterion is the absence of a fragmentation contribution to prompt photon production , hence we can drop the @xmath158 integration and the fragmentation function @xmath159 in eq . ( [ eq1 ] ) . we choose the renormalization and factorization scales @xmath160 . our first goal here is to show that the method based on eqs . ( [ eq7 ] ) and ( [ eq8 ] ) actually works also for the more complicated case of hadron - hadron collisions and correctly reproduces the result obtained within the direct , but `` slow '' , calculation via eq . ( [ eq : pp ] ) . also , we need to establish an optimal size of the grids that yields excellent accuracy but is still calculable in , say , a few hours of cpu time on a standard workstation . [ fig2 ] compares the results based on eqs . ( [ eq7 ] ) and ( [ eq8 ] ) , referred to as `` mellin technique '' , to those of eq . ( [ eq : pp ] ) , for various sizes of the grid in @xmath60 . here we have used again the polarized parton densities of @xcite ( `` standard '' set ) . for a more detailed comparison , we split up the contributions to the nlo prompt photon cross section into three parts , associated with the reactions @xmath161 and @xmath162 that are already present at born level , and all other processes that arise only at nlo . one notices that in each case already a grid size of @xmath163 values yields excellent accuracy . even a @xmath164 grid is acceptable apart from a minor deviation occuring for @xmath165 scattering in the vicinty of a zero in the partonic cross section . we have checked that the results in fig . [ fig2 ] do not depend on the actual choice of parton densities . the crucial asset of the mellin method is the speed at which one can calculate the full hadronic cross section , once the grids @xmath166 have been pre - calculated . for the @xmath167 grid , we found that 1000 evaluations of the full nlo prompt photon cross section take only about 10 - 15 seconds on a standard workstation . note that this number includes the evolution ( in moment space ) of the parton distributions from their input scale to the scale @xmath20 relevant to this case . clearly , an implementation into a full parton density fitting procedure is now readily possible . to give an example , we finally perform a `` toy '' global analysis of the available data on polarized dis @xcite and of _ fictitious _ data on prompt photon production at rhic @xcite , which we project by simply calculating @xmath168 in eq . ( [ eq11 ] ) to nlo using the sets of polarized and unpolarized parton distributions of @xcite and @xcite , respectively . for an estimate of the anticipated @xmath169 errors on the `` data '' for @xmath168 , we use the numbers reported in @xcite . we subsequently apply a random gaussian shift of the pseudo - data , allowing them to vary within @xmath169 . the `` data '' , as well as the underlying theoretical calculation of @xmath168 based on the spin - dependent parton densities of @xcite ( solid line ) , are shown in the left panel of fig . [ fig3 ] . next , we perform a large number of fits to the full , _ dis plus projected prompt photon _ , data set . we simultaneously fit _ all _ polarized parton densities , ( anti)quarks and gluons , choosing the distributions of @xcite as the input for the @xmath170 , @xmath171 , but using randomly chosen values for the parameters in the ansatz for the polarized gluon distribution at the input scale @xmath10 . regarding the details of the evolution , we stay again within the setup of @xcite , but we choose a more flexible ansatz for the polarized gluon density , @xmath172 which also allows for a zero in the @xmath13-shape of @xmath4 . @xmath173 is the unpolarized gluon density @xcite at the input scale of @xcite . note that the functional form for the polarized gluon density of @xcite , used for generating our pseudo - data , is included in eq . ( [ eq12 ] ) for @xmath174 . each fit takes only about @xmath175 minutes . ideally , thanks to the strong sensitivity of the prompt photon reaction to @xmath4 , the gluon density in each fit should return close to the function we assumed when calculating the fictitious prompt photon `` data '' , in the region of @xmath13 probed by the data . indeed , as shown in fig . [ fig3](b ) , this happens . the shaded band illustrates the deviations of the gluon densities obtained from the global fits to the `` reference @xmath4 '' @xcite used in generating the pseudo - data . it should be stressed that only those fits are admitted to the band that give a good simultaneous description of the dis _ and _ @xmath168 data . here we have tolerated a maximum increase of the total @xmath12 by up to four units from its minimum value . the shaded area in fig . [ fig3](a ) shows the corresponding variations in @xmath168 . as is expected , all gluon densities are rather tightly constrained in the @xmath13-region dominantly probed by the prompt photon data . this is true in particular at @xmath176 , as a result of the most precise data point for @xmath168 at @xmath177 . we note that one can also easily include the sidis data discussed in section 3 into the global analysis without any significant increase of computing time for each fit . however , so far these data have no impact on our results . to illustrate our _ present _ ignorance of @xmath4 , fig . [ fig3](b ) shows also two extreme gluon densities with first moments @xmath178 ( dotted lines ) , which are both in perfect agreement with all presently available dis data . the corresponding predictions for @xmath168 for these two sets are given in fig . [ fig3](a ) . it should be noted that future measurements of @xmath168 at rhic at @xmath179 and for similar @xmath20 values of the prompt photon would further reduce the uncertainties on @xmath4 in the @xmath13-region between 0.05 and 0.1 . although our analysis still contains a certain bias by choosing only the framework of @xcite for the fits as well as by our choice of what @xmath12 values are still tolerable , it clearly outlines the potential and importance of upcoming measurements of @xmath168 at rhic for improving our understanding of the spin structure of the nucleon , in particular of its spin - dependent gluon density . to conclude , we have presented and applied a powerful technique for implementing in a fast way , and without any approximations , higher - order calculations of partonic cross sections into global analyses of parton distribution functions . we have demonstrated that the approach works in practice for two examples : sidis and prompt photon production in @xmath0 collisions . in the first case it was possible to perform the mellin transform analytically and we have provided all necessary technical details for future analyses of polarized and unpolarized sidis data . for polarized prompt photon production we have presented a case study for a future global analysis based on fictitious data . the mellin transform method is certainly applicable to any other reaction of interest , and it could equally well be an improvement also in any global analysis of unpolarized parton distributions . we are grateful to g. sterman and a. vogt for useful comments , and to a. deshpande for helpful discussions . we also thank s. kretzer for providing us with the evolution code for the set of fragmentation functions in @xcite . the work of m.s . was supported in part by the national science foundation grant no . phy-9722101 . w.v . is grateful to riken , brookhaven national laboratory and the u.s . department of energy ( contract number de - ac02 - 98ch10886 ) for providing the facilities essential for the completion of this work . 99 european muon collaboration ( emc ) , j. ashman _ et al . _ , phys . lett . * b206 * , 364 ( 1988 ) ; 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we present a technique for implementing in a fast way , and without any approximations , higher - order calculations of partonic cross sections into global analyses of parton distribution functions . the approach , which is set up in mellin - moment space , is particularly suited for analyses of future data from polarized proton - proton collisions , but not limited to this case . the usefulness and practicability of this method is demonstrated for the semi - inclusive production of hadrons in deep - inelastic scattering and the transverse momentum distribution of `` prompt '' photons in @xmath0 collisions , and a case study for a future global analysis of polarized parton densities is presented . 17.0 cm 0.0 cm 0.0 cm -2.2 cm bnl - nt-01/14 + rbrc-193 + july 2001 + _ @xmath1c.n . yang institute for theoretical physics , suny at stony brook , + stony brook , new york 11794 3840 , u.s.a . _ + _ @xmath2riken - bnl research center , bldg . 510a , brookhaven national laboratory , + upton , new york 11973 5000 , u.s.a . _

the gravitational instability is commonly accepted as the process of large - scale structure formation in the universe . according to this scenario , structures formed by the growth of small inhomogeneities present in the early universe . gravitational instability gives rise to a coupling between the density and peculiar velocity fields of matter . on very large , linear scales , the relation between the peculiar velocity @xmath10 and the density contrast @xmath11 in co - moving coordinates is @xmath12 where @xmath13 is the hubble constant . [ for simplicity of notation , we use the notation ( @xmath14 , @xmath15 ) instead of ( @xmath16 , @xmath17 ) . ] the coupling constant , @xmath18 , carries information about the underlying cosmological model and is related to the cosmological matter density parameter , @xmath14 , and cosmological constant , @xmath15 , by @xmath19 @xcite . the linear amplitude of peculiar velocities is thus sensitive to @xmath14 ; on the other hand , it is quite insensitive to @xmath15 . hence , comparing the observed density and velocity fields of galaxies allows one to constrain @xmath14 , or the degenerate combination @xmath20 in the presence of so called galaxy biasing ( e.g. @xcite for a review ) . this is done by extracting the density field from all - sky redshift surveys such as the point source catalogue redshift survey ( pscz , * ? ? ? * ) , or the 2mass redshift survey ( 2mrs , * ? ? ? * ) and comparing it with the observed velocity field from peculiar velocity surveys . the methods for doing this fall into two broad categories . one can use equation ( [ eq : linear ] ) , calculating the divergence of the observed velocity field and comparing it directly with the density field from a redshift survey ; this is referred to as a _ density density comparison_. alternatively , one can use the integral form of equation ( [ eq : linear ] ) to calculate the predicted velocity field from a redshift survey , and compare the result with the measured peculiar velocity field ; this is called a _ velocity velocity comparison_. velocity velocity comparisons are generally regarded as more reliable , since they involve manipulation of the denser and more homogeneous redshift catalogue data , while density density comparisons require manipulation of the noisier and sparser velocity data . in both cases , the density and velocity fields need to be smoothed in order to reduce errors and shot noise . velocity comparisons require a smaller size of smoothing , of a few @xmath21 . for example , @xcite used a smoothing scale of @xmath22 @xmath21 . such scales are called _ mildly non - linear _ : the variance of the density field smoothed over the scale of a few @xmath21 is of order unity . mildly non - linear extensions of equation ( [ eq : linear ] ) have been developed by a number of workers . these extensions have been based either on various analytical approximations of non - linear dynamics ( @xcite ; bernardeau 1992 , hereafter @xcite ; @xcite ; @xcite ; @xcite ; @xcite ) , or numerical ( either n - body or hydrodynamic ) simulations ( @xcite ; kudlicki et al.2000 , hereafter @xcite ) , or both ( @xcite ; @xcite ; @xcite ; bernardeau et al.1999 , hereafter @xcite ) . unlike the linear case ( [ eq : linear ] ) , the non - linear relation between the velocity divergence and the density contrast at a given point is non - deterministic ( though in the non - linear regime the two fields remain highly correlated ) . therefore , for a full description of the relation , the conditional means ( mean @xmath23 given @xmath11 and vice versa ) are not sufficient : one has to describe the full bivariate distribution function for @xmath23 and @xmath11 , or at least the conditional scatter . these aspects of the velocity density relation were studied by @xcite and more extensively by @xcite . however , in practical applications the intrinsic scatter in the velocity density relation is much smaller than the one induced by observational errors , and the conditional means are sufficient . @xcite and @xcite found that very good fits to the mean relations , obtained for the mildly non - linear fields extracted from numerical simulations , were given by modifications of the formula of @xcite . this formula describes a non - linear relation between initially gaussian , random fields of @xmath23 and @xmath11 , under the assumption of a vanishing variance of the density field ( so the relation has no scatter ) . @xcite claimed his relation to be the same as the one exhibited in the spherical collapse model ( hereafter scm ) . in practical applications ( namely with non - zero variance of the density field ) , he predicted his formula to work well in voids , but ` to become very inaccurate for @xmath11 larger than 1 or 2 ' . in _ this _ paper we study the velocity density relation in the scm . the reason for such an approach is twofold . first , to derive his formula , @xcite used quite sophisticated methods ( summing up first non - vanishing contributions from the reduced part of _ all - order _ joint moments of @xmath23 and @xmath11 ) . on the other hand , the dynamics of the scm is very simple and should allow to re - derive the formula of @xcite in a straightforward way . more importantly , in the scm the relation can be easily extended to higher values of @xmath11 , with the hope that this modification will fit better the results of numerical experiments of @xcite and @xcite . the scm is in principle insensitive to the variance of the density field ( and the resulting velocity density relation is deterministic ) , but in practice the variance of the smoothed density field dictates how high density contrasts can be reached . the non - linear relation between @xmath11 and @xmath24 ( note the scaling @xmath25 ) depends very weakly on cosmological parameters . @xcite analysed the @xmath14-dependence of the scaled velocity density relation in the limit @xmath26 and found it to be very weak . @xcite showed that second and third order expansions for @xmath11 and @xmath27 depend extremely weakly on @xmath14 and @xmath15 . @xcite demonstrated that this is the case for _ all _ orders . specifically , they showed that perturbative solutions for the density contrast for arbitrary cosmology are , with a good accuracy , separable : @xmath28 , where @xmath29 is the linear growing mode for this cosmology and @xmath30 is the spatial part of the @xmath31-th order solution for the einstein de sitter model . using the continuity equation one can then prove , by induction , that the velocity divergence depends on @xmath14 and @xmath15 practically only through the factor @xmath32 . most generally , nusser & colberg ( 1998 ) ( hereafter @xcite ) showed _ the equations of motion _ of the cosmic pressureless fluid to be ` almost independent ' of cosmological parameters . the weak dependence of the scaled velocity density relation on the background cosmological model has been also confirmed by n - body numerical simulations ( @xcite ; @xcite ) . however , the @xmath14-dependence of the equations of motion of the cosmic dust stops to be weak when @xmath33 ( see eqs . 1314 of @xcite ) . this regime of @xmath14 is not physically relevant , since the currently preferred value of @xmath14 is much higher . still , @xcite derived his formula applying the limit @xmath34 . therefore , in the present paper we will neglect @xmath15 ( setting @xmath35 ) , but will retain the @xmath14-dependence of the equations of the spherical collapse and in particular examine the limit of small @xmath14 . the paper is organised as follows . section [ sec : csm ] presents general assumptions , terminology and basic formulae of the spherical model . in section [ sec : pp ] we focus on the factor @xmath18 , appearing in eq . ( [ eq : linear ] ) and commonly approximated by formula ( [ eq : f_omega_lambda ] ) , or its simplified version @xmath36 . section [ sec : smallom ] contains an analysis of the regime of very small @xmath14 and presents the resulting universal velocity density relation . in sections [ sec : voids ] and [ sec : overd ] , basing on analytical considerations , we derive approximations for the relation between the velocity divergence and the density contrast respectively for spherical voids and overdensities , for realistic values of @xmath14 . these approximations constitute the main results of this paper . section [ sec : comp ] gives a comparison of our fits with results of numerical simulations . we conclude in section [ sec : concl ] . let us consider an open friedman world model ( i.e. with @xmath37 ) without the cosmological constant , @xmath38 . we introduce the _ conformal time _ @xmath39 related to the cosmic time @xmath40 by the equation @xmath41 where @xmath42 is the curvature radius of the universe , @xmath43 and @xmath44 are respectively the velocity of light and the scale factor ; subscripts ` 0 ' and ( used later ) ` i ' refer to the present day and to some adequately chosen initial moment , respectively . now , the time evolution of the scale factor can be expressed in terms of the following parametric equations ( e.g. @xcite ) : @xmath45 where @xmath46 and @xmath47 are constants . moreover , in this model the conformal time @xmath39 is unambiguously related to the density parameter @xmath14 by @xmath48 if we now consider a _ top - hat _ spherical perturbation ( a sphere of homogeneous density embedded in a friedman universe ) , it can be analysed as a ` universe of its own ' ( as was noted for the first time by @xcite ) with a scale factor @xmath49 which is the radius of the perturbation . introducing the _ density contrast _ of the perturbation relative to the background , @xmath11 , as @xmath50 we obtain two cases to be taken into account . using the same terminology for spherical perturbations as for analogous friedman world models , an _ open _ perturbation is such that its initial density contrast @xmath51 is smaller than the _ critical density contrast _ @xmath52 ( the density contrast of an einstein de sitter type of perturbation , i.e. with @xmath53 ) , given by : @xmath54 it can be checked that the density parameter of thus defined open perturbation is @xmath55 , as expected . these results are valid under the assumption that the initial density of the background is sufficiently close to the critical density ( @xmath56 ) . the factor @xmath57 in eq . ( [ form : delta_c ] ) comes from the decomposition of the density field into two components , one related to the growing mode and the other to the decaying one ; we assume here the perturbation to be purely in the growing mode . for details see @xcite . the evolution of such a spherical perturbation is governed by equations analogous to ( [ eq : a_t_eta ] ) : @xmath58 the normalization factors are such that . of course , time @xmath40 is the same for the background as for the perturbation , which leads to the relation between @xmath59 and @xmath39 : @xmath60 where we have used @xmath61 ( for a detailed derivation see @xcite ) . if @xmath62 then @xmath63 , so @xmath64 , and vice versa for negative @xmath11 . in order to obtain similar relations for a _ closed _ perturbation ( @xmath65 or @xmath66 ) , one should make the following substitutions : @xmath67 remembering that in such a case @xmath68 . we can now express the density contrast in terms of the parameters @xmath39 and @xmath59 , using the relation @xmath69 : @xmath70 for open perturbations and similarly for closed ones , with the use of ( [ substitutions ] ) : @xmath71 ( cf . @xcite ; @xcite ) . note that always @xmath72 , but in principle the density contrast has no upper bound . however , if initially @xmath73 , then @xmath11 can not exceed a maximal value which can be calculated taking @xmath74 in ( [ form : delta fi eta ] ) : @xmath75 the above value becomes the minimal value of the density contrast for closed perturbations , i.e. it is a boundary value of possible density contrasts between closed and open perturbations for a given @xmath39 . the linear theory relates the density contrast of a perturbation to its _ peculiar velocity divergence _ @xmath76 ( eq . [ eq : linear ] ) . in the spherical model we obtain @xmath77 , where @xmath78 . for convenience we change units and sign , obtaining what will be called in this paper the ( dimensionless ) velocity divergence , @xmath79 : @xmath80 some simple algebra is sufficient to find the dependence of on @xmath39 and @xmath59 , which leads to the following expression ( @xcite ; @xcite ) : @xmath81 , \ ] ] valid for open perturbations on an open background ; substitution @xmath82 gives the relation for closed perturbations : @xmath83 .\ ] ] both the density contrast and the velocity divergence , as given by ( [ form : delta fi eta ] ) and ( [ form : teta fi eta ] ) , or ( [ form : delta fi eta closed ] ) and ( [ form : teta fi eta closed ] ) , are parametrically dependent on @xmath59 ( @xmath39 is fixed ) . our aim here is to eliminate this parameter ( at least approximately ) and to obtain the @xmath79@xmath11 relation in the spherical model in an analytic form . as a first step , it is useful to simplify the formula for @xmath79 including ` the easy part ' of the dependence on @xmath11 . this is done by calculating from ( [ form : delta fi eta ] ) and inserting the resultant expression into ( [ form : teta fi eta ] ) . then , owing to the hyperbolic identity @xmath84 and the relation ( [ form : omega of eta ] ) for @xmath14 , we finally obtain a simplified formula for the velocity divergence : @xmath85.\ ] ] these considerations were valid for open perturbations . if then we have @xmath86,\ ] ] where ` ' applies to the case @xmath87 and ` + ' to @xmath88 . formula ( [ form : teta open ] ) [ ( [ form : teta closed ] ) ] is simpler than ( [ form : teta fi eta ] ) [ ( [ form : teta fi eta closed ] ) ] , but the dependence on @xmath59 remains ; the parameter @xmath59 is related to @xmath11 by equation ( [ form : delta fi eta ] ) [ ( [ form : delta fi eta closed ] ) ] . the linear theory ( valid for small values of @xmath11 ) relates the velocity divergence as defined above to the density contrast through the equation @xmath89 [ cf . ( [ eq : linear ] ) ] , where the factor @xmath90 is given by @xmath91 the quantity @xmath29 is the growing mode of the perturbation . the factor @xmath18 has been a subject of study in many papers ( e.g. @xcite ; @xcite ; @xcite ; @xcite ; @xcite ; @xcite ; @xcite ) . the best - known and most widely used approximation ( often without reference ) is the one given by @xcite : @xmath92 in this part we will compare this fit with the exact formula for @xmath18 . the spherical model as described here allows us to calculate @xmath93 as the limit @xmath94 it can be checked that choosing @xmath95 is equivalent to taking @xmath96 [ eq . ( [ eq : sinh fi fi ] ) ] . moreover , from the relation ( [ eq : sinh fi fi ] ) it follows that in this case @xmath97 , where @xmath98 . using the first - order approximation @xmath99 and expanding hyperbolic functions around @xmath100 , we can linearize equations ( [ eq : sinh fi fi ] ) , ( [ form : delta fi eta ] ) and ( [ form : teta fi eta ] ) . as a result we get a linear relation between @xmath101 and @xmath102 and further on also linear dependencies of @xmath11 and @xmath79 on @xmath102 . diving thus obtained velocity divergence by the density contrast , we get the following formula for @xmath18 as a function of @xmath39 : @xmath103 a similar relation , but for a ` closed ' model of the background , can be found in @xcite . if we now make the substitution @xmath104 [ eq . ( [ form : omega of eta ] ) ] , then after some algebra we can express the parameter @xmath18 as a function of @xmath14 : @xmath105 @xmath106 - 18\ , \omega\ , \sqrt{1-\omega}}{12\sqrt{1-\omega}-8\sqrt{(1-\omega)^3 } - 6\omega\ln[2\omega^{-1}(1+\sqrt{1-\omega})-1]}. \label{form : f of omega}\ ] ] this is the exact expression for @xmath107 with @xmath38 and @xmath37 . it was already derived for example by @xcite . figure [ fig : fofomega ] presents a comparison of this relation with the peebles formula @xmath108 . it can be seen that the power - law approximation is sufficiently exact , especially for the currently favoured value of the density parameter ( @xmath109 ) . moreover , owing to the complicated form of ( [ form : f of omega ] ) , the latter is not very useful . however , one should always bear in mind that the formula ( [ form : peebles ] ) is merely an approximation and in some applications its usage may lead to errors . a much better fit is the one given in a footnote of @xcite : @xmath110 . its errors relative to the exact value for the model with @xmath38 are below 0.3% for @xmath111 . factor @xmath112 as a function of density parameter @xmath14 for world models with @xmath38 : exact relation ( solid line ) and approximation @xmath36 ( dashed line).,scaledwidth=50.0% ] let us now examine more thoroughly the limit of @xmath114 . we begin with checking the asymptotic behaviour of @xmath107 . this regime , although not physically interesting , allows to take a closer look on the bottom - right end of the diagram presented in fig . [ fig : fofomega ] , and the results obtained will be useful later in the paper . ( see also appendix [ app : empty ] . ) starting with the relation ( [ form : f of eta ] ) and remembering that the limit of small @xmath14 means @xmath115 , we get the following approximation : @xmath116 if we now observe that for such @xmath39 we also have @xmath117 and @xmath118 , we obtain an asymptotic formula for @xmath107 : @xmath119 figure [ fig : f of om small ] clearly shows that for sufficiently small @xmath14 , i.e. @xmath120 , the power - law of peebles could no longer be used . this plot is also a confirmation that in some cases the usage of log - log diagrams is well - grounded . factor @xmath107 in the limit @xmath121 : exact relation ( solid line ) , power - law approximation ( dashed line ) and asymptotic relation dotted line . note logarithmic scales on both axes.,scaledwidth=50.0% ] @xcite studied the cosmic statistical relation between the non - linear density contrast and the velocity divergence , evolving from gaussian initial conditions , in the limit of a vanishing variance of the density field . he found the result ` to be very close to ' @xmath122 \,.\ ] ] here , and from now on , the so - called _ scaled _ velocity divergence , @xmath123 , is defined as @xmath124 note that for @xmath95 , the non - linear formula ( [ form : bernard teta ] ) correctly reduces to @xmath125 , i.e. to the linear - theory relation ( [ eq : lin_the_f_del ] ) . as already mentioned , @xcite claimed his relation to be the same as the one exhibited in the scm . in turn , @xcite argued that the approximation ( [ form : bernard teta ] ) ` is strictly valid in the limit @xmath114 ' . here we check these statements , applying the regime @xmath126 to the equations of the scm . if @xmath121 then @xmath115 . therefore , since for voids ( @xmath127 ) we have @xmath128 , also @xmath129 . for overdensities ( @xmath130 ) , the limit applied to eq . ( [ form : delta lim ] ) gives @xmath131 . thus we can focus only on formula ( [ form : delta fi eta ] ) for @xmath11 . from eq . ( [ form : delta fi eta ] ) we see that in order to keep @xmath11 finite ( though arbitrarily large ) , also @xmath59 should tend to infinity . in other words , if @xmath115 , then also @xmath129 , both for voids and overdensities . hence , still from equation ( [ form : delta fi eta ] ) , we get , up to the leading order , @xmath132 and up to the second order @xmath133 { \rm e}^{-\eta } . \label{eq : phi2_ome_to_0}\ ] ] equivalently , @xmath134 \!. \label{eq : cosh_phi2_ome_to_0}\ ] ] applying this formula in equation ( [ form : teta open ] ) and using the large-@xmath39 limit of the function @xmath135 ( eq . [ form : f eta big ] ) we obtain @xmath136 where @xmath137 in the limit @xmath114 the second term in equation ( [ form : tetafal2 ] ) vanishes , hence @xmath138 this is exactly the same relation as for the linear regime ( where @xmath95 ) . however , here the density contrast can have an arbitrary value . thus , the formula of @xcite ( [ form : bernard teta ] ) does _ not _ describe the dynamics of perturbations in the limit @xmath114 . the relation ( [ eq : linear theory ] ) , being very simple , is a non - trivial result . when @xmath14 tends to 0 , then also the ( _ not _ scaled ) velocity divergence @xmath139 ( peculiar velocities vanish with diminishing @xmath14 ) . however , the quantity @xmath123 , as introduced by eq . ( [ form : teta ] ) , converges to a non - zero value for @xmath114 , due to the presence of the factor @xmath107 , approximated by ( [ form : f omega small ] ) for small @xmath14 . the normalisation used here leads to @xmath140 in the linear theory . why for very small values of @xmath14 this relation holds also in the non - linear regime ? it turns out that this is a general result of dynamics in a low - density universe , and does not rely on any symmetry . the derivation is presented in appendix [ app : empty ] . for large but finite values of @xmath39 , formula ( [ form : tetafal2 ] ) can be applied . specifically , it can be used for @xmath39 significantly greater than 3 ( @xmath14 significantly smaller than @xmath141 ) , which falls well below the presently accepted value of the cosmic density parameter . therefore , the approximation ( [ form : tetafal2 ] ) is of no practical importance ; we have to continue our search for a relevant relation . just for illustrative purposes , on figure [ fig : theta small om ] we plot the exact relation , the @xcite approximation , and the approximation ( [ form : tetafal2 ] ) , for an exemplary value of @xmath142 ( @xmath143 ) . we see that although for this value of @xmath14 the relation is still non - linear , the @xcite approximation drastically overestimates the degree of non - linearity . a comparison of the relation between density contrast @xmath11 and scaled velocity divergence @xmath144 for very small @xmath14 ( here @xmath142 ) : linear theory result @xmath140 dotted line , exact relation @xmath145 solid line , approximation for small @xmath14 crosses and @xcite approximation ( [ form : bernard teta ] ) dashed line.,scaledwidth=50.0% ] as _ voids _ we will understand any underdense perturbations , i.e. those for which @xmath2 . in this section we examine the behaviour of the velocity divergence vs. the density contrast for such inhomogeneities . when considering overdense perturbations ( with @xmath62 ) , the regime of @xmath146 is usually called _ weakly _ ( or at most _ mildly _ ) non - linear . it may thus seem that it should be similarly for the limit @xmath147 ( cf . however , if we analyse equation ( [ form : delta fi eta ] ) , which is valid both for voids and for open overdensities , we can see that for finite values of @xmath39 ( which correspond to non - zero @xmath14 ) , the condition @xmath148 may only be satisfied for @xmath149 . hence , the evolution of such a perturbation is _ highly _ non - linear when the density contrast approaches its minimum value . the scaled velocity divergence @xmath123 , as defined in eq . ( [ form : teta ] ) , is a monotonically increasing function of @xmath11 ( for @xmath39 , or @xmath14 , treated as a fixed parameter ) . its minimum value is @xmath150 ( dependent on @xmath39 ) , obtained easily by calculating the limit @xmath149 in ( [ form : teta fi eta ] ) : @xmath151 .\ ] ] for @xmath152 , equivalent to @xmath153 ( the einstein de sitter model of the universe ) , we get the value of @xmath154 , which can also be calculated otherwise . and @xmath155 ; adopting the empty world model ( milne model ) for the perturbation , we get @xmath156 and further on @xmath157 . ] the opposite limit of @xmath158 ( @xmath159 ) leads to @xmath160 ; this can be equally deduced from ( [ eq : linear theory ] ) . if we adopt the currently accepted value of @xmath161 ( @xmath162 ) , we obtain @xmath163 . thus , the @xcite approximation ( [ form : bernard teta ] ) , which gives @xmath164 independently of @xmath14 , has a relative error of approx . 5% in this limit for such @xmath165 . we would now like to find an ( approximate ) relation @xmath123@xmath11 for the whole range @xmath166 $ ] . @xcite derived his formula expanding the relation around @xmath167 . we adopt a different approach : we expand the relation around @xmath168 . ( that is , at a first step we assume @xmath169 ) . then , for arbitrary @xmath39 , the perturbation parameter @xmath170 . from equation ( [ form : delta fi eta ] ) we obtain @xmath171 , where @xmath172 and further on @xmath173 using equation ( [ eq : phi2_eta_arbitrary ] ) in equation ( [ form : teta open ] ) we get @xmath174 where @xmath175 - \ln(1+\delta ) \ , . \label{eq : phi1_eta_arbitrary}\ ] ] equation ( [ eq : theta2_eta_arbitrary ] ) satisfies explicitly the highly non - linear limit @xmath176 . also , in the limit @xmath177 , this equation reduces to asymptotic equation ( [ form : tetafal2 ] ) , as expected . the range of applicability of formula ( [ eq : theta2_eta_arbitrary ] ) is very limited : it starts to deviate from the exact relation for @xmath11 about @xmath178 . we would like to introduce such a modification so as to satisfy also the linear - theory limit : for @xmath179 , @xmath140 . therefore , we adopt the following three boundary conditions : 1 . @xmath176 , 2 . @xmath180 , 3 . . inspired by equation ( [ eq : theta2_eta_arbitrary ] ) , we write @xmath181 where @xmath182 and @xmath183 are arbitrary functions of @xmath39 . imposing the three boundary conditions a.c . on the above formula we find @xmath184 where @xmath185 as a function of @xmath14 [ cf . ( [ eq : theta_min ] ) ] is @xmath186 @xmath187}\right\ } \simeq\ ] ] @xmath188 [ here @xmath107 is given by ( [ form : f of omega ] ) ] and @xmath189 has the form of ( [ form : n of delta ] ) . indeed , formula ( [ eq : theta2_ansatz ] ) meets all the three boundary conditions : the last two are fulfilled since for small @xmath11 , @xmath190 , and the first one because @xmath191 . this simple approximation is robust for @xmath11 close to @xmath192 and around @xmath193 ; for intermediate values of @xmath11 it slightly underestimates the exact value of @xmath123 ( with a maximal relative error of 2% for @xmath194 ) . formula ( [ eq : theta2_ansatz ] ) is probably already sufficiently accurate for practical applications . still , it is of course possible to improve it . in order to do this , we expand the exact @xmath123@xmath11 relation around @xmath168 up to third - order in the perturbation parameter @xmath59 . the result is the following series : @xmath195 where @xmath196 are some functions of @xmath39 ( see appendix [ app : theta3 ] ) . from the six terms above we construct their linear combinations which fulfill the constraints a.c . this , together with the condition of simplicity , leads us to postulate @xmath197n(\delta ) + \alpha_1(\omega)\ , \delta\ , ( 1+\delta ) \ln(1+\delta ) \,+\ , & & \nonumber \\ \alpha_2(\omega ) ( 1+\delta)^2 \ln^2(1+\delta)\ , , \hphantom{x } & & \label{eq : theta3_ansatz}\end{aligned}\ ] ] fitting this formula to the exact relation gives @xmath198 and for @xmath199 . the fit is very accurate : it has a maximal error smaller than @xmath141% . in general , both @xmath200 and @xmath201 depend weakly on @xmath14 : we have @xmath202 and @xmath203 for figure [ fig : fit voids ] presents a comparison of the exact relation for @xmath145 , calculated for voids from ( [ form : teta open ] ) , with the fit ( [ eq : theta3_ansatz ] ) and the @xcite approximation ( [ form : bernard teta ] ) . as we can see , our fit lies accurately on the approximated curve and the @xcite formula slightly underestimates exact values of @xmath123 for @xmath11 close to @xmath192 . however , it should be admitted that the latter is considerably simpler than ours . relation between density contrast and scaled velocity divergence for spherical voids ( underdensities ) : linear theory ( dotted line ) , exact relation ( solid line ) , @xcite approximation ( dashed line ) and fit given by equation ( [ eq : theta3_ansatz ] ) ( crosses ) . the density parameter of the background is @xmath204.,scaledwidth=50.0% ] an _ overdensity _ is any perturbation for which @xmath62 . as already mentioned , these can be of two types , depending on the initial density contrast : ` open ' or ` closed ' . for a specific value of @xmath14 ( or , equally , @xmath39 ) , the boundary value of the density contrast , maximal for the first type and minimal for the second , is given by ( [ form : delta lim ] ) . for the currently accepted value of @xmath161 we have @xmath205 : such overdense but open perturbations ( @xmath206 ) fall within the weakly non - linear regime . in order to find an approximation for @xmath145 for overdense spherical regions , we will use a similar procedure as we did for voids , examining the highly non - linear regime ( @xmath207 ) . owing to the considerations above , it is sufficient to focus on closed perturbations ; the formula for @xmath123 is then of the form ( [ form : teta closed ] ) , with the ` + ' sign . highly non - linear infall means that the overdensity collapses to a point : the conformal time of the perturbation @xmath208 . this is in general not physical , as in practice for @xmath209 virialisation would occur and prevent further collapse . however , as in the case of voids , examination of this regime leads to interesting formulae . first of all , we can directly put @xmath210 into ( [ form : teta closed ] ) , getting the ` 1-st order approximation ' : @xmath211\,.\ ] ] we can see that the @xcite formula ( [ form : bernard teta ] ) , which was not intended to work in this regime , indeed will not work : already the slope of the curve is incorrect ( 2/3 instead of 1/2 ) . for realistic values of @xmath14 , @xmath212 . using this approximate equality and neglecting the constant term in equation ( [ form : teta 1 ] ) yields the ` 0-th order approximation ' , @xmath213 . the same relation can be deduced from dynamical considerations ( namely , from energy conservation in the highly non - linear infall ) . @xcite also found such a form of the weak @xmath14-dependence @xmath214 of the peculiar velocity in virialised regions . this is not surprising , since both in our and their case , @xmath207 and @xmath215 . expanding the relation ( [ form : teta closed ] ) around @xmath210 ( @xmath216 ) to higher order , we obtain the following series : @xmath217 \,,\end{aligned}\ ] ] where @xmath218 are functions of @xmath14 only . in order to obtain a fit that would both converge to ( [ form : teta 1 ] ) in the highly non - linear regime of @xmath219 and have proper behaviour in the vicinity of @xmath220 ( conditions b. and c. from section [ sec : voids ] ) , we proceed similarly as we did for @xmath2 . first , already here we neglect the fourth ( and all next ) component of the series . then we modify the expansion ( [ form : teta ser kolaps ] ) by introducing two parameters @xmath221 , @xmath222 and an integer @xmath31 : @xmath223 .\ ] ] imposing the conditions @xmath180 and @xmath224 , we obtain : @xmath225 in particular , for @xmath226 [ cf . ( [ form : teta ser kolaps ] ) ] we have @xmath227 and @xmath228 ( remembering that @xmath36 ) . inserting the above expressions for @xmath221 and @xmath222 into equation ( [ form : fit a , b , n ] ) with @xmath229 and neglecting the weak [ since @xmath230 , we obtain the following result , which can be treated as a generalisation of the @xcite formula : @xmath231\,.\ ] ] an interesting feature of this fit is that it has the same second - order taylor expansion around @xmath220 as the approximation given by @xcite : @xmath232 this means that in the weakly non - linear regime these two approximations give similar results . however , for mildly non - linear values of @xmath11 ( from @xmath233 up to the turn - around . in the spherical model as discussed here it occurs for @xmath234 ; the density contrast for the turnaround spans from @xmath235 for @xmath236 to @xmath237 for @xmath238 . if @xmath204 , then @xmath239 . ] ) our approximation works generally better than the formula of @xcite . the maximal error of our fit for such an interval of density contrasts is about 1.5% . figure [ fig : overdense to ] shows the discussed approximations for the weakly and mildly non - linear regime . a comparison of proposed approximations for @xmath145 with the relation for spherical overdensities in the mildly non - linear regime ( up to the turn - around ) . solid line shows the exact relation , the @xcite approximation ( [ form : bernard teta ] ) is illustrated by dashed line and crosses present the fit given by ( [ form : fit pot ] ) ; dotted line is the linear theory relation . the density parameter of the background equals to @xmath240 ; the density contrast of the turn - around is then @xmath241.,scaledwidth=50.0% ] for higher values of @xmath11 , neither the @xcite approximation , nor the fit ( [ form : fit pot ] ) are adequate . in case of the first one this is mainly due to a wrong slope of the curve ; in case of the second due to the negligence of the dependence on @xmath14 . for that reason in the regime of very big @xmath11 we prefer to use the fit ( [ form : fit a , b , n ] ) , of a more general form . the approximation ( [ form : fit pot ] ) suggests that the best choice of @xmath31 is @xmath229 ; however , it turns out that in practice , for highly non - linear density contrasts ( greater than the value for the turn - around ) , approximation ( [ form : fit a , b , n ] ) with @xmath242 works slightly better than with @xmath226 ( with the weak @xmath14-dependence included in both cases ) . in figure [ fig : overdense hnl ] we show the behaviour of the function @xmath145 in the highly non - linear regime . for comparison , we plot the formula of @xcite , the simple approximation ( [ form : fit pot ] ) and the approximation ( [ form : fit a , b , n ] ) with @xmath242 . an illustration of the behaviour of the function @xmath145 for spherical overdensities in the highly non - linear regime , i.e. up to the virialisation . the solid curve is the exact relation , the dashed line shows the @xcite approximation and crosses present two approximations described in the text : plus marks represent the formula ( [ form : fit pot ] ) and multiplication marks show the fit ( [ form : fit a , b , n ] ) with @xmath243.,scaledwidth=50.0% ] our results for the highly non - linear regime are rather of academic value , since , as stated earlier , highly non - linear infall is considerably modified by the effects of virialisation . to account for them ( and for deviations from spherical symmetry ) , @xcite constructed an _ improved _ ( extended ) semi - analytical spherical collapse model . for @xmath11 up to about @xmath244 ( which equals to @xmath245 , as the background assumed in the discussed paper is of the einstein de sitter type ) their model coincides with the standard spherical model ( studied here ) , while for larger density contrasts it deviates from the latter and under some additional assumptions matches well the results of n - body simulations presented by @xcite . indeed , formula ( 20 ) of @xcite , for @xmath246 ( the limit of the standard model ) , reduces to our equation ( [ form : teta closed ] ) ( their @xmath247 ) . the authors argue that for background universes with dark energy their formula is valid only for @xmath248 . they claim that for smaller values of @xmath11 , their results are not accurate . we disagree with these statements . as already stated , the weak @xmath14 _ and _ @xmath15 dependence of the scaled velocity density relation has been shown on the level of the equations of motion @xcite , so independently of the level of non - linearity . since for small redshifts dark energy behaves similarly to the cosmological constant ( e.g. @xcite ) , and since only for such redshifts the weak dependence of equations of motion on cosmological parameters starts to play any role ( because earlier we had @xmath249 ; @xcite ) , the velocity density relations for cosmological models with and without dark energy must be similar . @xcite studied the mildly non - linear velocity density relation using the cosmological pressureless parabolic advection ( cppa ) hydrodynamical code . they found that the mean relation between the scaled velocity divergence and the density contrast can be very well described by the so - called ` @xmath250-formula ' , @xmath251 + { { \epsilon}}\,,\ ] ] with @xmath252 . this formula is a modification of the @xcite formula with @xmath250 instead of @xmath5 . the offset @xmath253 is introduced to account for an effect of a finite variance of the density field : the value of @xmath254 is such that the global mean of @xmath123 is zero , as required . ( another effect of a finite variance is to modify the degree of non - linearity of the relation . ) without the offset , the above formula yields @xmath255 for @xmath256 , in significant difference with the value @xmath257 , obtained neglecting the weak of the exact limit , eq . ( [ form : teta min ] ) . however , for gaussian smoothing scales of a few mpc , employed in @xcite , the offset shifts the value of @xmath258 much closer to @xmath257 . @xcite analysed the velocity density relation using n - body simulations performed for various background cosmologies . they noticed a weak dependence of the relation on @xmath14 and @xmath15 . @xcite invented a somewhat more elaborate fit to the extracted mean relation , presented in the form of density in terms of velocity divergence , @xmath259 here , @xmath260 , slightly smaller than unity , plays a role of the offset @xmath254 in equation ( [ eq : theta_gamma ] ) : it assures that the global mean of @xmath11 is zero , as required . in equation ( [ eq : delta_b99 ] ) @xmath250 is not a constant , but is approximated as a following function of @xmath123 : @xmath261 the above equation quantifies the fact that for larger values of velocity divergence , the observed relation becomes more non - linear . indeed , @xmath250 grows with growing @xmath123 ( we recall that @xmath262 corresponds to the linear theory ) . moreover , for @xmath263 , we have @xmath264 , so then @xmath168 , as it was intended . [ note a typo in eq . ( 20 ) of @xcite : instead of @xmath265 ( in our notation , @xmath123 ) , there should be @xmath79 . ] how do these findings , based on fully non - linear simulations , relate to our results ? in overdensities , our formula ( [ form : fit pot ] ) follows closer to the exact relation in the scm than the formula of @xcite . moreover , our approximation is a formula with increasing effective index @xmath266 . its second order expansion is the same as that of @xcite , so for small @xmath11 , @xmath267 . for large density contrasts , the second term in equation ( [ form : fit pot ] ) becomes negligible , so asymptotically @xmath268 ( for @xmath207 ) . therefore , qualitatively our formula is consistent with the fit of @xcite , in a sense that @xmath250 , as a function of @xmath123 or @xmath11 , is growing . it is also consistent with the fit of @xcite , in a sense that the average @xmath250 is slightly larger than @xmath5 . clearly , our formula is a better fit to the results of numerical simulations than the formula of @xcite . of course , quantitatively there are discrepancies . first of all , it is strictly impossible to satisfy simultaneously the features of both fits : @xmath250 is _ either _ constant _ or _ increasing . this discrepancy between the results of the two groups is not necessarily a sign of a major flaw in any of their analyses . the two groups used different codes : n - body versus hydro . the first one follows accurately non - linear evolution , but provides naturally a mass- , not volume- , weighted velocity field , while the latter is needed . cppa , as any hydrodynamical code , provides naturally a volume - weighted velocity field , but follows the non - linear evolution after shell crossings only approximately . moreover , the density power spectra used in both simulations were different . also , fit ( [ eq : delta_b99 ] ) of @xcite was found for top - hat smoothed fields , while fit ( [ eq : theta_gamma ] ) of @xcite was elaborated for fields smoothed with a gaussian filter ( more appropriate for velocity density comparisons ) . the effects of smoothing , though small , are different for these two filters ( see e.g. table 1 of @xcite ) . finally , an inverse of the forward relation ( density in terms of velocity divergence ) does not strictly describe the mean inverse relation , due to scatter . which results better reflect real non - linear dynamics of cosmic random density and velocity fields ? instead of betting , it would be probably best to repeat the analysis using an output from high - resolution n - body simulations with a @xmath15cdm power spectrum , employing instead of a voronoi tessellation @xcite a much simpler algorithm of extracting volume - weighted velocity field of @xcite . voronoi tessellations are complicated and very cpu - consuming , so they can be applied only to a limited number of points , while the method of @xcite can be ( and actually has been ) applied to all simulation points ( @xmath269 in their work ) . if the actual relation is not more non - linear than in the highly non - linear regime of the scm ( @xmath270 ) , then we can use formula ( [ form : fit a , b , n ] ) , with neglected weak @xmath14-dependence and @xmath31 treated as a free parameter . let us write it explicitly : @xmath271 + { { \epsilon}}\,,\ ] ] where @xmath272 . [ for @xmath226 , it reduces to formula ( [ form : fit pot ] ) . ] for example , if the best - fit value of @xmath250 is found to be close to @xmath273 and fairly constant , then @xmath274 would provide an excellent fit . instead , significant ` run ' of the index @xmath250 would probably demand @xmath275 . if , on the other hand , the results of @xcite are found to be accurate , then for @xmath199 equation ( [ eq : gamma ] ) yields @xmath270 already for @xmath276 , and even more for higher @xmath123 . in this case , in order to describe the relation up to the turn - around , one should modify also the exponent of the leading term in formula ( [ eq : theta_fit_n ] ) ( @xmath277 instead of @xmath278 , with @xmath279 ) . and modify the offset to @xmath280 . ] it is a matter of choice if to fit one ` running ' exponent ( @xmath250 ) or two constant ( @xmath281 and @xmath31 ) . in any case , it is better to use an additive offset @xmath254 instead of the factor @xmath260 , appearing in equation ( [ eq : delta_b99 ] ) : in applications to velocity velocity comparisons the value of @xmath254 is not relevant at all . the mildly non - linear velocity field is vorticity - free to good accuracy , so the predicted velocity field ( from the density field ) is @xmath282\ , ( { { \bf r}}'-{{\bf r}})}{|{{\bf r}}'-{{\bf r}}|^3 } \ , , \label{eq : theta_int}\ ] ] and the contribution of the offset to velocity averages out to zero . an advantage of the @xmath250-formula over formula ( [ eq : theta_fit_n ] ) or its modification is that it works also for voids . for underdensities , the formula of @xcite is a very good description of the exact relation in the scm , except for the very tail @xmath283 ( where the weak @xmath14-dependence becomes important ) . results of numerical simulations show very limited need to modify the formula of @xcite for voids the discrepancies appear at larger density contrasts . as stated earlier , @xcite predicted this fact . our formulae for voids give results very similar to that of @xcite , but describe better the regime @xmath283 . this regime is important for predicting expansion velocities of almost completely empty voids ( e.g. , see @xcite ) . therefore , using approximation ( [ eq : theta2_ansatz ] ) for underdensities , we propose the following combined formula : @xmath284 here , @xmath285 is the ` @xmath281-modification ' of formula ( [ eq : theta_fit_n ] ) , @xmath189 is given by equation ( [ form : n of delta ] ) and @xmath254 , treated as a free parameter , is the same in both cases . alternatively , as the relation for voids , one could use more complicated and extremely accurate equation ( [ eq : theta3_ansatz ] ) . to sum up , we admit that it is disputable if to fit results of numerical simulations using our formula ( [ eq : theta_comb ] ) , or @xmath250-formula . what remains indisputable is that for overdensities , our standard formula ( with @xmath286 and @xmath226 ) is a better starting fit than the standard formula of @xcite ( with @xmath264 ) . the main motivation of this paper was to rederive the formula of @xcite in a simple way , using the spherical collapse model ( scm ) , and to extend it to larger density contrasts , where it is no longer valid . the undertaken project abounded in surprises : 1 . contrary to the claim of @xcite , the formula of @xcite is not exact in the limit of an empty universe . on the contrary , it completely fails in this regime : the exact relation in the scm is then @xmath287 , for an arbitrary @xmath11 . in fact , this is a general result of dynamics in a low - density universe . although the formula of @xcite fails for @xmath288 , where it was expected to work best , for realistic values of @xmath14 ( say , @xmath289 ) , it describes very well the scm velocity density relation in voids . it also works for overdensities up to @xmath290 @xmath22 . the velocity density relation in the scm is given in a parametric form . our goal here was to eliminate this parameter ( at least approximately ) and to provide the relation analytically . we aimed at describing the relation in the whole range @xmath291 ( realistically , up to @xmath292 ) . therefore , instead of expanding it around @xmath293 , we adopted an entirely different approach . namely , we derived asymptotes of the relation in the highly non - linear regime : @xmath294 ( @xmath295 ) for overdensities and @xmath296 for voids . ( although we also ` expanded ' around them , in a sense that we also calculated next - to leading - order terms . ) these two asymptotes turned out to be qualitatively different . inspired by their functional forms , we invented semi - phenomenological fits to the exact relation ( separately for overdensities and voids ) , fulfilling the linear theory condition @xmath297 . + for overdensities , our main result is formula ( [ form : fit pot ] ) . it describes well the exact relation in the scm up to the turn - around ( for @xmath199 , @xmath298 ) . as already stated , the formula of @xcite starts to deviate from the exact relation for @xmath299 . we have also fitted the regime @xmath300 , though virialisation and departures from spherical symmetry make practical applicability of the scm in this regime very limited . + in case of voids , the most important results of this paper are formulae ( [ eq : theta2_ansatz ] ) and ( [ eq : theta3_ansatz ] ) , with @xmath185 given by equation ( [ eq : theta_min ] ) . compared with the scm , simple formula ( [ eq : theta2_ansatz ] ) has a maximal error of about @xmath301% and is probably sufficient for practical applications . the formula of @xcite is an even better approximation , except for the limit @xmath302 , where for @xmath199 it has approximately @xmath303% relative error . our more complicated formula ( [ eq : theta3_ansatz ] ) is extremely accurate in the whole range @xmath304 : its maximal error is about @xmath141% . + an ultimate goal of studies such as the present one is to find the relation valid for realistic random cosmic velocity and density fields . unlike the work of @xcite , our calculations were greatly simplified by the strong assumption of spherical symmetry . there is therefore no guarantee that better agreement with the scm implies better agreement with the real relation . in order to check this issue we compared our formulae to fits to results of cosmological numerical simulations , that are present in the literature . we have found that in voids , our formulae , as well as the formula of @xcite , describe well the real relation . this is partly a consequence of the fact that voids are more spherical than overdensities . in overdensities , both our formula and that of @xcite require modification , but ours less this discrepancy is not a failure of the latter of the two , since it has never been intended to work for @xmath305 . our formula ( [ form : fit pot ] ) , having the same second - 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121 saunders w. et al . , 2000 , mnras , * 317 * , 55 - 63 scoccimarro r. , couchman h.m.p . , frieman j.a . , 1999 , apj , * 517 * , 531 - 540 shaw d.j . , mota d.f . , 2008 , apjss , * 174 * , 277 - 281 strauss m.a . , willick j.a . , 1995 , phr , * 261 * , 271 - 431 tully r.b . , shaya e.j . , karachentsev i.d . , courtois h.m . , kocevski d.d . , rizzi l. , peel a. , 2008 , apj * 676 * , 184 - 205 willick j.a . , strauss m.a . , dekel a. , kolatt t. , 1997 , apj , * 486 * , 629 - 664 yahil a. , 1985 , in richter o.g . , binggeli b. , eds . , _ the virgo cluster of galaxies _ , european southern observatory , garching , p. 359 the general equation of motion for the cosmic pressureless fluid in comoving coordinates is @xmath308 where @xmath309 is the peculiar gravitational acceleration , @xmath310 ( e.g. peebles 1980 ) . for @xmath95 we can neglect the non - linear term on the lhs of equation ( [ eq : motion ] ) . let us choose some instant of time , @xmath311 , of the evolution of an open universe when already @xmath33 . for such @xmath14 perturbations stop growing , so for @xmath312 , our equation ( [ eq : motion ] ) simplifies then to @xmath313 = \frac{{{\bf g}}_i({{\bf x}})}{a } . \label{eq : motion_empty}\ ] ] the solution is @xmath314 where the conformal time @xmath39 is in general defined in equation ( [ form : conft ] ) . the last term in equation ( [ eq : solut ] ) is the homogeneous part . here we do not assume _ a priori _ irrotationality of the velocity field , so we retain this term . ( though it does not contribute to the velocity divergence , because @xmath315 . ) the limit @xmath288 corresponds to @xmath316 . therefore , in the above equation we can neglect the terms @xmath317 and @xmath318 , as well as @xmath319 . this yields @xmath320 from equation ( [ eq : grav ] ) we have @xmath321 this yields in ( [ eq : solut_limit ] ) @xmath322 in an ( almost ) empty universe @xmath323 and @xmath324 , hence @xmath325 . also , the general relation ( [ form : omega of eta ] ) between @xmath14 and the conformal time simplifies then to @xmath326 . substituting this in equation ( [ eq : div_v ] ) we obtain @xmath327 . comparing this equation with equation ( [ form : f eta big ] ) , we identify the factor @xmath328 as the low-@xmath14 limit of the factor @xmath107 . hence , @xmath329 in agreement with the general linear theory prediction , equation ( [ eq : linear ] ) . now , we claim that in the limit @xmath288 , solution ( [ eq : solut_limit ] ) is also a solution of the general equation of motion ( [ eq : motion ] ) , _ for arbitrary _ @xmath11 . to prove this statement we have to demonstrate that in this limit , the non - linear term in equation ( [ eq : motion ] ) is negligible . substituting solution ( [ eq : solut_limit ] ) in this term gives @xmath330 the amplitude of the second term on the rhs is of order @xmath331 . the amplitude of the second term relative to the first is thus @xmath332 and in the limit @xmath288 it tends to zero . ( formally speaking , for arbitrary @xmath253 and arbitrary @xmath11 , there always exists @xmath333 such that for all @xmath334 , @xmath335 . ) thus , in the limit @xmath288 the non - linear term in the equation of motion becomes negligible , for arbitrary value of @xmath11 . this is why in every matter - only , open universe , the velocity density relation evolves towards the linear one . our aim here is to extend calculations of section [ sec : voids ] for voids up to third order in the perturbation parameter @xmath59 ( @xmath59 is assumed to be large , but not infinitely large ) . we begin applying to equation ( [ form : delta fi eta ] ) the equality @xmath337 and expand this equation up to terms of the order @xmath338 . solving perturbatively the resulting equation for @xmath339 we obtain where @xmath341 is given by equation ( [ eq : phi2_eta_arbitrary ] ) , @xmath342 by ( [ eq : phi1_eta_arbitrary ] ) and the second term on the rhs of the above equation is a small correction . this enables us to write here , @xmath346\ , \ln(1+\delta ) + 3\ln^2(2 g ) \nonumber \\ \!\!\!\!\!&-&\!\!\!\!\ ! 10 \ln(2 g ) + 10 \ , , \label{eq : f_delta_eta}\end{aligned}\ ] ] and @xmath347 is given by equation ( [ eq : g_eta ] ) . inspecting terms in the above equation we see that equation ( [ eq : theta3_fin ] ) can be indeed written in the form ( [ eq : theta3_general ] ) .

we study the cosmic velocity density relation using the spherical collapse model ( scm ) as a proxy to non - linear dynamics . although the dependence of this relation on cosmological parameters is known to be weak , we retain the density parameter @xmath0 in scm equations , in order to study the limit @xmath1 . we show that in this regime the considered relation is strictly linear , for arbitrary values of the density contrast , on the contrary to some claims in the literature . on the other hand , we confirm that for realistic values of @xmath0 the exact relation in the scm is well approximated by the classic formula of bernardeau ( 1992 ) , both for voids ( @xmath2 ) and for overdensities up to inspired by this fact , we find further analytic approximations to the relation for the whole range @xmath3 . our formula for voids accounts for the weak @xmath0-dependence of their maximal rate of expansion , which for @xmath4 is slightly smaller that @xmath5 . for positive density contrasts , we find a simple relation @xmath6 , \ ] ] that works very well up to the turn - around ( i.e. up to @xmath7 for @xmath8 and neglected @xmath9 ) . having the same second - order expansion as the formula of bernardeau , it can be regarded as an extension of the latter for higher density contrasts . moreover , it gives a better fit to results of cosmological numerical simulations . methods : analytical cosmology : theory dark matter large - scale structure of universe instabilities .

the gpe for the single - particle wave function @xmath0 , including a time - dependent ( frm - controlled ) nonlinear coefficient @xmath1 and an external potential @xmath2 , in normalized units is @xmath3 \psi \ , . \label{nls}\ ] ] we start by considering a bec in the ground state of a radial ( 2d ) parabolic trap with the ( time - dependent ) frequency @xmath4 , supplemented , in the longitudinal direction , by end caps " , induced by transverse light sheets . the configuration is like the one used to create soliton trains in the li@xmath5 condensate @xcite . then , a 1d lattice in the axial direction , whose period is normalized to be @xmath6 , is adiabatically switched on , by increasing its strength @xmath7 from @xmath8 at @xmath9 to a final value @xmath10 at @xmath11 , see fig . thus , the full potential is @xmath12 + ( 1/2)\omega _ { \perp } ^{2}(t)\varrho ^{2}+v_{0}(z)\ , , \label{v}\ ] ] where @xmath13 is the radial variable in the plane transverse to @xmath14 , and the axial end - cap potential @xmath15 is approximated by a deep and wide potential box . at some moment @xmath16 , we begin to linearly decrease an initially positive nonlinear coefficient @xmath1 . it vanishes at the moment @xmath11 , and remains zero up to @xmath17 , when we start to gradually switch on the rapid frm modulation of the nonlinear coefficient ( in fig . [ fig1 ] , @xmath1 is denoted as @xmath18 , up to @xmath17 ) . at @xmath19 , @xmath1 oscillates with a constant amplitude @xmath20 around a negative average value @xmath21 , @xmath22 finally , the radial confinement is switched off within the time interval @xmath23 . after that , a soliton , if any , may only be supported by the combination of the q1d lattice and frm ( the axial width of the established soliton is assumed to be much smaller than the distance between the end caps , hence they do not affect it ) . numerical experiments following the path outlined in fig . [ fig1 ] make it possible to create stable 3d solitons . before showing the results , we first resort to the va , in order to predict conditions on the strength of the ol and size of the negative average nonlinear coefficient @xmath21 , which are necessary to support 3d solitons . note that the eventual form of eq . ( [ nls ] ) , _ i.e. _ , with @xmath24 and @xmath25 taken , respectively , as in eqs . ( [ g ] ) and ( [ v ] ) , where @xmath7 is constant and @xmath26 , has an alternative physical interpretation in terms of nonlinear optics . upon interchanging variables @xmath27 and coordinates @xmath14 ( chosen to be a propagation direction ) eq . ( [ nls ] ) describes pulse propagation in a bulk ( 3d ) medium composed of alternating self - focusing and self - defocusing layers , similar to that introduced in ref . @xcite , with an additional periodic modulation of the refractive index in the transverse direction @xmath28 . stable 3d solitons in the present model imply the existence of stable _ _ fully three - dimensional _ _ spatiotemporal solitons ( light bullets " ) in this medium . thus far , only quasi-2d spatiotemporal solitons were created experimentally in bulk media @xcite . the va was successfully applied to the description of bec dynamics under diverse circumstances , see , _ e.g. _ , refs . @xcite and a review @xcite . equation ( [ nls ] ) is derived from the lagrangian @xmath29 \varrho \ , \upd \varrho \ , \upd z\ , . \label{l}\]]as it is frequently done , we choose a variational ansatz for the solution based on the complex gaussian with an amplitude @xmath30 , radial and axial widths @xmath31and @xmath32 respectively , @xmath33 and @xmath34 being the corresponding chirps " @xmath35 -z^{2}\left [ 1/(2v^{2})+i\beta\right]\right ) \ , , \label{ansatz}\ ] ] the reduced lagrangian is obtained by inserting the ansatz ( [ ansatz ] ) into eq . ( [ l ] ) . the equations obtained by varying the reduced lagrangian yield the conservation of the number of atoms , @xmath36 , and dynamical equations for the widths , @xmath37 a necessary condition for the existence of a 3d soliton in the present model can be derived from these equations in a crude approximation , cf . ref . @xcite . to this end , we assume that @xmath20 in eq . ( [ g ] ) is small , while @xmath38 is large . it is also conjectured that the average value @xmath39 of the soliton s radial size , @xmath40 , is large ( see below ) . further , in the lowest approximation , the soliton s size in the axial direction may be assumed constant , @xmath41 , as determined by the relation @xmath42 that follows from eq . ( [ variat1 ] ) where the last small term ( @xmath43 ) is dropped . equation ( [ v0 ] ) has real solutions if the ol strength exceeds a minimum ( threshold ) value,@xmath44at @xmath45 , eq . ( [ v0 ] ) has two real solutions , which implies the existence of two different solitons . it seems very plausible ( cf . @xcite ) that the narrower one , corresponding to smaller @xmath46 , is stable , and the other one is unstable . next , replacing @xmath32 by @xmath46 in eq . ( [ variat2 ] ) ( we set @xmath47 , to consider the possibility of the existence of the 3d soliton without the radial confinement ) and substituting @xmath1 from eq . ( [ g ] ) , we look for a solution as @xmath48 . for large @xmath38 , the variable part of the equation yields @xmath49 . then , the consideration of the constant part of eq . ( [ variat1 ] ) , with regard to the first correction generated by the product of the oscillating terms in @xmath50 and @xmath1 , produces a result,@xmath51an essential corollary of eq . ( [ w0 ] ) is that a necessary condition for the existence of the 3d soliton is ( recall @xmath21 is negative ) @xmath52 direct simulations presented in the next section show that this condition holds indeed , albeit approximately . note that the above approximation , which assumed large @xmath53 , is valid only when @xmath54 slightly exceeds the minimum value defined in eq . ( [ cond ] ) . we simulated both the full gpe ( eq . [ nls ] ) using an axisymmetric code , and the variational equations ( [ variat1 ] and [ variat2 ] ) . in both cases we used runge - kutta methods . in the former case , the simulations followed the path outlined in fig . example of the numerical results , which is quite generic for strong lattice , is displayed in figs . [ fig2 ] and [ fig3 ] . for instance . for @xmath55rb atoms , the ol period is @xmath56 , the frm and initial radial - confinement frequencies are , respectively , @xmath57 and @xmath58 , the lattice depth is @xmath59 recoil energies , and the effective nonlinear coefficient is @xmath60 , where @xmath61 is the number of atoms per the lattice cell , the total number of atoms being in the range of @xmath62 . the respective values of the normalized parameters are given in fig . [ fig2 ] caption . in fig . [ fig2 ] we show 3d snapshots of the wave - function pattern occupying five lattice cells , taken at times corresponding to various stages of the numerical experiment , cf . comparison of the last two snapshots , ( e ) and ( f ) , shows that condensate develops a robust structure , which remains unchanged over many frm cycles . figure [ fig3 ] displays evolution of the central - peak s amplitude in the same pattern . after an initial transient , the stable structure is established , featuring breathings without any systematic decay . actually , the stable pattern like the one shown in fig . [ fig2 ] is a set of uncoupled fundamental solitons , each being trapped in a single lattice cell . this conclusion follows from additional numerical experiments , in which removal of the atomic population from any subset of the cells did not , in any tangible way , affect the localized states in other cells ; in particular , the soliton sitting in a single cell is as stable as any multi - cell pattern . thus , the conclusion is that the frm may support a stable 3d soliton ( breather ) confined to a _ single cell _ of the q1d lattice , and the solitons trapped in adjacent cells do not interact . in fact , this conclusion complies with the variational ansatz ( [ ansatz ] ) , which ignores any possible spatial oscillations induced by the ol , hence it indeed implies a soliton essentially confined to a single cell ( cf . the va for stationary models with the multi - dimensional ols developed in refs . @xcite and @xcite ) . we have collected results of systematic gpe simulations and compared them with predictions of the va based on simulations of eqs . ( [ variat1 ] and [ variat2 ] ) , as shown in fig . [ fig4 ] . as is seen in fig . [ fig4](a ) , only the bottom part ( corresponding to smaller values of the frm frequency @xmath38 ) of the va - predicted stability region in the @xmath63 plane actually supports stable 3d solitons . the variational estimate ( [ cond ] ) for the minimum size of the average nonlinear coefficient necessary for the existence of the 3d soliton in the q1d lattice is borne out by the simulations , although approximately . lastly , the simulations definitely demonstrate the existence of a minimum of the ol strength @xmath7 which is necessary to support the 3d solitons , as it was predicted by the va , see eq . ( [ threshold ] ) . figure [ fig4](b ) shows regions of stability in the @xmath64 plane . from this figure we conclude that va predicts stability regions quite well , but the numerical value of the @xmath65 is somehow larger than that predicted by the simple approximation given by eq . ( [ threshold ] ) . for simulations presented in figs . [ fig2 ] and [ fig3 ] we have chosen the value of @xmath66 well above the threshold . in this work , we have proposed a scheme to stabilize 3d solitons in becs where the interatomic interaction is attractive , on average . the scheme is based on the combination of the feshbach - resonance management and quasi-1d optical lattice . in previous works , it has been shown that these two methods applied separately can stabilize 2d solitons , but not 3d ones . the combined method proposed here can be easily implemented in the experiment , and thus opens a way to the creation of 3d solitons in becs . another physical implication of the results is a stable 3d light bullet " in an optical medium with an alternating longitudinal self - focusing / defocusing structure , and periodic modulation of the refractive index in a transverse direction . the possibility to achieve the result was demonstrated within the framework of the variational approximation ( va ) and verified in direct simulations . in particular , the va predicts that the ol s strength and average value of the oscillating nonlinear coefficient must exceed certain minimum values . these predictions are indeed corroborated by the simulations . however , the full stability region predicted by the va extends much farther into the high - frequency region than the actual stability area found in the direct simulations . the stable patterns found in the simulations may feature a multi - cell structure , which in the case studied here form a set of non - interacting fundamental solitons , each trapped in a single cell of the ol , in good qualitative agreement with the description provided by the va . in weak lattices one may expect to observe interaction between individual solitons . this will be a subject of further investigation . m.m . acknowledges support from the kbn grant 2p03 b4325 , m.t . was supported by polish ministry of scientific research and information technology under the grant pbz min-008/p03/2003 . the work of b.a.m . was partially supported by the israel science foundation through the grant no .

we propose an experimentally relevant scheme to create stable solitons in a three - dimensional bose - einstein condensate confined by a one - dimensional optical lattice , using temporal modulation of the scattering length ( through ac magnetic field tuned close to the feshbach resonance ) . another physical interpretation is a possibility to create stable 3d `` light bullets '' in an optical medium with a longitudinal alternating self - focusing / defocusing structure , and periodic modulation of the refractive index in a transverse direction . we develop a variational approximation to identify a stability region in the parametric space , and verify the existence of stable breathing solitons in direct simulations . both methods reveal that stable solitons may be supported if the average value of the nonlinear coefficient ( whose sign corresponds to attraction between atoms ) and the lattice s strength exceed well - defined minimum values . stable localized patterns may feature a multi - cell structure . the creation of the bose einstein condensates ( bec ) in vapors of alkali metals has opened an opportunity to investigate nonlinear interactions of atomic matter waves . one of the most fundamental aspects of these studies is generation of solitons . dark solitons had been created in effectively one - dimensional ( 1d ) bec with repulsive interatomic collisions @xcite . then , bright solitons were observed in 1d becs with attractive collisions @xcite . an issue of obvious interest is to develop methods for control of the matter - wave solitons . a promising approach consists in varying the scattering length ( sl ) of the interatomic collisions by means of an external magnetic field through the zero - sl point close to the feshbach resonance @xcite . in particular , it was shown that an abrupt change of the sl can result in splitting of a soliton into a set of secondary ones @xcite . the application of ac magnetic field may induce a periodic modulation of the sl , opening a way to the feshbach - resonance management " ( frm ) @xcite . quite a noteworthy frm - induced effect is a possibility to create self - trapped oscillating bec solitons ( breathers ) without any external trap . the underlying mechanism is balance between compression and expansion cycles , corresponding to the time intervals when the sl is , respectively , negative and positive . in fact , this possibility was first realized in terms of the transverse light propagation in a bulk layered nonlinear medium , where the kerr coefficient alternates between positive and negative values @xcite . the respective model is formally equivalent to the two - dimensional ( 2d ) gross - pitaevskii equation ( gpe ) , see eq . ( [ nls ] ) below , in which the sl is periodically modulated in time " ( analog of the propagation distance in @xcite ) not harmonically , but as a piecewise - constant function . then , the bec model based on the gpe with the harmonic modulation of the sl was directly investigated in refs . @xcite , with a conclusion that the frm makes it possible to stabilize , without the use of an external trap , 2d breathers , but not the 3d ones . the absence of the stabilization in the 3d case was also concluded in the optical model considered in ref . @xcite , where the 3d soliton would correspond to a spatiotemporal light bullet " . a remarkable feature of these results is that the 2d breather is stable despite a possibility of the collapse in the 2d gpe with a negative sl . on the other hand , it has been recently demonstrated that solitons in becs with a constant negative sl may be completely stabilized by means of an optical lattice ( ol ) , _ i.e. _ , a spatially periodic potential . it is true in _ both _ 2d and 3d cases @xcite . moreover , it was also shown that the 2d and 3d bec solitons can be stabilized by _ low - dimensional _ ols , _ i.e_. , respectively , by a quasi-1d ( q1d ) lattice in the 2d case , and by a quasi-2d ( q2d ) lattice in the 3d space @xcite . however , 3d solitons _ can not _ be made stable in a q1d ol . these results suggest a question whether 3d solitons can be stabilized by a combination of a q1d lattice and frm . the issue has practical relevance , as a q1d ol can be easily created , illuminating the bec by a pair of counterpropagating laser beams that form a periodic interference pattern @xcite . this problem is different from that considered in ref . @xcite , where stabilization of a localized 3d structure was provided by adding a tight 1d parabolic trap to the model , which made it nearly two - dimensional . in this paper , we demonstrate that the combined ol - frm stabilization of 3d solitons is possible indeed . first , we introduce the model and propose an experimental scheme . then , we predict stability conditions for the 3d solitons by means of a variational approximation ( va ) . finally , we demonstrate the soliton s stability in direct simulations . we also demonstrate that these results find another physical realization in nonlinear optics : a possibility to create a stable 3d light bullet " ( spatiotemporal soliton ) in a bulk medium which combines an alternating self - focusing / defocusing structure in the longitudinal direction , and periodic modulation of the refractive index in one transverse direction .

Mr. Abbasi’s remarks, which included an announcement that Iran would start building two nuclear power plants in 2013, are bound to complicate the already difficult nuclear talks between Iran and the world powers, which are to be continued in Moscow on June 18. If the talks fail, the powers are planning to tighten sanctions on Iranian exports and financial dealings as early as July 1, including placing an embargo on all sales of Iranian oil to Europe. Iran’s enrichment of uranium is at the center of those discussions, with Western countries suspecting the country of stockpiling enriched uranium that could be rapidly converted into weapons-grade material. Iran says it only wants to produce civilian nuclear energy. Before the meeting in Baghdad, Mr. Abbasi had hinted that Iran was ready to compromise on its program of enriching uranium up to 20 percent with the isotope capable of sustaining nuclear fission, which it says it needs to fuel an aging United States-designed medical reactor. Iranian negotiators were under the impression that the Obama administration and its allies, in return, were willing to allow Iran to continue to enrich up to a lower percentage. But during the Baghdad meeting it became clear that such an offer was not on the table, at least for now. Instead, the world powers offered another proposal, which called for Iran to export its stockpile of the more highly enriched uranium and suspend any further production. In exchange, the country was to receive supplies of medical isotopes. Photo That plan was turned down by Iran’s negotiators, who made a counterproposal that would have allowed Iran to continue to enrich uranium. It also called for nuclear disarmament and, among other things, cooperation in the fight against Somali pirates in the Horn of Africa. Both sides expect the other to take the first significant steps, without wanting to compromise on critical issues, said a European diplomat familiar with the talks. Advertisement Continue reading the main story Iranian officials have been unclear about how much of the higher enriched uranium they want to produce. A Friday report by the International Atomic Energy Agency said that Iran had produced 145 kilograms of uranium enriched up to 20 percent, more than it ordered from Argentina in 1988, the last time it needed a stockpile for its medical reactor. In other words, it has already made enough to keep its reactor, which produces medical isotopes, running for another two decades. Iran’s insistence on producing more — though it has no reactor to burn the additional fuel — has increased suspicions about its intentions. Newsletter Sign Up Continue reading the main story Please verify you're not a robot by clicking the box. Invalid email address. Please re-enter. You must select a newsletter to subscribe to. Sign Up You agree to receive occasional updates and special offers for The New York Times's products and services. Thank you for subscribing. An error has occurred. Please try again later. View all New York Times newsletters. In April, Mr. Abbasi said that Iran planned to build five more medical reactors, and that it needed to create a stockpile of fuel for that purpose. Western powers fear that Iran, if needed, could quickly enrich the uranium to weapons-grade levels of 90 percent or above. But that would require a repiping of its equipment and would most likely be detected by the energy agency’s inspectors. The energy agency’s report also said that in one instance uranium enriched up to 27 percent was found. Mr. Abbasi said it was a technical or operational mistake. Western experts on Friday agreed that such an explanation was plausible. President Mahmoud Ahmadinejad of Iran, who has been largely sidelined in the nuclear talks by Iran’s supreme leader, Ayatollah Ali Khamenei, urged the country’s Parliament on Sunday to stand with him against the “evil ones” who he said had encircled the nation. On Saturday, Mr. Abbasi, a former nuclear scientist who survived an assassination attempt two years ago that is believed to have been mounted by Israel, also highlighted complications in the talks with the energy agency, which took place in Tehran two days before the meeting with the world powers. After the talks wrapped up, the energy agency’s secretary general, Yukiya Amano, who had flown to Tehran for the first time since his appointment in 2009, said that he was near an agreement with the Iranians on extra inspections, including at Parchin, a military base near the capital where the agency suspects military nuclear activities are under way. Iran’s nuclear chief made clear that such an agreement would only be signed if the agency presented evidence that proved Iran was pursuing illegal nuclear activities on the site. “The reasons and documents have still not been presented by the agency to convince us to give permission for this visit,” Mr. Abbasi was quoted as saying by the Fars news agency on Saturday. ||||| Iran to launch new nuclear plant project: state TV TEHRAN — Iran is to build a new nuclear power plant, alongside its sole existing one in the southern city of Bushehr, by early 2014, state television reported on Sunday, quoting the head of the country's Atomic Energy Organisation. "Iran will build a 1,000-megawatt nuclear power plant in Bushehr next year," the television quoted Fereydoon Abbasi Davani as saying. He was referring to the Iranian calendar year running from March 2013 to March 2014. The Mehr news agency suggested the timeline could be longer, quoting Abbasi Davani as saying: "We will begin plans for a 1,000-megawatt plant in Bushehr next year." He said foreign contractors would be needed for its construction. The Mehr and ISNA news agencies both reported another nuclear plant was also planned and could be built in coming years. ISNA quoted Abbasi Davani as saying that designs for a 360-megawatt facility in Darkhovin, in the southwestern province of Khuzestan near the border with Iraq, "have been finished and we are reviewing it." He did not elaborate. Darkhovin, a project initiated by France but abandoned after Iran's 1979 Islamic revolution, has been stalled because of European sanctions against Tehran. In September 2011, deputy nuclear chief Mohammad Ahmadian said Iran was seeking foreign help to finish the project. The current Bushehr nuclear plant was started by German engineers in the 1970s and was completed by Russia, which continues to help keeping it running and provides fuel for it. Inaugurated in 2010, it is due to come fully on-line in November this year. In addition, Iran has a research reactor operating in Tehran that is used to make medical isotopes for patients with cancer and other illnesses. A new Bushehr plant would boost electricity production in Iran, which has some of the world's biggest reserves. State television made its announcement in the wake of talks in Baghdad on Wednesday and Thursday between Iran and world powers that focused on Tehran's controversial nuclear programme. Those talks almost collapsed because of the very different positions held by the two sides, but agreement was finally reached to hold another round in Moscow on June 18-19. Iran insists its nuclear programme is exclusively peaceful and aimed at producing energy and medical isotopes. The world powers -- the Britain, China, France, Germany, Russia and the United States -- suspect the programme could include work towards developing a nuclear weapons capability, and they have backed UN Security Council resolutions demanding Iran curb its activities. Copyright © 2013 AFP. All rights reserved. More »

– Iran plans to build two new nuclear reactors and retract an earlier offer to stop enriching uranium up to 20%, the nation's top nuclear official told state news today, the New York Times reports. "Iran will build a 1,000-megawatt nuclear power plant in Bushehr next year," Fereydoon Abbasi Davani said, according to AFP. He said the second plant is planned for southwestern Iran sometime in the coming years. Designs for the 360-megawatt facility near the Iraqi border "have been finished and we are reviewing it," he said. Abbasi Davani's announcement is sure to complicate future nuclear talks between Iran and Western powers, the Times notes. Suspension of uranium enrichment was a central demand in several United Nations Security Council resolutions. “We have no reason to retreat from producing the 20% because we need 20% uranium just as much to meet our needs,” Abbasi Davani was quoted as saying. The state news report follows a leak this week that Iran had enriched some uranium as high as 27%.

pancreatic cancer remains a disease of unknown pathogenesis , and despite advances in diagnosis and the treatment of cancer diseases , it still has a very poor prognosis . it occupies the fourth place as a cause of death from cancer , and the mortality rate from pancreatic cancer is similar to the number of newly detected cases and continues to grow [ 13 ] . pancreatic cancer in the early stages of the disease does not give clinical symptoms , making it difficult for early diagnosis that gives hope for a successful therapy . although there is progress being made in the knowledge on the pathogenesis of pancreatic cancer , only surgery performed in the early stages of the disease can significantly increase the survival . unfortunately , due to the late diagnosis , only 5 - 6% of patients with pancreatic cancer survive five years [ 46 ] . at the time of diagnosis of pancreatic cancer , the tumor is unresectable in 80% of patients and there are already distant metastases ; only in a few percent of patients the tumor is in the early stages of development , which in this group ( for stage i invasive cancer with tumors < 2 cm in diameter ) may increase the 5-year survival after surgery by 58% , and in patients with tumor < 1 cm even to 100% [ 79 ] . the median survival reported for the resected pancreatic cancer ranges from 17 to 27 months and the 5-year survival is approximately 20% . a previous study demonstrated that neoadjuvant therapy was associated with improved survival in resectable pancreatic adenocarcinoma , but a recent meta - analysis did not show a significant effect on overall survival among resectable patients after receiving neoadjuvant or adjuvant treatments [ 11 , 12 ] . the survival time of patients diagnosed with unresectable pancreatic tumor is on average 6 months and may increase only slightly ( to 11 months ) after the application of a complex chemotherapy ( folfirinox ) , which confirms the resistance of pancreatic cancer to this type of treatment . another study reported significantly improved survival in patients with metastatic pancreatic cancer treated with gemcitabine and nab - paclitaxel compared to gemcitabine as a single therapy . the median overall survival was 8.5 months in the nab - paclitaxel gemcitabine group as compared with 6.7 months in the gemcitabine group ; the survival rate was 35% in the nab - paclitaxel gemcitabine group vs. 22% in the gemcitabine group at 1 year , and 9% vs. 4% at 2 years . it should be noted that among patients with metastatic disease , the 5-year survival rate is only 2% , and 1-year survival rates of 17 - 23% with gemcitabine have been reported [ 13 , 15 , 16 ] . the results of previous studies clearly indicate the need for more effective diagnostics that would enable early detection of pancreatic cancer a highly heterogeneous disease . currently , it is difficult to expect a dramatic improvement in early diagnosis of pancreatic cancer , conducted mainly based on generally accessible , convenient , expensive and potentially invasive methods performed usually after the onset of symptoms ; these include endoscopic ultrasound ( eus ) and magnetic resonance imaging ( mri ) of the abdomen with cholangiopancreatography or computerized tomography scan . the aforementioned methods mainly allow the assessment of the possibility of surgical treatment , but in some patients they are also helpful in identifying premalignant lesions ( e.g. , cystic precursor lesions ) [ 1820 ] . problems associated with the detection of small tumors of the pancreas ( < 1 cm in diameter ) , and distinguishing benign tumors from malignant , delay the surgery . however , in some cases of incorrect preoperative diagnosis of pancreatic cancer , pancreatoduodenectomy is performed in chronic pancreatitis , exposing these patients to early and late complications associated with major surgery and removal of the pancreas ( 30 - 60% of the morbidity rate ) [ 21 , 22 ] . this is supported by the fact that most large series of pancreatic resections for carcinoma show that 5 - 10% of cases of inflammatory mass masquerade as pancreatic carcinoma . the eus - guided fine needle aspiration ( fna ) provides success rates of 90 - 95% , as an additional diagnostic modality for diagnosis of solid pancreatic neoplasms . eus has the unique ability to obtain specimens for histopathological diagnosis , and can , therefore , play a crucial role in the evaluation of patients with inconclusive findings on initial examinations . additionally , molecular imaging techniques such as pet or mrs provide information on metabolic and signaling pathways . considering the parametric data from these imaging approaches ( anatomic , molecular , and physiological ) such parametric characterization could provide insight into tumor metabolism , cellular density , protein expression , focal perfusion and vascular permeability of tumors . as demonstrated by previous research , pancreatic ductal adenocarcinoma ( pdac ) develops from the most frequent precursors , i.e. , pancreatic intraepithelial lesions ( pancreatic intraepithelial neoplasia panin ) , intraductal papillary mucinous neoplasms ( ipmns ) , mucinous cystic neoplasms ( mcns ) and the newly added intraductal tubular papillary neoplasms ( itpns ) [ 2731 ] . panin , ipmns and mcns lead to invasive pdac by gene alterations and distant metastasis occurs late during the genetic evolution of pancreatic cancer [ 32 , 33 ] . for instance , molecular changes in panins can be classified as early ( kras2 mutations , telomere shortening , p21 up - regulation ) , intermediate ( cyclin d1 up - regulation , expression of proliferation antigens ) or late ( brca2 and tp53 mutations , dpc4/smad4/madh4 inactivation ) . studies in patients with a strong family history of pancreatic cancer revealed a correlation between multifocal neoplastic precursor lesions ( panin ) and lobular atrophy of the pancreas on eus [ 34 , 35 ] . thus , early detection of precursor lesions of the pancreas and surgical removal should significantly improve the results of pancreatic cancer treatment . our review is aimed at exploring the current knowledge about the pathogenesis and diagnosis of pancreatic cancer based on the genetic aspects of signaling pathway disorders associated with innate antibacterial response . the discovery of tlrs has enabled a better understanding of disorders of the innate antibacterial response in patients with various diseases , in particular in cancer patients . toll - like receptors are a family of pattern - recognition receptors , which play a crucial role in the activation of innate and adaptive immunity , and can be expressed in several types of cells , such as macrophages , dendritic cells ( dcs ) , b cells , t cells , monocytes or epithelial cells [ 36 , 37 ] . tlr proteins recognize a large number of pathogen - associated molecular patterns , such as bacterial lipopolysaccharides or viral rna . all tlrs , with the exception of tlr3 , signal via the myd88 adapter protein ( myeloid differentiation factor 88 ) [ 38 , 39 ] . myd88 , traf6 ( tnf- receptor - associated factor 6 ) , trif ( toll / il-1-receptor domain - containing adapter inducing interferon ) and tram ( trif - related adaptor molecule ) proteins are key molecules in the cytoplasmic signaling cascade of the antibacterial response initiated by tlrs . traf6 is a member of the tnf receptor - associated factor family of proteins and is an e3 ubiquitin ligase , which catalyzes the synthesis of lysine polyubiquitin chain involved in the downstream activation of nf-b . tlr4-induced tak1 autophosphorylation and activation require translocation of the myd88-traf6-ubcl3-ciap - tak1-ikk signaling complex from tlr4 into the cytosol , which depends on traf6 and ciaps . the myd88-dependent pathway involves the early phase of nf-b activation , which leads to the production of inflammatory cytokines . the myd88-independent pathway activates interferon ( ifn)-regulatory factor ( irf3 ) and involves the late phase of nf-b activation , both of which lead to the production of ifn- and expression of ifn - inducible genes . tlr2 and tlr4 receptors were found to mediate the effects of hmgb1 ( high mobility group box-1 ) in neutrophils and macrophages . hmgb1 is an important protein binding to dna , stabilizing nucleosomes and facilitating nf-b activation and gene transcription [ 43 , 44 ] . hmgb1 modulates the inflammatory cascade in lps - activated macrophages by inducing the production of pro - inflammatory cytokines tnf- and il-1 , while attenuating the release of anti - inflammatory mediators , il-10 and tgf-1 . tlrs might influence tumor initiation and progression through regulating the activation of transcription factors , such as nf-b , interferon regulatory factors ( irfs ) or ap-1 via mitogen - activated protein kinase ( mapks ) signaling integrators [ 4650 ] . tlrs caused derangements in several tumor suppressor proteins ( such as p16 , p21 , p27 , p53 and prb ) , induced stat3 activation and promoted epithelial - mesenchymal transition ( emt ) as well as oncogene - induced senescence . the abnormal expression of tlr receptors may be associated with sepsis and autoimmune diseases ( lupus erythematosus , rheumatoid arthritis , type 1 diabetes ) [ 5256 ] . interestingly , tlr receptors have been also detected in many tumor cell lines and tumors , including pancreatic ductal adenocarcinoma , whereas they are not expressed in the normal pancreatic tissue , and may be used as potential therapeutic targets [ 5760 ] . tlrs were found to be involved in tumor cell proliferation , apoptosis and angiogenesis , while the high expression of toll - like receptor 4/myeloid differentiation factor 88 was correlated with poor prognosis in patients with colorectal cancer [ 6165 ] . most studies on pancreatic cancer refer to changes in tlr4 and tlr2 receptor signaling pathways . tlr4 was overexpressed in pancreatic cancer and tlr4 signaling via the myd88-independent trif pathway modulated pancreatic carcinogenesis , because targeting tlr4 or trif prevented cancer progression . these findings also suggest that there may be a possible participation of endogenous lps derived from gut bacteria in modulating pancreatic carcinogenesis . lps may act through the tlr4-myd88-nfb signaling pathway that induces mmp-9 overexpression . as reported by an earlier study , activation of tlr4 signaling by lps profoundly increased the emt of pancreatic cancer cells , and m2-polarized tams promoted the emt in pancreatic cancer cells , partially through the tlr4/il-10 signaling pathway . tlr4 activation was shown to accelerate pancreatic cancer development , while myd88 blockade using synthetic inhibitors accelerated pancreatic fibro - inflammation and carcinogenesis . more specifically , this meant that myd88 blockade resulted in an invasive pancreatic adenocarcinoma within 3 weeks in p48cre;kras mice treated with caerulein compared with the development of early panin lesions in age - matched mice with intact myd88 signaling . according to these finding , upon myd88 blockage , dcs seemed to induce the formation of pancreatic antigen - restricted th2-deviated cd4 t cells . in that study , stromal leukocytes collected from patients showed increased tlr4 expression , and such up - regulation was also reported both in epithelial and stromal cells in kras - mutated mice . interestingly , inhibition of tlr4 in these mice had a protective effect against tumorigenesis ( slower tumor growth ) . dcs were found in large quantities in pancreatic cancer and tumor - draining lymph nodes , and the number of tumor - infiltrating th2 cells inversely correlated with survival in human pancreatic cancer . an in vitro study revealed that the invasive capacity of human pancreatic cancer cells was based on the tlr4-dependent nf-b activation . another study correlated the level of tlr4 expression with tumor size , lymph node involvement , venous invasion and pathological stage . lipopolysaccharide ( lps ) is a well - established agonist of tlr4 and could be a triggering factor in the initiation and progression of pancreatic cancer [ 67 , 73 ] . lps , a putative ligand of tlr4 , may promote tumor progression by acting directly on cancer cells and increasing the invasive ability of pancreatic cancer cells through the tlr4/myd88 signaling pathway [ 72 , 74 ] . these results also suggest that the tlr / myd88/nf-b signaling pathway plays a significant role in connecting inflammation with cancer invasion and progression . in contrast , the lipid a analogue ( om-174 ) , with a dual stimulating effect on tlr2 and tlr4 receptors , induced regression of several tumor types in animal models [ 7577 ] . induction of myd88 and trif , downstream of tlr pathways , perturbed cell cycle regulation in pancreatic cancer . other data demonstrated that protein ( mrna ) expression of tlr4 , nf-b p65 and hif-1 ( hypoxia - inducible transcription factor 1 ) in pancreatic tumor tissues was increased by 69% , 66% and 70% , respectively , which was significantly higher compared to adjacent normal tissues . this indicated that tlr4 might be partly involved in up - regulating hif-1 , and they both could synergistically promote the development of pancreatic adenocarcinoma . another study suggested that tlr4 expression in pancreatic cancer cells was up - regulated via hif-1 in response to hypoxic stress and underscored the crucial role of hif-1-induced tlr4 in tumor growth . most studies have shown that increased expression of tlr4 is not limited to pancreatic cancer . toll - like receptors ( tlrs ) are involved in the development of infectious diseases , autoimmune and neurodegenerative diseases and cancer . tlr4 expression was also detected in head and neck cancer , breast cancer , lung cancer , gastric cancer , hepatocellular carcinoma , colorectal cancer , ovarian cancer , cervical cancer , prostate cancer and melanoma [ 58 , 62 ] . the results of these studies indicate that the evaluation of tlr4 expression does not differentiate cancerous tumors , which makes diagnosis and treatment difficult . toll - like receptor 2 ( tlr2 ) is a promising target for immune system stimulation during cancer immunotherapy and a cell - surface marker for pancreatic cancer . tlr2 stimulation may produce significant antitumor activity by enhancing the innate immunity , t - cell immunity , cytotoxic antibody function and induction of apoptosis [ 8082 ] . malp-2 ) , which activated tlr2 and tlr6 receptors , resulted in a significant tumor growth reduction in a mouse model . intratumoral injection of the toll - like receptor 2/6 agonist malp-2 , in a limited number of patients with pancreatic carcinoma , caused a decrease in pancreatic tumor proliferation and metastasis . another agonist of tlr2 receptor protein - bound polysaccharide - k ( psk , mushroom extract ) promoted apoptosis and inhibited tumor growth in various human pdac cell lines . it was found that tlr2 receptors were highly expressed in 70% of pancreatic tumors , but their expression was low in the surrounding normal pancreas tissue ; they were also found on tumor - infiltrated myeloid - derived suppressor cells ( mdsc ) and tumor - associated macrophages ( tam ) , which after activation promoted tumor expansion , invasion , and metastasis . interestingly , the disruption of tlr2-dependent antitumor pathways by pancreatic adenocarcinoma up - regulated factor ( pauf protein ) could contribute to tumor persistence and facilitate tumor growth [ 87 , 88 ] . treatment with anti - recombinant human pancreatic adenocarcinoma up - regulated factor in vitro and in vivo reduced proliferation , migration , invasion , and tumorigenic capacity . these findings suggest that the new cancer - associated ligand , pauf , may activate the tlr - mediated erk signaling to produce the pro - tumorigenic cytokines , but it inhibits the tlr - mediated nf-b signaling , thereby facilitating tumor growth . more specifically , pauf induces the extracellular signal - regulated kinase ( erk ) phosphorylation and activates the ikk--mediated tpl2/mek / erk signaling pathway through tlr2 and stimulates an increased expression of protumorigenic cytokines ( rantes , mif ) . in addition , pauf was also reported to be associated with the cxc chemokine receptor ( cxcr4)-tlr2 complex and to inhibit the cxcr4-dependent , tlr2-mediated nf-b activation . another study showed that pauf could induce the activation and maturation of dcs and activate nf-b by stimulating the toll - like receptor signaling pathway . the pauf - mediated dc activation and immune stimulation are dependent on tlr4 and provide evidence supporting that this protein could be a promising adjuvant for dc - based therapies . the expression of pauf was also elevated in ovarian tumors and it was found to be more frequently expressed in mucinous adenocarcinoma than in its benign and borderline counterparts , which was associated with a shorter overall survival of patients . novel high - affinity tlr2 agonists were synthesized to develop targeted agents for cancer imaging and therapy . the latter study demonstrated tumor - specific retention of a fluorescently labeled agonist ligand that could potentially be used for the intraoperative detection of pancreatic cancer cells . vaccination with tlr2-l slp conjugates led to the efficient induction of antitumor immunity in mice challenged with aggressive transplantable melanoma or lymphoma . these data show that tlr2-l slp conjugates are promising synthetic vaccine candidates for active immunotherapy against cancer . therefore , most of the presented studies , which were aimed at improving the outcomes of pancreatic cancer patient treatment , were focused on the activation of tlr2 receptor signaling pathways . fewer studies concerned the tlr3 , tlr7 and tlr9 receptors , expressed intracellularly on endosomal membranes of several types of immune cells ( mainly apcs , leukocytes ) , e.g. , macrophages , b cells and dcs . these receptors recognize dinucleotides ( cpg motifs ) found in bacteria and viruses . the activation of stat3 and notch receptors through nfb and mapk contribute to the aggressive tumor phenotype induced by tlr7 activation . chimeric mice with tlr4/ or tlr7/ bone marrows were partially protected from pancreatic carcinogenesis [ 19 , 34 ] . furthermore , tlr2 , tlr7 and tlr9 were shown to be involved in the initiation of type 1 diabetes mellitus and tlr2 , tlr4 played a major role in the onset of type 2 diabetes mellitus . in addition , peroxisome proliferator activated receptor- ( ppar ) , which is a nuclear receptor transcription factor implicated in the regulation of metabolism , differentiation and inflammation , was also involved in pdac , which made it an interesting target for pharmacological prevention of pdac in obese and diabetic patients . tlr7 was found to be highly expressed both in inflammatory ( in 40 - 65% of the tumor microenvironment cells ) and cancer cells ( in 50% of the advanced tumors ) and the role of tlr7 in pancreatic cancer was also reported [ 51 , 90 ] . for instance , tlr7 was reported to regulate pancreatic carcinogenesis in mice and humans , while tlr7 activation induced a loss of the p16/ink4a gene that is commonly mutated in human pdac at a relatively early stage . in that study , cancer aggressiveness induced by tlr7 agonists was associated with higher expression of cyclin b1 , the c - myc oncoprotein and the anti - apoptotic bcl - xl protein . the decrease in cyclin d1 , pten , p16 along with the up - regulation of several other tumor - suppressor proteins , such as p53 , p21/waf , prb or p27/ kip1 was also observed . interestingly , both kras mutations and tlr7 stimulation are necessary for malignant transition . in addition , tlr7 ligation was shown to induce stat3 activation and interfere with notch as well as canonical nf-b and map kinase pathways , but the down - regulated expression of notch target genes and blockade of tlr7 protected against carcinogenesis . the therapeutic mechanism of tlr7 agonist ( imiquimod ) was associated with the activation of immune cells involved in an effective antitumor immune response b lymphocytes , plasma cells , nk and langerhans cells . treatment with imiquimod down - regulated mhc class i molecules on tumor cells and these results indicated that the stimulation of tumor cells with tlr3 or tlr7 ligands enhanced the cytotoxic activity of t cells of cancer patients in vitro . as recently presented in the pdac cell line , the enhanced cox-2 expression and increased release of the cox-2 metabolite , prostaglandin e2 ( pge2 ) , promoted resistance against t cell - mediated lysis ; in addition , the application of tribody [ ( her2)2 v9 ] that enhances t - cell cytotoxicity , and cox-2 inhibitors that overcome the pge2-mediated resistance of pdac cells to the cytotoxic activity of t cells , might offer a promising combined immunotherapy for pancreatic cancer . a recent study demonstrated that tlr7 and tlr8 were highly expressed by the primary human ductal pancreatic cancer and tlr7/tlr8 expression increased tumor growth in vivo . stimulation of panc1 cells overexpressing tlr7/tlr8 resulted in elevated nf-b and cox-2 expression , increased cancer cell proliferation and reduced chemosensitivity . these data demonstrate stage - dependent up - regulation of both tlr7 and tlr8 expression in pancreatic cancer . tlr9 was shown to signal through the myd88-dependent pathway , leading to the production of pro - inflammatory cytokines , but the participation of tlr9 is better known in acute pancreatitis than in pancreatic cancer . the expression of tlr9 was shown to be more pronounced in pancreatic cancer tissue and the tlr9 gene was found to be correlated with the invasive and metastatic potential of human pancreatic carcinoma . the percentage of positive cells expressing tlr9 protein in human pancreatic tissues , paracancerous tissues and normal tissues was 73.3% , 33.3% and 20.0% , respectively . in acute pancreatitis , a similar pattern of staining in exocrine pancreas was reported for tlr4 . on the other hand , tlr2/4/9 agonists seemed to be good candidate molecules prolonging survival in patients with different types of cancer by inducing the expression of tumor necrosis factor ( tnf- ) and inducible nitric oxide synthase ( inos ) that activate dendritic cell trafficking and its associated tumor - specific cytotoxic t - cell responses [ 103106 ] . evaluation of the efficacy of the iscom ( immune stimulatory complexes)vaccine in a murine pancreatic carcinoma model revealed that the iscom vaccine effectively induced ag - specific ctl capable of killing tumor cells , but did not affect tumor growth , and this lack of efficacy was correlated with increased numbers of treg . it should be emphasized that when the authors of the latter study depleted treg with anti - cd25 mab , ctl induction and prolonged survival was restored , and adding a low - dose of cpg to the iscom vaccine reduced the number of treg , enhanced ctl responses and initiated regression of pancreatic tumors in a cd8(+ ) t cell - dependent manner . interestingly , concomitant gemcitabine therapy negatively affected dc vaccine - induced cd8(+ ) t - cell and b - cell responses , but improved clinical efficacy in a murine pancreatic carcinoma model . despite the reduced number of tumor - reactive t - cells in peripheral blood , in vivo cytotoxicity assays revealed that the cytotoxic t - cell ( ctl)-mediated killing was preserved . another study showed that immunomodulatory oligonucleotide ( imo ) , tlr9 agonist , interfered with egfr - dependent signaling ( overexpressed in 50 - 60% of human pancreatic adenocarcinoma ) , modulating the functional interaction between tlr9 and egfr , and markedly inhibited the growth of k - ras mutant colon and pancreatic cancers in vitro [ 109 , 110 ] . furthermore , imo and cetuximab combination caused a potent and long - lasting cooperative antitumor activity in colorectal cancer and in orthotopic pancreatic cancer models in vivo . in an orthotopic mouse model of a human pancreatic tumor xenograf , the antitumor chemotherapy effects ( gemcitabine ) these studies showed that the tumor spread in the peritoneal cavity was reduced to a greater extent in combined therapy than with gemcitabine alone , and it significantly improved the survival time . considering the fact that the body of evidence is still limited , it is impossible to conclude whether tlr3 and tlr9 play an important role in patients with pancreatic cancer . similarly as tlr2 and tlr4 , tlr3 is expressed in various tumors , including colorectal , ovarian , breast , hepatocellular , laryngeal cancer and melanoma [ 112115 ] . the tlr3 gene codes for an endoplasmic receptor of the pattern - recognition receptors ( prrs ) family that recognizes double - stranded rna ( dsrna ) and plays an important role in the innate immune response triggered by viral infection . several studies demonstrated that activation of tlr3 by dsrna directly inhibited cell proliferation and induced apoptosis in tumor cells [ 116118 ] . synthetic dsrnas ( e.g. , polyinosine - cytosine , poly i : c ; polyadenylic - polyuridylic , poly a : u ) were demonstrated to be one of the agents in tumor chemotherapy demonstrating favorable outcome in clinical trials . tlr3 agonist ( polycytidylic acid ) was found to induce lysis of pancreatic cancer cell lines by enhancing the cytotoxic activity of t cells in vitro , but this agonist could also acceleratepancreatic carcinogenesis in kras - mutated mice . the presence of constitutively activated tlr3/wnt5a expression in human pancreatic cancer and malignant melanoma cell lines was decreased by phenylmethimazole , which in turn inhibited the growth and migration in both of these cancer cell lines . in colon carcinoma , cell line anticancer drugs ( e.g. , 5-fu ) increased the tlr3 expression and intensified the poly i : c - induced apoptosis via p53-dependent and -independent pathways . the results of other studies suggested that ifn- enhanced tlr3-mediated antiviral cytokine expression in human endothelial and epithelial cells by up - regulating tlr3 expression . recent data indicated that mucin1 cytoplasmic tail ( muc1-ct ) , a negative regulator of tlr inflammatory signaling mediated through the myd88 adaptor protein , was able to counter - regulate the apoptotic and inflammatory responses of airway epithelial cells through the constitutive association with tlr3 , thereby inhibiting poly(i : c)-induced recruitment of trif to tlr3 . muc1 is a membrane - tethered mucin glycoprotein expressed on the apical surface of mucosal epithelial cells and was originally cloned in pancreatic cancer cells . overexpression of muc1 in cancer is caused by the increased gene dosage and the level of transcription , as well as by the loss of post - transcriptional regulation ; muc1 overexpression leads to metastasis and poor prognosis in pancreas cancer patients . importantly , by targeting the egf receptor(s ) , the stat1 axis attenuates tumor growth and metastasis through down - regulation of the muc4 mucin in human pancreatic cancer . in those studies , canertinib or afatinib therapy resulted in a reduction of muc4 ( muc4 mucin de novo expression occurs in 70 - 90% of pancreatic cancer patients)and abrogation of in vitro and in vivo oncogenic functions of muc4 in pancreatic cancer cells . furthermore , canertinib and afatinib treatment also inhibited the proliferation , migration and survival of pancreatic cancer cells by attenuating signaling molecules , including perk1/2 ( t202/y204 ) , cyclin d1 , cyclin a , pfak ( y925 ) and pakt ( ser473 ) . unfortunately , the low level of serum muc4 limits its diagnostic / prognostic potential , however , the present data open a new range of therapeutic applications for tlr3 agonists as cytotoxic agents and for efficient drug delivery in selected cancers with specific tumor markers . research aimed to elucidate the mechanisms underlying the development of pancreatic cancer drew attention also to other innate immunity receptors / protein signaling pathways . it has been shown that bacterial flagellin is a natural ligand of tlr5 receptor , which is also an attractive candidate for therapeutic targeting in cancer . bacterial flagellin and flagellin - expressing bacteria ( salmonella ) exhibited antitumor effects in mouse models of colon and liver metastasis of pancreatic cancer , although these effects required tlr5 expression by the tumor cells and production of cytokines ( g - csf , il-6 , il-8 , and il-10 ) by cells recruited to the tumor [ 130 , 131 ] . the results of a recent study have defined the liver as a key mediator of tlr5-dependent effects in vivo and suggested clinical applications for tlr5 agonists as hepatoprotective and antimetastatic agents . in a mouse xenograft model of human breast and colon cancer cells , tlr5 activation by flagellin mediated innate immune response induced a potent antitumor activity that suppressed cell proliferation and inhibited tumor growth [ 133 , 134 ] . in addition , it was shown that tlr5 was also highly expressed on gastric carcinoma cells , and those authors found that the expression of tlrs ( tlr4 , tlr5 , tlr9 ) enabled gastric carcinoma cells to interact with h. pylori . moreover , other findings suggest that genetic polymorphisms in tlr2 and tlr5 may play important roles in the process of h. pylori - related gastric carcinogenesis . to date , the specific function and detailed mechanism of tlr5 signaling pathways in the development of pancreatic cancer are still unknown . among the genes involved in innate antibacterial signaling pathways that affect the development of pancreatic cancer , hmgb1 and traf6 are important in the regulation of the local inflammatory response . hmgb1 is one of the most characteristic genes deregulated in solid tumor tissue and serum , including pancreatic cancer [ 137 , 138 ] . studies in cell lines showed that hmgb1 was strongly up - regulated in breast cancer , colon cancer , melanoma , pancreatic cancer and prostate cancer ; up - regulated hmgb1 activated tlr2 and tlr4 expressed on immune cells and induced cancer progression and metastasis . moreover , hmgb1 and s100a9 two damps that bind tlr4 were detected in the pancreas of pdac patients . the serum level of hmgb1 showed a tendency to increase with the progression of gastric and pancreatic cancers and is considered a powerful diagnostic biomarker for pancreatic ductal adenocarcinoma [ 137 , 140 ] . hmgb1 overexpression was associated with tumor progression and poor prognosis in pancreatic cancer and was an independent prognostic indicator for patients survival . overexpression of hmgb1/rage ( receptor for advanced glycation end products ) was associated with reduced apoptosis and prolonged cancer cell survival . the hmgb1/rage inflammatory pathway was demonstrated to promote pancreatic tumor growth by regulating mitochondrial bioenergetics . the lack of rage , or inhibition of hmgb1 release , diminished the production of atp and slowed tumor growth in vitro and in vivo . an experimental study showed that traf6 ( tnf receptor - associated factor 6 ) acted as an oncogene , which was important for ras - mediated oncogenesis and provided a mechanistic explanation for the already apparent importance of constitutive nf-b activation in the ras - driven lung cancer . the nuclear transcription factor-b rela was also found to be constitutively activated in human pancreatic adenocarcinoma cells . the participation of the traf6 gene in the pathogenesis and progression of pancreatic cancer is not clear . tumor necrosis factor receptor - associated factor 6 is an adapter protein involved in the activation of the tlr - mediated nuclear factor-b ( nf-b ) signaling pathway that induces the production of pro - inflammatory cytokines . traf6 as a part of signaling complex ( myd88-irak4-irak1-traf6 ) is required for the pro - inflammatory cytokine production induced by tlr7 and tlr9 signaling . traf6 was shown to up - regulate the expression of hypoxia - inducible factor ( hif-1 ) and promote tumor angiogenesis . however , it was demonstrated that poor vascularization was a characteristic feature of pancreatic cancer . the expression of traf6 was up - regulated in pancreatic cancer tissues and over - expression of traf6 in pancreatic cancer cells promoted cell proliferation and migration , whereas down - regulation of traf6 impaired the tumorigenicity of pancreatic cancer cells in vitro and in vivo . these results suggested that traf6 might represent a potential therapeutic target . in an orthotopic xenograft model of scid mice , a combination of proteasome inhibitor ( mg132 ) and ionizing radiation therapy resulted in a significant increase in the tumor growth delay and a decreased tumor tissue expression of traf6 . additionally , we have recently proposed that overexpression of tlr4 , nod1 and traf6 genes and lower myd88 gene expression in peripheral blood leukocytes of patients with pancreatic cancer , could contribute to chronic inflammation and tumor progression by the up - regulation of the innate antibacterial response ( e.g. , to lps ) . although the evidence suggesting carcinogenic and therapeutic effects of stimulation or inhibition of tlrs is increasingly growing , it still remains unclear what kind of changes in gene expression of the tlr signaling pathways in leukocytes are associated with pancreatic cancer . the results of our study clearly indicated an abnormal gene expression in the innate antibacterial signaling pathways in peripheral blood leukocytes of patients with pancreatic cancer , which might lead to leukocyte dysfunction . we postulate that the pathologic gene expression of receptors and proteins regulating the innate antibacterial response to various stimuli must be primarily included in the analysis of a multistep sequence of events leading to the development and progression of pancreatic cancer . in our opinion , the adjuvant therapy of pancreatic cancer should also focus on the regulation of gene expression in peripheral blood leukocytes . hypothetically , the influx and recruitment of leukocytes to the tumor microenvironment with the formation of inflammatory infiltration may facilitate cancer cell escape from the control of the immune system in poorly defined mechanisms , for instance , chronic inflammation and immune suppression in the tumor microenvironment with immune responses mediated by treg , dendritic cells , mdscs ( myeloid - derived suppressor cells ) and th17 cells , mmps - matrix metalloproteinases and hif--hypoxia - inducible transcription factor overexpression or increased production of il-10 and h2o2 . changing the microenvironment of the tumor cells by regulating the expression of genes encoding proteins of the innate antibacterial signaling pathway ( e.g. , using immunonutrition ) in leukocytes infiltrating the tumor cells is a novel therapeutic approach ( fig . 1 ) . this applies to both the main tumor mass , which can not always be removed surgically , and micrometastases that are beyond the reach of diagnostic tests . furthermore , the assessment of the gene expression profile in leukocytes can be useful for monitoring the course of disease and genetic effectiveness of the treatment . our previous study in a small group of malnourished pancreatic cancer patients with overexpression of the tlr4 gene in peripheral blood leukocytes revealed that enteral supplementation of glutamine ( diet consisting of 20 g glutamine per day ) could decrease tlr4 expression within five days prior to surgery . this surprising effect of immunonutrition in pancreatic cancer patients could be associated with a decrease in the amount of stimulants reaching the tlr4 receptor ( e.g. , by blocking lps or damps damage - associated molecular pattern molecules , interacting with tlr4 receptor ) . an experimental study showed that enteral administration of glutamine reduced the elevated expression of tlr4 , signal adaptor protein myd88 and traf6 mrna in the intestinal mucosa in response to lps - induced endotoxemia in rats . investigations on the effect of this treatment on the number of infectious complications and course of the disease are in progress . it is also known that fatty acids ( omega-3 ) can have a selective inhibitory effect on the signaling cascade related to the innate antibacterial response by blocking the interaction of endotoxin with the tlr4 receptor and intracellular signaling proteins . similar studies in patients with pancreatic cancer have not been performed , but it is well recognized that glutamine is an important fuel ( nitrogen donor in nucleotide and amino acid biosynthesis ) for the growth of tumor cells . other studies suggested that inhibiting lps - induced tlr4 signaling ( e.g. , by eritoran / e5564 , tlr4 small molecule antagonist ) could improve therapeutic outcomes by preventing cancer metastasis during the perioperative period of colorectal cancer resection . using a unique ability of pancreatic cells to accumulate omega-3 fatty acids , epa and dha were found to induce ros accumulation and caspase-8-dependent cell death in human pancreatic cancer cells ( mia - paca-2 and capan-2 ) in vitro . previous studies demonstrated that epa inhibited the proliferation of all human pancreatic cancer cell lines in a dose - dependent fashion , and apoptosis was found to be associated with the activation of caspase-3 and suppression of cyclo - oxygenase-2 expression . polyunsaturated fatty acids ( pufas ) induced apoptosis also in normal gastric and gastric carcinoma cells . most studies showed that pufas caused selective cytotoxicity towards cancer cells via apoptosis , little or no toxicity to normal cells and potentially increased the sensitivity of tumor cells to conventional therapies . a promising phase iii trial demonstrated that intravenous -3 fas in combination with gemcitabine improved the activity and quality of life ( qol ) in patients with advanced pancreatic cancer . moreover , the tlr4 protein and mrna level were markedly down - regulated by pufa 1 : 1 compared with sfa , however , rats fed the pufa 1 : 4 diet failed to exhibit these changes . these data highlight the role of the pufa 1 : 1 diet in the prevention of obesity and related metabolic disorders by suppressing the activation of tlr4 , a critical modulator of pro - inflammatory cytokines . an additional nutritional therapy reducing the expression of tlr4 on tumor cells would probably also inhibit its growth and local inflammation in patients with pancreatic cancer , but these mechanisms are not fully understood . a better known mechanism of omega-3 fatty acid action applies to their pro - apoptotic and anti - inflammatory activity on tumor cells ( e.g. , regulation of bcl-2 , bax and c - myc , and effects on lipids metabolism ) [ 161163 ] . tissue samples derived from patients with head and neck , esophageal , gastric , colorectal , liver , pancreatic , skin , breast , ovarian , cervical , and breast cancer were shown to express increased amounts of tlr4 , indicating that modulation of the tlr4 signaling pathway would have a beneficial effect on most common cancers . schematic diagram of tlr4 , myd88 and traf6 down - regulation following glutamine administration in lps - stimulated peripheral blood leukocytes of pancreatic cancer patients . n-3 pufas inhibition of tlr signaling pathway at the extracellular ( dha interfere with tlr4 receptor ) and intracellular level : inhibition of the phosphorylation and degradation of the ib , inhibition of the nf-b activation and inflammatory cytokines production apart from tlrs , a significant role in the recognition of pathogen - related molecular patterns and regulation of the innate antibacterial response is also played by other proteins belonging to the pathogen - associated molecular pattern ( pamp ) receptors , including peptidoglycan recognition proteins , cytosolic nod ( nucleotide - binding oligomerization domain ) proteins and trem1 receptor ( triggering receptor expressed on myeloid cells 1 ) . both tlr and nlr pathways are mediated through different adaptor proteins , but they are commonly found to activate the nf-b , which induces the expression of proinflammatory cytokines . the nucleotide - binding oligomerization domain is expressed in a wide variety of cell types of both hematopoietic and non - hematopoietic origin . proteins with this domain ( e.g. , nlrs nod - like receptors : nod1 , nod2 ) possess the ability to bind lps and bacterial peptidoglycan ; they can also transmit a signal independently of tlrs , which also results in nf-b activation and stimulation of the expression of cytokine - coding genes ( for nod1 : tnf- and il-6 , and for nod2 : tnf- and il-1 ) and adhesive molecules . nod1 recognizes the compounds ( meso - diaminopimelic acid with peptidoglycan ) of gram - negative and some gram - positive bacteria , whereas muramyl dipeptide is the ligand for nod2 , derived from the wall of gram - positive and gram - negative bacteria [ 169 , 170 ] . nod - like signaling is involved in the regulation of immune homeostasis in the gut . nod2 deficiency in mice could lead to a compromised epithelial barrier and impaired immune response to commensal microbiota . in turn , nod1 deficiency resulted in increased tumor formation associated with the inflammation of the colon in mice . nod1 and nod2 are involved in the pathogenesis of diabetes , presumably through the recognition of the gut microbiota . it was reported that a nod2 gene mutation might be also a predisposing factor for colorectal cancer characterized by a higher average age of disease onset in subjects who do not harbor any other genetic predisposition to the disease . polymorphisms in nod1/card4 and nod2/card15 genes may shift the balance between pro- and anti - inflammatory cytokines , thereby modulating the risk of infection , chronic inflammation and cancer . nod1/card4 and nod2/card15 gene polymorphisms may be associated with altered risk of gastric , colorectal , breast , ovarian , prostate , testicular , lung , laryngeal , liver , gallbladder , biliary tract , pancreatic , small bowel , kidney , urinary bladder and skin cancer as well as non - thyroid endocrine tumors , lymphoma and leukemia . in another meta - analysis , nod2 rs2066844 c / t , rs2066845 c / g and rs2066847 ( 3020insc ) polymorphisms were potentially associated with an increased cancer risk ; moreover , in the cancer type subgroup analysis , the insc / insc+insc/2 genotype was significantly associated with an increased risk of colorectal cancer , gastric cancer , malt lymphoma , breast cancer , lung cancer and laryngeal cancer , but not with urogenital cancer , pancreatic cancer , melanoma and non - hodgkin lymphoma . furthermore , signaling pathway analyses in a genome - wide association study ( data from 3,851 pancreatic cancer cases ) revealed that the nod1 gene was associated with the risk of pancreatic cancer ( h. pylori further , large - scale and well - designed studies are still needed to confirm the relationship between the nod gene expression and the risk of pancreatic cancer . the results of the studies on the various markers in peripheral blood are strongly affected , i.a . , by local disorders of the innate and acquired immune response . increased expression of biomarkers in peripheral blood reflects a variety of metabolic / immune / genetic disorders associated with both host and tumor defence reactions . these disorders are conducive to the escape of cancer cells out of control of the immune system , they inhibit the response to cancer cells and enhance the status of tolerance / immunosuppression . of significant importance in this process is simultaneously increasing lack of energy substrates , hypoxia of the pancreas tumor tissue caused by poor vascularization and increasing tumor activity accompanied by changes in the number and activity of tumor - infiltrating cell . most frequently , local change of immunity includes : lymphocyte / neutrophil ratio , changes in subpopulations of t cells ( treg , tc , th1/th2 , cd8 + , cd45ro+ density ) , dendritic cells , myeloid suppressor cells ( mdsc ) , m1/m2 macrophages , growth factors ( e.g. , egf , fgf , vegf ) or cytokines ( e.g. il-5 , 6 , 10 , 13 ) ; these changes are not specific to pancreatic cancer , as they are also found in other gastrointestinal tract cancers [ 178181 ] . in pancreatic cancer patients , local cellular immunity disorders ( e.g. , high or low lymphocyte density in cancer infiltration ) have a significant impact on survival . on the other hand , studies of cellular immunity disorders in the peripheral blood showed that mdscs and tregs were statistically significantly elevated in pancreatic , esophageal and gastric cancer compared with controls . moreover , elevated mdsc percentage was associated with an increased risk of death , while in a multivariate analysis , mdsc level was an independent prognostic factor for survival . these studies highlighted basic mechanisms inhibiting or promoting tumor growth , with particular emphasis on their practical diagnostic and therapeutic significance . as demonstrated by the presented works , in order to increase the effectiveness of methods for early detection of disorders leading to the development of pancreatic cancer , first of all , the knowledge of the local mechanisms regulating signaling pathways associated with innate antibacterial response should be broadened . it should be emphasized that disorders of innate antibacterial response are of fundamental importance in the development of gastrointestinal cancers , including pancreatic cancer . in interpreting the results of disorders of the innate antibacterial immunity mechanisms , the nutritional status of patients and peripheral cellular immunity disorders ( e.g. , lymphocyte - related apoptosis ) previously cited research results indicate that the number of lymphocytes in tumor infiltration ( especially the density of tumor infiltrating effector cells ) is reduced compared to neutrophils , which is of important prognostic significance . in most studies , the problem of nutritional status disorders of patients ( lack of nutritional substances for the proper functioning of the immune system ) is omitted , although it is known that malnutrition is an inherent factor associated with gastrointestinal tract cancers worsening the prognosis . nutritional deficiencies should be compensated in these patients by appropriate nutritional therapy , which may have a beneficial effect on changing the tumor environment and cancer cells metabolism . metabolic reprogramming is linked to the activation of oncogenes but also to the inhibition of tumor suppressor genes . interestingly , human pancreatic ductal adenocarcinoma cells rely on a different metabolic pathway than normal pancreatic cells , and , for example in cancer cells , glutamine - derived aspartate is transported into the cytoplasm where it can be converted into oxaloacetate by aspartate transaminase . furthermore , these studies show that the reprogramming of glutamine metabolism is mediated by oncogenic kras , the signature genetic alteration in pdac , through the transcriptional upregulation and repression of key metabolic enzymes in this pathway . in a recent study , targeting the glutamine metabolism sensitized pancreatic cancer to the parp - driven metabolic catastrophe induced by -lapachone , which is an nadph : quinone oxidoreductase ( nqo1)-bioactivatable drug that leads to nadph depletion ( nqo1 expression it should also be noted that in comparison to other cells , pancreatic cancer cells have a unique property of polyunsaturated fatty acid ( omega-3 ) accumulation , which allows to induce apoptosis in them . additionally , these data also suggest that treating pancreatic cancer cells with omega-3 fatty acid alone , or in combination with gemcitabine , result in an increased inhibition of proliferation , and the mechanism of this inhibition is related to apoptosis progression . dysregulation of signaling pathways associated with innate antibacterial immunity is important factor playing a crucial role in pathogenesis , development , prognosis and therapy of pancreatic cancer . the increased interest in this line of research stems mainly from an elevated expression of tlrs and signaling pathway proteins associated with these receptors in pancreatic cancer cells when compared with healthy pancreatic gland . the most interesting are multi - regulatory properties of the tlr receptors ( e.g. , regulation of proliferation , the activity of nf-b , gene transcription of apoptosis proteins , regulation of angiogenesis , hif-1 protein expression ) used in experimental studies to better understand the pathogenesis of pancreatic cancer ( assessment of bacterial factor participation ) and the possibility of therapeutic intervention . this is supported by a number of examples of agonists discussed here ( e.g. , tlr2/5 ligands , tlr6 , tlr9 ) exhibiting antitumor activity , although parallel stimulation of other tlrs ( tlr7/tlr8 ) produced the opposite effect , while reducing the sensitivity of the tumor to chemotherapy . on the other hand , it appeared that blocking selected tlrs ( tlr4 , tlr7 ) could inhibit the development of mouse and human pancreatic cancer cells , while inhibiting the myd88 signaling pathway in dendritic tumor - infiltrating cells paradoxically stimulated the development of pancreatic cancer . the direction of these studies is promising , but the small number of them does not allow for an accurate assessment of the impact of expression disorders of tlrs , proteins of these signaling pathways , or attempts to block or stimulate them , on the results of treatment of pancreatic cancer patients . it is still difficult to determine whether these disorders may precede the development of pancreatic cancer or whether the discussed parameters can be used as early markers . it is known , however , that the expression disorders of proteins of innate antibacterial response signaling pathways occur not only in tumor tissue but also in peripheral blood leukocytes of pancreatic cancer patients ( e.g. , increased expression of tlr4 , nod1 , traf6 ) , which is one of the most important factors facilitating further tumor development . new hopes for the improvement of pancreatic cancer treatment are associated with genetic testing of microrna expression changes , the aim of which is to better understand the pathogenesis as well as diagnostic and therapeutic possibilities . micrornas are small non - coding rnas ( 19 - 24 nucleotides long ) that regulate gene expression by affecting translation of messenger rna . micrornas are aberrantly expressed in many tumors and elicit oncogenic or tumor - suppressive functions . importantly for cancer diagnosis and better understanding of their pathogenesis , altered expression of micrornas can be determined in the serum and tumor tissues , including paraffin sections . similarly to investigating cell infiltrations of pancreatic tumor , the assessment of changes in the expression of micrornas can be a valuable complement to the routine tests ( e.g. , immunohistochemistry ) . micrornas mediate signaling network of apoptosis pathways and down - regulation of mutationally activated oncogenic kras and its downstream signaling pathways in pdac . a large body of evidence has revealed dysregulation of mirnas in pdac , ipmn and panin lesions , suggesting their use as biomarkers for early diagnosis of pancreatic cancer .

disorders of innate antibacterial response are of fundamental importance in the development of gastrointestinal cancers , including pancreatic cancer . multi - regulatory properties of the toll - like receptors ( tlrs ) ( e.g. , regulation of proliferation , the activity of nf-b , gene transcription of apoptosis proteins , regulation of angiogenesis , hif-1 protein expression ) are used in experimental studies to better understand the pathogenesis of pancreatic cancer , for early diagnosis , and for more effective therapeutic intervention . there are known numerous examples of tlr agonists ( e.g. , tlr2/5 ligands , tlr6 , tlr9 ) of antitumor effect . the direction of these studies is promising , but a small number of them does not allow for an accurate assessment of the impact of tlr expression disorders , proteins of these signaling pathways , or attempts to block or stimulate them , on the results of treatment of pancreatic cancer patients . it is known , however , that the expression disorders of proteins of innate antibacterial response signaling pathways occur not only in tumor tissue but also in peripheral blood leukocytes of pancreatic cancer patients ( e.g. , increased expression of tlr4 , nod1 , traf6 ) , which is one of the most important factors facilitating further tumor development . this review mainly focuses on the genetic aspects of signaling pathway disorders associated with innate antibacterial response in the pathogenesis and diagnosis of pancreatic cancer .

SECTION 1. SHORT TITLE; REFERENCES. (a) Short Title.--This Act may be cited as the ``Natural Disaster Student Aid Fairness Act''. (b) References.--References in this Act to ``the Act'' are references to the Higher Education Act of 1965 (20 U.S.C. 1001 et seq.). SEC. 2. ALLOCATION AND USE OF CAMPUS-BASED HIGHER EDUCATION ASSISTANCE. (a) Waiver of Matching Requirements.--Notwithstanding sections 413C(a)(2), 443(b)(5), and 463(a)(2) of the Act (20 U.S.C. 1070b- 2(a)(2); 42 U.S.C. 2753(b)(5); 20 U.S.C. 1087cc(a)(2)), with respect to funds made available for academic years 2004-2005 and 2005-2006-- (1) in the case of an institution of higher education located in an area affected by a Gulf hurricane disaster, the Secretary shall waive the requirement that a participating institution of higher education provide a non-Federal share or a capital contribution, as the case may be, to match Federal funds provided to the institution for the programs authorized pursuant to subpart 3 of part A, part C, and part E of title IV of the Act; and (2) in the case of an institution of higher education that has accepted for enrollment any affected students, the Secretary may waive that matching requirement after considering the institution's student population and existing resources, using consistent and objective criteria. (b) Waiver of Reallocation Rules.-- (1) Authority to reallocate.--Notwithstanding sections 413D(d), 442(d), and 462(I) of the Act (20 U.S.C. 1070b-3(d); 42 U.S.C. 2752(d); 20 U.S.C. 1087bb(I)), the Secretary shall-- (A) reallocate any funds returned under any of those sections that were allocated to institutions of higher education for award year 2004-2005 to an institution of higher education that is eligible under paragraph (2) of this subsection; and (B) waive the allocation reduction for award year 2006-2007 for an institution returning more than 10 percent of its allocation under any of those sections. (2) Eligible institutions for reallocation.--An institution of higher education may receive a reallocation of excess allocations under this subsection if the institution-- (A) participates in the program for which excess allocations are being reallocated; and (B)(i) is located in an area affected by a Gulf hurricane disaster; or (ii) has accepted for enrollment any affected students in academic year 2005-2006. (3) Basis of reallocation.--The Secretary shall determine the manner in which excess allocations shall be reallocated to institutions under paragraph (1), and shall give additional consideration to the needs of institutions located in an area affected by a Gulf hurricane disaster. (4) Additional waiver authority.--Notwithstanding any other provision of law, in order to carry out this subsection, the Secretary may waive or modify any statutory or regulatory provision relating to the reallocation of excess allocations under subpart 3 of part A, part C, or part E of title IV of the Act in order to ensure that assistance is received by affected institutions for affected students. (c) Availability of Funds Date Extension.--Notwithstanding any other provision of law-- (1) any funds available to the Secretary under sections 413A, 441, and 461 of the Act (20 U.S.C. 1070b; 42 U.S.C. 2751; 20 U.S.C. 1087aa) for which the period of availability would otherwise expire on September 30, 2005, shall be available for obligation by the Secretary until September 30, 2006 for the purposes of the programs authorized pursuant to subpart 3 of part A, part C, and part E of title IV of the Act, respectively; and (2) the Secretary may recall any funds allocated to an institution of higher education for award year 2004-2005 under section 413D, 442, or 462 of the Act that, if not returned to the Secretary as excess allocations pursuant to any of those sections, would otherwise lapse on September 30, 2005, and reallocate those funds in accordance with subsection (b)(1). SEC. 3. EMERGENCY DESIGNATION. Section 2 of this Act is designated as an emergency requirement pursuant to section 402 of H. Con. Res. 95 (109th Congress). SEC. 4. TERMINATION OF AUTHORITY. The provisions of this Act shall cease to be effective one year after the date of the enactment of this Act. SEC. 5. DEFINITIONS. In this Act: (1) Secretary.--The term ``Secretary'' means the Secretary of Education. (2) Affected student.--The term ``affected student'' means an individual who has applied for or received student financial assistance under title IV of the Act, and who-- (A) was enrolled or accepted for enrollment, as of August 29, 2005, at an institution of higher education in an area affected by a Gulf hurricane disaster; (B) was a dependent student enrolled or accepted for enrollment at an institution of higher education that is not in an area affected by a Gulf hurricane disaster, but whose parents resided or were employed, as of August 29, 2005, in an area affected by a Gulf hurricane disaster; or (C) suffered direct economic hardship as a direct result of a Gulf hurricane disaster, as determined by the Secretary using consistent and objective criteria. (3) Gulf hurricane disaster.--The term ``Gulf hurricane disaster'' means a major disaster that the President declared to exist, in accordance with section 401 of the Robert T. Stafford Disaster Relief and Emergency Assistance Act (42 U.S.C. 5170), and that was caused by Hurricane Katrina or Hurricane Rita. (4) Area affected by a gulf hurricane disaster.--The term ``area affected by a Gulf hurricane disaster'' means a county or parish, in an affected State, that has been designated by the Federal Emergency Management Agency for disaster assistance for individuals and households as a result of Hurricane Katrina or Hurricane Rita. (5) Affected state.--The term ``affected State'' means the State of Alabama, Louisiana, Mississippi, or Texas. (6) Institution of higher education.--The term ``institution of higher education'' has the meaning given that term in section 102 of the Higher Education Act of 1965 (20 U.S.C. 1002). Speaker of the House of Representatives. Vice President of the United States and President of the Senate.

Natural Disaster Student Aid Fairness Act - Authorizes, and in certain cases requires, the Secretary of Education to waive certain matching funds requirements and reallocation rules, and to extend the availability of certain funds, with respect to campus-based student assistance programs under the Higher Education Act of 1965, for institutions of higher education that: (1) are located in areas affected by a Gulf hurricane disaster caused by Hurricane Katrina or Hurricane Rita; or (2) have accepted for enrollment any students who were affected by such disaster. States that such students may be affected by reason of: (1) having been enrolled or accepted by an institution in the affected area; (2) being dependent on parents residing or employed in such an area; or (3) having suffered direct economic harm as a direct result of such disaster, as determined by the Secretary using consistent and objective criteria.

bootstrap percolation was originally introduced by chalupa , leath and reich @xcite in the context of magnetic disordered systems in 1979 . since then , it has been studied extensively by physicists and sociologists , mainly due to its connections with various physical models and a variety of applications such as neuronal activity @xcite and jamming transitions @xcite . bootstrap percolation can be essentially considered as an activation process on networks : ( ) nodes are either active or inactive ; ( ) once activated , a node remains active forever ; ( ) initially , each node is in an active state with a given probability @xmath5 ; ( ) subsequently , inactive nodes become active if they have at least @xmath6 active neighbors ; ( ) nodes are activated in an iterative manner according to the condition in ( ) , until no more nodes can be activated . this process has been investigated on different kinds of networks including lattices @xcite , trees @xcite , random networks @xcite , and so on . bootstrap percolation has found applications in modeling the spreading of information @xcite , the propagation of infection @xcite , the adoption of new products and social behaviors @xcite such as trends , fads , political opinions , belief , rumors , innovations and financial decisions . for instance , one may decide to buy a product when recommended by more than @xmath6 users and trust a message when told by at least @xmath6 neighbors ; cf . the well - known rule , `` what i tell you three times is true '' @xcite . in this way , the process leads initially localized effects propagating throughout the whole network . moreover , a broad range of generalized formulations of bootstrap percolation on social networks are investigated , such as watts model of opinions @xcite , in which @xmath6 is replaced by a certain fraction of the neighbors , and disease transmission models with different degrees of severity of infection @xcite . real networks are often embedded in space @xcite and social networks are no exception . previous empirical studies on online social networks @xcite , email networks @xcite and mobile phone communication networks @xcite have confirmed a spatial scaling law , namely , the probability density function ( pdf ) of an individual to have a friend at distance @xmath0 scales as @xmath1 , @xmath7 @xcite . in fact , prior to these empirical observations , kleinberg @xcite has proposed a spatial network model by adding long - range links to a 2-dimensional lattice , and he has proved that when @xmath8 , the structure is optimal for information navigation . recently , hu _ et al . _ @xcite suggested the optimization of information collection as a possible explanation for the origin of this spatial scaling law . although extensive studies have shown that the spatial organization can change the dimension , which dominates many important physical properties of networks @xcite , how it influences the spreading process on social networks under the framework of bootstrap percolation remains unclear . in this paper , we numerically study bootstrap percolation on kleinberg s network , which is a typical artificial social network , being well - accepted by academic society . setting the size of the giant active component as the order parameter , we find the distribution of long - range links lengths can change the order of phase transition . in particular , a critical exponent is found to be @xmath9 , above which a hybrid phase transition ( mixed of first order and second order ) is observed . surprisingly , we find both the first - order and the second - order critical points are constant when @xmath10 , insensitive to @xmath6 and other parameters . when @xmath11 , the second - order critical point increases as the decreasing of @xmath4 . meanwhile , as the decreasing of @xmath4 , there is either a decreasing first - order critical point or the absence of the first - order phase transition , which depends on @xmath6 and other parameters . these results indicate that the spatial scaling exponent @xmath12 , observed in real social networks , may be resulted from some deep - going principles in addition to the optimization of navigation and information collection , which is not yet fully understood now . ) and one long - range link ( colored black ) . the probability density function of a node to have a long - range link at manhattan distance @xmath0 scales as @xmath13 . for the target node @xmath14 ( colored red ) , when @xmath15 , there are eight candidate nodes ( colored green ) , from which we can choose an uncoupled node @xmath16 to make a connection . for another target node @xmath17 , we can choose to connect it with @xmath18 when @xmath19.,width=359 ] kleinberg model @xcite is a typical spatial network model , which has been well justified by empirical data @xcite . in this paper , kleinberg s network is constrained on a 2-dimensional periodic lattice consisting of @xmath20 nodes . in addition to its initially connected four nearest neighbors , each node @xmath14 has a random long - range link to a node @xmath16 with probability @xmath21 , where @xmath4 is a tunable exponent and @xmath22 denotes the manhattan distance , which quantifies the length of the shortest path between node @xmath14 and node @xmath16 , following strictly the horizontal or vertical links in lattices . since the number of nodes at distance @xmath0 to a given node is proportional to @xmath23 in a @xmath24-dimensional lattice , the probability @xmath25 can be mapped to a probability density function , @xmath26 . in the present 2-dimensional case , the probability density function scales as @xmath1 . an illustration of a 2-dimensional kleinberg s network can be found in figure [ fig1:lattice ] . in order to numerically implement the spatial scaling law @xmath27 , we add long - range links to a 2-dimensional periodic lattice in a smart way as follows . first , a random length @xmath0 between 2 and @xmath28 is generated with probability @xmath1 , which ensures the scaling in advance . second , random segmentations of length @xmath0 to @xmath29 and @xmath30 with the only constraint that @xmath31 are done to determine candidate nodes , where @xmath29 and @xmath30 are both integers . namely , for an uncoupled node @xmath14 with coordinates ( @xmath32 , @xmath33 ) , named target node , all candidate nodes are these with coordinates ( @xmath34 , @xmath35 ) such that @xmath31 . the above procedure ensures all candidate nodes at distance @xmath0 from the target node are uniformly distributed . hence , we can randomly choose an uncoupled candidate node ( i.e. , a node withour any long - range link ) to make an undirected link to target node @xmath14 . in exceptional cases that all candidate nodes have been coupled , we randomly choose an uncoupled node from the whole network to accomplish the linking . we repeat such procedure for the rest uncoupled nodes until each node of the network has one undirected long - range link such that the degree of each node is exactly 5 . we focus on the following three indicators : ( ) the relative size of the giant active component ( @xmath36 ) at the equilibrium , i.e. , the probability that an randomly selected node belongs to the giant active component ; ( ) the number of iterations ( @xmath37 ) to reach the equilibrium , which is usually used to determine the critical points for the first - order phase transition @xcite ; ( ) the relative size of the second giant active component ( @xmath38 ) , which is usually used to detect the critical points for the second - order phase transition @xcite . figure [ fig2:sgc ] shows rich phase transition phenomena when taking @xmath36 as the order parameter . when @xmath10 , @xmath36 shares almost the same behavior and the system undergoes a hybrid phase transition ( see figure [ fig2:sgc](a ) ) . we can see that @xmath36 has a continue increasing at @xmath39 ( the second - order critical point ) , where the second - order phase transition is present . in contrast , @xmath36 has a discontinue jump directly from about 0.60 to exact 1 at @xmath40 ( the first - order critical point ) , where the first - order phase transition occurs . to our surprise , we find that these two critical points are constant when @xmath10 , as indicated by the four overlapping @xmath41 curves in figure [ fig2:sgc](a ) . when @xmath11 , there is only a second - order phase transition with an increasing @xmath42 as the decreasing of @xmath4 ( see figure [ fig2:sgc](b ) ) . specifically , the second - order critical point is @xmath43 when @xmath44 and @xmath45 when @xmath46 . although @xmath36 goes up sharper after @xmath5 exceeds @xmath42 as the decreasing of @xmath4 , simulations justify that the curve of @xmath36 is continuous . that is to say , the type of phase transition is fundamentally second - order when @xmath11 . ( a ) and ( b ) , @xmath37 ( c ) and @xmath38 ( d ) as a function of @xmath5 for different @xmath4 after @xmath47 bootstrap percolation on kleinberg s networks . two different types of @xmath48 are observed , including a hybrid phase transition and a second - order phase transition . when @xmath10 , @xmath36 shares the same pattern and a hybrid phase transition is present . @xmath36 abruptly jumps to 1 at @xmath40 , where @xmath37 reaches its maximum . when @xmath11 , there is only a second - order phase transition with an increasing critical point as the increasing of @xmath4 , where @xmath38 reaches its maximum at different @xmath42 . dash lines mark identification of critical points . results are obtained by simulations on networks with size @xmath49 and averaged over 1000 realizations.,width=396 ] finding critical points via simulations is always a difficult task that requires high precision . when @xmath10 , where the hybrid phase transition is present , we are able to determine @xmath50 by calculating the number of iterations ( @xmath37 ) in the cascading process , since @xmath37 sharply increases when @xmath5 approaching @xmath50 for the first - order phase transitions @xcite . accordingly , @xmath50 is calculated by plotting @xmath37 as a function of @xmath5 ( see figure [ fig2:sgc](c ) ) . we can see that @xmath37 reaches its maximum at the same @xmath5 when @xmath10 , which is the evidence that @xmath40 is constant . analogously , by plotting the size of the second largest giant active component @xmath38 as a function of @xmath5 , we can precisely identify @xmath42 @xcite , at which @xmath38 reaches its maximum ( see figure [ fig2:sgc](d ) ) . it is found that @xmath42 increases as @xmath4 decreases , as @xmath39 ( @xmath10 ) , 0.176 ( @xmath44 ) and 0.256 ( @xmath46 ) . and @xmath51 . ( a ) and ( b ) are @xmath36 and @xmath37 in the case of @xmath12 under different network size @xmath52 , respectively . there is an intersection point at @xmath53 , while @xmath37 reaches its maximum at @xmath54 in the case of @xmath55 . thus , @xmath50 is identified as the average @xmath56 . ( c ) and ( d ) are @xmath36 and @xmath37 at @xmath57 under different exponent @xmath4 , respectively . for @xmath58 , @xmath36 has two phases , while @xmath37 reaches its maximum at @xmath59 . thus , @xmath60 is identified as the average @xmath27 . in figure [ fig3:points](c ) and [ fig3:points](d ) , dark curves respectively represent average values of @xmath36 and @xmath37 , obtained from @xmath61 realizations , and each data point stands for one realization.,width=396 ] although to justify the first - order phase transition and to determine the critical exponent @xmath60 by simulations in a discrete system are not easy , we solve this problem by a cross - validation on @xmath50 and @xmath60 . firstly , we fix @xmath12 to determine @xmath50 . on the one hand , there is an intersection for curves of @xmath36 at @xmath53 under different network sizes ( see figure [ fig3:points](a ) ) , which can be considered as the critical point according to the finite scale analysis @xcite . on the other hand , the corresponding @xmath37 reaches its maximum at @xmath54 when @xmath55 ( see figure [ fig3:points](b ) ) . combining these two evidences , a more accurate first - order critical point is identified as @xmath62 . conversely , we fix @xmath57 to determine @xmath60 . from figure [ fig3:points](c ) we can see that @xmath36 has two phases : exact 1 or around 0.58 when @xmath63 . there is a strong evidence that @xmath36 undergoes a first - order phase transition . if the increasing of @xmath36 is continuous , it is impossible to observe such gap between the two phases . from figure [ fig3:points](d ) , we can see that the corresponding averaging @xmath37 reaches its maximum at @xmath64 . combining these two evidences , we precisely identify the critical exponent as @xmath65 . in addition , the critical point for @xmath66 should be constant , otherwise we can not observe the separation of two phases in figure 3(c ) for a fixed value @xmath57 . bootstrap percolation in the @xmath67 plane for kleinberg s network . the color marks @xmath36 . the dashed lines with solid blue squares and red circles represent the first - order critical point @xmath50 and the second - order critical point @xmath42 , respectively . separated by the vertical dashed line @xmath12 , hybrid phase transition is observed in the right region with two constant critical points @xmath40 and @xmath39 . in the left region , only second - order phase transition is present with an increasing critical point up to @xmath68 , obtained in the case of @xmath69 , as @xmath4 decreases . results are averaged over 1000 realizations with fixed network size @xmath70.,width=377 ] a representative phase diagram for @xmath36 in the @xmath67 plane is shown in figure [ fig4:phase ] . we find that the varying of @xmath4 , which dominates the distribution of long - range links lengths , can change the order of phase transition . two kinds of phase transitions are observed , consisting of the second - order phase transition and the hybrid phase transition . overall , @xmath71 is confirmed to be the critical exponent , above which the hybrid phase transition ( the region labeled ii ) is present . once again , we confirm that both the first - order and the second - order critical points for hybrid phase transition are constant as @xmath40 and @xmath39 when @xmath10 . in the first - order phase transition region , @xmath48 curves are overlapped , suggesting that the properties of bootstrap percolation on kleinberg s spatial networks have no difference if @xmath10 . when @xmath11 , the first - order phase transition is absent , leaving @xmath36 undergoes only a second - order phase transition ( the region labeled i ) with an increasing critical point as the decreasing of @xmath4 . the maximum of @xmath42 is about 0.259 when @xmath69 , where all long - range links lengths are 2 . we have tested our findings for different threshold parameters @xmath6 and the number of long - range links associated with a node @xmath72 . some significant observations are robust : ( i ) the existence of critical point @xmath73 , above which a hybrid phase transition occurs with two constant critical points , whose values depend on @xmath6 and @xmath74 , and ( ii ) the existence of a second - order phase transition when @xmath11 , with an increasing critical point @xmath42 as the decreasing of @xmath4 . in contrast , in some parameter spaces , the first - order transition could be observed even when @xmath11 , but with a decreasing critical exponent @xmath50 as the decreasing of @xmath4 . the first - order transition may disappear at a certain @xmath4 smaller than -1 . phase diagrams of two representative examples , @xmath75 and @xmath76 , are presented in figure 5 . , where the color marks @xmath36 . ( a ) phase diagram of @xmath47 bootstrap percolation in the @xmath67 plane for networks where each node has @xmath77 long - range links . separated by the vertical dashed line @xmath12 , hybrid phase transition is observed in the right region with two constant critical points , @xmath78 and @xmath79 . ( b ) phase diagram in the case of @xmath80 and @xmath81 . the critical value is also @xmath82 , above which a hybrid phase transition with two constant critical points , @xmath83 and @xmath84 , is observed . results are averaged over 1000 realizations with fixed network size @xmath49.,title="fig:",width=226,height=226 ] , where the color marks @xmath36 . ( a ) phase diagram of @xmath47 bootstrap percolation in the @xmath67 plane for networks where each node has @xmath77 long - range links . separated by the vertical dashed line @xmath12 , hybrid phase transition is observed in the right region with two constant critical points , @xmath78 and @xmath79 . ( b ) phase diagram in the case of @xmath80 and @xmath81 . the critical value is also @xmath82 , above which a hybrid phase transition with two constant critical points , @xmath83 and @xmath84 , is observed . results are averaged over 1000 realizations with fixed network size @xmath49.,title="fig:",width=238,height=226 ] we have studied bootstrap percolation on spatial networks , where the distribution patterns of long - range links are found to be able to affect the order of phase transition . in particular , we find a robust critical point @xmath82 , above which the @xmath48 curves are almost the same and the two critical points are constant . such result indicates that the topological properties of kleinberg s networks are close to each other when @xmath85 in 2-dimensional space . in fact , the critical point @xmath12 has been empirically observed in many real networks @xcite , which may be resulted from complex self - organizing processes toward optimal structures for information collection @xcite and/or navigation @xcite . since the cascading processes of kleinberg s networks show almost the same features when @xmath10 , this critical point @xmath82 is indeed corresponding to the structure with the smallest average geographical length of links , which can exhibit as effective spreading of information as networks with even longer shortcut links . this is to some extent relevant to the principle of least effort in human behavior @xcite . our results are also relevant to the control of information spreading . for example , when @xmath86 , if we would like to make as more as possible people to know the information , the optimal choice of the fraction of initially informed people should be @xmath87 , since larger initially informed population provides no more benefit ( as shown in figure 2(a ) ) but requires higher cost . furthermore , we expect to verify our findings in an analytical way based on kleinberg s networks , spatial embedded random networks @xcite and multiplex networks @xcite . besides , to assign each node one long - range link is a high - cost strategy when generating spatial networks , we leave individualized number of long - range links associated with each node and partial spatial embedding as future works . we acknowledge jun wang and panhua huang for useful discussions . this work is partially supported by national natural science foundation of china under grants nos . 61203156 and 11222543 . j.g . acknowledges support from tang lixin education development foundation by uestc . t.z . acknowledges the program for new century excellent talents in university under grant no . ncet-11 - 0070 , and special project of sichuan youth science and technology innovation research team under grant no .

we numerically study bootstrap percolation on kleinberg s spatial networks , in which the probability density function of a node to have a long - range link at distance @xmath0 scales as @xmath1 . setting the ratio of the size of the giant active component to the network size as the order parameter , we find a critical exponent @xmath2 , above which a hybrid phase transition is observed , with both the first - order and second - order critical points being constant . when @xmath3 , the second - order critical point increases as the decreasing of @xmath4 , and there is either absent of the first - order phase transition or with a decreasing first - order critical point as the decreasing of @xmath4 , depending on other parameters . our results expand the current understanding on the spreading of information and the adoption of behaviors on spatial social networks .

the peaks of solar oscillation modes observed in velocity and intensity power spectra are asymmetric ( duvall et al . 1993 ) . moreover , the asymmetry between the velocity and intensity line profiles is reversed . this latter was a puzzling result , and it was initially thought to be an error in the observations ( abrams & kumar 1996 ) . however , recently it was confirmed by soho / mdi observations ( nigam et al , 1998 ) . the velocity power spectrum has negative asymmetry ( more power on the low frequency side of the peak ) , while the intensity power spectrum has positive asymmetry ( more power on the high frequency side of the peak ) . in general , the asymmetry is a result of excitation of solar oscillations by a localized source . it originates from the interference of direct waves from the source with waves that start inward and are refracted back out . the asymmetry is a strong function of frequency , and varies weakly with angular degree @xmath0 . the reversal of asymmetry between velocity and intensity is due to the presence of correlated background noise , whose level depends on characteristics of granulation ( nigam et al , 1998 ) . since the model of nigam et al ( 1998 ) is a phenomenological one , the physics of the correlated noise is not yet fully understood . roxburgh & vorontsov ( 1997 ) proposed that the reversal in asymmetry occurs in velocity . observations suggest that the reversal occurs in intensity as proposed by nigam et al ( 1998 ) . it is therefore desirable to test these ideas . realistic 3d hydrodynamic simulations of upper layers of the solar convection zone ( e.g. , stein & nordlund , 1989 ; stein & nordlund , 1998 ) have p and f modes with similar asymmetries and asymmetry reversals as the observed modes . these simulations can therefore be used to study the characteristics of the correlated noise . another interesting property of solar oscillation modes is the phase difference between velocity and intensity , which was first observed by deubner & fleck ( 1989 ) and studied theoretically by marmolino & severino ( 1991 ) . it may provide an useful diagnostic of the excitation mechanism of the oscillations . severino et al . ( 1998 ) , straus et al . ( 1998 ) , oliviero et al . ( 1999 ) and nigam & kosovichev ( 1999 ) attribute the phase behavior to the interaction of the correlated background with the oscillations . these phase relations can also be studied using the realistic hydrodynamic simulations of the near surface layers of the sun . we use the numerical code of stein and nordlund ( 1998 ) to make a physically realistic three - dimensional simulation of the shallow upper layers of the solar convective zone . the code solves the compressible hydrodynamic equations and includes ionization in the equation of state and lte radiative transfer in the energy balance . the horizontal boundary conditions are periodic , while the top and bottom boundaries of the computational domain are transmitting . the horizontal size of the domain is 6 by 6 mm . it ranges in depth from 2.5 mm below the @xmath1 surface to 0.5 mm above it , reaching the height of the temperature minimum of the solar atmosphere . the computational grid of @xmath2 mesh points gives a spatial resolution of 100 km @xmath3 100 km horizontally and 35 90 km vertically . the system becomes thermally relaxed after several turnover times ( a turnover time is approximately 1 hour ) . we have generated data for 43 hours of solar time , which provide 6.4 @xmath4hz frequency resolution . we calculate power spectra of the velocity and intensity and their phase differences to study properties of the oscillations generated in this simulation box . in the simulation , the first set of nonradial modes corresponds to a harmonic degree @xmath5 ( or @xmath6 mm@xmath7 ) , the second set corresponds to @xmath8 ( @xmath9 mm@xmath7 ) etc . solar oscillations in velocity and intensity are measured from the ni i 6768@xmath10 absorption line which is formed about 200300 km above the photosphere . the mdi instrument on soho spacecraft records filtergrams ( intensity images at five wavelengths ) which span the absorption line . the velocity signal is obtained by differencing the filtergrams on opposite sides of the line which is sensitive to doppler shift and minimizes the effect of intensity fluctuations . the intensity signal is obtained by summing the filtergrams in a way to approximate the continuum intensity in the vicinity of the spectral line and minimize the effects of doppler shifts ( scherrer et al . 1995 ) . for the comparison with the numerical simulations , we use a time series of the spherical harmonic transform of the full - disk data for @xmath11 . the effect of solar differential rotation is removed ; and the oscillation power spectra are summed over all @xmath12 @xmath13 values . we note that mdi measures the continuum intensity in the vicinity of the ni i 6768@xmath10 line , which is different from the broad - band continuum data obtained from the simulations . this might be a source of some of the divergences between the model and the observations . in the numerical model , the vertical component of velocity , @xmath14 , is calculated at a height of 200 km above the @xmath1 surface , close to the formation height of the observed mdi doppler velocities . the simulated continuum intensity ( the emergent continuum specific intensity ) , @xmath15 , is calculated by solving the feautrier equation along a vertical ray , in lte , using an opacity distribution function . to extract the nonradial modes we multiply @xmath14 and @xmath15 by @xmath16 , @xmath17 , @xmath18 and @xmath19 , where @xmath20 or @xmath21 are horizontal wave numbers equal to @xmath22 , where @xmath23 mm is the horizontal dimension of the simulation box ( the same for both @xmath24 and @xmath25 directions ) , and @xmath26 is the number of nodes in horizontal direction . then we average the products of @xmath27 and @xmath28 with these sines and cosines over the horizontal planes . this corresponds to the 2-dimensional fourier transform of the data with specific horizontal wave numbers . we then take fourier transforms in time to obtain the power spectra , @xmath29 and @xmath30 , and sum these four different spectra to obtain a power spectrum for a particular horizontal wave number @xmath31 . this corresponds to summing the observational power spectra over azimuthal degree @xmath13 . since the line profiles for @xmath9 mm@xmath7 ( @xmath32 ) and higher are rather noisy , we present the results for @xmath6 mm@xmath7 ( @xmath33 ) only . the @xmath6 mm@xmath7 spectra are obtained either for @xmath34 and @xmath35 or @xmath36 and @xmath37 . the modulus and phase of the cross spectra @xmath38 give the coherence and phase difference between intensity and velocity . in figures [ vpower1 ] and [ ipower2 ] we compare the observed and simulated mode power spectral densities in velocity and intensity for @xmath33 . the observational data represent 5 days of the observations of a quiet - sun region with a spatial resolution of 2 arcsec / pixel ( @xmath39 km ) and temporal resolution 1 min . the simulation data are for the lowest non - radial mode of the same angular degree , @xmath33 ( @xmath6 mm@xmath7 ) calculated from a 43 hour run with a horizontal grid spacing of 100 km and time spacing of 0.5 min . in order to make our comparison more appropriate , we took only 43 hours of the observational data and every other snapshot in the simulated data to have the same 1 min time step as in observations . the simulated and observed velocity power are similar between the peaks at low frequency , but the peak power is larger in the simulation than the observations because the same excitation and damping processes are supplying energy to fewer modes with smaller mode mass . the simulation power also falls off much more rapidly at high frequencies , probably due to the low resolution of the simulation . the frequency separation between the simulated modes is larger than the separation between the observed modes because of the shallow computational domain . it is only 2.5 mm deep , whereas @xmath33 modes in the sun have the turning points below @xmath40 mm . as a result , the resonant frequencies in the simulation are different from the frequencies of solar modes . also , the simulated modes have less inertia and larger amplitudes than the solar modes . because of the smaller inertia ( mode mass ) the damping rate is much larger in the simulation than the sun , so the simulated line profiles are broader than the observed ones . however , these differences do not prevent us from studying the mode physics with the numerical simulations . the lowest frequency mode in the power spectra is the f mode , which is essentially a surface gravity mode . it does not exist in radial oscillations , but in the nonradial data , it is very strong and shows the same asymmetry behavior as do p modes . interestingly enough , in the simulations the amplitude of the f mode is greater than the amplitudes of the p modes , whereas in the observational data the f - mode amplitude is smaller than the amplitude of the p@xmath41 mode . for both the simulations and the observations the velocity and intensity line profiles are clearly asymmetric , with opposite asymmetries in velocity and intensity ( figures [ vpower1 ] and [ ipower2 ] ) . also , the slopes of the power spectra in velocity and intensity have a power law behavior in both the simulation and observations . figure [ v - i - phase3 ] compares the observed and simulated phase differences between the intensity and velocity signals , @xmath42 , as a function of frequency . both the observations and simulations have negative phase difference @xmath42 at low frequency . in both cases , the phase difference departs from the @xmath43 phase difference predicted by the adiabatic theory of trapped standing waves . in both cases , there are jumps in phase of @xmath44 at the mode frequencies . the phase differences approach zero for high frequency propagating waves as expected for adiabatic acoustic waves . mode asymmetry in the spectral domain is a result of the interference pattern of waves from a localized source not being symmetrical relative to the mode resonant frequencies . constructive and destructive interference occurs between waves from the source that propagate outward with those that propagate inward and are refracted outward . destructive interference causes characteristic `` troughs '' on one side of the modal lines , where the amplitude is minimal . the frequencies of the `` troughs '' depend on the source location and type ( duvall et al . 1993 , vorontsov et al . 1998 , nigam and kosovichev , 1999 ) . in the solar case , the destructive interference occurs at frequencies slightly higher than the resonant frequencies . this corresponds to the negative line asymmetry . the interference pattern may be also affected by the presence of an additional signal correlated with the source . variations of the continuum intensity in the convective granules , which are associated with the process of excitation of solar oscillations , are such a signal ( nigam et al . , 1998 ) . this correlated signal shifts the frequencies of the `` troughs '' . if the correlated signal is sufficiently strong the `` troughs '' may be shifted to the other side of the mode resonant frequencies , and thus reverse the asymmetry of the modal lines . this reversal of the asymmetry is observed in both the mdi intensity data and the intensity spectra obtained in the numerical simulations . the numerical results allow us to verify that variations in the background intensity in the granules are indeed correlated with the oscillations ( nordlund and stein 1998 ) . in the mdi doppler velocity measurements this correlated variation is essentially cancelled by taking differences of values on opposite sides of the line . in the intensity measurement it is enhanced by summing contributions from opposite sides of the line . the correlated component of the noise must be large enough to reverse the asymmetry in the intensity power spectrum , but not sufficiently large to reverse the asymmetry in the velocity power spectrum ( nigam et al . 1998 ) . these results are consistent with the observations of goode et al . ( 1998 ) , where it appears that the acoustic events occur in cool and narrow intergranular dark lanes . prior to an acoustic event there is darkening in the intensity . this darkening is also correlated to the strength of the event . strong events are preceded by longer darkening . the reversal of asymmetry in intensity due to a correlated background has been confirmed by kumar & basu ( 1999 ) and rast ( 1999 ) . however , there is , as yet , no complete theory of the influence of the background variations on the observed properties of solar oscillations . the variations of the phase difference between the intensity and velocity signals with frequency can also be explained by the presence of the correlated noise ( nigam & kosovichev 1999 ) . the intensity - velocity cross spectrum is the product @xmath45 and the intensity - velocity phase difference is @xmath46 away from a mode the noise contribution dominates , while at an eigenfrequency the mode amplitude is large and dominates . if the intensity and velocity are nearly @xmath43 out of phase , as they are expected to be for adiabatic waves , then they will contribute primarily to the imaginary part in the numerator , but have little effect on the denominator . at the mode eigenfrequency there will be a large jump in mode amplitude , producing a large jump in the ratio @xmath47 , and hence a change in @xmath48 of order @xmath44 . the phase and asymmetry behavior of the modes constrains the nature of the excitation mechanism of solar oscillations . in this letter , we have compared observed asymmetries of the oscillation line profiles in the velocity and intensity power spectra with those obtained in 3d hydrodynamic simulations of solar convection . the basic characteristics of the observed mode peak asymmetries are reproduced in the simulations : the modes are asymmetric , with the velocity and intensity having opposite asymmetries . the reversal in asymmetry occurs in the intensity signal ( possibly due to the process of radiative transfer , which causes additional signal in the intensity fluctuations correlated with the oscillation ) . this is consistent with the result of nigam et al ( 1998 ) . this is an important step in studying the physical properties of solar oscillations and their interaction with turbulence . the basic characteristics of the observed intensity velocity phase difference are also reproduced in the simulations . the similarity of the oscillation mode properties in the simulation and observations means that the simulations can be used to investigate the origin of mode behavior . this work was supported by the soi - mdi nasa contract nag5 - 3077 at stanford university and by nasa grant nag 5 - 4031 and nsf grant ast 9521785 to msu . d.g . expresses her gratitude to sasha kosovichev for the possibility of performing a part of this work at stanford , and to maurizio oliviero for useful discussions on phase differences . the calculations were performed at michigan state university and the national center for supercomputing applications . soho is a project of international cooperation between esa and nasa . abrams , d. , & kumar , p. 1996 , apj , 472,882 deubner , f .- l . , & fleck , b. 1989 , astronomy and astrophysics , 213 , 423 duvall , t.l . , jr . , jefferies , s.m . , harvey , j.w . , osaki , y. , & pomerantz , m.a . 1993 , apj , 410 , 829 goode , p.r . , strous , l.h . , rimmele , t.r . , & stebbins , r.t . 1998 , apj , 495 , l27 kumar , p. , & basu , s. 1999 , apj , 519 , 389 marmolino , c. , & severino , g. 1991 , astronomy and astrophysics , 242 , 271 nigam , r. , & kosovichev , a.g . 1998 , apj , 505 , l51 nigam , r. , & kosovichev , a.g . 1999 , apj , 510 , l149 nigam , r. , kosovichev , a.g . , scherrer , p.h . , & schou , j. 1998 , apj , 495 , l115 nordlund , . & stein , r.f . 1998 , in f. l. deubner , j. christensen - dalsgaard , & d. kurtz , ( eds . ) new eyes to see inside the sun and stars : pushing the limits of helio- and asteroseismology with new observations from the ground and from space , iau symp 185 , ( kluwer : dordrecht ) 199 oliviero , m. , severino , g. , straus , t. , jefferies , s.m . , & appourchaux , t. 1999 , apj , 516 , l45 rast , m.p . 1999 , apj , in press roxburgh , i.w . , & vorontsov , s.v . 1997 , mnras , 292 , l33 scherrer , p.h . , bogart , r.s . , bush , r.i . , hoeksema , j.t . , kosovichev , a.g . , schou , j. , et al . 1995 , solar physics , 162 , 129 severino , g. , straus , th . , & jefferies , s. m. 1998 , in soho 6/gong 98 workshop , structure and dynamics of the interior of the sun and sun - like stars , vol . 1 , ed . s. korzennik & a. wilson ( esa sp-418 ; noordwijk : esa ) , 53 stein , r. f. , & nordlund , a. 1989 , apj , 342 , l95 stein , r. f. , & nordlund , a. 1998 , apj , 499 , 914 straus , t. , fleck , b. , severino , g. , deubner , f .- l . , marmolino , c. , & tarbell , t. 1998 , in e.r.priest ( ed . ) , a crossroads for european solar and heliospheric physics : recent achievements and future mission possibilities , tenerife , esa sp-417 , 293 vorontsov , s. v. , jefferies , s. m. , duvall , t. l. , & harvey , j. w. , 1998 , mnras , 298 , 464

we use the three - dimensional hydrodynamic code of stein and nordlund to realistically simulate the upper layers of the solar convection zone in order to study physical characteristics of solar oscillations . our first result is that the properties of oscillation modes in the simulation closely match the observed properties . recent observations from soho / mdi and gong have confirmed the asymmetry of solar oscillation line profiles , initially discovered by duvall et al . in this paper we compare the line profiles in the power spectra of the doppler velocity and continuum intensity oscillations from the soho / mdi observations with the simulation . we also compare the phase differences between the velocity and intensity data . we have found that the simulated line profiles are asymmetric and have the same asymmetry reversal between velocity and intensity as observed . the phase difference between the velocity and intensity signals is negative at low frequencies and jumps in the vicinity of modes as is also observed . thus , our numerical model reproduces the basic observed properties of solar oscillations , and allows us to study the physical properties which are not observed .

The city of Orlando has reached a deal to buy the Pulse nightclub for $2.25 million and plans to eventually transform the site of the deadliest mass shooting in U.S. history into a memorial. Orlando Mayor Buddy Dyer told the Orlando Sentinel on Monday that the city won't rush to change the club, once a mainstay in the gay community that has become a gathering place for visiting and local mourners alike. "There are lots of people that are making a visit to the site part of their trip, part of their experience of Orlando, so I think 12 to 18 months of leaving it as-is would be appropriate," Dyer said. In the meantime, the city plans to solicit ideas from the community for what form the lasting memorial should take. Dyer said the city hasn't ruled out leaving part of the club intact permanently, such as the roadside sign featuring its now-iconic logo. The city's ultimate goal, he said, will be to "create something to honor the memory of the victims that are deceased [and] those that were injured, and a testament to the resilience of our community." CAPTION The report said OPD policy and procedures were followed, but the protective plan “was not written with an attack of this magnitude in mind.” The report said OPD policy and procedures were followed, but the protective plan “was not written with an attack of this magnitude in mind.” CAPTION The report said OPD policy and procedures were followed, but the protective plan “was not written with an attack of this magnitude in mind.” The report said OPD policy and procedures were followed, but the protective plan “was not written with an attack of this magnitude in mind.” CAPTION The owner of Pulse nightclub, Barbara Poma spoke at a ceremony honoring the 49 people lost in Pulse massacre. The owner of Pulse nightclub, Barbara Poma spoke at a ceremony honoring the 49 people lost in Pulse massacre. CAPTION Barbara Poma, founder of the onePULSE Foundation and former owner of the Pulse nightclub, reflects on the second anniversary of the Pulse massacre, Monday, June 11, 2018. (Joe Burbank/Orlando Sentinel) Barbara Poma, founder of the onePULSE Foundation and former owner of the Pulse nightclub, reflects on the second anniversary of the Pulse massacre, Monday, June 11, 2018. (Joe Burbank/Orlando Sentinel) CAPTION Pulse related events around Orlando are scheduled Monday and Tuesday to honor the victims of the mass shooting on June 12, 2016. Pulse related events around Orlando are scheduled Monday and Tuesday to honor the victims of the mass shooting on June 12, 2016. CAPTION Two years after a gunman killed 49 people at Orlando's Pulse nightclub, the city has more metal detectors, panic buttons, active-shooter drills, trauma counseling and grief-stricken parents and partners than it did in 2016. But for some, it also has more compassion and progress and purpose. Two years after a gunman killed 49 people at Orlando's Pulse nightclub, the city has more metal detectors, panic buttons, active-shooter drills, trauma counseling and grief-stricken parents and partners than it did in 2016. But for some, it also has more compassion and progress and purpose. The price negotiated by city staff is more than the $1.65 million appraised value of the nightclub, a 4,500-square-foot building occupying a third of an acre at South Orange Avenue and West Esther Street. Dyer said the sale price was a compromise reached during negotiations with the club's owners, whose attorney did not return a call seeking comment Monday. The sales contract with the city was signed Friday by Rosario Poma, who owns the club with his wife, Barbara. Orlando's City Council, which has the final say on the deal, will weigh in on it next week. The nightclub has been empty since June 12, when a gunman opened fire during a Latin-themed dance party, killing 49 people and wounding dozens more. Since the massacre, mourners have flowed steadily to the site to pay their respects, leaving behind photos, notes, stuffed animals and other remembrances. Many of the items have since been collected for preservation by the Orange County Regional History Center. The visitors have at times been disruptive to nearby businesses and residents, creating parking troubles, crowding sidewalks and prompting safety concerns. The club was also the victim of at least one break-in about a month after the tragedy. Dyer said purchasing the property will help with security and safety issues, as the city will no longer need to coordinate with a private owner to enter or change the property. "Now, we can actually secure it like we would any other piece of city property," he said. In September, the city removed the black chain-link fence that had surrounded the club since soon after the shooting, replacing it with a new barrier farther back from the road, wrapped in a screen which features images created by local artists. Those killed in the Pulse massacre have been commemorated in many ways, but the city has kept mum on the specifics of its plans for a permanent memorial. Dyer first floated the idea of buying the nightclub in a radio interview in August. The club has already drawn onlookers from across the globe, as far flung as the prime minister of Luxembourg. Democratic presidential nominee Hillary Clinton laid flowers outside the club during a visit to Orlando in July. Dyer said the city will seek memorial ideas from other communities, not unlike how local officials brought in Kenneth Feinberg, a national authority on victim compensation in mass tragedies, to administer the $29.5 million OneOrlando Fund for Pulse shooting victims. "We're still gathering information," Dyer said. "We're looking around the country for some people that have done something like this before. There are some folks with expertise related to this." Barbara Poma opened the bar in 2004, naming it Pulse in honor of her brother John, who died of AIDS in 1991. It was a local landmark in the gay community, often the first bar a gay or lesbian young person would visit in Orlando. Poma was the first to pledge the Pulse site would become a memorial to those lost, in a statement issued through a spokeswoman days after the killings. jeweiner@orlandosentinel.com or 407-420-5171 ||||| ORLANDO, Fla. (AP) — The city of Orlando, Florida, has announced plans to purchase the Pulse nightclub and eventually convert the site of the deadliest mass shooting in modern U.S. history into a memorial. Orlando Mayor Buddy Dyer told the Orlando Sentinel (http://bit.ly/2eHO6t6 ) on Monday that the city has reached a deal to buy the gay nightclub for $2.25 million. Dyer says the site should probably remain as-is for the next 12 to 18 months, as it has become a gathering place for mourners. He says the city will reach out to the community for advice on how plans for the memorial should proceed. The purchase price is $600,000 more than its appraised value. The June 12 attack left 49 people dead and 53 wounded. Gunman Omar Mateen was killed by SWAT team members. ___ Information from: Orlando Sentinel, http://www.orlandosentinel.com/

– The city of Orlando, Florida, has announced plans to purchase the Pulse nightclub and eventually convert the site of the deadliest mass shooting in modern US history into a memorial, the AP reports. Orlando Mayor Buddy Dyer told the Orlando Sentinel on Monday that the city has reached a deal to buy the gay nightclub for $2.25 million. Dyer says the site should probably remain as-is for the next 12 to 18 months, as it has become a gathering place for mourners. He says the city will reach out to the community for advice on how plans for the memorial should proceed. The purchase price is $600,000 more than its appraised value. The June 12 attack left 49 people dead and 53 wounded. Gunman Omar Mateen was killed by SWAT team members.

the new ruling and abandonment of the former article 59 of the international code of botanical nomenclature ( icbn ) not only has abandoned the intricacies of dual nomenclature for pleomorphic fungi but also sacrificed the formerly recognized precedence of teleomorph - typified names over those of the associated anamorphs ( mcneill et al . this precedence was not an expression of sexism , but it simply recognized that with the description of a teleomorph anamorph association the knowledge of a fungus was more complete and more thorough than without it . it is not a matter of chance that the suprageneric classification is and remains generally based on teleomorph names . according to the new rules , many teleomorph - generic names will have to be replaced by older anamorph - generic names in cases where each morph of a fungus can unequivocally be tied to a particular taxon . hawksworth ( 2012 ) analyzed the consequences of the new rules in coping with the names involved in a period of transition . he did , however , not question the rigid priority of all kinds of names and analyze and propose a solution for the two problems addressed here . the examples below are given not to criticize the respective authors , who tried to find the best solution for a difficult nomenclature . for example , when an author did not give preference to the older anamorph - generic name against the corresponding teleomorph name , he / she still followed the new code correctly which states ( art . 14.13 icn ) : lists of names may be submitted to the general committee , which will refer them to the nomenclature committee for fungi ( see div . iii ) for examination by subcommittees established by that committee in consultation with the general committee and appropriate international bodies . accepted names on these lists , which become appendices of the code once reviewed and approved by the nomenclature committee for fungi and the general committee , are to be listed with their types together with those competing synonyms ( including sanctioned names ) against which they are treated as conserved ( see also art . these lists do thus not dictate that a particular taxonomy has to be adopted ; that choice remains a matter of judgement ; the list indicates only the choice of names in whatever taxonomy an author wishes to adopt . we maintain that it is important that the list entries not be made before a careful analysis and a decision taken by the competent committees . we are aware that difficulties may have arisen from misleading formulations in the code and thus indicate the need for clarification . ( 2012 ) pointed out the desirability of calling the preferred / listed names prioritized to distinguish the situation from that of conservation . the opposite would have been a suppressed name ( which in certain situations can still be used ) . therefore we speak now of list - accepted and list - demoted names , in order to distinguish the situation from that of conservation / rejection . i. the new rules would imply that an older epithet coined in a list - demoted genus has to be recombined in the list - accepted genus this would entail a very high number of undesirable name changes in some genera . if the genus name trichoderma 1794 is listed with preference over hypocrea 1825 , the older epithet of hypocrea schweinitzii ( fr . 1883 would have to be recombined in trichoderma , displacing the established name trichoderma citrinoviride bissett 1984 . conversely , according to this suggestion , the now established name hypocrea citrina ( overton et al . 2006 ) would have to be called trichoderma lacteum bissett 1992 , a so far hardly used name that may also not be desirable , because hypocrea lactea is now regarded as a synonym of h. citrina . ( 2011 ) , in a paper written just before the new rules were set , retained nectria canadensis ellis & everh . ellis 1882 ) seifert 1985 is older . similarly : nectria pseudotrichia berk . & m.a . 1991 ) baral 1999 , simply because of the available older anamorph epithet of drechslerella brochopaga ( drechsler 1937 ) m. scholler et al . 1999 . its explicit statement that names introduced before 2013 separately for teleomorphs and associated anamorphs are not automatically each other s ( legitimate or illegitimate ) synonyms as they are based on different types permits retention of either name . names published prior to 1 january 2013 for the same taxon , but based on different morphs , are neither considered to be alternative names according to art 34.2 nor superfluous names according to art . 52.1 , i.e. they are legitimate ( if not illegitimate due to other reasons ) . such synonyms are valid names , and valid names remain available for use . therefore individual authors and committees establishing lists of protected names should generally not recombine older epithets from a list - demoted genus into the list - accepted genus , when another one from pre-2013 is already available in that genus . kew rule , adopted in the first volumes of index kewensis but never in the code , which says : under this rule , priority within a genus was reckoned from the date when a specific epithet was first associated with that generic name . older epithets , previously associated with species placed in other genera , were ignored ( stevens 1991 ) . ii . presently the concepts of correlated teleomorph and anamorph genera are often incongruent , while both of them are meaningful . enforcing congruence leads to unnatural and unworkable procrustean beds and loss of information procrustes , in greek mythology , a son of poseidon who placed his guests on an iron bed , stretching them or cutting off their legs , so as to force them to fit the size of the bed . procrustes , in greek mythology , a son of poseidon who placed his guests on an iron bed , stretching them or cutting off their legs , so as to force them to fit the size of the bed . in such cases , retaining the most suitable generic name is imperative , even when this is subordinated to another list - accepted generic name . orphan species ( hawksworth 2012 ) remain anyhow , which can not yet be properly classified . ( 2009 ) found mycosphaerella sensu stricto to phylogenetically coincide with species having anamorphs in ramularia , and gave preference to binomials in that genus , but the same author ( crous 2009 ) happily continued to use the generic name mycosphaerella for the hundreds of species that are not yet phylogenetically reorganized . scopulariopsis bainier 1907 is predated by the associated teleomorph - generic name microascus zukal 1885 , but older than kernia nieuwl . merging these genera into one would be confusing and undesirable . in the monophyletic genus hypocrea , a name to be subordinated under the older anamorph name trichoderma , as accepted by a majority of members of the international subcommission on trichoderma and hypocrea ( isth ) , certain species lack an anamorph or have anamorphs quite different from trichoderma . above , it would be the simplest solution to retain for the species in question the anamorph name drechslerella brochopaga , because the generic name drechslerella , like arthrobotrys and other anamorph - generic names for nematode - trapping species , conveys phylogenetic and ecological information that would be lost by merging all species in orbilia . unpublished morphological and phylogenetic data on a vast number of species of orbiliaceae indicate that the nematode - trapping fungi form a comparatively young clade out of many further taxonomic groups that comprise very numerous species . these remaining groups are rather well - defined by teleomorphic features and possess various other , non - nematophagous anamorphs . when treating the nematode - trapping group as three or four different genera , the remaining groups would then need to be handled similarly . the associated anamorphs are only diagnostic for some of these genera in regard to conidial morphology , and trapping organs are unknown in all of them . hence , a classification according to teleomorph and dna characteristics may be the preferable option.classifying the nematode - trappers in the genera arthrobotrys , drechslerella , dactylellina and gamsylella , as proposed by scholler et al . such a procedure could eventually lead to the erection of numerous genera within the large genus orbilia as presently circumscribed . as a further complication , trapping organs are also known in lecophagus and hyalorbilia , two quite basal genera of the orbiliomycetes with no genetic connection to the nematode - trapping taxa . cordyceps militaris ( l. 1753 ) link 1833 is the oldest and indispensable name of a well - known fungus , in contrast to its still not definitely named and less known lecanicillium anamorph . it would , however , be totally irresponsible to combine all species of the paraphyletic genus lecanicillium into cordyceps . some kind of cryptic dual generic nomenclature is therefore bound to persist . for binomials of species many systematists seem to forget that our task is to name fungal taxa , and not just clades . we therefore strongly recommend to retain binomials in genera where they are most informative . when following these recommendations , the upheaval of fungal nomenclature ensuing from abandoning the old art . if the genus name trichoderma 1794 is listed with preference over hypocrea 1825 , the older epithet of hypocrea schweinitzii ( fr . 1883 would have to be recombined in trichoderma , displacing the established name trichoderma citrinoviride bissett 1984 . conversely , according to this suggestion , the now established name hypocrea citrina ( overton et al . 2006 ) would have to be called trichoderma lacteum bissett 1992 , a so far hardly used name that may also not be desirable , because hypocrea lactea is now regarded as a synonym of h. citrina . ( 2011 ) , in a paper written just before the new rules were set , retained nectria canadensis ellis & everh . 1991 ) baral 1999 , simply because of the available older anamorph epithet of drechslerella brochopaga ( drechsler 1937 ) m. scholler et al . 1999 . its explicit statement that names introduced before 2013 separately for teleomorphs and associated anamorphs are not automatically each other s ( legitimate or illegitimate ) synonyms as they are based on different types permits retention of either name . names published prior to 1 january 2013 for the same taxon , but based on different morphs , are neither considered to be alternative names according to art 34.2 nor superfluous names according to art . 52.1 , i.e. they are legitimate ( if not illegitimate due to other reasons ) . such synonyms are valid names , and valid names remain available for use . therefore individual authors and committees establishing lists of protected names should generally not recombine older epithets from a list - demoted genus into the list - accepted genus , when another one from pre-2013 is already available in that genus . kew rule , adopted in the first volumes of index kewensis but never in the code , which says : under this rule , priority within a genus was reckoned from the date when a specific epithet was first associated with that generic name . older epithets , previously associated with species placed in other genera , were ignored ( stevens 1991 ) . ii . presently the concepts of correlated teleomorph and anamorph genera are often incongruent , while both of them are meaningful . enforcing congruence leads to unnatural and unworkable procrustean beds and loss of information procrustes , in greek mythology , a son of poseidon who placed his guests on an iron bed , stretching them or cutting off their legs , so as to force them to fit the size of the bed . procrustes , in greek mythology , a son of poseidon who placed his guests on an iron bed , stretching them or cutting off their legs , so as to force them to fit the size of the bed . in such cases , retaining the most suitable generic name is imperative , even when this is subordinated to another list - accepted generic name . orphan species ( hawksworth 2012 ) remain anyhow , which can not yet be properly classified . crous et al . ( 2009 ) found mycosphaerella sensu stricto to phylogenetically coincide with species having anamorphs in ramularia , and gave preference to binomials in that genus , but the same author ( crous 2009 ) happily continued to use the generic name mycosphaerella for the hundreds of species that are not yet phylogenetically reorganized . scopulariopsis bainier 1907 is predated by the associated teleomorph - generic name microascus zukal 1885 , but older than kernia nieuwl . merging these genera into one would be confusing and undesirable . in the monophyletic genus hypocrea , a name to be subordinated under the older anamorph name trichoderma , as accepted by a majority of members of the international subcommission on trichoderma and hypocrea ( isth ) , certain species lack an anamorph or have anamorphs quite different from trichoderma . above , it would be the simplest solution to retain for the species in question the anamorph name drechslerella brochopaga , because the generic name drechslerella , like arthrobotrys and other anamorph - generic names for nematode - trapping species , conveys phylogenetic and ecological information that would be lost by merging all species in orbilia . unpublished morphological and phylogenetic data on a vast number of species of orbiliaceae indicate that the nematode - trapping fungi form a comparatively young clade out of many further taxonomic groups that comprise very numerous species . these remaining groups are rather well - defined by teleomorphic features and possess various other , non - nematophagous anamorphs . when treating the nematode - trapping group as three or four different genera , the remaining groups would then need to be handled similarly . the associated anamorphs are only diagnostic for some of these genera in regard to conidial morphology , and trapping organs are unknown in all of them . hence , a classification according to teleomorph and dna characteristics may be the preferable option.classifying the nematode - trappers in the genera arthrobotrys , drechslerella , dactylellina and gamsylella , as proposed by scholler et al . such a procedure could eventually lead to the erection of numerous genera within the large genus orbilia as presently circumscribed . as a further complication , trapping organs are also known in lecophagus and hyalorbilia , two quite basal genera of the orbiliomycetes with no genetic connection to the nematode - trapping taxa . cordyceps militaris ( l. 1753 ) link 1833 is the oldest and indispensable name of a well - known fungus , in contrast to its still not definitely named and less known lecanicillium anamorph . it would , however , be totally irresponsible to combine all species of the paraphyletic genus lecanicillium into cordyceps . some kind of cryptic dual generic nomenclature is therefore bound to persist . for binomials of species many systematists seem to forget that our task is to name fungal taxa , and not just clades . we therefore strongly recommend to retain binomials in genera where they are most informative . when following these recommendations , the upheaval of fungal nomenclature ensuing from abandoning the old art . at the moment we can only offer guidelines for taxonomic revisions and the work of committees involved in establishing lists of names to be protected . it is hoped that such mechanisms of fine - tuning will eventually also find their way into subsequent editions of the code .

the new rules formulated in article 59 of the international code of nomenclature for algae , fungi , and plants ( icn ) will cause numerous , often undesirable , name changes , when only phylogenetically defined clades are named . our task is to name fungal taxa and not just clades . two suggestions are made here that may help to alleviate some disadvantages of the new system . ( 1 ) officially an epithet coined in a list - demoted genus that is older than the oldest one available in the list - accepted genus would have to be recombined in the accepted genus . we recommend that individual authors and committees establishing lists of protected names should generally not recombine older epithets from a demoted genus into the accepted genus , when another one from pre-2013 is available in that genus . ( 2 ) because the concepts of correlated teleomorph and anamorph genera are often incongruent , enforced congruence leads to a loss of information . retaining the most suitable generic name is imperative , even when this is subordinated to another , list - accepted , generic name . some kind of cryptic dual generic nomenclature is bound to persist . we therefore strongly recommend the retention of binomials in genera where they are most informative . with these recommendations , the upheaval of fungal nomenclature ensuing from the loss of the former art . 59 can be reduced to an unavoidable minimum .

kyphoplasty is a surgical technique for height restoration and cement augmentation of vertebral bodies following osteoporotic vertebral compression fractures or osteolytic lesions.1,2,3,4 most studies reveal a low rate of procedure - related adverse events.5,6,7 however , when fluoroscopic imaging is used , radiation exposure of the surgeon and patient are of concern . many of the complications of kyphoplasty have to do with inaccurate cannula placement . to examine the proposition that computer - guided cone - beam ct technology could be used to perform balloon kyphoplasty and subsequently reduce patient and physician radiation exposure from that occurring with the fluoroscopic technique without prolonging the procedure or foregoing acceptable positioning of cannulas within pedicles . inclusion criteria : a cadaveric study to examine the use of cone - beam ct and fluoroscopic assistance during a kyphoplasty . exclusion criteria : cadavers with spinal malformations and/or deformities were excluded from this study . cone - beam ct provided imaging assistance on one of the cadavers and fluoroscopy for the second cadaver . in each of the two cadavers , the vertebra t69 ( thoracic ) and t11l2 ( thoracolumbar ) were selected . kyphoplasty : the thoracic and the thoracolumbar vertebral pedicles were accessed by placing a jamshidi needle percutaneously in the pedicle and then a guide wire . subsequently , both cone - beam ct and fluoroscopic images in each cadaver respectively were taken at each level when the cannulas were in the proper position . cone - beam ct : the procedure was guided through images obtained from the breakaway o - arm ( medtronic inc . , louisville , co ) . a high - speed drill , guided with navigation system ( medtronic inc . , louisville , co ) was used to percutaneously bore a pilot hole down the center of the target pedicle and then place a guide wire in the pilot hole . when the cannulas were in proper placement in the pedicle of both the cadavers , ap and lateral x - rays were taken to assess position of the cannulas . outcomes and analysis primary outcomes : procedure time , radiation exposure to the surgeon and cadaver , and acceptable positioning of cannula within pedicles was assessed during the procedure for both cone - beam ct and fluoroscopic assistance . additional information regarding technical and methodological aspects can be found in the web appendix at www.aospine.org/ebsj . the time required to perform each procedure with fluoroscopy and cone - beam ct was not significantly different ( table 1 ) . radiation exposure to cadaver from the cone - beam ct was equivalent to the exposure to a patient undergoing a kyphoplasty would experience during cannula insertion ( table 1 ) . assessment of the cannula position revealed no cannula malpositions or procedure - related complications for either technique . a cone - beam ct image profile includes images from a single rotation of the cone beam around the cadaver , as well as a digital image that projects instrumental targeting trajectory ( fig . . cone - beam ct image as displayed on the stealth navigation workstation screen position of cannulas were assessed in anteroposterior ( ap ) and lateral views during fluoroscopic imaging . radiation is a concern to both the surgeon and patient during a kyphoplasty with minimal available information regarding cone - beam ct exposure.8,9 both fluoroscopy and cone - beam ct assisted in allowing the acceptable placement of the cannula within pedicles , without a significant difference . these conditions included whether the cannula remained within the pedicle or if it violated the cortical boundaries of the pedicle . when helpful , the system provides imaging assistance with projection of trajectory for cannula placement . limitation : the study may have not included enough cadavers to detect possible surgical performance problems . with this possibility , there may have been differences in procedure time . fluoroscopy and cone - beam ct imaging both provide necessary imaging assistance to perform a kyphoplasty . cone - beam ct provides additional tools which may be beneficial in minimally invasive procedures and zero radiation exposure to the surgeon . a multicenter trial utilizing both fluoroscopy and cone - beam ct during a kyphoplasty may provide stronger evidence for the accuracy and benefit of the two imaging options . using the cone - beam ct kyphoplasty technique : fluoroscopy and cone - beam ct have similar imaging capabilities with equivalent time and accuracy .

study design : equivalence trial ( irb not required for cadaveric studies).objective : to compare computer - guided and fluoroscopic kyphoplasty . factors of interest were radiation exposure , position of cannula within pedicles and procedure time.methods : kyphoplasty was performed on two cadavers . computer - navigated , cross - sectional images from a cone - beam ct were used for one and fluoroscopic imaging for the other . in each , t69 and t11l2 vertebrae were selected . for both imaging methods , anteroposterior and lateral x - rays were taken . radiation exposure for both procedures was measured by four dosimeters . procedure time , radiation to surgeon and cadaver , and position of cannula placement within pedicles were recorded . the surgeon wore one under the lead gown , another on the lead gown at shoulder level , and a third as a ring on the dominant hand . a dosimeter was also placed on the cadaver.results : the radiation from the cone - beam , computer - guided imaging system was 0.0 mrem to the surgeon and 0.52 rads to the cadaver . using fluoroscopic imaging , surgeon 's and cadaver 's exposure was 5 mrem and 0.047 rads , respectively . procedure times were similar and neither device resulted in cannula malposition.conclusions : cone - beam ct appears as accurate as the fluoroscopy ; radiation exposure to the surgeon is eliminated , and radiation levels to the patient are acceptable .

endodontic retreatment of the teeth with intra - radicular posts is usually a difficult situation for clinicians , increasing the risk of perforations , fractures and weakness of the remaining structure of the teeth . removing such posts is performed with different methods and instruments including the masserann technique , pivots - extracting forceps post excavator , post puller , gonon extractor and other techniques using the rotary instruments or ultrasound . . these instruments especially are effective when zinc phosphate or glass ionomer cements are used . the force needed to remove the cemented posts has shown to be related to the post type ( cast or prefabricated ) , the post design ( tapered or parallel , smooth , serrated or threaded ) , the post length and the type of cement used . studies on the effect of ultrasound on removal of posts cemented with resin cements have shown conflicting results . while some studies showed that these vibrations had no effect on retention of posts , bergeron et al . demonstrated that using ultrasound increased the retention of stainless steel posts cemented with resin cement . however , other studies expressed that application of ultrasound decreased the retention of cast posts cemented with resin cements . all the above studies except one used panavia cement ( kuraray medical , japan ) , which is a self - etch resin cement . considering inferior shear bond strength of self - adhesive resin cements to dentin , it may be hypothesized that these cements may have different characteristics when exposed to ultrasonic vibrations . the purpose of this study was to assess the effect of ultrasonic vibrations from a piezoelectric device on retention of prefabricated metal posts cemented with self - etch and self - adhesive resin cements . in this in vitro study , forty eight extracted premolars were selected according to the form and length of the root ( straight with single canal roots and approximately 13 mm in length and round cross - section ) . the crowns were cut - off using a diamond disk under running water , leaving a 13 mm long root . the root canals were instrumented with k - file ( mani , japan ) up to file # 35 and flared using gates - glidden drills # 1 to # 4 ( mani , japan ) . apical 5 mm of the root canals were obturated with gutta - percha ( gapadent , china ) and ah26 sealer ( dentsply , germany ) employing vertical condensation method . the roots were placed in an incubator ( behdad , iran ) for 48 h in 37c and 100% humidity . the remaining 8 mm of the canal space was prepared by peeso reamers # 2 and # 3 ( mani , japan ) for placing a long dentorama prefabricated post # 2 ( svenska dentorama ab , sweden ) . the peeso reamer # 3 and long dentorama prefabricated post # 2 have the same diameter ( 1.1 mm ) . the posts were examined to have an inactive fit in the canals by placing 8 mm inside the canal without having any mobility in the place . specimens that did not have suitable fitness for a long dentorama post # 2 were eliminated . the roots were embedded in self - curing acrylic resin blocks ( marlic medical ind . canals were cleaned with 97% ethanol and dried with paper cones ( ariadent , iran ) . the specimens were randomly assigned to 4 groups ; in groups 1 and 2 the posts were cemented in the canals using panavia f 2.0 cement ( kuraray medical , japan ) and in groups 3 and 4 using maxcem elite cement ( kerr , usa ) . each cement was prepared according to its manufacturer 's instruction . a black - banded lentulo spiral ( ffdm - pneumat , france ) was used to introduce cement into the preparation and coat the walls of the canal . the posts were coated with cement and inserted in the canals to the prepared depth and held in place for 1 min to ensure complete seating according to manufacturer 's instruction . after initial setting of the cements , all specimens were placed in thermocycling machine ( vafaei , iran ) to simulate the thermal changes of the oral cavity ( 5 - 55c , 500 cycles , 20 s dwell time and 10 s transfer time ) . the posts in groups 2 and 4 received ultrasonic vibrations for 4 min using a piezoelectric unit with the blunt - ended tip ( je 27000 , juya electronic , iran ) with maximum power and minimum water as coolant . for transferring the vibrations to the specimens , the tip of the instrument was placed on buccal , lingual , mesial and distal aspects between the post and dentine ( on cement surface ) , 30 s for each . then , the tip of the instrument touched the post and rotated around it for 2 min . the specimens were fixed in a custom made holder [ figure 1 ] and placed in a universal testing machine ( dartec , england ) . tensile force was introduced to each post along the long axis of the root with a crosshead speed of 1 mm / min until the post came out of the canal . custom made holder for tensile force testing statistical analysis was performed using spss software ( version 11.5 , spss inc . kruskal - wallis test was used to assess the differences between groups at a 5% level of significance . a total of 8 specimens were missed during the traction test as their roots came out of the acrylic block before the posts dislodged , 4 specimens in group 1 , 3 specimens in group 3 and 1 specimen in group 4 . means and standard deviations of dislodgement forces in each group are summarized in table 1 . statistical analysis showed no significant difference between the 4 groups ( p = 0.488 ) ; hence , neither cement type nor ultrasonic vibrations affected the dislodgement force significantly . when a post is to be removed from the root canal , ultrasound may be used to make some fractures in cement until the post comes out with less extraction force . this study shows that ultrasound did not reduce the retention of the posts cemented with panavia or maxcem elite resin cements . these findings are in agreement with previous reports on resistance of resin cements to ultrasonic vibrations . this may be due to the viscoelastic nature of resin cements , which tends to soften the vibrations and absorb the energy transmitted to the post . . this variety could be due to differences in method of the study : type of the post ( custom versus prefabricated ) , type , duration and method of using ultrasonic devices as well as using or not using water . in the study , which showed increase in the retention of the panavia cemented posts by ultrasound application great standard deviation was considered as a main cause of this increase . in the majority of studies , which used custom posts ultrasound decreased the retention of panavia cemented posts except the study by gomes et al . which showed the neutral effect of ultrasound on retention of custom posts . this variety is in duration of using ultrasound , location of the ultrasonic tip on the post , using water or not as a coolant , type of the tip of ultrasonic instrument and etc . about the time period of using ultrasound , some issues have been proposed on how to use ultrasonic instruments including duration of time and water cooling . some authors have recommended 8 - 10 min of ultrasonic application to effectively dislodge cemented posts , and hauman et al . reported that 16 min is not enough for the posts cemented with resin cements . in the current study , smith reported that the average time of ultrasound application needed to extract the post in clinical conditions is about 25% of the time at in vitro conditions . he demonstrated that the leakage of restorative materials , cementation under unfavorable conditions and the forces induced to the posts soon after cementation are the main causes of this difference . in this study , regarding water cooling , it has been shown that ultrasonic vibrations with water coolant is less effective on post removal than without it . this can be caused by the fact that resin cements are not friable and there is no tendency to micro fracture in the cement ; unlike zinc phosphate cement , which is friable . furthermore , due to high viscoelastic characteristic of the resin cement , which are categorized as a plastic material , it tends to absorb energy from posts . however , it can not be assumed that application of ultrasound without water can decrease the retention of resin cemented posts since it can be caused by the generated heat by the ultrasonic device . watanabe et al . found that attachment capacity of resin cements decreased gradually by thermal cycles . therefore , by increasing temperature , resins expand and lose their adhesive characteristic and as a result , their retention . in this study , we used minimum water cooling to simulate clinical situation where high temperatures should be avoided . our results showed no significant differences between removal forces of posts cemented with either panavia ( a self - etch resin ) or maxcem elite ( a self - etch self - adhesive resin ) cements . although it has been shown that self - etch self - adhesive resin cements have inferior bonding strength to dentin , it seems that this does not affect retention of posts in the root canal , where a well - fitting post is to be retained inside a cylindrical preparation . further research seems necessary to confirm the effect of ultrasound on retention of different cements in clinical situations where the materials are subject to different thermal and loading conditions . within the limitations of the current study , the efficacy of ultrasound on reducing the retention of prefabricated metal posts cemented with panavia or maxcem elite resin cements is in doubt .

background : ultrasonic vibrations are used to remove a cemented post from a root canal requiring endodontic retreatment . various results have been reported from the studies that evaluated the effect of ultrasonic instruments in removing the posts cemented with resin cements . the aim of this study was to evaluate the effect of ultrasonic energy on the retention of prefabricated metal post cemented with panavia or maxcem elite cements.materials and methods : in this in vitro study , forty eight extracted single root premolars were decoronated with a diamond disc leaving a 13 mm long root and endodontically treated . the root canals were obturated by gutta - percha up to 5 mm with vertical condensation method and the 8 mm post - space was prepared to receive a no . 2 long dentorama post . the roots were placed in an incubator for 48 h in 37c and 100% humidity . after mounting the teeth in acrylic blocks , posts were cemented in the root canals using panavia f2.0 in 24 specimens and maxcem elite in 24 others . for half of the specimens in each subgroup , an ultrasonic device was applied for 4 min . universal testing machine was used to measure the force needed to remove the posts with a crosshead speed of 1 mm / min until the post came out of the canal . kruskal - wallis test was used for statistical analysis at 5% level of significance.results:the removal force was not significantly different among the groups ( p > 0.05).conclusion : ultrasonic energy did not decrease the retention of posts cemented with panavia or maxcem elite cements . furthermore , it seems that there is no significant difference between removal force of self - etch ( panavia ) and the self - etch self - adhesive ( maxcem elite ) resin cements .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Emergency Forest Rescue Act of 2002''. SEC. 2. FINDINGS. Congress finds that-- (1) fire and land management policies have contributed to the increasing severity and intensity of wildfires over the past few decades; (2) a large proportion of Federal forest land is in a condition of serious degradation because of trees that are-- (A) diseased; or (B) dying because of-- (i) insect infestation; (ii) invasive plant species; or (iii) other natural disasters (including blowdowns and wildfires); (3) the drought conditions of 2002 are exacerbating the conditions on Federal forest land, making the Federal forest land particularly susceptible to an increased threat of wildfires; (4) in addition to threatening Federal forest land, wildfires threaten thousands of communities that are located on the border or within the boundaries of the Federal forest land; (5) the 2000 and 2002 fire seasons demonstrate the devastation that is possible if emergency action is not taken to reduce the increased threat of wildfire from diseased and dying trees; (6) the combination of drought and diseased and dying trees creates even more dangerous conditions under which-- (A) the severity of wildfires increases; and (B) wildfires pose a greater threat to public health and safety; and (7) it is critically important that the heads of Federal agencies responsible for managing Federal forest land have the authority to declare as emergency mitigation areas any Federal forest land that has a dangerous buildup of dead or dying trees because of disease, insect infestation, invasive plant species, or other natural disasters, for the purposes of-- (A) reducing the threat of wildfires; and (B) protecting Federal forest land and the communities located near or adjacent to the Federal forest land. SEC. 3. DEFINITIONS. In this Act: (1) Designee.--The term ``designee'' means-- (A) the Chief of the Forest Service; (B) the Director of the Bureau of Land Management; or (C) the Director of the United States Fish and Wildlife Service. (2) Emergency mitigation area.--The term ``emergency mitigation area'' means an area designated by the Secretary under section 4(a). (3) Federal forest land.--The term ``Federal forest land'' means any forest land under the jurisdiction of the Secretary. (4) Secretary.--The term ``Secretary'' means-- (A) in the case of Federal forest land under the jurisdiction of the Forest Service, the Secretary of Agriculture; or (B) in the case of Federal forest land under the jurisdiction of the Bureau of Land Management or the United States Fish and Wildlife Service, the Secretary of the Interior. SEC. 4. EMERGENCY MITIGATION AREAS. (a) Designation.--The Secretary or a designee shall designate as an emergency mitigation area any Federal forest land that-- (1) is experiencing a severe drought; and (2) has a large quantity of trees that are dead or dying because of disease, insect infestation, an invasive plant species, or other natural disaster. (b) Emergency Circumstance.--Designation of an emergency mitigation area under subsection (a) is an emergency circumstance within the meaning of part 1506.11 of title 40, Code of Federal Regulations (or a successor regulation). (c) Alternative Arrangements.-- (1) In general.--On designation of an emergency mitigation area under subsection (a), the Secretary or a designee shall request from the Council on Environmental Quality authority to use any alternative arrangement (including timber harvesting) in the emergency mitigation area that is necessary to protect trees in the emergency mitigation area from disease, insect infestation, an invasive plant species, or other natural disaster. (2) Exemption from applicable law.--In carrying out an alternative arrangement approved by the Council on Environmental Quality under paragraph (1), the Secretary of Agriculture or a designee shall be exempt from the requirements of section 322 of the Department of the Interior and Related Agencies Appropriations Act, 1993 (16 U.S.C. 1612 note).

Emergency Forest Rescue Act of 2002 - Directs the Secretary of Agriculture and the Secretary of the Interior to: (1) designate Federal forest land that is at wildfire risk because of severe drought and dead and dying trees as an emergency mitigation area; and (2) request authority from the Council on Environmental Quality to use alternative arrangements (including timber harvesting) to protect trees in such an area from disease, insect infestation, invasive plant species, or other natural disaster.

Socialite Ivana Trump kicked off an airliner after 'foul-mouthed tirade at noisy children' Belligerent: Ivana Trump was kicked off a flight Socialite Ivana Trump had to be escorted off a plane after launching a foul-mouthed tirade at noisy children. The former wife of billionaire property mogul Donald Trump started screaming the F-word as several excited youngsters ran up and down the first-class aisle. The grandmother of one became even angrier as flight attendants tried to calm her down, allegedly rushing towards the cockpit. When the pilot asked her to leave the New York-bound flight before take-off, the hysterical Miss Trump refused to budge. The former Olympic skier and model, 60 - who split from her much younger fourth husband this month - was eventually 'physically escorted' back to the terminal by security guards, officials said. 'From the initial contact until Miss Trump left the property, she was saying "f*** you" to all the deputies and called the children "little f******",' said a police spokesman. 'She was so belligerent towards other passengers and crew that the plane returned to the terminal.' She had apparently started complaining as soon as she boarded the aircraft, demanding to be moved to another seat in first class. At first she was said to have put on a set of headphones to block out the noise, but a crying baby sent her over the edge. Scene of the set-to: Palm Beach Airport where Ivana was escorted off the plane Split: Ivana has recently split from fourth husband Rossano Rubicondi Passenger Vincent Cone said: 'She was swearing at the baby. 'The reason she got so upset was the children and she started screaming, "I want to go back home". 'The pilots asked her to leave and she sat back down and refused to leave. Then they went and got a security guy. She kept saying, "Let go of me!". 'Everyone was leaning into the aisle, trying to get a good look, saying how crazy she was and how annoyed they were at how she was delaying the flight.' The ruckus meant the Delta-Northwest flight from Palm Beach, Florida, was postponed for two hours. Miss Trump was not charged with any crime, however, and although the FBI was informed about the incident on Saturday, an investigation was not launched. Her Italian husband, Rossano Rubicondi, 37, was said to be in Europe at the time that Miss Trump announced she was ending their 20-month marriage. She said they had struggled to find time to get together while he mainly worked and lived in Italy and she was busy with hotel and resort development projects around the world. Her spokesman was not available for comment last night. ||||| Ivana Trump, the first ex-wife of billionaire Donald Trump , was escorted by sheriff's deputies off a flight Saturday afternoon at Palm Beach International Airport after she screamed and cursed at children, authorities said.Trump, 60, of Palm Beach, was seated in first class and apparently became irate because children were running up and down the aisle and screaming, Palm Beach County sheriff's officials said.Trump, who last week filed for divorce from her third husband, has not been charged in the incident. The FBI declined to investigate, sheriff's officials said.Flight attendants on the LaGuardia-bound Delta flight told deputies that they tried to calm Trump by offering her another seat and headphones. Trump instead became more belligerent.The plane was just leaving gate C1 when the incident occurred, and the pilot decided to pull back to the gate and call for help, officials said.According to the Sheriff's Office, Trump used the "f" word toward the crew and passengers, including children. Officials said she began screaming in vulgar terms for children to shut up.Deputies asked Trump to voluntarily exit the plane, but they said she refused numerous times. Deputies then "physically escorted her off the aircraft," officials said.Deputies said Trump repeatedly cursed at them as well. Trump's driver picked her up at the airport soon after.

– Ivana Trump was kicked off a plane Saturday following an F-bomb-laced tirade directed at children on the Palm Beach-to-NYC flight. Ivana, first ex-wife of Donald Trump, became enraged by some kids who were running up and down the first-class aisles but refused offers of another seat or headphones, sheriff’s officials tell the South Florida Sun-Sentinel. The pilot then returned to the gate, where deputies “physically escorted her off the aircraft.” Trump, 60, allegedly called the kids “little fuckers” and used similar terms to address deputies and flight attendants. She swore at a crying baby as well, one passenger tells the Mail. She was not charged with any crime. As the New York Post points out, this isn’t Trump’s first airplane meltdown: She also complained about her seat assignment and called nearby kids “barbarians” on a September flight.

in a recent paper lada et al . ( 1994 ) have illustrated the method of mapping the distribution of dust , and therefore gas , in dark clouds by using stellar extinction measurements in the near - infrared . the method is based on the use of multi - channel array cameras that allow the simultaneous determinations of the colors of hundreds to thousands of stars through a molecular cloud . the infrared color excess is proportional to the dust column density , and the dust - to - gas ratio is known to be nearly constant in interstellar clouds ; therefore cloud maps can be obtained . the maps obtained measuring the infrared excess are considerably more accurate than the maps based purely on stellar counts . the gas column density is given by @xmath0 where the visual extinction in magnitudes is @xmath1 and the color excess is @xmath2 and finally @xmath3 ( see equations 1 - 4 in lada et al . 1994 ) . the extinction data are used in two complementary ways , one exploiting an ordered sampling ( information on large scale structure ) , the other a random sampling ( information on scales below the resolution of the map ) . in the first method of analysis the data are spatially binned like in stellar count and millimeter wave observations . at any position a few stars are found so that an average extinction @xmath4 can be measured . the result is an extinction map that compares well with the stellar count map and the cs map . the second method is that of plotting the mean extinction , @xmath4 , and its standard deviation , @xmath5 , measured at any position . lada et al . ( 1994 ) found that the dispersion grows with the average extinction , and realized that this behavior contains information about the structure of the extinction ( therefore of the gas mass distribution ) in the cloud , on scales smaller than the resolution of the extinction map . they give examples of mass distributions that would generate or not generate such a plot , but their interpretation of the plot does not go very far . in this work we focus on the second method of using the extinction data , that is on the meaning of the @xmath6 plot as a tracer of structure on scales below the resolution of the map . fig.1 , which is the equivalent of fig.7 in lada et al . ( 1994 ) , shows the @xmath6 plot obtained from the original data , kindly provided to us by the authors . the measurements are taken for a dark cloud complex near the young cluster ic 5146 in cygnus . the cloud has been mapped in @xmath7co and @xmath8co by dobashi et al . ( 1992 ) , who named it ` cloud c ' . in sections 3 and 4 we show that the @xmath6 plot is due to the ` intermittent ' distribution of the dust ( that is of the gas density field in the cloud ) , and we show how to constrain such distribution using randomly generated fields with given statistics and power spectra . before giving such details , though , we present in the next section the results of recent numerical simulations , concerning the density field in isothermal random supersonic flows . it will be clear , in section 4 and in the following discussion , that random supersonic flows are in fact excellent candidates to interpret the extinction data and to explain the origin of the distribution of dust in dark clouds . nordlund and padoan ( 1996 ) and padoan , nordlund and jones ( 1996 ) have recently discussed the importance of supersonic flows in shaping the density distribution in the cold interstellar medium ( ism ) . they have run numerical simulations of isothermal flows randomly forced to high mach numbers . their experiments are meant to represent a fraction of a giant molecular cloud : @xmath9 in size and @xmath10 in mass . the simulated random supersonic motions are in fact observed in molecular clouds . it is found that most of the mass concentrates in a small fraction of the total volume of the simulation , with a very intermittent distribution . the probability density function ( pdf ) of the density field is well approximated by a log - normal distribution : @xmath11 \label{5}\ ] ] where @xmath12 is the relative number density : @xmath13 and the standard deviation @xmath14 and the mean @xmath15 are functions of the rms mach number of the flow , @xmath16 : @xmath17 and @xmath18 or for the linear density : @xmath19 where @xmath20 . therefore the standard deviation grows linearly with the rms mach number of the flow . it is also found that the power spectrum , @xmath21 , of the density distribution is consistent with a power law : @xmath22 where @xmath23 is the wavenumber . we will show in the following sections that the extinction data are consistent with these theoretical predictions . in order to interpret the extinction data we have generated random 3d density distributions with given statistics and power spectra , projected them in 2d , and sampled them randomly as it happen when stars are found through the cloud . the stars are assumed to be uniformly distributed in space . then a grid has been created on the distribution and the mean extinction , @xmath4 , and its dispersion , @xmath5 , have been measured in every bin using the position selected by the few ` stars ' found in the bin . in fig.2 we show the case of a gaussian distribution , to be compared with the case of a log - normal distribution , shown in fig.3 . it is only in the case of the log - normal distribution that the plot @xmath6 is similar to the observational one ( fig.1 ) . clearly some sort of intermittent tail is needed in order to produce the growth in the dispersion with the growth in mean extinction . intermittency is a natural explanation of the plot and it is also the main feature of the density distribution in supersonic turbulence . note that having only high density clumps ( e.g. steep power spectrum ) is not enough to generate the plot , as already shown by lada et al . we have studied the sensitivity of the plot to different power spectra and standard deviations in the 3d density distribution . this is an important point because the power spectrum can not be measured accurately at the moment in the numerical simulations of supersonic turbulence , since it requires a huge dynamical range , and therefore it is interesting to find constraints for it via observations of the projected density field in dark clouds with supersonic random motions . the standard deviation is instead measured in the numerical simulations as a function of the rms mach number of the flow , @xmath24 , and may be directly compared with the observed one , if the rms velocity in the cloud is measured , as is done by millimeter wave observations . fig.4 shows a @xmath6 plot from a random distribution with standard deviation larger than the in the case of fig.3 : the slope of the plot increases together with the standard deviation of the density field . this behavior is easily understood . in fact the plot is related to the structure of the density field on a scale below the resolution of the extinction map : if there were no structure on such small scale , @xmath5 would be close to zero . the larger the fluctuations on small scale , the larger @xmath5 . fig.1 shows the observational @xmath6 plot . a linear regression analysis gives : @xmath25 where the value of the constant is irrelevant in the present work , because the numerical version of the plot can be freely translated along @xmath4 . note that even the values @xmath26 due to the presence of only a single star in the bin are used . the elimination of those values would give the linear regression coefficient found by lada et al . ( 1994 ) . we want to understand now how the linear regression is affected by the errors in the color excess . lada et al . ( 1994 ) estimated a maximum error in the color excess of @xmath27 mag , that translates into an error of @xmath28 mag in @xmath4 . in order to study the effect of the color excess errors we have randomly added such errors to the original data , both with a normal and with a uniform distributions this can be done many times , until any correlation @xmath6 is completely lost . by applying the errors once , we find on the average a coefficient @xmath29 . this is an encouraging result , because it means that , even after the addition of the errors , the uncertainty in the coefficient is still low . of course the coefficient has decreased a bit , because the correlation between @xmath5 and @xmath4 is diminished every time errors are added . the @xmath6 relation to be compared with the numerical ones is therefore : @xmath30 as we mentioned in the previous section the slope of the numerical plot depends on both the power spectrum index , @xmath31 , and the standard deviation of the 3-d density distribution , @xmath32 . we can therefore draw lines of constant @xmath6 linear regression coefficient , @xmath33 , on the plane @xmath34 , as shown in fig.5 . since the value of @xmath33 is known observationally with very small uncertainty ( see ( [ 11 ] ) ) , its contours on the numerical plane @xmath34 may in principle be used to constrain the power index of the 3-d density field when its standard deviation is known , or vice - versa . in fact fig.5 shows that the lines of constant @xmath33 are almost lines of constant @xmath32 , which means that the plane @xmath34 is can constrain the value of @xmath32 , but not that of @xmath31 . given the observational value of @xmath33 and the value of @xmath31 determined below , one gets : @xmath35 this is the value of the standard deviation of the 3-d density distribution in the ` cloud c ' , as given by stellar extinction measurements . the @xmath34 plane does not constrain directly the index of the ( power law ) power spectrum of the 3-d density distribution . nevertheless it is indirectly useful because it gives the 3-d standard deviation , that can be compared with the observed 2-d standard deviation , in order to constrain the spectral index . in fact the projection into 2-d of the 3-d distribution is such that the two standard deviations are related in a way that depends on the value of the power spectrum index . this can be shown using the numerically generated random distributions . in fig.6 , lines of constant spectral index are plotted in the plane @xmath36 . for a fixed 3-d standard deviation , the value of the projected 2-d standard deviation decreases towards steeper spectra . the 2-d standard deviation , @xmath37 , is measured in the extinction map , on a regular grid that contains on average about 5 stars per bin . its standard deviation is : @xmath38 entering the plane @xmath36 with this value and with the previously determined value of @xmath32 , one gets : @xmath39 this is the value of the power index of the 3-d density distribution in the ` cloud c ' . we have seen that the origin of the @xmath6 plot is the intermittency in the 3-d density distribution of the dark cloud ; i.e. , the occurrence of huge density fluctuations with a significant probability . we were inspired towards this explanation of the plot by recent results emerging from our numerical experiments of highly supersonic turbulence . the numerical experiments showed that most of the mass concentrates in a small fraction of the total volume , that very large ( orders of magnitude ) density contrasts appear in the flow , that the distribution of mass density is well described by a log - normal , and that the standard deviation of the statistics grows linearly with the rms mach number of the flow . nevertheless the extinction map itself shows that the distribution of the projected density has an intermittent tail that resembles a log - normal , and even the distribution based on the sampling of column density star by star , which is a random sampling , is qualitatively the same . the problem here is a typical one in astronomy : extracting whole 3-d fields from their integrated 1-d ( eg velocity fields at any point ) or 2-d ( eg scalar fields in space ) counterparts that are observed from our fixed point of view . one way to do this is to build a model for the 3-d field and simulate the observational procedure on that field . the result of the numerical observation is compared with the actual observation , and one may conclude whether or not the model field is consistent with the observation . this method is good only as far as the observations are difficult to reproduce , that is as far as there is no more than one reasonable model that fits the observational data . we have shown how the generation of random fields with given statistics and power spectra ( assumed to be power laws ) leads to the plot of contours of constant value of the slope of the @xmath6 relation , on the plane @xmath34 , and how one may extract both standard deviation and spectral index of the original 3-d field of the dark cloud . clearly _ the contours of @xmath33 on the plane @xmath34 , obtained with numerically generated random distributions , is a powerful tool to investigate the 3-d structure of a dark cloud , down to scales smaller than the resolution of the extinction map , when stellar extinction determinations through the cloud are available . _ if it is assumed that the power spectrum is a universal property of turbulence in this regime ( highly supersonic and super - alfvnic , isothermal equation of state ) , that its shape is in fact a power law , and that dark clouds are in fact in such a turbulent state ( as this work indicates ) then the observational constraint on the power spectrum obtained in the present work is a prediction that numerical simulations will be able to check more firmly in a few years , when larger numerical simulations ( n=500@xmath40 - 1000@xmath40 ) will be available . in the meanwhile , this prediction is very useful for order to model the origin of the mass distribution of protostars , given the statistics and the power spectrum of the density field , in a similar way as it is done in cosmology for predicting the mass distribution of galaxies ( press & schecther 1974 ) . this has in fact been done with considerable success ( padoan , nordlund , & jones 1996 ) . it should be noted that the method of using dust extinction measurements in order to constrain the 3-d density field of dark clouds has several advantages , when compared with the traditional method of using maps of molecular emission lines . first of all it is a much smaller observational effort . secondly the translation of the flux at one given line of one given molecule into column density through the whole cloud is far more complex than the transformation of stellar color excess into column density . finally the random sampling of points in space ( random locations of single stars behind the cloud ) allows for the extraction of information from scales smaller than the resolution of the extinction map , based on averaging at any position a few of the randomly selected points . the information is extracted by using the observational @xmath6 plot , together with the numerical prediction of the slope of that plot in the @xmath34 plane . the extra information one gets can be summarized in the following points : * there must be structure on scales at least ten times smaller than the resolution of the extinction map , that is down to 0.02 pc . * the density distribution is consistent with a log - normal * standard deviation and power index are measured the present work suggests that the dust extinction measurements are consistent with a scenario where the origin of the complex density field in dark clouds is supersonic turbulence , or more generally the presence of supersonic motions in dark clouds , whatever their origin might be . such a scenario is appealing , for the simple reason that supersonic motions have indeed been observed and measured in dark clouds for the last twenty years ! the connection between the observations and supersonic turbulence is not only qualitative in nature ( log - normal shape of the 3-d density distribution ) , but also quantitative . in fact , in our numerical experiments ( nordlund & padoan 1996 ) we have determined the relation between the standard deviation of the 3-d density field , @xmath32 , and the rms mach number of the flow , @xmath41 cf . ( [ 9 ] ) . the same may be done observationally , since cloud c has been studied in some details by dobashi et al ( 1992 ) in @xmath7co and @xmath8co . they obtain measurements of temperature and velocity dispersion in the three main cores , c1 , c2 and c3 , that are included in the area where stellar extinction is measured by lada et al . using those values one gets @xmath42 . given the value @xmath43 obtained in the present work , one sees that the relation between standard deviation of the density field and rms mach number of the flow is consistent with the one predicted in our numerical experiments of supersonic turbulence . moreover , the spectral index estimated from our simulations , @xmath44 , is consistent with that obtained from the observational data ( see fig.7 ) . the values of the standard deviation and of the spectral index are useful for modeling the origin of the mass distribution of protostars , given the statistics and the power spectrum of the density field , in a similar way as it is done in cosmology for predicting the mass distribution of galaxies ( press & schecther 1974 ) . this has in fact been done with considerable success ( padoan , nordlund , & jones 1996 ) . in the present work we have re - interpreted the observational results obtained by lada et al . ( 1994 ) , i.e. the fact that the mean stellar extinction at any given position in space increases together with the dispersion of the extinction , where the averages are taken among the stars found at that position in space . * structure must be present down to scales smaller that the extinction map resolution ; * generic models for the cloud structure ( eg uniform or in clumps ) do not easily reproduce the @xmath6 plot ; * the @xmath6 plot is a basic test for any model for the dynamics and structure of the cold interstellar medium . * the statistics of the 3-d density field in the dark cloud is certainly very intermittent ; in particular it is consistent with a log - normal distribution ; * the standard deviation of the statistics is @xmath45 ; * the index of the power spectrum ( assumed to be a power law ) , of the 3-d density field , is @xmath46 ; * the relation between the rms mach number of the flow and the standard deviation of the 3-d density field is about @xmath47 ; we therefore conclude that the scenario for star formation and for the dynamics of dark clouds proposed by padoan ( 1995 ) , nordlund & padoan 1996 ) , and padoan , nordlund , & jones ( 1996 ) is fully consistent with the dust extinction measurements in ` cloud c ' by lada et al . ( 1994 ) . in that scenario the dynamics of dark clouds is characterized by supersonic random motions , which are responsible for fragmenting the mass distribution . in the cited works we showed that a miller - scalo stellar mass function is a natural consequence of that scenario . here we have shown that the shape , the standard deviation , and the spectral index of the density distribution , predicted with numerical simulations of supersonic turbulence and used in that scenario , are consistent with the observations of stellar extinction .

lada et al . ( 1994 ) have described a method for studying the distribution of dust in dark clouds using infrared imaging surveys . in particular they show that the method provides some information about the structure of the gas ( dust ) on scales smaller than their resolution . in the present work we clarify the nature of the information provided by their method . we show that : * the 3d density field of the gas is well described by a log - normal distribution down to very small scales ; * the power spectrum and the standard deviation of the 3d density field can be constrained ; * the origin of such a structure of the density field is likely to be the supersonic turbulence in the gas . in fact we find a qualitative and quantitative agreement between the predictions based on recent numerical simulations of supersonic turbulence ( nordlund and padoan 1996 ; padoan , nordlund and jones 1996 ) and the constraints given by the infrared dust extinction measurements .

percutaneous , transthoracic fine needle aspiration cytology ( fnac ) is a well established diagnostic method used in the cytological evaluation of thoracic mass lesions for the last three decades . nowadays , computed tomography ( ct)-guided fnac of lesions of the lungs and the mediastinum is widely practised in several institutions where the facilities of standard imaging techniques and cytopathology are available . this procedure provides a safe , rapid , and accurate diagnosis in patients having thoracic mass lesions.[13 ] moreover , ct - guided fnac plays an extremely vital role in small thoracic mass lesions and deep mediastinal nodes in which needle placement is correctly possible by avoiding any surrounding blood vessels and adjacent cardiac structures . in a well conducted series , wallace et al . concluded that ct - guided fnac of small thoracic mass lesions ( one cm or smaller ) can provide high diagnostic accuracy rates approaching those of larger lesions . in cases of malignancy of the lungs , cytopathological examination of material obtained by ct - guided fnac offers a quick and specific diagnosis which helps clinicians implement appropriate anticancer measures like chemotherapy and radiotherapy . it has also been demonstrated in literature that ct - guided fnac is an accurate and sensitive way of diagnosing malignancy of the lungs.[79 ] on the other hand , postprocedure complications are fewer except for pneumothorax , pulmonary hemorrhage , and hemoptysis in a small percentage of cases . severe chronic obstructive pulmonary disease , bleeding diathesis , and pulmonary arterial hypertension are the relative contraindications . the purpose of the current study was to analyse the age , sex , and topographic distribution , the size and cytopathological diagnosis of thoracic mass lesions using ct - guided fnac . this study included 57 patients who had thoracic mass lesions that were suspected to be neoplastic disease in most of the cases by chest radiograph and ct scan . consecutive ct - guided fnac of lung and mediastinal mass lesions of these patients was performed in our institution from july 2007 to june 2008 with immediate cytological assessment . proper aseptic care was taken by cleaning the skin surface with povidone iodine before every fnac . aspiration was done using 21 g , 88 mm long spinal needle through percutaneous and transthoracic approaches , identifying the lesion in the exact section by ct scan after the measurement of the site of entry of the needle , route of the needle , and the distance between the skin and lesion on the ct scan monitor . the patient 's position was supine , prone , or lateral decubitus depending on the location of the thoracic mass lesions . following placement of the needle , a ct scan slice was taken to ascertain whether the tip of the needle was within the mass . the aspirate was obtained by to and fro and rotating movements of the needle within the lesions and five to ten smears were prepared immediately from the sample in the ct scan room . air - dried smears were stained with may - grnwald - giemsa stain whereas alcohol - fixed smears were stained with papanicolaou and hematoxylin and eosin stains for rapid cytopathological evaluation of the lesions . a follow - up ct scan was done in every patient immediately after the procedure to rule out pneumothorax . although all patients with postprocedural complications were observed carefully , no active treatment was required for any of these patients . out of 57 cases involved in our present study , 45 ( 78.9% ) were male and 12 ( 21.1% ) were female . the youngest patient was a female of 34 years whereas the oldest was a male of 79 years ; the overall mean age of all the patients was 56.8 years . a genderwise examination of the patients ages revealed that the mean age was 59.2 years for the males and 47.1 years for the females . two significant findings of our study were that 20 out of 45 male patients were in the age group of 51 - 60 years whereas there were no female patients in the age group of 71 - 80 years [ table 1 ] . age and sex distribution of patients there were 54 ( 94.7% ) parenchymal ( lung ) tumors : 31 were found in the right lung and 23 in the left lung field ; only three cases ( 5.3% ) were located in the anterior mediastinum . among 54 cases of parenchymal ( lung ) tumors , 21 cases ( 36.8% ) were located in the upper zone , followed by 16 cases ( 28.1% ) in the parahilar region , eight cases ( 14.0% ) in the lower zone , and six cases ( 10.6% ) in the mid - zone . two very big tumors ( 3.5% ) involved both the upper and mid zones and one very big tumor ( 1.7% ) involved both the mid and lower zones . according to the ct findings , the size of the lesions varied from 1.2 to 13.6 cm in diameter . only 16 cases ( 14 lung mass and two mediastinal mass ) were five cm in diameter . the size of 38 lesions ( 37 lung mass and one mediastinal mass ) varied from 5.1 to 10 cm whereas the remaining three cases were very big ( > 10 cm in diameter ) . among the lung masses , the pleura were infiltrated in seven cases and in nine cases , the mass was very close to pleura , i.e . , the distance was one cm . out of 57 cases of thoracic mass lesions , definitive cytological diagnosis was obtained in 54 cases and the rest three cases were inconclusive and descriptive report was given to the patients . among 54 cytologically diagnosed cases , 52 were malignant ( including both lung and mediastinal tumors ) and the remaining two cases were diagnosed as granulomatous inflammation that was consistent with tuberculosis [ table 2 ] . all the 23 squamous cell carcinomas diagnosed in our series were located centrally although in the case of the larger tumors , peripheral parts of the lung were also involved . in the case of the 16 adenocarcinomas , distribution of various thoracic mass lesions only one metastatic lung tumor was diagnosed in a known case of clear cell type of renal cell carcinoma , where we obtained cellular smears having cohesive clusters of cells with abundant vacuolated cytoplasm and mildly pleomorphic , round nuclei [ figure 1 ] . the single mediastinal hodgkin 's disease showed the presence of typical reed - sternberg cells . in two cases of mediastinal non - hodgkin 's lymphoma , the cytological smears were highly cellular , consisting of discrete , monotonous populations of cells , having enlarged nuclei with immature chromatin and inconspicuous nucleoli [ figure 2 ] . photomicrograph of fnac smears ( obtained by ct guided fnac ) showing the malignant cells in metastatic lung tumor from renal cell carcinoma ( mgg , 400 ) photomicrograph of fnac smears ( obtained by ct guided fnac from anterior mediastinal mass ) showing the cells of non - hodgkin 's lypmhoma ( mgg , 400 ) postprocedural complications were seen in three cases : post fnac ct scans showed small amounts of pulmonary hemorrhage in two cases and one of the patients suffered from hemoptysis on one occasion just after the aspiration . in the present study , all the 57 patients were adults with even the three cases of mediastinal tumors being found in adults patients . the peak age incidence ( 5160 years ) was the same as that documented in one recent study . the mean age ( 56.8 years ) was also almost similar ( 56.4 years ) to a study conducted by singh et al . however , wallace et al . showed a slightly higher mean age of 61.3 years in the case of ct - guided fine needle aspiration biopsy of small ( one cm ) pulmonary lesions . the age range varied in most of the series from the third to the eighth decade , whereas in a study of 190 cases of thoracic mass lesions , the age range varied from six to 83 years which included three pediatric patients . male patients ( 78.9% ) showed significant preponderance in our study compared to females ( 21.1% ) . in two recent national studies , the percentage of male patients was a little higher than in our series , i.e . , however , the study by sing et al , showed a significantly lower incidence of male patients ( 52.0% ) . in two international studies , the percentage of male patients was found to be 55.7 and 71.1% . in this study , we tried to make a zone - wise distribution of lung tumors on the basis of ct scan findings and found that the upper zone is the most common site followed by the parahilar region . the lesions were quite large in our series : the majority of the thoracic mass lesions ( 37 out of 57 cases ) were 510 cm in diameter . the thoracic mass lesions were more variably sized ( 1.2 - 13.6 cm ) than those reported in another series ( 1.2 - 5.6 cm ) . consistent with findings from study by sing et al , we observed a notable correlation of complications with the distance of the pleura from the lesion . all complications like pulmonary hemorrhage ( in two cases ) and hemoptysis ( in one case ) were seen where the lesions were the furthest , i.e . , this was likely to be due to larger amounts of normal lung tissue that had to be traversed by the needle . however , pneumothorax , the most common complication of other studies , was not found in any case in our study . the overall rate of complications ( 5.2% ) in our study was also remarkably less than other series where the range varied from six to 50%.[1471112 ] this was thought to be due to the larger size of the tumor masses in our series and also due to our meticulous and proper aspiration procedure . cytological diagnosis was made in 54 out of 57 cases ( 94.7% ) and the high incidence of malignancy ( 96.5% ) was comparable with that found in other studies . among all 48 cases of primary lung tumors , the most common ( n = 23 ; 42.6% ) was squamous cell carcinoma followed by 29.6% of adenocarcinoma and 9.3% of small cell carcinoma . this order of frequency was also found in two recently published national studies . in our study , both large cell carcinomas and poorly differentiated carcinomas were equally prevalent ( 3.7% each ) . however , in two studies : one national and one international , the prevalence of large cell carcinoma was more than the present series . the incidence of adenocarcinoma was reported to be significantly higher than that of squamous cell carcinoma in a study by tan et al . all three mediastinal tumors ( 5.6% ) were malignant which included two cases of non - hodgkin 's lymphoma and one case of hodgkin 's disease . both the benign non - neoplastic lesions were diagnosed as granulomatous inflammation consistent with tuberculosis . the incidence of inconclusive ( unsatisfactory for diagnosis ) cases ( 5.6% ) in our series was less than that in other studies . these three cases were later diagnosed histopathologically and treated in other institutions as squamous cell carcinomas . the diagnosis and treatment of various thoracic mass leisions were delayed due to the poor socio - economic status of this region . during aspiration , the majority of cases of the primary lung tumors ( n = 33 ) and the single case of metastasis died within three to six months of diagnosis after getting a few courses of chemotherapy . the remaining 15 cases of primary lung tumor and all the three cases of mediastinal tumor were lost during follow - up . ct - guided fnac of thoracic mass lesions is a safe , rapid , and reliable procedure with minimal complications . it provides very early diagnosis and exact subclassification of various lung tumors on the basis of cytomorphology . the results of this study are mostly comparable with those of other national and international series . the early and accurate diagnosis obtained by ct - guided fnac helps to formulate immediate , effective management of thoracic mass lesions .

background : computed tomography ( ct)-guided fine needle aspiration cytology ( fnac ) is regarded as a rapid , safe , and accurate diagnostic tool in examining thoracic mass lesions for the last three decades.aims:to assess the role of ct - guided fnac in thoracic mass lesions , to analyse the results , and to compare the results with other studies.materials and methods : fifty - seven patients were studied over a year ( july 2007 to june 2008 ) for their age , sex , and topographic distribution , pleural infiltration ( based on ct findings ) , and cytological diagnoses.results:out of 57 cases , 78.9% ( n = 45 ) were male and 21.1% ( n = 12 ) were female . the age range varied from 34 to 79 years with the peak in the fifth decade . there were 54 parenchymal ( lung ) tumors and the remaining three tumor cases were mediastinal . the most common tumor was squamous cell carcinoma ( 42.6% ) followed by adenocarcinoma ( 29.6% ) and small cell carcinoma . postprocedural complications were minimal and were noted in only three cases ( a little pulmonary hemorrhage in two and hemoptysis in one).conclusions : ct - guided fnac of thoracic mass lesions provides a rapid and safe diagnostic procedure with minimal complications . the categorical diagnosis can also be achieved on the basis of cytomorphology . the figures obtained from this study are comparable with other studies except for a few differences .

in multiple myeloma ( mm ) , precise quantification of monoclonal immunoglobulin ( m - ig ) and its variations during the course of the disease , discrimination between monoclonal and polyclonal isotype particularly at low concentrations of m - igs , information about the ratio of clonal and polyclonal plasma cells and about the amount of immunosuppression is important for prognostication , response evaluation and treatment selection . international guidelines recommend the use of serum protein electrophoresis ( spep ) and nephelometry ( neph ) for quantification of monoclonal immunoglobulins ( m - ig ) in mm , with immunofixation electropheresis ( ife ) being used to confirm complete response ( cr ) . however , the usefulness of spep is limited at low m - ig levels , when the m - igs co - migrate with other serum proteins , as commonly observed in iga and less frequently in igg mm , and when the m - ig fails to resolve as a discrete band . however , they tend to overestimate the amount of m - ig at high concentrations , particularly in igg and igm paraproteinemias , but do not discriminate between m - ig and normal polyclonal immunoglobulins , which becomes particularly relevant at low m - ig concentrations . novel antibodies have been produced ( heavy / light chain ( hlc ) antibodies ) , which separately identify the different light chain types of each immunoglobulin class , that is , igg , igg , iga , and iga. they allow accurate quantification of the involved and uninvolved immunoglobulin of the patient 's affected isotype . furthermore , a ratio of the monoclonal and the polyclonal immunoglobulin of the same isotype , that is , of igg/igg , can be calculated ( hlc ratio ) in the same manner as serum - free light chain ( flc ) / ratios . preliminary studies employing the hlc assay have shown that hlc ratios may be of use in screening , monitoring and risk stratifying of patients with mm , al amyloidosis , waldenstrm 's macroglobulinemia and mgus ( monoclonal gammopathy of undetermined significance ) . in addition , they may provide the only sensitive marker of disease progression in some patients . here , we compare the use of igg/igg and iga/iga hlc assays with conventional measurements for quantification of m - igs and for response assessment , and evaluate the advantages and limitations of the new test . in addition , we assess the prognostic relevance of the hlc ratio in patients started on first - line therapy and followed by sequential serum measurements . in all , 156 previously untreated patients with mm and measurable disease as defined by the international myeloma working group criteria were included . patients had been treated with one of the following treatment protocols : thalidomide - dexamethasone ( 27 ) , melphalan dexamethasone , followed by autologous stem cell transplantation ( 23 ) , vincristine melphalan cyclophosphamide prednisolone ( 19 ) , bortezomib thalidomide dexamethasone with or without cyclophosphamide ( 42 ) and lenalidomide dexamethasone ( 30 ) . all patients gave written informed consent for therapy , and their characteristics are shown in table 1 . the imwg criteria were applied to classify very good partial response ( vgpr ) and cr , and the european group for blood and marrow transplantation ( ebmt ) criteria were used to categorize partial response ( pr ) , minor response ( mr ) , stable disease ( sd ) and progressive disease ( pd ) . in addition , the response class ncr ( ife - positive cr ) , was used to denote those patients who had normalization of the isotype concentration of their involved immunoglobulin class , but still a monoclonal band detectable on ife . immunoglobulin hlc pairs ( igg/igg and iga/iga ) were assessed using polyclonal antibodies targeted at unique junctional epitopes between heavy - chain and light - chain constant regions of intact ig ( hevylite , binding site , birmingham , uk ) on a binding site spaplus analyzer . measurements of these parameters were used to derive igg/igg and iga/iga ratios , which were compared with reference ranges . hlc ratios outside of the reference range were considered to be indicative of a clonal process . tests were run independently in birmingham and vienna , and results were read by experienced qualified clinical chemists . immunoelectropheresis was run on sebia hydrasys ( sebia , evry , france ) in both laboratories and results were compared . concentrations of conventional parameters such as iga , igg , 2-microglobulin ( 2-m ) , flc , lactate dehydrogenase , and creatinine were assessed by standard techniques . patients were categorized using hlc ratio and flc ratio prognostic values , which were broadly identified using receiver operator characteristic ( roc ) analysis with final cut - offs being identified by trial and error . patients were stratified into different treatment - induced response groups , and distribution of hlc values at baseline according to response category was assessed by the welch test . meier survival curves were compared using the log - rank test , whereas univariate and multivariate analysis were performed by cox proportional regression analysis ( spss version 18 , ibm , armonk , ny , usa ) . patients were followed up for a median of 46.1 months ( range : 0.5157.8 ) . previous assessment of hlc concentrations in normal blood donors established median hlc ratios and 95% ranges of 1.74 ( 1.123.21 ) for igg/igg and of 1.18 ( 0.781.94 ) for iga/iga. results of hlc testing revealed 5% of control sera lying outside but very close to the verge of the normal range , and an abnormal hlc ratio in all patients of this study ( figures 1a and b , respectively ) including 18 patients with oligosecretory disease ( < 10 accurate measurement of m - ig by spep densitometry was not possible in 46% ( 26/56 ) iga and 4% ( 4/100 ) igg patients because the m - ig had been obscured by other proteins , mostly because of migration toward the region . quantitative hlc measurements were possible in all patients , even in those with m - ig difficult to be quantified by spep . summated ig+ig correlated well to total ig for each isotype measures ; igg ( r=0.93 ) , iga ( r=0.94 ) . cr and ncr were noted in 31 ( 20.8% ) and 17 ( 11.4% ) of all patients ; 18 ( 12.1% ) were categorized as vgpr , 46 ( 30.9% ) as pr and 18 ( 12.1% ) as minor response , respectively , yielding an overall response rate ( cr pr ) of 75.2% . eight ( 5.4% ) patients presented with stable disease and 11 ( 8% ) with progressive disease . at time of best response , exact quantification by spep was not possible in two patients with minor response , seven patients with pr , and one patient with vgpr . hlc ratios could be determined in all of those patients and were abnormal in all . the distribution hlc ratios at baseline was similar in patients with subsequent different response categories ( p=0.451 ) , thus baseline hlc levels did not predict the quality of response after induction therapy ( figure 2 ) . measurement of hlc ratio at best response yielded significantly different results in the various response groups ( p<0.006 ) . table 2 shows the results of hlc , flc , ife and spep testing in patients at time of best response . of note , an abnormal hlc ratio was seen in 8 of the 31 patients in cr ; four of them had abnormal hlc ratio only , whereas in the other four both an abnormal hlc and flc ratio were noted . in the 17 patients with ncr and the 18 patients with vgpr , an abnormal hlc ratio was observed in 9 and 14 patients , respectively , with 8 and 10 each having both abnormal hlc and flc ratio . figures 3a and b show a typical follow - up of individual patients with sequential testing and the additional use of hlc ratios . patient a achieved a cr established by spep and ife , but an abnormal hlc ratio indicated the presence of m - ig at a time when an m - ig was no longer detectable by ife ( figure 3a ) . with further follow - up and continued cr , the hlc ratio became normal . in this patient , the kinetics of flc ratio corresponded with the changes of the hlc ratio during the entire follow - up . patient b already achieved cr after induction therapy . at the time of first documentation of cr , which occurred before the start of high - dose melphalan , the patient remained in ife - negative cr for 14 months , but the hlc ratio became abnormal 7 months after the first achievement of a normal hlc ratio , indicating an evolving relapse . at that time , total iga and iga were still within the normal range . during subsequent testing , ife became positive 5.5 months after the hlc ratio had changed from normal to abnormal . later , spep became positive , with further increase in the hlc ratio . with marked delay these patterns indicated the presence of m - ig , while ife already had become negative or pointing to imminent relapse while ife was still negative , have been observed in three patients each . when patients were stratified according to either abnormal ( 0.02245 ) or highly abnormal ( < 0.022 or > 45 ) presentation hlc ratio values , survival was significantly shorter in those with highly abnormal ratios ( median 40.5 months vs median not reached , hazards ratio ( hr ) : 2.07 , confidence interval ( ci ) : 1.153.75 , p=0.016 ) ( figure 4a ) . the survival rates at 5 years were 33.4% for the former and 58.9% for the latter group ( p=0.01 ) . for patients with a highly abnormal flc ratio ( < 0.1 or > 30 ) , a statistically not significant tendency for shorter survival was noted ( 40.8 months vs median not reached , hr : 1.72 , ci : 0.933.17 , p=0.08 ) compared with those with less abnormal flc ratios ( 0.130 ) . when survival was analyzed from time of first achievement of maximal response ( pr or better ) , patients with hlc ratios remaining abnormal had a significantly shortened survival as compared with those achieving a normal hlc ratio ( 40.5 months ; ci : 1765 vs median not reached , hr : 2.8 , ci : 0.998.3 , p<0.03 ) ( figure 4b ) . a similar , but statistically not significant tendency was noted in the patients who achieved vgpr or better ( median not reached , hr : 2.1 , ci : 0.67.5 , p=0.2 ) ( figure 4c ) . univariate cox analysis associated an increasingly abnormal hlc ratio ( < 0.022 , > 45 ) and a 2-microglobulin concentration of > 5.5mg / l at presentation with shorter survival ( hr 1.88 , ci : 1.13.1 , p=0.015 and hr 2.2 , ci : 1.33.9 , p=0.016 , respectively ) , whereas for the other parameters tested ( flc ratio , albumin > results of multivariate cox analysis proved a highly abnormal hlc ratio and highly abnormal 2-microglobulin as parameters independently associated with survival ( hr : 1.94 , ci : 1.13.3 , p=0.016 , and hr : 2.01 , ci : 1.13.6 , p=0.016 , respectively ) . our study shows that the hlc assay can overcome an important limitation of measuring m - igs with conventional techniques . the m - igs of patients with iga myelomas frequently migrate into the region of the spep , where they are obscured by proteins such as transferrin , lipoprotein and c3 , which precludes quantification by spep . this problem occurred in 46% of our iga and in 4% of our igg patients . a similar observation was previously reported by wang et al . , and recently by avet - loiseau et al . , who were unable to quantify iga levels by spep in 57% and 33% of their patients , respectively . 10g / l ) , characterized by subtly abnormal hlc ratio , changes in hlc ratio reflected response and relapse , and therefore could be used as an additional monitoring tool in difficult - to - quantify patients . a further important advantage of the hlc assay is its ability to detect clonality at low m - ig concentrations . this can not be achieved with total immunoglobulin measurements because these assays are unable to distinguish between the involved and uninvolved immunoglobulin of the respective isotype . spep , particularly capillary spep , may provide more reliable measurements , but has important limitations in assigning the m - ig fraction to a specific band , for example , when the m - ig is polymerized and therefore spread over a larger distance in the electrophoresis curve . table 2 shows discordance between hlc and flc ratios seen in several patients with cr ; it shows that both tests are needed to exclude presence of minimal amounts of m - ig . persistent disease was indicated by an abnormal hlc ratio in 8/31 patients who achieved cr with four of them showing abnormal hlc , but normal flc ratios ( table 2 ) . the demonstration of abnormal hlc ratios in patients with ife - negative cr suggests a higher sensitivity for the detection of residual m - ig , and this is corroborated by the association of abnormal hlc ratios with shorter survival times from maximal response . somewhat contradictory to this assumption is the observation of a normal hlc ratio in 12/35 ife - positive patients achieving ncr or vgpr . patients responding to therapy will have an increased polyclonal immunoglobulin production which , in the presence of low levels of monoclonal immunoglobulin , may yield a normal ratio . the low - level m - ig could be due to a prolonged half - life , which has previously been reported , or be due to the persistence of a small clone that has not been cleared by treatment . the latter is unlikely in light of the observation that irrespective of ife positivity a normal hlc ratio predicts a good patient outcome in this study . paiva et al . reported superior prognostic relevance of immunophenotypically defined response over stringent cr ( scr ) . the achievement of scr was not associated with improved survival compared with patients achieving cr only , but patients with immunophenotypically defined cr had significantly improved survival . this concurs with our data showing significantly better survival from onset of pr in patients with normal hlc ratio ( figure 4b ) . for patients who achieved vgpr , a similar , albeit statistically not significant , normalization of the flc ratio , in contrast , did not correlate with overall survival , neither in the entire patient group nor in those achieving pr , orvgpr . patients with > vgpr and an hlc normalization after induction therapy before transplant had a lower risk of treatment failure and a longer progression free survival , whereas for normalization of flc ratios no such association was noted . on the basis of the available evidence , normalization of the hlc ratio seems to be of greater predictive value than flc normalization . further studies should compare immunophenotyping with hlc measurements , which can be performed repetitively without the need for bone marrow aspiration or biopsy . sequential testing in our patients ( figures 3a and b ) showed that patients who are deemed having achieved cr by conventional testing ( spep , neph and ife ) may still have residual disease by hlc testing . vice versa , conversion of a normal to an abnormal hlc ratio indicated evolving relapse , weeks or months before relapse became evident by conventional methods . flc ratios frequently concurred with the hlc ratios , but in some patients results were discordant . this finding underlines the variability in clonal evolution during the course of mm and highlights the emergence of various clones . the original clone may persist as single clone , but probably more often subclones with truncated ability for production of intact immunoglobulins do emerge . they may produce light chains , or as shown in some patients in our study , intact immunoglobulins ( heavy and light chains ) only , and may coexist with the original population of intact molecule secreting myeloma cells . thus , the hlc assay likely will provide additional information on the clonal evolution in myeloma . the finding of a significant association of baseline hlc ratios with overall survival is remarkable . this was true when hlc ratios were considered as linear variable ( p=0.016 ) or stratified according to the extremity of the hlc ratio ( < 0.022 or > 45 vs 0.02245 excluding normal ranges ) . an association of extreme hlc ratios with significantly shorter progression - free survival has already previously been reported by avet - loiseau et al . notably , for highly abnormal flc ratios only , a tendency for shorter survival was noted in our cohort , which is at variance with some studies showing prognostic significance of abnormal flc ratios . the results of univariate and cox multivariate regression analysis confirmed the prognostic relevance of the hlc ratio together with 2-microglobulin , whereas for flc ratio , lactate dehydrogenase and albumin no significant association was noted . one of the limitations of this report is that we did not analyze the relevance of the iga and igg hlc ratio separately , because of the limited number of iga patients . furthermore , our patients have been studied retrospectively in order to enable long - term follow - up for survival analysis , but studies need to be designed to prospectively assess the value of the assay . in conclusion , the findings presented here indicate a considerable potential of the hlc assay . alongside clinical evaluation this test likely will be used to confirm and quantify m - igs , identify patient responses , early relapse and aid in the recognition of minimal residual disease in patients with mm and several other paraproteinemic disorders .

the novel heavy / light chain ( hlc ) assay was used for the detection and measurement of monoclonal immunoglobulins , response evaluation and prognostication . this test allows identification and quantification of the different light chain types of each immunoglobulin class ( for example , igg and igg ) and enables calculation of ratios of monoclonal / polyclonal immunoglobulin ( hlc ratio ) . sequential sera of 156 patients with igg or iga myeloma started on first - line therapy and followed for a median of 46.1 months were analyzed . results were compared with those obtained with conventional techniques ( serum protein electrophoresis ( spep ) , immunofixation electrophoresis ( ife ) , nephelometry ( neph ) , and the free light chain test ( flc ) ) . our data show that the hlc assay allowed quantification of monoclonal proteins not accurately measurable by spep or neph . when both hlc and flc testing were applied for response assessment , clonal excess was noted in 14/31 patients with complete response ( cr ) . hlc ratio indicated presence of disease in 8/31 patients who achieved cr and , in sequential studies indicated evolving relapse in three patients before ife became positive . highly abnormal hlc ratios at presentation were significantly associated with shorter overall survival ( 40.5 months vs median not reached , p=0.016 ) . multivariate analysis revealed hlc ratio ( p=0.03 ) and 2-microglobulin ( p<0.01 ) as independent risk factors for survival .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Traumatic Brain Injury Act of 2006''. SEC. 2. PROGRAMS OF CENTERS FOR DISEASE CONTROL AND PREVENTION. (a) Prevention of Traumatic Brain Injury.--Clause (ii) of section 393A(b)(3)(A) of the Public Health Service Act (42 U.S.C. 280b-1b) is amended by striking ``from hospitals and trauma centers'' and inserting ``from hospitals and emergency departments''. (b) National Program for Traumatic Brain Injury Surveillance and Registries.--Part J of title III of the Public Health Service Act (42 U.S.C. 280b et seq.) is amended-- (1) by redesignating the first section 393B (relating to the use of allotments for rape prevention education) as section 392A and moving such section so that it follows section 392; and (2) by amending section 393B-- (A) in the section heading, by inserting ``surveillance and'' after ``national program for traumatic brain injury''; and (B) by striking ``(a) In General.--''; and (C) in the matter preceding paragraph (1), by striking ``may make grants'' and all that follows through ``to collect data concerning--'' and inserting ``may make grants to States or their designees to operate the State's traumatic brain injury surveillance system or registry to determine the incidence and prevalence of traumatic brain-related injury disability, to ensure the uniformity of reporting under such system or registry, to link individuals with traumatic brain injury to services and supports, and to link such individuals with academic institutions to conduct applied research that will support the development of such surveillance systems and registries as may be necessary. A surveillance system or registry under this section shall provide for the collection of data concerning--''. (c) Authorization of Appropriations.--Section 394A of the Public Health Service Act (42 U.S.C. 280b-3) is amended-- (1) by striking ``For the purpose'' and inserting ``(a) For the purpose''; (2) by striking ``and'' after ``for fiscal year 1994;''; (3) by striking ``and'' after ``through 1998,''; (4) by striking the second period at the end; and (5) by inserting ``, and such sums as may be necessary for each of fiscal years 2006 through 2010'' before the period at the end. SEC. 3. PROGRAMS OF NATIONAL INSTITUTES OF HEALTH. Section 1261 of the Public Health Service Act (42 U.S.C. 300d-61) is amended-- (1) in subparagraph (D) of subsection (d)(4), by striking ``head brain injury'' and inserting ``brain injury''; and (2) in subsection (i), by inserting ``, and such sums as may be necessary for each of fiscal years 2006 through 2010'' before the period at the end. SEC. 4. STUDY ON TRAUMATIC BRAIN INJURY. (a) Amendment.--Part J of title III of the Public Health Service Act (42 U.S.C. 280b et seq.) is amended by inserting after section 393B the following: ``SEC. 393C. STUDY ON TRAUMATIC BRAIN INJURY. ``(a) Study.--The Secretary, acting through the Director of the Centers for Disease Control and Prevention with respect to paragraph (1) and the Director of the National Institutes of Health with respect to paragraphs (2) and (3), shall conduct a study with respect to traumatic brain injury for the purpose of carrying out the following: ``(1) In collaboration with appropriate State and local health-related agencies-- ``(A) determining the incidence and prevalence of traumatic brain injury in all age groups in the general population of the United States, including institutional settings, such as nursing homes, correctional facilities, psychiatric hospitals, and residential institutes for people with developmental disabilities; ``(B) obtaining and maintaining data on the incidence and prevalence of mild traumatic brain injury and report to Congress; and ``(C) collecting, maintaining, and reporting national trends in traumatic brain injury. ``(2) Identifying common therapeutic interventions which are used for the rehabilitation of individuals with such injuries, and, subject to the availability of information, including an analysis of-- ``(A) the effectiveness of each such intervention in improving the functioning, including return to work or school and community participation, of individuals with brain injuries; ``(B) the comparative effectiveness of interventions employed in the course of rehabilitation of individuals with brain injuries to achieve the same or similar clinical outcome; and ``(C) the adequacy of existing measures of outcomes and knowledge of factors influencing differential outcomes. ``(3) Developing practice guidelines for the rehabilitation of traumatic brain injury at such time as appropriate scientific research becomes available. ``(b) Dates Certain for Reports.--Not later than 3 years after the date of the enactment of the Traumatic Brain Injury Act of 2006, the Secretary shall submit to the Congress a report describing findings made as a result of carrying out subsection (a). ``(c) Definition.--For purposes of this section, the term `traumatic brain injury' means an acquired injury to the brain. Such term does not include brain dysfunction caused by congenital or degenerative disorders, nor birth trauma, but may include brain injuries caused by anoxia due to near drowning. The Secretary may revise the definition of such term as the Secretary determines necessary. ``(d) Authorization of Appropriations.--There are authorized to be appropriated to carry out this section such sums as may be necessary for each of the fiscal years 2006 through 2010.''. (b) Conforming Amendment.--Public Law 104-166 (42 U.S.C. 300d-61 note) is amended by striking section 4. SEC. 5. PROGRAMS OF HEALTH RESOURCES AND SERVICES ADMINISTRATION. (a) State Grants for Projects Regarding Traumatic Brain Injury.-- Section 1252 of the Public Health Service Act (42 U.S.C. 300d-52) is amended-- (1) in subsection (a)-- (A) by striking ``may make grants to States'' and inserting ``may make grants to States and American Indian consortia''; and (B) by striking ``health and other services'' and inserting ``rehabilitation and other services''; (2) in subsection (b)-- (A) in paragraphs (1), (3)(A)(i), (3)(A)(iii), and (3)(A)(iv), by striking the term ``State'' each place such term appears and inserting the term ``State or American Indian consortium''; and (B) in paragraph (2), by striking ``recommendations to the State'' and inserting ``recommendations to the State or American Indian consortium''; (3) in subsection (c)-- (A) in paragraph (1), by striking ``$1 for each $2 of Federal funds'' and inserting ``$1 for each $5 of Federal funds''; and (B) by striking the term ``State'' each place such term appears and inserting ``State or American Indian consortium''; (4) in subsection (e), by striking ``A State that received'' and all that follows through the period and inserting ``A State or American Indian consortium that received a grant under this section prior to the date of the enactment of the Traumatic Brain Injury Act of 2006 may complete the activities funded by the grant.''; (5) in subsection (f)-- (A) in the subsection heading, by inserting ``and American Indian Consortium'' after ``State''; (B) in paragraph (1) in the matter preceding subparagraph (A), paragraph (1)(E), paragraph (2)(A), paragraph (2)(B), paragraph (3) in the matter preceding subparagraph (A), paragraph (3)(E), and paragraph (3)(F), by striking the term ``State'' each place such term appears and inserting ``State or American Indian consortium''; (C) in clause (ii) of paragraph (1)(A), by striking ``children and other individuals'' and inserting ``children, youth, and adults''; and (D) in subsection (h)-- (i) by striking ``Not later than 2 years after the date of the enactment of this section, the Secretary'' and inserting ``Not less than bi-annually, the Secretary''; and (ii) by inserting ``section 1253, and section 1254,'' after ``programs established under this section,''; (6) by amending subsection (i) to read as follows: ``(i) Definitions.--For purposes of this section: ``(1) The terms `American Indian consortium' and `State' have the meanings given to those terms in section 1253. ``(2) The term `traumatic brain injury' means an acquired injury to the brain. Such term does not include brain dysfunction caused by congenital or degenerative disorders, nor birth trauma, but may include brain injuries caused by anoxia due to trauma. The Secretary may revise the definition of such term as the Secretary determines necessary, after consultation with States and other appropriate public or nonprofit private entities.''; and (7) in subsection (j), by inserting ``, and such sums as may be necessary for each of the fiscal years 2006 through 2010'' before the period. (b) State Grants for Protection and Advocacy Services.--Section 1253 of the Public Health Service Act (42 U.S.C. 300d-53) is amended-- (1) in subsections (d) and (e), by striking the term ``subsection (i)'' each place such term appears and inserting ``subsection (l)''; (2) in subsection (g), by inserting ``each fiscal year not later than October 1,'' before ``the Administrator shall pay''; (3) by redesignating subsections (i) and (j) as subsections (l) and (m), respectively; (4) by inserting after subsection (h) the following: ``(i) Data Collection.--The Administrator of the Health Resources and Services Administration and the Commissioner of the Administration on Developmental Disabilities shall enter into an agreement to coordinate the collection of data by the Administrator and the Commissioner regarding protection and advocacy services. ``(j) Training and Technical Assistance.-- ``(1) Grants.--For any fiscal year for which the amount appropriated to carry out this section is $6,000,000 or greater, the Administrator shall use 2 percent of such amount to make a grant to an eligible national association for providing for training and technical assistance to protection and advocacy systems. ``(2) Definition.--In this subsection, the term `eligible national association' means a national association with demonstrated experience in providing training and technical assistance to protection and advocacy systems. ``(k) System Authority.--In providing services under this section, a protection and advocacy system shall have the same authorities, including access to records, as such system would have for purposes of providing services under subtitle C of the Developmental Disabilities Assistance and Bill of Rights Act of 2000.''; and (5) in subsection (l) (as redesignated by this subsection)-- (A) by striking ``and'' after ``fiscal year 2001,'' ; and (B) by inserting ``and such sums as may be necessary for each of the fiscal years 2006 through 2010''. (c) National Grants of Significance.--Part E of title XII of the Public Health Service Act (42 U.S.C.300d-52 et seq.) is amended by adding at end the following: ``SEC. 1254. NATIONAL GRANTS OF SIGNIFICANCE. ``(a) In General.--The Secretary, acting through the Administrator of the Health Resources and Services Administration, may make grants to, or enter into contracts or cooperative agreements with, nonprofit organizations, education institutions, States, and other such entities for projects of national significance that-- ``(1) support the development of national and State policies that reinforce and promote self-determination, independence, productivity, integration, and inclusion in all facets of community life for individuals with traumatic brain injury; ``(2) hold promise to improve or expand opportunities for such individuals, including projects or initiatives significant in scope that-- ``(A) improve access to services and systems of care and support that reflect best practices that can be demonstrated and replicated through technical assistance, training, and education; ``(B) assist States in developing service capacity such as community living options and housing; programs and services that address challenging behaviors of individuals with traumatic brain injury and individuals with dual diagnosis, such as substance abuse; case management; respite; information and referral; and family and community supports; ``(C) improve the capability of systems to monitor and evaluate quality of rehabilitation, long-term care, community services and supports; and ``(D) address emerging needs such as aging caregivers, aging individuals with traumatic brain injury, and servicemen, servicewomen and veterans with traumatic brain injury; v. address trends and issues in State service delivery through data collection and reporting of funding, policies, and services on a periodic basis. ``(b) Definitions.--For purposes of this section, the term `traumatic brain injury' means an acquired injury to the brain. Such term does not include brain dysfunction caused by congenital or degenerative disorders, nor birth trauma, but may include brain injuries caused by anoxia due to trauma. The Secretary may revise the definition of such term as the Secretary determines necessary, after consultation with States and other appropriate public or nonprofit private entities. ``(c) Authorization of Appropriations.--For the purpose of carrying out this section, there are authorized to be appropriated such sums as may be necessary for each of the fiscal years 2006 through 2010.''.

Traumatic Brain Injury Act of 2006 - Amends the Public Health Service Act to: (1) revise the national program for traumatic brain injury registries to include grants for a traumatic brain injury surveillance system; and (2) authorize appropriations through 2010 for the prevention and control of injuries. Requires the Secretary of Health and Human Services, acting through the Director of the Centers for Disease Control and Prevention (CDC) and the Director of the National Institutes of Health (NIH), to conduct a study to: (1) determine the incidence and prevalence of traumatic brain injury; (2) maintain data on the incidence and prevalence of mild traumatic brain injury; (3) report national trends in traumatic brain injury; (4) identify common therapeutic interventions used for the rehabilitation of individuals with such injuries; and (5) develop practice guidelines for such rehabilitation. Allows the Secretary, acting through the Administrator of the Health Resources Services Administration (HRSA), to make grants to states and American Indian consortia to improve access to rehabilitation and other services regarding traumatic brain injury. Requires the Administration and the Commissioner of the Administration on Developmental Disabilities to coordinate the collection of data regarding protection and advocacy services. Directs the Administrator to make a grant for training and technical assistance to protection and advocacy systems, if funds permit. Allows the Secretary, acting through the Administrator, to provide for projects of national significance that: (1) support the development of policies that reinforce and promote self-determination, independence, productivity, integration, and inclusion in all facets of community life for individuals with traumatic brain injury; and (2) hold promise to improve or expand opportunities for such individuals.

the practical applicability of theoretical aspects of modern condensed - matter systems , including electronic , magnetic , spectroscopic , thermodynamic and quantum chemical properties of matter have been greatly simplified by the advent of density functional theory(dft)@xcite . dft , is one of the most successful approach to address the complex effects of the many electron phenomenon and continues to be the same . tremendous advances beyond the local density approximation(lda ) are achieved through the development of wide range of semilocal and non - local exchange - correlation(xc ) functionals @xcite with varying properties in order to accurately describe the ground state in three dimensions(3d ) . however , cutting edge research in low dimensions including , atomistic to artificial structures e.g. , quantum dots , modulated semiconductor layers , quantum hall systems and artificial graphene has also gained momentum and keenly attracted the attention of researchers so far as the theoretical and experimental findings are concerned @xcite . the methodology applied successfully to describe 3d systems can not be applied directly to its two dimensional(2d ) counterpart due to various limitations @xcite . therefore , the search for accurate non - local and semilocal xc functionals for describing such systems is a growing research field @xcite . the higher order functionals are proposed depending on their complexity and efficiency . one rung higher of the 2d - lda is 2d - gga , which is only the functional of reduced density gradient . despite of its grand success in achieving accuracy , still demands potentiality in describing various electronic regime . for example , the shell structure of parabolic quantum dots is visualized through the topology of electron localization factor(elf ) @xcite . the elf is functional of density gradient and kinetic energy density . therefore , in order to separate out different physical regions using different ingredients is of prime importance . so that one region can be distinguished from the other . in this context , the ks - ke density along with reduced density gradient play significant role . the ks - ke dependent functionals are knows as meta - ggas . not only that the meta - ggas are the most accurate functional described within semilocal formalism of 2d - ks - dft @xcite . also , the behavior of the ks - ke plays a significant role in designing the meta - gga functionals . the behavior of the ks kinetic energy density has been studied thoroughly in 3d @xcite but due to the aforementioned time lag between the inception of the 3d and 2d metagga xc functionals , the behavior of the ks - ke in 2d has not been explored much as compared to its 3d counterpart . the mainstay of this paper is to study the behavior of ks - ke in 2d by considering 2d quantum harmonic oscillator as a test case . it has been suggested through the elf that @xcite , near nucleus ( i.e. at origin ) and asymptotic region , the ks - ke behaves one electron like and therefore reduces to von weizscker ke . however , it has been noticed that near the nuclear cusp and at the asymptotic region the ks - ke differs from its von weizscker counterpart significantly as contributions from different orbitals play crucial role . as a matter of which , several 2d meta - gga ingredients can be formed by using the ratio of different kinetic energy densities because they remain invariant under uniform density scaling . not only that , by constructing exactly the enhancement factor , the correct asymptotic behavior of the exchange energy density and potential at meta - gga level can also be deduced . here , we have considered completely a different and intriguing approach to study various regions of 2d systems . the work is organized as follow : in the next section we will derive a theoretical framework to thoroughly study the nature of ks - ke near the nuclear cusp and far away from it i.e. , asymptotic region . then , the behavior of different meta - gga ingredients will be derived by taking the ratios of the kinetic energy densities at different regions of the density profile . lastly , an exchange only functional from meta - gga ingredients with correct asymptotic potential and exchange energy density will be constructed using formally exact properties of enhancement factor . the total electronic energy within density functional formalism is given by , @xmath0 = t_{ks}[\rho ] + u[\rho ] + \int~\rho(\vec{r})v_{ext}(\vec{r})d^2r + e_{xc}[\rho ] , \label{eq1}\ ] ] where @xmath1 is ground state density , @xmath2 $ ] be the ks non - interacting ke , @xmath3 is the hartree energy , @xmath4 is the external potential ( in our case @xmath5 ) and @xmath6 is the xc energy . only the hartree energy and ks non - interacting ke are exactly known in terms of density and orbitals respectively . the exact form of xc energy is the unknown ingredient in dft and need to be approximated . in dft , the spin polarized positive definite ks kinetic energy density is defined as , @xmath7 where @xmath8 is the occupied ks spin orbitals . but it is not unique as any term whose integral vanishes may be added to construct different form of the ke density . however , eq.([eq2 ] ) is physically and numerically most important because it is stable due to involvement of only the first order derivative of orbitals . in 3d , it has been suggested that near nucleus and asymptotic region ks - ke behaves as vw kinetic energy density @xcite . however , the behavior of @xmath9 for 2d has not been explored much which is the mainstay of this work . lets now begin by considering the single electron non - interacting eigenstates of 2d isotropic harmonic oscillator having external potential @xmath10 , @xmath11 being the confinement strength of the oscillator . this simple system is very useful to gain better physical insight of the kinetic energy of finite systems in 2d . we will investigate in details the two important avenues i.e. , @xmath12 and @xmath13 . the eigenstates of the above oscillator are characterized by the radial and orbital quantum numbers @xmath14 and @xmath15 and given by , @xmath16 where @xmath17(it may be @xmath18 or @xmath19 ) is the spin index , @xmath20 and @xmath21 are the radial distance and the azimuthal angle in the cylindrical coordinates . the density corresponding to the above eigenstate , @xmath22 ^ 2(r)e^{-r^2 } , \label{eq4}\ ] ] where @xmath23 is the radial function associated with the laguerre polynomials . the corresponding contribution to the ks kinetic energy density is given by , @xmath24 ^ 2e^{-r^2}+\frac{l^2\rho_{nl}^{\sigma}}{r^2}~. \label{eq5}\end{aligned}\ ] ] the @xmath25 term on the right side of eq.([eq5 ] ) is related to vw - kinetic energy density . the vw - kinetic energy density is obtained by substituting the expression of @xmath26 , eq.([eq4 ] ) in vw - kinetic energy density i.e. @xmath27 and together with eq.([eq5 ] ) one obtains , @xmath28 + \frac{l^2\rho_{nl}^{\sigma}(r)}{r^2}. \label{eq6}\ ] ] this is the paramount equation of our investigation . since , the total positive defined ks kinetic energy density is @xmath29 as , in general @xmath30 $ ] , i.e. , total vw - ke density may or may not be equal to the sum of separate orbital vw - ke density . therefore , the ks kinetic energy density in general not equal to @xmath31 . but equality holds only for linear case . thus , eq.([eq6 ] ) is valid for any shell of the parabolic external potential for 2d system . now , we will rigorously elaborate upon the behaviors of ks kinetic energy in two physically important regions , namely at @xmath12 and @xmath13 . asymptotic region is equally important in density functional formalism as several exchange energy functionals have been designed using the asymptotic behavior of exchange potential , @xmath59 or energy density , @xmath60 such as 2d - b88 @xcite , 2d - br @xcite and 2d - bj @xcite functionals . however , the property of ks - ke in this region is very useful in designing functionals for 2d systems with correct asymptotic behavior at meta - gga level . construction of meta - gga type functional for 2d systems recently gained momentum because of first ever construction of a density matrix expansion based exchange energy functional @xcite . in asymptotic region , the contributions of the outermost valence shells only count . we denote the outer shells as @xmath61 , @xmath62 and @xmath63 , where the prime denotes the asymptotic quantities . now we consider , eq.([eq6 ] ) and from this we define a quantity @xmath64 which accounts for the deviation of the ks kinetic energy density from its vw counterpart i.e. , @xmath65 from the above expression , it is quite clear that if we consider @xmath66 type outer shell , then @xmath67 exactly approaches to @xmath68 . on the other hand if @xmath69 , then the contributions of the other outer shells also count . in that case , @xmath70 decays as @xmath71 . ) , n = 12 ( @xmath72 ) and n = 20 ( @xmath73 ) . for n = 6 ( @xmath74 ) the behavior of @xmath75 is also shown.,width=326,height=192 ] in fig.([fig1 ] ) , we have plotted the deviation of ks kinetic energy term from vw - kinetic energy density for @xmath76 and @xmath77 electrons confined in a parabolic quantum dot with different confinement strengths . the behavior of @xmath78 for @xmath79 is also shown in the figure . it is also evident that , as @xmath13 , @xmath80 . in that case , @xmath81 . thus , in @xmath13 , the correct vw behavior is achieved by ks kinetic energy density . here , all the calculations are done using kli @xcite exact exchange(exx ) as implemented in octopus @xcite code and the output is used as the reference input for our calculations . [ cols="^,^,^,^ " , ] the nature of the ks - ke ( as discussed in previous section ) , is important to design different meta - gga ingredients depending on their behavior in different regions for finite systems in 2d . in 3d , the ks - ke , vw and uniform kinetic energy density are used to design several reduced density gradients for meta - gga functionals . analogously , in 2d , different meta - gga ingredients can also be constructed . in 2d , ks and vw kinetic energy densities remains invariant under uniform density scaling i.e. @xmath82 = \gamma^4\tau^{\sigma - x}[\rho(\gamma \vec{r})]$ ] , where x = ks or vw . therefore , ratio of any two ke densities can form the ingredient for 2d meta - ggas . for one electron ground state , @xmath83 , with @xmath84 be the reduced density matrix . now , define a quantity @xmath85 which can serve as an iso - orbital indicator and equals to @xmath57 when @xmath86 . however , the quantity @xmath87 is an iso - orbital indicator , becomes @xmath57 for one electron or two electron singlet state ( characteristic as @xmath12 and @xmath13 i.e. , near origin or asymptotic region ) and other regions having values between @xmath56 and @xmath57 . also , it remains invariant under unitary transformation of ks occupied orbitals . all these conditions prefer @xmath88 to be an adequate iso - orbital indicator for 2d but it suffers from the order of limit problem . to elaborate on it , we define another meta - gga ingredient , @xmath89 with @xmath90 , the uniform ke density in 2d . now expressing @xmath88 in terms of @xmath91 and reduced density gradient @xmath92 as , @xmath93 we obtain , @xmath94 this problem arises in iso - orbital regions , where @xmath95 approaches zero . the order of limit problem is not new in 3d @xcite . exemplification of this problem for 2d finite system is shown in fig.([fig2 ] ) . the meta - gga ingredient , @xmath91 is @xmath56 for one or two electron singlet state and becomes @xmath57 in uniform density limit . this can also be used to form the electron localization factor as is done earlier @xcite . here , it will be used to design a asymptotic corrected meta - gga functional for 2d systems in the following section . other meta - gga ingredient that can be used to design functionals for 2d are @xmath96 in homogeneous density limit , @xmath97 and in tail region @xmath98 . also , @xmath99 approaches @xmath57 as @xmath100 . whereas , @xmath101 , when @xmath102 . the slowly varying density limit of @xmath99 is achieved by using the semi - classical expansion of the kinetic energy density . this gives , @xmath103 where @xmath104 is the reduced laplacian density gradient . another important ingredient for meta - gga functionals is proposed by becke @xcite . recently , becke s proposed ingredient has been used to obtain the meta - gga functional for 2d systems @xcite . also , attention has been paid to construct such functionals @xcite . the 2d ingredient proposed by becke is @xmath105~. \label{eq21}\ ] ] this inhomogeneity parameter can be used to diffuse or compact the exchange hole surrounding an electron . if the exact quadratic term i.e. the term containing inhomogeneity parameter is larger than its homogeneous counterpart . then , it represents more the compact hole . if not , then the diffuse exchange hole . the @xmath106 , vanishes for uniform density and ranges from @xmath107 to @xmath108 . as near the origin , @xmath109 . so due to the presence of the laplacian term in @xmath110 , it becomes @xmath107 and at the exponential tail region it is @xmath108 . it is also invariant under uniform coordinate scaling . a generalized coordinate transformation based @xmath110 can also be formed as is given in @xcite . the iso - orbital indicator obtained in eq.([eq16 ] ) by assuming that the orbitals are real . but there is a possibility of non - zero current density especially in the case of applied electromagnetic field . in that case , the current density should be added to the vw kinetic energy term and at the same time one has to ensure that for one electron and two electron singlet state it becomes @xmath57 . therefore , the following modification can be done to @xmath88 , @xmath111 with , @xmath112 where @xmath113 the asymptotic region is a physically important in 2d dft . at asymptotic region , the exchange energy density and potential behave as : @xmath114 and @xmath115 respectively ( see appendix - a for details ) . now asymptotic corrected semilocal exchange energy functionals at meta - gga level can be constructed using the ingredients of the previous section . in 2d , any gga or meta - gga exchange energy functional can be written in terms of 2d - enhancement factor as , @xmath116 with @xmath117 be the spin polarized exchange energy per particle given by @xmath118 where @xmath119 is the exchange energy per particle within lda , @xmath120 and @xmath121 is the spin polarized enhancement factor need to be formed from meta - gga ingredients . now , to construct @xmath121 having correct asymptotic behavior of exchange density and potential we have consider the following form , @xmath122 the exchange energy density can be written using this enhancement factor as , @xmath123 with @xmath124 now to prove the asymptotic behavior of the @xmath117 , we can plugin eq.([eq14 ] ) into eq.([eq28 ] ) and obtain , @xmath125 thus , exact asymptotic behavior is achieved , if @xmath126 can be included in the expression of enhancement factor . now to obtain the asymptotic behavior of @xmath127 , lets consider the functional derivatives of exchange energy functional , @xmath128 \psi_{i}^{\sigma}-\vec{\nabla}\big(\frac{\partial(\rho^\sigma\epsilon_\sigma)}{\partial\tau^{\sigma - ks}}\big ) \vec{\nabla}\psi_{i}^{\sigma}\\ -\frac{\partial(\rho^\sigma\epsilon_{x\sigma})}{\partial\tau^{\sigma - ks}}\vec\nabla^2\psi_{i}^{\sigma}\\ = \frac{\partial(\rho^{\sigma}\epsilon_{x\sigma})}{\partial\rho^\sigma}-\vec{\nabla}\cdot\big[\frac{\partial ( \rho^{\sigma}\epsilon_{x\sigma})}{\partial\vec{\nabla}\rho^\sigma}\psi_{i}^{\sigma}+\frac{\partial(\rho^\sigma \epsilon_{x\sigma})}{\partial\tau^{\sigma - ks}}\vec\nabla\psi_{i}^{\sigma}\big]\\ + \big(\frac{\partial(\rho^{\sigma}\epsilon_{x\sigma})}{\partial\vec{\nabla}\rho^\sigma}\big)\cdot\vec{\nabla } \psi_{i}^{\sigma } \label{eq31 } \end{split}\ ] ] the terms containing eq.([eq28 ] ) are obtained by performing the functional derivative . this gives , @xmath129 and also , @xmath130 @xmath131 now substituting eq.([eq32 ] ) and eq.([eq34 ] ) back in eq.([eq31 ] ) leads to @xmath132+\frac{\partial(\rho^{\sigma}\epsilon_{x\sigma})}{\partial\tau^{\sigma - ks } } \frac{|\vec{\nabla}\rho^{\sigma}|}{2\rho^{\sigma}}\big\{\frac{|\vec{\nabla}\rho^{\sigma}|}{2\rho^{\sigma } } \psi_{i\sigma}\\-\vec{\nabla}\psi_{i}^{\sigma}\big\}~. \label{eq35 } \end{split}\ ] ] this is the exchange potential for meta - gga type exchange . in dft , the highest occupied ks orbital is significant to explore the asymptotic property of the potential . in that case , we denote the orbital as @xmath133 ( @xmath134 is the asymptotic density as given in eq.([eq14 ] ) ) and have considered the occupation of the highest occupied label to be equal to @xmath57 . now , substituting @xmath135 in eq.([eq35 ] ) , one can observe that the term inside the curly braces vanishes . thus , @xmath136 which on imposing the asymptotic condition on @xmath137 becomes , @xmath138 therefore , asymptotic behavior of @xmath127 will be achieved if , @xmath139 in appendix - a , we have given a scheme for obtaining all the parameters using exact or nearly exact constraints that should be satisfied by a 2d exchange energy functional . meta - gga functionals are the most accurate and advanced semilocal functionals within dft . it uses positive definite kinetic energy density , reduced density gradient and reduced laplacian gradient as its ingredients . behavior of the kinetic energy density plays a crucial role in designing such functionals . the behavior of positive defined kinetic energy density for finite systems in 2d is obtained rigorously using parabolic quantum dot as a model system . it has been demonstrated that at origin , the ks kinetic energy density not only contains the vw kinetic energy density for @xmath140-states but @xmath141-states also contribute . thus , ks - ke density becomes sum of the vw kinetic energies obtained from different orbitals . similarly , at asymptotic region , the outermost shells contribute and the correct vw behavior of the ks kinetic energy density obtained near the origin . deviation of the ks kinetic energy density from its vw counterpart at asymptotic region with varying number of particles in a finite parabolic quantum dot is also discussed . next , we have obtained the behavior of several meta - gga ingredients for the finite 2d systems i.e. , parabolic quantum dots , which can be used to separate out different physical regions of interest . the order of limit problem of the ks kinetic energy density is also exemplified . as the meta - gga ingredients are very useful in designing the desired enhancement factors with various properties . one such property i.e. the correct asymptotic behavior at the meta - gga level for exchange energy and potential . we have obtained that property by making use of an wellknown meta - gga ingredient . then , proposed an enhancement factor which leads to a semilocal functional for exchange which is applicable to two dimensional quantum systems . the authors would like to acknowledge the financial support from the department of atomic energy , government of india . in this appendix , we will discuss the exact behavior of the enhancement factor at @xmath142 and @xmath143 , using the 2d isotropic harmonic oscillator as an example . to do this , we consider the normalized ground state single particle wavefunction , @xmath144~. \label{aeq1}\ ] ] using single particle density matrix , @xmath145 the cylindrically averaged exchange hole is defined as , @xmath146 this is further used to obtain the exchange energy density as , @xmath147 now using single electron wavefunction , eq.([aeq1 ] ) , the above exchange energy density reduces to @xmath148i_0(\alpha^2r^2/2 ) , \label{aeq5}\ ] ] where @xmath149 is the zeroth order modified bessel function . we are interested in two regions , namely @xmath150 and @xmath151 . for @xmath58 , @xmath152 and for @xmath153 region , @xmath154 . thus , @xmath155 the above results are used to obtain the asymptotically correct exchange energy functional using the meta - gga ingredients . having established the desired behavior of the exchange energy density , we now derive the @xmath156 and @xmath157 behavior of the enhancement factor @xmath158 thus , @xmath159 for slowly varying density , by making use of the semi - classical approximation of the kinetic energy density , one can obtain the form of @xmath91 that has been used to construct the enhancement factor . this gives @xmath160 as the enhancement factor has the form @xmath161^{\frac{1}{2}}\approx 1 - p^{\sigma } + \frac{4}{3}q^{\sigma}~. \label{aeq10}\ ] ] the exchange energy becomes , @xmath162~. \label{aeq11}\ ] ] on performing integration by parts , the reduced laplacian gradient can be transformed into reduced density gradient . thus we obtain , @xmath163 , \label{aeq12}\ ] ] where @xmath164 is the coefficient of enhancement factor for slowly varying density obtained through the small density gradient approximation of enhancement factor @xcite . the values of enhancement factor obtained in different regions are as follows : all these exact or nearly exact constraints can be used to design the meta - gga ingredients based exchange energy functionals . one such functional , we have obtained above . not only that , this is also useful to obtain other meta - gga ingredient based enhancement factors . c. f. von weizscker , z. phys . * 96 * , 431 ( 1935 ) . m. a. l. marques , a. castro , g. f. bertsch , and a. rubio , comput . . commun . * 151 * , 60 ( 2003 ) . p. perdew , jianmin tao , victor n. staroverov and gustavo e. scuseria , chem . phys . * 120 * , 6898 ( 2004 ) .

the positive definite kohn - sham kinetic energy(ks - ke ) density plays crucial role in designing semilocal meta generalized gradient approximations(meta - ggas ) for low dimensional quantum systems . it has been rigorously shown that near nucleus and at the asymptotic region , the ke - ks differ from its von weizscker ( vw ) counterpart as contributions from different orbitals ( i.e. , s and p orbitals ) play important role . this has been explored using two dimensional isotropic quantum harmonic oscillator as a test case . several meta - gga ingredients with different physical behaviors are also constructed and further used to design an accurate semilocal functionals at meta - gga level . in the asymptotic region , a new exchange energy functional is constructed using the meta - gga ingredients with formally exact properties of the enhancement factor . also , it has been shown that exact asymptotic behavior of the exchange energy density and potential can be attained by choosing accurately the enhancement factor as a functional of meta - gga ingredients .

the rebirth of the focus on nonlinear maps has opened unsuspected new perspectives in physics . among them , the logistic map @xcite has achieved a paradigmatic rank . but not only dissipative maps have been playing important roles ; also conservative and symplectic ones , like the standard map , have their places . these simple nonlinear models exhibit essential features of ordered and chaotic systems , and also of the transition between them . when we deal exactly with the critical points , these models present many typical behaviors of complex systems , for instance , slow dynamics , break of ergodicity , power - laws , self - similarity , among others . one of the important contributions that comes from the study of these maps aims to understand the fundamental connections between dynamics and thermodynamics . in fact , the relation between these two main branches of physics is not yet fully understood and there are many points that deserve further investigations @xcite . once these systems have low - dimensionality , it is possible to computationally investigate them in its full phase space , something that is very hard ( not to say impossible ) to implement for high - dimensional systems . there are also important analytical results regarding the logistic maps at the edge of chaos @xcite . it is very impressive that features exhibited by high - dimensional hamiltonian systems @xcite may be found in some of these maps ( conservative @xcite or even dissipative @xcite ) , e.g. , the meta - stationary non - boltzmannian state with a crossover to a stationary boltzmannian state ( crossover that is shifted in time as the system grows ) , indicating that the scenario conjectured in @xcite is somehow ubiquitous . there are basically two computational paths for investigating such dissipative systems , along nonextensive lines : sensitivity - based and relaxation - based approaches . by _ nonextensive _ we mean the use of the nonextensive entropy ( written in its dimensionless form ) @xmath4 and the concepts it implies . the first step of both approaches is to define a partition of the phase space into @xmath5 equally spaced cells ( the graining ) . then the graining is made finer ( by increasing @xmath5 ) . in the sensitivity - based approach , we choose one of the @xmath5 cells of the phase space , put within it @xmath6 points ( typically @xmath7 ) , and then follow the dynamical evolution of these points . its initial entropy is @xmath8 , @xmath9 , ( complete knowledge ) so it increases with time . the chosen initial cell is taken as that ( or those ) that rapidly spread the points over the phase space . it is possible to estimate the value of the entropic index , here called @xmath10 , by at least three different methods , all of them giving the same results . to see a description of these methods , when they were first employed , see @xcite . in the second ( relaxation - based ) approach @xcite , we initially take @xmath7 points uniformly distributed in the whole phase space . its initial entropy @xmath11 is a maximum , @xmath9 ( complete lack of information ) . at the edge of chaos and as @xmath12 , the distribution of points do not occupy the whole phase space , but a fractal subspace of it . so the entropy decreases ( relaxes ) with time . the shrinking of the occupied volume permits to estimate the proper entropy index , here called @xmath13 . these two approaches to the same problem generate different entropic indexes : the sensitivity - based approach generates @xmath14 , while the relaxation - based approach generates @xmath15 . in ref . @xcite it was found for the logistic map that the entropic index @xmath13 depends on the graining @xmath5 , and that there exists the following scaling - law relation : @xmath16 in the present work we further investigate this scaling relation for the henon map ( preliminary results were given in @xcite ) . the existence of a scaling - law between sensitivity - based and relaxation ( graining dependent)-based approaches for different systems , including high - dimensional ones , was suggested in @xcite . we also perform a preliminary study of a linearized version of the henon map , according to the sensitivity - based approach . before going on , let us make a few comments about nomenclature . in early papers on nonextensive statistical mechanics , there were no awareness of the duality of the @xmath17 indexes , so they were simply called @xmath17 , or , sometimes , @xmath18 . the existence of the duality was shown in @xcite and then commented in @xcite . in that paper it was adopted the expression _ mixing _ in the sense of sensitivity to initial conditions , and _ equilibrium _ in the sense of relaxation to the stationary state attractor . so it was then employed the nomenclature @xmath19 and @xmath20 . in some later papers on the subject , this nomenclature has gradually changed . in the present work we adopt @xmath10 in the place of @xmath19 , and @xmath13 in the place of @xmath20 , due to the generality of the concepts . such adaptation of concepts and nomenclature is natural in a still evolving branch of science . we analyze two examples of two - dimensional maps . the first one is the henon map @xcite : @xmath21 the parameter @xmath22 recovers the logistic map when it is set to zero . if @xmath23 , the henon map is conservative . we are particularly interested at small values of @xmath22 ( dissipative systems ) at the edge of chaos ( critical points at which the standard lyapunov exponent changes sign ) . the table [ tab : henon ] presents the critical values of the parameter @xmath24 for different values of @xmath22 , as well as the limits of the phase space in each case . .critical parameter @xmath25 for the henon map , at the edge of chaos . @xmath26 , @xmath27 , @xmath28 and @xmath29 represent the limits of the phase space along @xmath30 and @xmath31 axis , respectively . [ cols="^,^,^,^,^,^",options="header " , ] we also analyze the approximation of the lozi map made at ref . @xcite . the lozi map is a piecewise linearization of the henon map . in @xcite the authors have made a smoothness in the original lozi formulation by inclusion of a third parameter @xmath32 : @xmath33 and @xmath34 is defined as @xmath35 with @xmath36 . the limit @xmath37 recovers the original lozi map . in order to establish a connection between @xmath10 and @xmath13 , we follow the procedure adopted in ref . @xcite , that we briefly describe in the following : we begin with @xmath6 points inside a properly chosen single cell ( similar to the sensitivity - based approach ) . the initial cell is chosen as that one which gives the maximum spread of the points a maximum overshoot in the curve @xmath38 vs. time ( see fig . [ fig : sq - vs - time](a ) , illustrated with the henon map ) . the entropy is evaluated with the value @xmath10 , as determined by the sensitivity - based methods . [ fig : sq - vs - time](a ) may be divided into two parts : the `` uphill side '' is governed by the sensitivity to the initial conditions ; the `` downhill side '' is governed by the relaxation to the final stationary value of @xmath38 . these `` two sides '' are a visual expression of the non - commutability of the limits @xmath39 and @xmath40 . the former expresses that complete knowledge never meets a stationary state . on the other hand , the later order of limits expresses that a stationary state is only possible with lack of information . this non - commutability was conjectured in ref . @xcite for many - body hamiltonian systems , if we substitute the present variable @xmath5 for the number of particles . we particularly focus on the `` downhill side '' and define the variable @xmath41 . the time evolution of @xmath42 gradually displays a power - law , as @xmath5 ( and proportionally @xmath6 ) increases ( fig . [ fig : sq - vs - time](b ) ) . the slope ( in a log - log plot ) of the curve , in the range @xmath42 follows a power - law , is identified with the power of a decreasing @xmath17-exponential ( without cutoff ) , @xmath43^{1/(1-q_{rel})}$ ] ( @xmath44 ) . it is somehow subjective to decide when the power - law begins and when it ends . so we average over many possible intervals ( different beginnings and endings ) , taking into account those with higher correlation coefficient . the sensitivity - based approach to this map was applied previously @xcite , when it was found @xmath3 , the same value found for the logistic map @xcite . when the relaxation - based method is applied to the henon map ( * ? ? ? 1 ) , once again it was found the same value of the logistic map for infinite fine graining , @xmath45 . these results may include the henon map into the family of the logistic map . we then examine the relation between these two @xmath17 indexes : we approximately find the scaling law , eq . ( [ eq : scaling ] ) . the scaling law is found when we analyze the projection of the map in its _ logistic subspace _ ( @xmath30 axis ) , so we use @xmath46 instead of @xmath5 in eq . ( [ eq : scaling ] ) . [ fig : scaling](a ) shows our results for the henon map . the errors associated with the obtained results are relatively large when compared with those of the logistic map . this may be due to the fact that two - dimensional maps demand higher number of cells @xmath5 , and consequently higher number of points @xmath6 . once the computer capabilities are , of course , limited , the graining we can achieve in two - dimensional maps are coarser than in one - dimensional ones . for this reason , the extrapolated curves for @xmath47 in fig . [ fig : scaling](a ) for @xmath48 should be viewed as indicative . we also conclude that the logistic limit @xmath49 is slowly reached . we call attention that in ref . @xcite we were not able ( at that moment ) to see that it was necessary to analyze the logistic subspace , once we had only one value of @xmath22 ; in that paper we adopted @xmath5 in the scaling law . only now we amend that conclusion : fig . [ fig : scaling](b ) shows that the use of the full partition of the phase space @xmath5 , in the two - dimensional henon map is not fair , once @xmath49 does not recover the logistic case . let us now address our results for the smoothed lozi map , eq . ( [ eq : lozi ] ) , at the edge of chaos ( when @xmath50 , @xmath51 for @xmath52 , and @xmath53 for @xmath54 ) . we have focused this map according to the sensitivity - based approach . the analysis of the sensitivity to initial conditions at the edge of chaos ( see @xcite for details of this method ) shows a vanishing standard lyapunov exponent . the positive @xmath17-lyapunov parameter , @xmath55 , expresses that the system follows a complex dynamics , whose upper bound of the sensitivity @xmath56 evolves through a slow dynamics , @xmath57^{1/(1-q_{sen})}$ ] , with @xmath58 . [ fig : lozi](a ) identifies the slope of the upper bound with the power of the previous @xmath17-exponential equation for @xmath56 . a different method related to this sensitivity - based approach , namely the rate of increase of @xmath59 @xcite , is also presented ( fig . [ fig : lozi](b ) ) . the proper value of @xmath17 is that one which generates a linear increase of entropy ( a _ finite _ rate of entropy production ) . both methods give @xmath60 , the same value of the logistic map . it is still missing the analysis of this smoothed lozi map according to the relaxation - based method , as well as the correlation between its entropic indexes @xmath10 and @xmath13 . the duality among the @xmath17-indexes , one related to approaches based on sensitivity to initial conditions , @xmath10 , and other related to approaches based on relaxation to stationary states , @xmath13 , and the connection between them , being verified for the first time for the logistic map ( ref . @xcite ) , has been approximately verified in a two - dimensional ( henon ) map , which belongs to the logistic family . the relation is verified in the logistic subspace of the two - dimensional map . the results straighten the validity of the scaling relation , eq . ( [ eq : scaling ] ) . possibly similar scaling laws exist for different phenomena , as suggested in ref . @xcite , and further studies along these lines would be very welcome . the preliminary analysis of the smoothed lozi map , that introduces a linearization in the henon map , indicates that , as far as the sensitivity to initial conditions are concerned , this map presents the same value of @xmath10 as that of the logistic and henon map . further studies are necessary to evaluate the characteristic values @xmath13 , as well as the connection between them . recently it has been conjectured in @xcite that the complete characterization of a system may demand not only two , but _ three _ entropic indexes . the third one would be related to the stationary state itself , named @xmath61 . these indexes would certainly be related among themselves . detection and estimation of @xmath61 , as well as the discovery of how these three indexes are connected , are essential steps towards the closure of the nonextensive statistical mechanics theory . this work has been partially supported by the turkish academy of sciences , in the framework of the young scientist award program ( ut / tuba - gebip/2001 - 2 - 20 ) . fulvio baldovin is acknowledged for his remarks . the authors gratefully acknowledge the hospitality of the organizers of the second sardinian s next 2003 meeting . f. baldovin , l.g . moyano , a.p . majtey , a. robledo , c. tsallis , _ ubiquity of metastable - to - stable crossover in statistically describable weakly chaotic dynamical systems _ ( submitted to this volume of physica a ) [ also available at http://arxiv.org/cond-mat/0312407 ] . borges , u. tirnakli , _ mixing and relaxation dynamics of the henon map at the edge of chaos _ , to be published in a special volume of physica d , entitled _ anomalous distributions , nonlinear dynamics and nonextensivity _ , eds . swinney and c. tsallis ( 2004 ) [ also available at http://arxiv.org/cond-mat/0302616 ] . c. tsallis , what should a statistical mechanics satisfy to reflect nature ? _ , to be published in a special volume of physica d , entitled _ anomalous distributions , nonlinear dynamics and nonextensivity _ , eds . swinney and c. tsallis ( 2004 ) .

the sensitivity to initial conditions and relaxation dynamics of two - dimensional maps are analyzed at the edge of chaos , along the lines of nonextensive statistical mechanics . we verify the dual nature of the entropic index for the henon map , one ( @xmath0 ) related to its sensitivity to initial conditions properties , and the other , graining - dependent ( @xmath1 ) , related to its relaxation dynamics towards its stationary state attractor . we also corroborate a scaling law between these two indexes , previously found for @xmath2-logistic maps . finally we perform a preliminary analysis of a linearized version of the henon map ( the smoothed lozi map ) . we find that the sensitivity properties of all these @xmath2-logistic , henon and lozi maps are the same , @xmath3 nonextensive thermostatistics , dynamical systems , two - dimensional maps 05.45.-a , 05.45.ac , 05.20.-y

evolutionary , or explicit , phylogenetic networks are graphical models that model reticulate evolutionary histories @xcite . such evolutionary histories arise when processes such as horizontal gene transfer or hybridization occur . research into mathematical properties , complexity results , and algorithmic techniques has exploded recently , as evident by the publication of three recent books on the subject @xcite . a main premise behind the use of phylogenetic networks is that when a single tree is not sufficient to model the evolutionary history of a set of sequences or characters , a phylogenetic network that encompasses several trees is used . for example , the phylogenetic network in fig . [ fig : net](a ) depicts an evolutionary history that involves hybridization between taxon d and the most recent common ancestor ( mrca ) of taxa b and c. with one reticulation node ( a ) and two trees it displays ( b , c).[fig : net],width=240 ] central to research on phylogenetic networks has been the notion of trees _ displayed _ by a phylogenetic network . we say that a phylogenetic network displays a tree if the tree can be obtain be removing a set of reticulation edges " of the network . [ fig : net ] shows the two trees displayed by the network given in the figure . given a phylogenetic network @xmath0 , we denote by @xmath1 the set of all trees displayed by @xmath0 . when incongruence in the gene trees inferred on different genomic regions across a genome alignment is assumed to be caused only by reticulation ( e.g. , hybridization ) , then the observed gene trees are taken to be a subset of the set of trees displayed by the ( unknown ) phylogenetic network for the set of genomes . this is why the set @xmath1 has played a fundamental role in most results established for phylogenetic networks . examples of the prominent use of @xmath1 include : ( 1 ) parsimonious phylogenetic networks that fit the evolution of a sequence of sequences under the infinite sites model @xcite ; ( 2 ) extending the maximum parsimony and maximum likelihood criteria from trees to networks @xcite ; ( 3 ) inferring minimal networks from sets of gene trees @xcite ; ( 4 ) establishing identifiability results related to networks @xcite ; ( 5 ) establishing complexity results related to networks @xcite ; and ( 6 ) identifying special trees within the network @xcite . one of the evolutionary phenomena that has been extensively documented in recent analyses and targeted for computational developments is _ deep coalescence _ , or _ incomplete lineage sorting _ @xcite . this phenomenon amounts to gene tree incongruence due to population effects ( e.g. , the size of an ancestral population or the time between two divergence events ) . when this phenomenon is present in a reticulate evolutionary history , a major challenge faces all the aforementioned works : the set of trees displayed by a network is no longer adequate to fully capture gene evolution within the network . to resolve this issue , we define the set of parental trees of a phylogenetic network to supplant the set of displayed trees . based on this set , we make three contributions . first , we extend the concept of anomaly zone to phylogenetic networks and establish results based on this concept . it is important to note here that sols - lemus _ et al . _ @xcite recently discussed the issue of anomaly in the presence of reticulation where they focused on the species tree " inside the network . here , we define the anomaly zone in terms of the whole set of parental trees and do not designate a species tree inside the network . second , we address the problem of inferring a backbone tree inside the network that could serve as a starting tree for network searches and/or provide information on a potential species tree despite reticulation . as in the first contribution , the work here differs from that of @xcite in focusing on all trees displayed by a network , rather than just a designate species tree . third , we propose a novel clustering - based approach to phylogenetic network inference from gene trees by which the gene trees are first clustered , parental trees are inferred from the clusters , and then the parental trees are combined into a phylogenetic network . gori _ et al . _ @xcite recently studied the performance of various combinations of dissimilarity measures and clustering techniques in clustering gene trees . our work differs from that of @xcite in that our focus is on phylogenetic network inference via clustering . we believe our work will open up new venues for research into computational methods and mathematical results for reticulate evolutionary histories . we focus here on binary evolutionary ( or , explicit ) phylogenetic networks @xcite . the topology of a phylogenetic network @xmath0 is a rooted directed acyclic graph @xmath2 such that @xmath3 contains a unique node with in - degree @xmath4 and out - degree @xmath5 ( the root ) and each of the other nodes has either in - degree @xmath6 and out - degree @xmath5 ( an internal tree node ) , an in - degree @xmath6 and out - degree @xmath4 ( an external tree node , or leaf ) , or in - degree @xmath5 and out - degree @xmath6 ( a reticulation node ) . the phylogenetic network has branch lengths @xmath7 , such that @xmath8 denotes the length , in coalescent units ( in coalescent units , the length of an edge in number of generations is divided by twice the size of the effective population size of the population associated with that edge , and is a standard unit used in coalescent theory ) , of branch @xmath9 in @xmath0 . as we discussed in the background section and illustrated in fig . [ fig : net ] , the notion of trees displayed by a network has played a central role in analyzing and inferring networks . let @xmath0 be a phylogenetic network . a tree @xmath10 is displayed by @xmath0 if it can be obtained by removing for each reticulation node one of the edges incident into it followed by repeatedly applying forced contractions until no nodes of in- and out - degree @xmath6 remain . we denote by @xmath1 the set of all trees displayed by @xmath0 . [ fig : net ] shows a phylogenetic network @xmath0 along with @xmath1 . let us consider tracing the evolution of a recombination - free genomic region of four individuals @xmath11 , @xmath9 , @xmath12 , and @xmath13 , sampled from the four taxa a , b , c and d within the branches of the phylogenetic network @xmath0 of fig . [ fig : net ] . if @xmath9 and @xmath12 coalesce at the most recent common ancestor ( mrca ) of b and c , and no events such as deep coalescence or duplication / loss occur anywhere in the phylogenetic network , then the genealogy of the genomic region is one of the two trees in the set @xmath1 . this is precisely the reason why much attention has been given to the set @xmath1 , as discussed in the background section . however , let us now consider a scenario where @xmath9 and @xmath12 did not coalesce at the mrca of b and c. one potential outcome in terms of the resulting genealogy for @xmath11 , @xmath9 , @xmath12 , and @xmath13 is illustrated in fig . [ fig : dc](a ) . the probability that @xmath9 and @xmath12 fail to coalesce at the mrca of b and c has to do with the quantity @xmath14 in the figure : the smaller it is , the more likely it is that @xmath9 and @xmath12 would fail to coalesce @xcite . ( shown in fig . [ fig : net ] ) capture this scenario . the length in coalescent units of the branch between the reticulation node and the mrca of b and c is @xmath14 . ( b ) an abstract representation of the network , assuming both reticulation edges have the same length @xmath15 . [ fig : dc],width=211 ] interestingly , for the scenario illustrated in fig . [ fig : dc](a ) , neither of the two trees in the set @xmath1 can capture the shown genealogy . this brings us to define the set of parental trees inside a phylogenetic network to appropriately represent the network as a mixture of trees that adequately model the evolution of genes in the presence of deep coalescence . @xcite gave an algorithm for the simple task of converting a phylogenetic network @xmath0 to a multi - labeled tree , or mul - tree , @xmath16 . proceeding from the leaves of the network toward the root , the algorithm creates two copies of each subtree rooted at a reticulation node , attaches them to the two parents of the reticulation node , and deletes the two reticulation edges . [ fig : net2](a ) for an illustration . notice that multiple leaves could be labeled with the same taxon name , and hence the mul - tree naming . due to page limitations , we provide the pseudo - code of the algorithm in the appendix . as phylogenomic analyses are increasingly involving multiple individuals per species , we provide a general definition that applies to cases with multiple individuals per species . let @xmath17 be the set of species and @xmath18 denote the number of genomes sampled from species @xmath19 . let @xmath16 be a mul - tree . we denote by @xmath20 a tree obtained from @xmath16 by retaining , for each taxon @xmath19 , @xmath21 or fewer leaves labeled by @xmath22 and deleting the remaining leaves labeled by @xmath22 , followed by repeatedly applying forced contractions until no nodes of in- and out - degree @xmath6 remain . let @xmath0 be a phylogenetic network on set @xmath17 of taxa and @xmath16 be its mul - tree . a parental tree inside @xmath0 is a tree @xmath10 such that @xmath23 . we denote by @xmath24 the set of all parental trees inside @xmath0 . [ fig : net2 ] shows the set @xmath24 for the phylogenetic network in fig . [ fig : net ] . in fig . [ fig : net](a ) . the set @xmath24 consists of the four trees in ( b)(e ) , assuming one individual is sampled per species . [ fig : net2],width=432 ] the genealogy shown in fig . [ fig : dc](a ) can be captured by the parental tree in fig . [ fig : net2](d ) . indeed , _ et al . _ @xcite gave mass and density functions for gene trees on phylogenetic networks in terms of the set of parental trees inside the network . while it is obvious that @xmath25 , the two sets can differ significantly in terms of their properties . for example , if @xmath0 has @xmath26 reticulation nodes , then @xmath27 . however , @xmath28 could be much larger than @xmath29 , as it is a function of the numbers of leaves under the reticulation nodes as well as the numbers of individuals sampled per species . given a species tree topology @xmath0 and its branch lengths @xmath7 , the gene tree topology @xmath30 can be viewed as a discrete random variable whose mass function @xmath31 was derived in @xcite . in the case of phylogenetic networks , we also associate with every pair of edges @xmath32 and @xmath33 that are incident into the same reticulation node @xmath34 nonnegative real values @xmath35 and @xmath36 such that @xmath37 @xcite . these quantities , which we call inheritance probabilities , indicate the proportions of lineages in hybrid populations that trace each of the two parents of that population . in this case , the phylogenetic network s topology @xmath0 and branch lengths @xmath7 , along with the inheritance probabilities @xmath38 , are sufficient to describe the mass function of gene trees @xmath39 under the multispecies network coalescent @xcite . in this section we describe the three main contributions of this work . first , we extend the concept of anomaly zones @xcite to phylogenetic networks and establish conditions for their existence . second , we address the question of whether it is possible , from an inference perspective , to obtain a tree that can be augmented into the correct network by adding reticulation edges between pairs of the tree s edges . third , we propose a clustering approach to network inference by clustering the gene trees , inferring parental trees , and then combining the parental trees into a network . these results have direct implications not only on understanding the relationships between trees and networks , but also the practical task of developing computational methods for network inference . in a seminal paper , degnan and rosenberg @xcite showed that the branch lengths of a species tree could be set such that the most likely gene tree disagrees with the species tree . such a gene tree is called an _ anomalous gene tree _ and the set of all branch length settings that result in an anomalous gene tree is the _ anomaly zone_. we now provide what , to the best of our knowledge , is the first definition of anomaly zones for phylogenetic networks . note that in @xcite , sols - lemus _ et al . _ discussed anomalous gene trees in the presence of ils and gene flow . however , in their work , the anomaly was still defined with respect to a designated species tree ( they viewed the phylogenetic network as a species tree with additional horizontal edge between pairs of its branches ) . here , we do not designate any of the parental trees of the network as a species tree ; instead , we define the anomaly zone directly in terms of the entire set . let @xmath0 be a phylogenetic network , @xmath7 be its branch lengths , and @xmath38 be the inheritance probabilities associated with its reticulation edges . we say gene tree topology @xmath40 is anomalous for @xmath41 if @xmath42 a phylogenetic network @xmath0 is said to produce anomalies if there exists branch lengths @xmath7 and inheritance probabilities @xmath38 such that there exists an anomalous gene tree @xmath40 for @xmath41 . the anomaly zone for a phylogenetic network @xmath0 is a set of @xmath43 values for which @xmath0 produces anomalies . degnan and rosenberg @xcite showed that three - taxon and symmetric four - taxon species trees have no anomaly zones , but that non - symmetric four - taxon trees and all species trees with five or more taxa have anomaly zones . one practical implication of these results was that the simple approach of sampling a very large number of loci , building gene trees and taking the most frequent gene tree as the species tree ( an approach dubbed the democratic vote " method ) does not always work . since the multispecies coalescent is a special case of the multispecies network coalescent , it immediately follows that any phylogenetic network with @xmath44 leaves produces anomalies . we now show that three - taxon phylogenetic networks do not produce anomalies , but that symmetric phylogenetic networks with @xmath45 leaves could produce anomalies . note that according to @xcite , 3-taxon networks could still generate anomalous gene trees . the seeming discrepancy between the two results is due to to the fact that here we define the anomaly zone in terms of all the parental trees inside the network and not just one designate species tree . ( proof is in the appendix . ) consider now the symmetric phylogenetic network @xmath0 in fig . [ fig : dc](b ) and whose set of parental trees in given in fig . [ fig : net2 ] . the four gene trees that are identical to the parental trees of the network are @xmath46 , @xmath47 , @xmath48 and @xmath49 . we plotted the most probable gene tree of this network when @xmath22 and @xmath14 are both small in fig . [ fig:4taxaspecialprob ] , in which yellow region and orange region stand for the anomaly zone of this network , and blue region is where the most probable gene tree be the backbone tree . this figure shows the existence of anomaly zone of the network in fig . [ fig : dc](b ) ( where @xmath15 is set to @xmath4 ) , which means that symmetric phylogenetic networks with @xmath45 leaves could produce anomalies . ( b ) ( with @xmath50 ) with @xmath51 ( left ) and @xmath52 ( right ) . the y - axis is branch length @xmath14 . the x - axis is branch length @xmath22 . blue : gene tree @xmath47 in both panels , and gene tree @xmath46 additionally in the left panel ; yellow : gene tree @xmath53 ; orange : gene trees @xmath54 and @xmath55 ; brown : gene trees @xmath48 and @xmath49 . [ fig:4taxaspecialprob],title="fig:",scaledwidth=40.0% ] ( b ) ( with @xmath50 ) with @xmath51 ( left ) and @xmath52 ( right ) . the y - axis is branch length @xmath14 . the x - axis is branch length @xmath22 . blue : gene tree @xmath47 in both panels , and gene tree @xmath46 additionally in the left panel ; yellow : gene tree @xmath53 ; orange : gene trees @xmath54 and @xmath55 ; brown : gene trees @xmath48 and @xmath49 . [ fig:4taxaspecialprob],title="fig:",scaledwidth=40.0% ] a very important question in the area of phylogenetic network inference is whether there exists a tree that can be augmented into the network by adding reticulation edges between pairs of the tree s edges . here , we refer to such a tree as the network s _ backbone tree_. a biological significance of this tree lies in its potential designation as the species tree ( e.g. , see the species tree underlying the phylogenetic network of mosquitos in @xcite ) . francis and steel @xcite recently introduced the notion of _ tree - based networks _ to capture those networks that can be obtained by augmenting a backbone tree ( they called it the base tree " ) . we now show that even if a network is tree - based , it is not necessarily the case that the most likely gene tree is its base , a result that is related to the anomalous gene trees discussed above . let us consider again the network of fig . [ fig : dc](b ) . this network is tree - based and each of the two trees in fig . [ fig : net ] could serve as its base ( indeed , the same network is drawn in fig . [ fig : net ] in a way that clearly demonstrates that it is tree - based ) . the probabilities of all 15 gene trees under this phylogenetic network are given in table [ tab : table1 ] in the appendix . while there are 15 possible gene tree topologies on taxa @xmath11 , @xmath9 , @xmath12 , and @xmath13 , as branch length @xmath22 in the network tends to infinity , the probability of seven of the 15 gene tree topologies converges to @xmath4 and only eight gene trees have non - zero mass : @xmath46 , @xmath47 , @xmath48 , @xmath49 , @xmath56 , @xmath57 , @xmath54 , and @xmath55 . the probabilities in this case are given in table [ tab : table1x ] in the appendix and visualized as a function of varying branch length @xmath14 for two different settings of @xmath58 in fig . [ fig:4taxa_chart ] in the appendix . when @xmath51 and @xmath59 , which is equivalent to @xmath60 , the most likely gene tree given @xmath0 is not one of its base trees ( that is , the network can not be obtained by a adding a single reticulation edge to the most likely gene tree ) . this also demonstrates that if we defined anomalies in terms of the set @xmath1 instead of set @xmath24 , the phylogenetic network would still produce anomalous gene trees . given that the most likely gene tree is not necessarily a backbone of the phylogenetic network , we now turn our attention to three recent methods whose goal is to infer a species tree despite horizontal gene transfer . it is very important to point out upfront that the assumptions of these methods do not necessarily match the scenarios we investigate here , but our goal is to assess how well they do at recovering a backbone tree inside the network of fig . [ fig : dc](b ) . in @xcite , _ showed that astral - ii @xcite performed best among species tree inference methods in terms of recovering the species tree in the presence of reticulation ( under a specific model of horizontal gene transfer ) . they further proved that the method is statistically consistent in terms of recovering the species tree under the same model . in @xcite , steel _ et al . _ showed that triplet - based approaches to species tree inference are consistent in terms of inferring a species tree in the presence of horizontal gene transfer ( also under a specific model ) . this technique was implemented as the primordial tree " in dendroscope @xcite . both astral - ii and the primordial tree method in dendroscope take gene trees as input . the method of daskalakis and roch @xcite takes as input gene trees with branch length and compute the distance between every two taxa @xmath61 and @xmath34 as the median of the gene - tree distances between @xmath61 and @xmath34 over all gene trees in the data set ( given a gene tree with branch lengths , the gene - tree distance between two leaves is the sum of the branch lengths on the simple path between the two leaves ) . we simulated gene tree data sets under the phylogenetic network of fig . [ fig : dc](b ) using ms @xcite while varying branch length @xmath14 to take on values from the set @xmath62 ( @xmath15 was set to @xmath4 and @xmath22 was set to @xmath63 so as to rule out deep coalescence involving the two branches incident with the root ) . data sets with @xmath64 , @xmath65 , @xmath66 and @xmath67 gene trees were generated , and for each configuration of branch length @xmath14 and number of gene trees , 100 data sets were simulated . the accuracy of each method for a setting of branch length @xmath14 and number of gene trees is the fraction , out of the 100 data sets , of times that the method returned one of the two trees displayed by the network . the results for all three methods on the simulated data are shown in fig . [ methods : perf ] .

phylogenetic networks model reticulate evolutionary histories . the last two decades have seen an increased interest in establishing mathematical results and developing computational methods for inferring and analyzing these networks . a salient concept underlying a great majority of these developments has been the notion that a network displays a set of trees and those trees can be used to infer , analyze , and study the network . in this paper , we show that in the presence of coalescence effects , the set of displayed trees is not sufficient to capture the network . we formally define the set of parental trees of a network and make three contributions based on this definition . first , we extend the notion of anomaly zone to phylogenetic networks and report on anomaly results for different networks . second , we demonstrate how coalescence events could negatively affect the ability to infer a species tree that could be augmented into the correct network . third , we demonstrate how a phylogenetic network can be viewed as a mixture model that lends itself to a novel inference approach via gene tree clustering . our results demonstrate the limitations of focusing on the set of trees displayed by a network when analyzing and inferring the network . our findings can form the basis for achieving higher accuracy when inferring phylogenetic networks and open up new venues for research in this area , including new problem formulations based on the notion of a network s parental trees .

The father of the late actor Heath Ledger has attacked reports that Philip Seymour Hoffman helped counsel his son about his supposed "drug addiction", calling them a "complete and disrespectful fabrication". The reports, which surfaced on a website called Popdust and have since been repeated by British tabloid The Daily Mail, claim Ledger was "just one of many friends Phil tried to help". Oscar-winning actor Philip Seymour Hoffman was found dead in his New York apartment yesterday. Credit:Reuters It was the second time in as many days The Daily Mail ran false reports related to Hoffman, after falling for a hoax about an alleged hoax that preceded his death. ||||| A haggard Philip Seymour Hoffman knew he was trapped in a downward spiral, readily admitting, “I’m a heroin addict,’’ to a stranger two weeks ago. The Oscar-winning actor made the bizarre admission to magazine publisher John Arundel at the Sundance Film Festival in Park City, Utah, after the businessman didn’t immediately recognize him and asked what he did for a living. “He said, ‘I’m a heroin addict,’ ” the Washington Life Magazine associate publisher recalled for The Post on Monday. Arundel said Hoffman then took off his “sloppy hat” and the publisher realized his mistake and said, “Oh, you’re Philip Seymour Hoffman.” “Bingo!” the actor replied, according to Arundel. Before Hoffman walked away, Arundel recalled, the “Capote’’ actor added, “I just got out of rehab.” “Obviously, he wanted people to know he was in recovery mode,’’ Arundel said. Or at least think he was. In reality, Hoffman — who had struggled with drug and alcohol addiction since his early 20s — was in the middle of a relapse that claimed his life at age 46 on Sunday. His addiction had gotten so bad that Hoffman’s girlfriend of 14 years, costume designer Mimi O’Donnell, had kicked him out of the Jane Street pad in Greenwich Village where they lived with their three young kids, pals said. “It was known that he was struggling to stay sober, and his wife had given him some tough love and told him he needed some time away from the kids and to get straight again,’’ a Hollywood source told The Post. The screen and stage star began renting a $9,800-a-month pad on Bethune Street, less than three blocks away, around three months ago, neighbors said. Hoffman was found dead of an apparent heroin overdose in a bathroom of that apartment, with a hypodermic needle still sticking out of his left forearm. Cops recovered more than 20 empty heroin envelopes from the apartment, a plastic cup with 20 used syringes in it, at least 50 more envelopes of heroin and bags of fresh needles, sources said. A charred spoon was found in the sink. “He was apparently in the throes of a major heroin addiction,’’ a law-enforcement source said. The actor — known for his vivid portrayals of troubled souls — had said he had been clean for more than 20 years before suffering a relapse in 2012 and entering rehab for 10 days last year. A source who was on the same 5:30 a.m. flight as Hoffman out of Los Angeles International Airport last month said the dad of three was in first class knocking back bloody marys. And three days ago, Hoffman was spotted looking “drunk and disheveled” in a bar in downtown Atlanta, sources told TMZ. The star was making “multiple trips’’ to the bathroom, a source said. On the flight home from Atlanta, he was spotted passed out in his seat. Hoffman was supposed to be at the Jane Street pad at 9 a.m. Sunday to pick up son Cooper, 10, and daughters Tallulah, 7, and Willa, 5, sources said. O’Donnell told cops she last saw the actor on the street Saturday afternoon, then talked to him by phone at 10 p.m. — and he seemed high, sources said. When he failed to show the next morning, she got worried and started calling around. Hoffman’s playwright pal, David Bar Katz, and the actor’s personal assistant, Isabella Wing-Davey, discovered his body in the bathroom, sources said. Hoffman, a native of upstate Fairport, was discovered in his underwear lying on his right side on the bathroom floor. “He was cold” and had been there “for hours,” sources said. Katz and Wing-Davey told cops they didn’t know how often Hoffman used drugs or where he got them, sources said. Neither responded to requests for comment. Wing-Davey was spotted Monday afternoon coming out of the Jane Street home. Actress and family friend Cate Blanchett, who appeared with Hoffman in 1999’s “The Talented Mr. Ripley,” also showed up there laden with toys for the three children. Blanchett exited a black Cadillac XTS carrying two huge bags from FAO Schwarz and a telescope under her arm. Her driver carried in a third bag of toys. She declined comment. A pastor named Dan Martin showed up minutes later to counsel the family. Hoffman’s body remained at the morgue Monday, an autopsy still incomplete, officials said. Broadway will dim its lights in his memory Wednesday night. Additional reporting by Kevin Sheehan, Lorena Mongelli and Kate Sheehy ||||| Philip Seymour Hoffman turned his West Village apartment into a drug den. Seventy glassine baggies of heroin packed for individual sale — at least 50 of them unopened — were discovered in the $10,000-a-month rental where the Oscar-winning actor was found dead Sunday with a needle stuck in his left arm, sources said. Some of the envelopes had the words “Ace of Spades” written on them, and others were stamped with the name “Ace of Hearts.” Both are brands of heroin that are often cut with a powerful pain reliever called fentanyl, and have become a plague in Pennsylvania, where they were used in 22 overdose deaths. The body of Philip Seymour Hoffman, the Oscar-winning actor found dead Sunday, is removed from his Bethune St. home. (James Keivom/New York Daily News) Police said they haven’t seen heroin with the Ace of Hearts stamp in New York City since 2012. Cops also removed from Hoffman’s Bethune St. apartment several bags brimming with about 20 hypodermic needles. (JR/New York Daily News) Hoffman’s remains were autopsied on Monday to determine the cause of death, and the heroin is being analyzed to try to determine whether it came from a particular batch currently being hawked on the street. Police, however, are pretty certain they know what killed the supremely talented but drug-addicted actor. “We still think it’s going to be an overdose,” one NYPD source said. Phillip Seymour Hoffman is seen nodding off on a plane from Atlanta to New York City last week, three days before his death. Hoffman was seen at an Atlanta bar drinking prior to his flight. (TMZ) Hoffman, dressed in boxers and a T-shirt, was found dead at 11:30 a.m. Sunday in a bathroom of the fourth-floor apartment by a pal, screenwriter David Katz, and personal assistant Isabella Wing-Davey. Katz had gone to check up on Hoffman after the actor had failed that morning to pick up his three kids from the care of their mother, his estranged girlfriend, Mimi O’Donnell. Not far from Hoffman’s stone-cold body authorities discovered a charred spoon that the 46-year-old appeared to have used to heat up his last high, sources said. The door was double-locked, and there was no indication that anyone other than Hoffman had been inside his pad, the sources added. Once he landed in New York, Phillip Seymour Hoffman was reportedly quickly put on a waiting airport cart. (TMZ) Now police are checking Hoffman’s cell phone records and computer, and checking for security video footage of his recent visitors, in an effort to identify his drug dealer. According to Hoffman’s phone records, at 8 p.m. Saturday he talked to O’Donnell, sources said. Then, at 9 p.m., he spoke to Katz. “The direction of the investigation is going to depend, in large part, on the findings of the medical examiner and the findings of the lab tests on the drugs,” said Deputy Police Commissioner Stephen Davis, the NYPD’s top spokesman. Philip Seymour Hoffman walks with his son, Cooper, in October 2011 in New York’s West Village. Hoffman also had two daughters: Willa and Tallulah. (James Devaney/FilmMagic) Police will use a database to try to determine the origin of the heroin, a law enforcement source said. A source said investigators face a challenging task. “No one’s got a trademark registered on Ace of Hearts” — meaning any dealer can use that name and that because it has that name doesn’t necessarily indicate it came from a batch by the same name found elsewhere, the source said. Philip Seymour Hoffman was photographed in an Atlanta bar three days before he died. (TMZ.com) Hoffman, who won the 2005 Best Actor Oscar for playing the title role in “Capote,” admitted last year to falling off the wagon after two decades of being drug-free and returning to the heroin habit that sent him to rehab. Police found five different prescription drugs in the Bethune St. apartment, which was outfitted like a shooting gallery. One of the five was buprenorphine, which heroin addicts take to help kick the habit, sources said. Philip Seymour Hoffman with girlfriend Mimi O'Donnell at the 80th Academy Awards in 2008. The couple had three children together, and O'Donnell reportedly booted the actor after he started using drugs again. (Andrew Ross/Corbis) As investigators worked the case on Monday, Hoffman’s celebrity friends and supporters stopped by the West Village apartment on Jane St., where Hoffman had lived with O’Donnell, 46, and their three children — Cooper, 10, Tallulah 7, and Willa, 5 — until his relapse. O’Donnell reportedly booted the actor after he started using again. Cate Blanchett, with whom Hoffman acted in the 1999 thriller “The Talented Mr. Ripley,” came bearing gifts for the three kids. She had tears in her eyes. A makeshift memorial with bouquets of flowers, pictures and candles was placed on the front steps of the building where Philip Seymour Hoffman was found dead in his apartment Sunday. (Alex Rud) A short time later, the Rev. James Martin arrived. Martin is a Jesuit priest who met Hoffman in 2005 when the actor was directing “The Last Days of Judas Iscariot.” Actor Justin Theroux, a close friend of Hoffman’s, was also seen leaving O’Donnell’s apartment. O’Donnell did not speak to media gathered outside the residence. Neighbors described her as too distraught over Hoffman’s passing to make a public statement. Cate Blanchett, who starred with Philip Seymour Hoffman in the 1999 thriller 'The Talented Mr. Ripley,' arrives at Mimi O'Donnell's Jane St. apartment Monday holding gifts. (Marcus Santos/New York Daily News) “Just a lost, wonderful soul,” Barbara Meyers, 73, who lives next door, said of Hoffman. “A great guy. A doll. Always looked like a schlepper, baseball cap and hair this way and that, riding around on his bike.” In Los Angeles, actor John Leguizamo told the Daily News he saw Hoffman a week ago at the swanky Chateau Marmont hotel, and they were “talking about theater and how tough it is.” Justin Theroux, a close friend of Philip Seymour Hoffman, leaves Mimi O'Donnell's home on Monday. (Jeff Bachner for New York Daily News) Leguizamo chuckled sadly when he recalled how Hoffman had quoted famed artist Pablo Picasso. “It’s like Picasso said, ‘I do the impossible ’cause everybody else does the possible,’ ” Hoffman said, according to Leguizamo. “I’m not saying I’m Picasso, but theater is like doing the impossible.” Leguizamo, 49, said he and Hoffman “laughed, agreed and went our separate L.A. ways.” Police and members of the media camp outside the apartment of actor Phillip Seymour Hoffman in the West Village on Monday. (Andrew Burton/Getty Images) Mayor de Blasio called the tragic actor a “quintessential New Yorker, in the sense of just everything we love about this place, his creativity and his amazing ability to portray the human condition.” “It’s absolutely tragic,” he said on Brian Lehrer’s radio show on WNYC. “What I can say about his life is even someone of that extraordinary achievement grapples with the demon of substance abuse.” Philip Seymour Hoffman's personal assistant Isabella Wing-Davey (L) and screenwriter David Katz (R) found the actor dead in his apartment Sunday morning. (Jeff Bachner for New York Daily News, FILMMAGIC) Hoffman was also a Tony Award-nominated stage actor who got rave reviews for his portrayal of Willy Loman in the 2012 revival of “Death of a Salesman.” In his memory, Broadway’s theaters will dim the lights on their marquees for a minute at 7:45 p.m. Wednesday. Philip Seymour Hoffman poses for a portrait during the 2010 Sundance Film Festival, where he debuted his first film as a director, 'Jack Goes Boating.' (Matt Carr/Getty Images) In his brown Carhartt coat, ever-present baseball cap and rumpled slacks, Hoffman was a familiar and friendly presence in his neighborhood. Neighbors said they saw the actor as recently as Saturday and he seemed just fine. “He looked like he had just come from California or Florida, he was looking really good,” said 74-year-old Avri Ohana, who lives down the block. Hoffman had in fact been in the South — he was spotted in Atlanta last Thursday at a restaurant near the Hyatt hotel in downtown, according to TMZ.com. Witnesses told the outlet Hoffman had made “multiple trips” to the bathroom and later appeared “drunk and disheveled” at the airport. At the Bethune St. building on Monday, a dozen bouquets of flowers, including roses and orchids, mingled with single flowers on the front steps. There were also two pictures of Hoffman and a handful of candles that were lit until they were doused by a steady snowfall. “He’s the only celebrity we ever cared about,” said 34-year-old Nathan Driver, who lives a couple of blocks away and walked over with wife Tara and their 2-year-old daughter, Scarlett, to pay their respects. With Nancy Dillon, Caitlin Nolan, Erin Durkin, Chelsia Rose Marcius, Joe Dziemianowicz and Dale W. Eisinger tmoore@nydailynews.com Sign up for BREAKING NEWS Emails privacy policy Thanks for subscribing! ||||| As Hollywood continues to remain stunned at the heroin overdose death of Oscar-winner Philip Seymour Hoffman, found in his New York apartment Sunday with up to 70 bags of heroin, 20 hypodermic needles and 5 Rx meds, RadarOnline.com has the seven latest developments. Painful Premonition Hoffman, sensing the wheels of his own self-destruction gain momentum, predicted his own death less than two months before it happened. The actor, who had been going to AA meetings on and off while in the middle of a six-week heroin binge, told one peer in the program, “If I don’t stop I know I’m gonna die.” Before his tragic downfall, the Boogie Nights star had been a steadfast attendee at AA meetings and was well-regarded by others for his motivational speaking. Candid Confession During last month’s Sundance Film Festival in Utah, Hoffman admitted to a magazine publisher his fatal foible over the course of a nondescript chat. Washington Life Magazine publisher John Arundel told the NY Post he didn’t immediately recognize the actor, who was wearing a hat. When Arundel asked him what he did for a living, Hoffman said, “I’m a heroin addict,’’ taking off his hat to reveal himself. After Arundel recognized him, Hoffman clarified he’d just finished rehab. “He wanted people to know he was in recovery mode,’’ Arundel said. PHOTOS: Stars Who OD’d Trouble on the Homefront Mimi O’Donnell, Hoffman’s girlfriend of 15 years and the mother of his three children, had given the actor a dose of “tough love” in his final months, kicking him out of their $4.4 million New York home on Jane Street due to his spiraling battle with heroin addiction, insiders told the NY Post Monday. O’Donnell “told him he needed some time away from the kids and to get straight again,” a source told the paper. The eviction notice from O’Donnell led to the talented actor to rent the Greenwich Village apartment he was found in Sunday. An insider told the paper that O’Donnell, who last spoke with her longtime love Saturday night, remained “distraught” over Hoffman’s passing. Comforting Presences Hoffman’s The Talented Mr. Ripley co-star Cate Blanchett was seen bringing toys to the New York home of the late actor’s three kids, Cooper, 10, Tallulah, 7, and Willa, 5, on Monday. The actress, 44, was teary as she got out of a Cadillac XTS with two large bags and a telescope, staying mum while reporters peppered her with questions. A pastor who said his name was Dan Martin was also seen entering the somber home. PHOTOS: A Look Inside The Condo Phillip Seymour Hoffman Died In Heath Ledger Connection Multiple reports indicate Hoffman took part in an intervention for actor pal Heath Ledger, who died in Jan. 2008 after overdosing on a lethal cocktail of prescription medications. Hoffman, who maintained sobriety for more than 20 years prior to his recent tailspin, was reportedly active in AA, and lent his best efforts to wean the talented Aussie actor off heroin and other substances. Ledger’s father Kim, who sent his condolences to Hoffman’s family, told the Sydney Morning Herald he found the notion his son was a drug addict offensive. “This is a complete and disrespectful fabrication of circumstances surrounding any relationship Heath and Philip Seymour Hoffman may have had and very offensive to the memory of Heath for his family and friends,” Kim told the paper, adding, that Heath’s death was not linked to addiction issues, but rather was “an accidental overdose of prescription drugs whilst suffering severe pneumonia and sleep deprivation.” Expert: Long Dormancy May Have Led Hoffman To Overestimate Tolerance High Watch Recovery Center CEO Janina Kean told the NY Daily News that because the actor had been sober for such a long time, he might have overestimated the amount of heroin he needed to get his fix, triggering the fatal overdose. Kean explained that when heroin users stop using, “The brain begins to reset itself and is no longer able to withstand the same potency … an amount that was once tolerable could easily cause an overdose.” Kean said the gifted actor “may have misjudged how much would have stopped his respiratory center,” a common instance in accidental drug deaths. PHOTOS: Hollywood & Heroin: 28 Stars Who Used What Killed Cory Monteith ‘That Sh*t Took Out Another Great One’ Comedian Artie Lange, whose own battle with heroin and prescription pills — culminating in a 2010 suicide attempt — was well-chronicled in his final four years on The Howard Stern Show and two books (Too Fat To Fish, Crash & Burn), tweeted of the actor’s death, “Phillip Seymour Hoffman please find peace … I hope Phillip is ok now. I pray for his family. That sh*t took out another great one.” Lange, whose toxic tailspin led to his severance from Stern’s radio show, lauded Hoffman as “the best actor” of his time. Stay with Radar for more on the death of Philip Seymour Hoffman.

– Philip Seymour Hoffman apparently had a tragic premonition of his own death: Both Radar and TMZ are running stories today claiming that less than two months ago, Hoffman was on a heroin binge and told a friend, "If I don't stop, I know I'm gonna die." Sources tell TMZ he was also drinking heavily, and though he attended AA meetings in an attempt to get back on the wagon, he couldn't. The latest reports say as many as 70 bags of heroin and 20 hypodermic needles were found at his home. Bizarrely, a magazine publisher tells the New York Post that he didn't recognize Hoffman when he ran into him at Sundance two weeks ago—and when he asked Hoffman what he did for a living, the actor said, "I'm a heroin addict" before taking off his hat so the publisher could recognize him. Hoffman then added, "I just got out of rehab." Prior to his relapse, Hoffman was reportedly considered a "guru" of sobriety at AA meetings, and multiple reports claim he once participated in an intervention for Heath Ledger (though Ledger's dad refutes the idea that his son was an addict). But in recent months, things were so bad that girlfriend Mimi O'Donnell kicked him out of the home they shared, sources say. That's why he was renting the $9,800-a-month apartment where he was eventually found dead. O'Donnell told police she last spoke with him at 10pm Saturday; he was found the next morning after not picking his kids up at 9am as planned. Broadway will dim its lights tomorrow night in a tribute to Hoffman, the New York Daily News reports.

Story highlights Lost rigid contact lens was encapsulated by eyelid It stayed in her eye for 28 years without problems (CNN) Calling all contact lens users: Do not panic. (Shuddering is fine.) Imagine going to the eye doctor because your upper eyelid is swollen and painful. The doctor tells you it's a cyst and operates. Inside the blister, the surgeon finds a contact lens: a rigid gas-permeable one. But you haven't worn that type of contact in 28 years! That's what happened to a 42-year-old British woman, according to a report recently published in the journal BMJ Case Reports The encapsulated contact can be seen on an MRI. Starting as a pea-sized lump just below her left eyebrow, the cyst grew over a six-month period until it was visible on an MRI. In addition to swelling and later pain when touched, her left eyelid drooped. Read More ||||| The full text of all Editor's Choice articles and summaries of every article are free without registration The full text of Images in ... articles are free to registered users Only fellows can access the full text of case reports (apart from Editor's Choice) - become a fellow today, or encourage your institution to, so that together we can grow and develop this resource ||||| Published on Aug 15, 2018 Nearly three decades ago, a 14-year-old in the UK got hit in the eye during a game of badminton and lost her contact lens. No big deal, right? Well, 28 years later, doctors found the missing contact… embedded in a cyst in her left eyelid. Matt Yurus reports. ||||| Every contact lens user has thought about it at least once — what if this thing gets stuck in my eye? Well, hold on tight. The woman had gone to her doctor with swelling in her upper-left eyelid, as well as mild ptosis — meaning her upper eyelid was drooping. The swelling had started as a pea-sized lump that grew larger and painful to touch. A 42-year-old woman in the UK managed to go 28 years with a contact lodged in her eye without even noticing, according to a paper published in the journal BMJ Case Reports . Once the cyst was out, it ruptured and revealed a single, cracked contact lens. The lens turned out to be a rigid gas permeable (RGP) lens. Unlike the soft contact lenses that are mostly in use these days, RGP lenses are an older type that was first used in the 1960s. They’re harder than modern lenses, which means they can be uncomfortable at first. They’re also more likely to accidentally pop out of the eye. That’s how doctors figured out the lens had been in the woman’s eye for 28 long years. The last time the patient had worn that type of lens was when she was 14 years old. That’s when she was hit in the eye with a badminton shuttlecock (also known as a birdie). Everyone had assumed the contact lens had simply fallen out, but they were very wrong. “We can infer that the RGP lens migrated into the patient’s left upper eyelid at the time of trauma and had been in situ for the last 28 years,” wrote Dr. Sirjhun Patel, of the department of ophthalmology at the University of Dundee in Dundee, UK, and colleagues.

– Nearly everyone who wears contacts has fallen asleep with their lenses in at one point or another, but very few people can say they've done so for almost 30 years straight. Enter a 42-year-old woman from the UK, who, since one long-ago day when she was 14, had a contact lens lodged under the lid of her left upper eyelid without even knowing it. BuzzFeed reports on the odd case described in BMJ Case Reports, an event the journal describes as a "28-year trauma." CBS Dallas-Fort Worth reports the woman had experienced a swollen and droopy eyelid for about six months, and when she finally went to get it checked out, an MRI scan revealed a cyst just above her left eye. Doctors went in to remove the cyst, and what was inside it puzzled them: There was a rigid gas permeable (RGP) contact lens embedded, a type of hard contact lens that predates the softer ones most people use today. As everyone scratched their heads as to why she would have this type of lens in her eye, her mother remembered that when her daughter was 14, she'd been slammed in the eye by a badminton birdie while wearing her contacts and suffered minor injuries that fully healed. They all just figured her lost contact had popped out and dropped to the ground when the birdie hit her face, and CNN notes she never wore RGP contacts again. Since the lens has been removed, the woman's more recent eye problems have dissipated. (This woman had 27 contact lenses stuck in one eye.)

SECTION 1. SHORT TITLE. This Act may be cited as the ``American Energy First Act''. SEC. 2. FEDERAL GOVERNMENT ACTION REQUIRED AS CONDITION FOR DRAWDOWN FROM STRATEGIC PETROLEUM RESERVE. No petroleum product may be drawn down and sold or exchanged from the Strategic Petroleum Reserve unless the President has taken all of the actions required by sections 3 through 8 of this Act. SEC. 3. EFFECTIVENESS OF OIL SHALE REGULATIONS, AMENDMENTS TO RESOURCE MANAGEMENT PLANS, AND RECORD OF DECISION. (a) Regulations.--The President shall direct the Secretary of the Interior and the heads of all other relevant Federal agencies to treat the final regulations regarding oil shale management published by the Bureau of Land Management on November 18, 2008 (73 Fed. Reg. 69,414), as satisfying all legal and procedural requirements under any law, including the Federal Land Policy and Management Act of 1976 (43 U.S.C. 1701 et seq.), the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.), the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.), and the Energy Policy Act of 2005 (Public Law 109-58), and the Secretary of the Interior shall implement those regulations, including the oil shale leasing program authorized by the regulations, without any other administrative action necessary. (b) Amendments to Resource Management Plans and Record of Decision.--Notwithstanding any other law or regulation to the contrary, the President shall direct the Secretary of the Interior and the heads of all other relevant Federal agencies to treat the November 17, 2008, U.S. Bureau of Land Management Approved Resource Management Plan Amendments/Record of Decision for Oil Shale and Tar Sands Resources to Address Land Use Allocations in Colorado, Utah, and Wyoming and Final Programmatic Environmental Impact Statement as satisfying all legal and procedural requirements under any law, including the Federal Land Policy and Management Act of 1976 (43 U.S.C. 1701 et seq.), the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.), the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.), and the Energy Policy Act of 2005 (Public Law 109-58), and the Secretary of the Interior shall implement the oil shale leasing program authorized by the regulations referred to in subsection (a) in those areas covered by the resource management plans amended by such amendments, and covered by such record of decision, without any other administrative action necessary. SEC. 4. REQUIREMENT TO CONDUCT PROPOSED OIL AND GAS LEASE SALE 216 IN THE CENTRAL GULF OF MEXICO. (a) In General.--The President shall direct the Secretary of the Interior to conduct offshore oil and gas Lease Sale 216 under section 8 of the Outer Continental Shelf Lands Act (33 U.S.C. 1337) as soon as practicable, but not later than 4 months after the date of enactment of this Act. (b) Environmental Review.--For the purposes of that lease sale, the Environmental Impact Statement for the 2007-2012 5-Year OCS Plan and the Multi-Sale Environmental Impact Statement are deemed to satisfy the requirements of the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.). SEC. 5. REQUIREMENT TO CONDUCT PROPOSED OIL AND GAS LEASE SALE 218 IN THE WESTERN GULF OF MEXICO. (a) In General.--The President shall direct the Secretary of the Interior to conduct offshore oil and gas Lease Sale 218 under section 8 of the Outer Continental Shelf Lands Act (33 U.S.C. 1337) as soon as practicable, but not later than 8 months after the date of enactment of this Act. (b) Environmental Review.--For the purposes of that lease sale, the Environmental Impact Statement for the 2007-2012 5-Year OCS Plan and the Multi-Sale Environmental Impact Statement are deemed to satisfy the requirements of the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.). SEC. 6. REQUIREMENT TO CONDUCT PROPOSED OIL AND GAS LEASE SALE 222 IN THE CENTRAL GULF OF MEXICO. (a) In General.--The President shall direct the Secretary of the Interior to conduct offshore oil and gas Lease Sale 222 under section 8 of the Outer Continental Shelf Lands Act (33 U.S.C. 1337) as soon as practicable, but not later than June 1, 2012. (b) Environmental Review.--For the purposes of that lease sale, the Environmental Impact Statement for the 2007-2012 5-Year OCS Plan and the Multi-Sale Environmental Impact Statement are deemed to satisfy the requirements of the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.). SEC. 7. KEYSTONE XL PIPELINE PERMIT APPROVAL. (a) Permit Approval.--The President shall direct the Secretary of State to approve the permit described in subsection (b). (b) Description of Permit.--The permit approved under subsection (a) is the permit with respect to certain energy-related facilities and land transportation crossings on the international boundaries of the United States for the Keystone XL pipeline project, an application for which was filed on September 19, 2008 (including amendments). (c) Requirements.--The permit granted under subsection (a) shall require the following: (1) The permittee shall comply with all applicable Federal and State laws (including regulations) and all applicable industrial codes regarding the construction, connection, operation, and maintenance of the United States facilities. (2) The permittee shall take all appropriate measures to prevent or mitigate any adverse environmental impact or disruption of historic properties in connection with the construction, operation, and maintenance of the United States facilities. (3) For the purpose of the permit approved under subsection (a) (regardless of any modifications under subsection (d))-- (A) the final environmental impact statement issued by the Secretary of State on August 26, 2011, satisfies all requirements of the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.) and section 106 of the National Historic Preservation Act (16 U.S.C. 470f); (B) any modification required by the Secretary of State to the Plan described in paragraph (4)(A) shall not require supplementation of the final environmental impact statement described in that paragraph; and (C) no further Federal environmental review shall be required. (4) The construction, operation, and maintenance of the facilities shall be in all material respects similar to that described in the application described in subsection (b) and in accordance with-- (A) the construction, mitigation, and reclamation measures agreed to by the permittee in the Construction Mitigation and Reclamation Plan found in appendix B of the final environmental impact statement issued by the Secretary of State on August 26, 2011, subject to the modification described in subsection (d); (B) the special conditions agreed to between the permittee and the Administrator of the Pipeline Hazardous Materials Safety Administration of the Department of Transportation found in appendix U of the final environmental impact statement described in subparagraph (A); (C) if the modified route submitted by the Governor of Nebraska under subsection (d)(3)(B) crosses the Sand Hills region, the measures agreed to by the permittee for the Sand Hills region found in appendix H of the final environmental impact statement described in subparagraph (A); and (D) the stipulations identified in appendix S of the final environmental impact statement described in subparagraph (A). (5) Other requirements that are standard industry practice or commonly included in Federal permits that are similar to a permit approved under subsection (a). (d) Modification.--The permit approved under subsection (a) shall require-- (1) the reconsideration of routing of the Keystone XL pipeline within the State of Nebraska; (2) a review period during which routing within the State of Nebraska may be reconsidered and the route of the Keystone XL pipeline through the State altered with any accompanying modification to the Plan described in subsection (c)(4)(A); and (3) the President-- (A) to coordinate review with the State of Nebraska and provide any necessary data and reasonable technical assistance material to the review process required under this subsection; and (B) to approve the route within the State of Nebraska that has been submitted to the Secretary of State by the Governor of Nebraska. (e) Effect of No Approval.--If the President does not approve the route within the State of Nebraska submitted by the Governor of Nebraska under subsection (d)(3)(B) not later than 10 days after the date of submission, the route submitted by the Governor of Nebraska under subsection (d)(3)(B) shall be considered approved, pursuant to the terms of the permit approved under subsection (a) that meets the requirements of subsection (c) and this subsection, by operation of law. (f) Private Property Savings Clause.--Nothing in this section alters the Federal, State, or local processes or conditions in effect on the date of enactment of this Act that are necessary to secure access from private property owners to construct the Keystone XL pipeline. SEC. 8. REQUIREMENT TO EXPEDITE PERMITTING FOR EXISTING OIL AND GAS LEASES. The President shall direct the Secretary of the Interior to expedite permitting of activities under oil and gas leases for Federal onshore lands and Federal submerged lands in the Gulf of Mexico.

American Energy First Act - Prohibits petroleum product from being drawn down, sold, or exchanged from the Strategic Petroleum Reserve (SPR) unless the President has taken the actions required by this Act. Instructs the President to direct the Secretary of the Interior (Secretary) and the heads of other relevant federal agencies to treat certain Bureau of Land Management final regulations regarding oil shale management as well as the November 17, 2008, U.S. Bureau of Land Management Approved Resource Management Plan Amendments/Record of Decision for Oil Shale and Tar Sands Resources to Address Land Use Allocations in Colorado, Utah, and Wyoming and Final Programmatic Environmental Impact Statement as satisfying all legal and procedural requirements under specified laws. Directs the Secretary to implement the oil shale leasing program authorized in those areas covered by the resource management plans amended by such amendments, and covered by such record of decision, without any other administrative action necessary. Instructs the President to direct the Secretary to conduct offshore oil and gas: (1) Lease Sale 216 in the Central Gulf of Mexico within four months after enactment of this Act, (2) Lease Sale 218 in the Western Gulf of Mexico within eight months after enactment of this Act, (3) Lease Sale 222 in the Central Gulf of Mexico not later than June 1, 2012. Deems the Environmental Impact Statement for the 2007-2012 5-Year OCS Plan and the Multi-Sale Environmental Impact Statement to satisfy the requirements of the National Environmental Policy Act of 1969 for the purposes of such lease sales. Instructs the President to direct the Secretary to: (1) approve a certain permit concerning certain energy-related facilities and land transportation crossings on the international boundaries of the United States for the Keystone XL pipeline project, and (2) expedite permitting of activities under oil and gas leases for federal onshore lands and federal submerged lands in the Gulf of Mexico. Prescribes Keystone XL pipeline permit requirements, including: (1) reconsideration of routing of the Keystone XL pipeline within Nebraska; (2) a review period during which routing within Nebraska may be reconsidered and the route of the Keystone XL pipeline through the state altered with any accompanying modification to a specified Plan; and (3) the obligation of the President to coordinate review with the state of Nebraska, provide necessary data and reasonable technical assistance material to the review process, and approve the route within Nebraska submitted by its governor to the Secretary of State. Deems approved, within 10 days after its date of submission, the route submitted by the governor of Nebraska pursuant to the permit approved under this Act if the President does not approve that route.

hepatitis b virus ( hbv ) is a partially double - stranded dna virus and an important cause of morbidity and mortality worldwide . about 2 billion people were reported to be infected with hbv and among them , 350 million are chronically infected cases . most of the chronically - infected subjects live in developing countries and are high - risk for liver cirrhosis and hepatocellular carcinoma . in high endemic countries , the seroprevalence of hepatitis b surface antigen ( hbs ag ) is more than 8% ; in countries with intermediate endemicity is 27% ; and in low endemic areas is less than 2% . in southeast asia , china and africa , the prevalence of hbs ag is high and approximately 10% of the population are chronic carriers . high - risk groups in hbv infection are intravenous drug users , attendees of sexually transmitted disease clinics , homosexual men , hemodialysis patients , children born from hbs ag positive mothers and health care workers . three major routes of vertical , horizontal and sexual transmission were reported for hbv infection . in developing countries , vertical transmission from an infected mother to newborns , horizontal transmission among children , sexual transmission , transfusion of infected blood or blood products , needle stick injury were demonstrated as common routes of transmission . the disease has no seasonal distribution , but the carrier rate is higher in tropical regions . the prevalence as carriers varies widely from 0.1% in the developed countries to 20% in the developing nations . the prevalence in bangkok was shown 4.6% for hbs ag and 20% for hbe ag . in croatia , a study in pakistan revealed 2.56% positivity for hbs ag in the general population . in turkey , among 802 school children , the overall anti - hbs , anti - hbc , and hbs ag were 724 ( 90.2% ) , 56 ( 7% ) , and 22 ( 2.7% ) children respectively . due to more referrals of hbv patients from akbar abad village in kavar district in fars province , sothern iran to our center , this population - based cross - sectional study was conducted to determine the prevalence and risk factors of hbv in this population . from august 2007 to march 2008 , 3739 ( age range of 188 years old ) individuals from akbar abad village in kavar district in fars province , sothern iran were enrolled including more than 95% of the population in the area while just 143 subjects did not participate in this study . the village is 50 km far from shiraz , the capital of fars province while most of the residents were truck drivers . a questionnaire was provided to collect the information on demographic data , marital status , history of vaccination , being in prison , any blood transfusion , any current use of intra venous substances , any tattooing and any sexual contact with persons having hepatitis or jaundice . individuals were divided into three groups ( 115 , 1649 and older than 50 years ) . in relation to the level of education , the subjects were divided into two groups of low ( lower than high school diploma ) and high educational levels ( university level ) . considering marital status , subjects were divided into three groups of single , married and widow . one physician , two laboratory technicians and one trained interviewer who completed the questionnaire were included in our team . blood samples were obtained from each person , and their sera were transferred to the central laboratory in the gastroenterology and hepatology research center and stored at 70c for further tests . an informed written consent was provided from each participant , and if less than 12 years old , it was taken from their parents . all data were statistically analyzed by spss software ( version 11.5 , chicago , il , usa ) using chi - square , students , and fisher exact tests for comparison of the data . out of 3739 subjects , 2317 ( 62% ) were female and 1422 ( 38% ) were male , among them 7.1% were positive for hbc ab and 2.2% for hbs ag and 3.8% ( 143 subjects ) had missing data in the questionnaire who were excluded from the study . out of 266 positive cases for hbc ab , 161 ( 7.3% ) were female , and 105 ( 7.6% ) were male and the difference was not statistically significant ( p = 0.376 ) . out of 83 positive cases for hbs ag , 49 ( 2.2% ) were female and ( 2.5% ) were male and the difference was not statistically significant ( p = 0.351 ) . the minimal rates of hbc ab ( 5.4% ) and hbs ag ( 1.5% ) were noticed in the age group 1 - 15 year old . this rate increased with age and reached 8.6% of hbc ab and 2.7% of hbs ag in the age group > 50 years old . the difference between various age groups were not statistically significant ( p = 0.372 , p = 0.08 , respectively ) . the highest positivity was observed among unemployed individuals ( 22% for hbc ab and 11% for hbs ag ) . among subjects with low educational level , 7.5% were positive for hbc ab and 2.4% for hbs ag , but these figures were 7.2% and 2% respectively for hbc ab and hbs ag in subjects with high level of education having an inverse relationship with increasing level of education . the differences were not statistically significant ( p = 0.46 and p = 0.39 for hbc ab and hbs ag , respectively ) . regarding marital status , the highest prevalence was visible in the widow group ( 22.2% for hbc ab and 11% for hbs ag ) and the lowest in married persons ( 5.4% for hbc ab and 1.8% for hbs ag , respectively ) . the difference was statistically significant ( p = 0.0001 for hbc ab and p = 0.029 for hbs ag , respectively ) . one of the risk factors for hbv infection was opium addiction that had a significant relationship with hbc ab ( p = 0.008 ) . the prevalence of hbv seropositivity tended to be higher in the central regions ( drivers ) than surrounding territories ( farmers ) . a significant correlation was observed between the localities ( p = 0.0001 for hbc ab and p = 0.0 5 for hbs ag ) . the prevalence of hbs ag positivity was higher in groups that had a history of dental treatments and family history of liver diseases . the prevalence of hbc ab was higher in groups with a history of blood transfusion and tattooing . no significant relationship was visible between the factors of family history of liver diseases or hepatitis , history of being in prison , history of blood transfusion , hemophilia , major thalassemia , iv drug abuse , alcohol consumption , sexual activity , dental treatments and tattooing . regarding hbv infection , the world can be classified into three regions of high , intermediate and low hbv endemicity . in the middle east , countries such as bahrain , iran , israel and kuwait are considered as areas of low endemicity , with hbs ag carrier rates of less than 2% ; while , cyprus , iraq and the united arab emirates are areas of intermediate endemicity that the carrier rate in these countries ranges from 2% to 5% . the areas of high endemicity include egypt , jordan , oman , palestine , yemen and saudi arabia , with carrier rate from 2% to 18.5% . the prevalence of hbs ag in iran was reported between 2.5% and 7.2% in 1979 by farzadegan . in our study , 2.2% and 7.1% of participants were positive for hbs ag and anti - hbc ab respectively , which is lower than some studies in our country . alavian et al . reported a prevalence of 0.80% for hbs ag and5.02% for hbc ab in kurdistan , which is lower than our study . in another study , alavian et al . showed that the prevalence for hbs ag in kermanshah was 1.3% that is lower than our study . noticed a prevalence of 3.38% for hbs ag and 23.58% for hbc ab in sistan and baluchistan , which is higher than our study . southern iran reported a prevalence of hbs ag , anti - hbc antibody , hbe ag and anti - hbe antibody in 8 ( 6.72% ) , 24 ( 25.16% ) , 2 ( 1.68% ) and 3 ( 2.52% ) patients , respectively . older than fifteen years in tehran , iran reported that 70 ( 34.7% ) subjects were infected with hepatitis b. among iranian blood donors during 19982007 , the prevalence of hbv infection among 14,599,783 donations declined from a 1.79% ( 1789/100 000 donations ) in 1998 to 0.41% ( 409/100 000 donations ) in 2007 . in fars province , hbs ag prevalence decreased from 0.89% in 92 999 donations in 1998 to 0.34% in 148 014 donations in 2007 . the variation may be due to different vaccination coverage schedules and the protective antibody titers . in our study , the prevalence of hbs ag and anti - hbc ab of 2.2% and 7.1% , respectively is still lower than many studies in the world . among female prisoners in gois , hbs antigen carriage was shown to include 1.84.9% of the population . in northern australia , it was demonstrated that 49% of patients were hepatitis be antigen positive , and 48% were hepatitis b e antibody positive . , in their study among health care workers in public teaching hospitals in khartoum state , sudan showed that the prevalence of anti - hbc , hbs ag , hbsab , and hbeag was found to be 57% , 6% , 37% and 9% respectively . findings revealed that among 209,822 immigrants and refugees in montreal , canada , the overall seroprevalence of infection for hbv was 7.2% . in china , national surveys denoted to a prevalence of 10% for chronic hbv infection in the general population . hbv infection in 225 individuals in the western brazilian amazon was shown to be 79.1% . results indicated that the seroprevalence of hbv among 2946 new blood donors at the nianankoro fomba hospital ( nfh ) was 5.3% . in our study , the prevalence of hbs ag and anti - hbc ab of 2.2% and 7.1% respectively , which are higher than some studies in the world . among children and adolescents in singapore , 4 of the 1,200 samples epidemiology of viral hepatitis b in ibb city , yemen was reported to be 1.81% . in 1980s in iran , the hbs ag prevalence rate was reported 3% ranging from 1.7% in fars province to 5% in sistan - balouchestan province . the prevalence rate of hbs ag in shiraz , southern iran among 7897 healthy voluntary blood donors was 1.07% ( 85 subjects ) were positive for hbs ag . in a study on 39841 persons from all parts of iran , the rate of hepatitis carriers in different provinces of the country varied between zero and 3.9% . in a population - based study on 6,583 subjects aged between 18 and 65 years from three provinces of tehran , golestan , and hormozgan in iran , the prevalence of hbs ag and anti - hbc antibody was 2.6% and 16.4% , respectively . predictors for hbs ag or anti - hbc antibody in multivariate analysis included older age , educational level less than high school diploma , residing in rural areas , and history of liver diseases . the seroprevalence of hbv , hcv , and hiv infections was evaluated in uzbekistan in 1918 subjects for hbs ag , anti - hcv , and anti - hiv was 13.3% , 13.1% , and 0% , respectively . in another study on 4671 chinese adult patients with at least one office visit during a 2-year period , hbs ag testing was available in 64% ( 3012/4671 ) of cases . the overall hbs ag seroprevalence rate was 11.1% ( 335/3012 ) and in persons aged 3039 years was 14.9% . hbe ag testing was available for 75% ( 250/335 ) of hbs ag + cases . seventy - five percent ( 188/250 ) were hbe ag positive . in yemen as a high endemic area for hbs ag , in a study of 178 individuals , 13.2% of mothers and 4% of infants aged 612 months were positive for hbs ag . another study on 26,874 blood donors in kuwait in 2002 showed that the prevalence of hbs ag among kuwaiti national and non - kuwaiti arab donors was 1.1% and 3.5% and for anti - hbc was 17% and 33.3% , respectively . the efficacy of the hbv vaccination program was evaluated by 2 large seroepidemiological studies before and after mass vaccination . the overall seropositivity rate showed no significant decline between 1991 and 1999 except in the age group 214 years , while the rates reduced significantly ( 1.3% vs. 0.8% ) . this decrease was more prominent in rural ( 1.5% vs. 0.8% ) than urban areas ( 1.1% vs. 0.9% ) . in saudi arabia , a steady decrease in the hbs ag ( 2.58 and 1.67% ) , and anti - hbc ab rates ( 15.32 and 9.15% ) the trend of hbv seroprevalence over the 16 years between 1989 and 2004 among blood donors in turkish populations showed that the overall prevalence of hbs ag was 4.19% during the study period . the annual prevalence of hbs ag gradually increased from 4.92% in 1989 to 5.23% in 1991 and gradually decreased to 2.10% in 2004 . this could be related to a significant increase in the number of volunteer blood donors that increased from 135,779 to 197,815 . age was an important element in the current survey that was a determinant in hbv seroprevalence . the lowest prevalence was noticed among 115 years age group ( 5.4% for hbc ab and this difference may be due to national neonatal vaccination against hbv infection as part of our expanded program on immunization that was implemented since 1993 and a reach over 80% of the population . a case - control study was carried out on 632 subjects with chronic hepatitis b referred to karaj hepatitis center , tehran province , iran . logistic regression analysis showed that only male sex , old age , being married , close contact history within family , extramarital sexual activity , undergoing major surgeries , history of intravenous drug abuse , experimental dentist visit , phlebotomy and high risk jobs ( police , driver , and barber ) were independent risk factors for prediction of hepatitis b infection . among female prisoners in gois , brazil hbv prevalence was more in age > 30 years , a low education level , sex with a sexually transmitted diseases carrier , and a male sexual partner serving in the same penitentiary . among 387 hbv patients , hbv patients were younger , more frequently men , more often of asian or african origin , and less frequently contaminated by transfusion or intravenous drug use . in another study conducted by zali et al . , the age group 29 years had the least prevalence rate ( 1.2% ) while the highest level ( 2.9% ) was seen in the age group of 5059 years . differences among the various age groups were statistically significant . based on the results of this study , the prevalence rate among males and females was 2.2% and 2.5% for hbs ag and 7.3% and 7.6% for hbc ab . it may be due to a higher chance of hbv chronicity among men compared to women . in zali et al . 's study , 1.5% of female and 1.9% of male participants were positive for hbs ag ( p = 0.0033 ) . the prevalence of hbv infection was higher in central parts than the surrounding territories which may be due to poorer socioeconomic and sanitary conditions of the locality . on the other hand , central parts had more population and a more rate of family marriage and the occupation in central parts for men was driver and in the surrounding was farmers . therefore , the chance of transmission and number of infected subjects showed a rising trend . in zali et al . 's survey , investigation of individuals on the basis of their area of habitation revealed that 335 ( 1.5% ) of urban and 343 ( 2.0% ) of rural populations were positive for hbs ag , respectively ( p < 0.0001 ) . in another study including 226 gypsies from shahr - e - kord , southwest of iran with a mean age of 20.7 years , 35 subjects ( 18% ) were hbs ag positive . also , 44 persons ( 23.9% ) were positive for hbc ab . another important element in the current study was educational level that without considering the age factor , there was an inverse relationship with the prevalence rate of seropositivity . the seroprevalence was higher among low educated subjects ( 7.5% for hbc ab and 2.5% for hbs ag ) . it may be due to an intimate relationship between the level of education and the socioeconomical status . the carrier rate of hbs ag in another study in iran also revealed an inverse correlation with increasing level of education . regarding marital status , subjects in our study were divided into three groups of married , divorced or widowed and never married individuals . the prevalence of hbv infection was higher in widows that may be due to high - risk sexual behavior . results of another study revealed that marital status is one of the most important factors affecting the prevalence rate of hbs ag carrier state ( p = 0.0006 ) . the prevalence of hbv infection was different in various occupational groups with the highest in unemployed individuals . it may be due to their being away from the family and their high - risk sexual behaviors . had reported the highest level of infection in farmers ( 3.2% ) which is different to our results . the prevalence of hbs ag in 1,113 iranian large vehicle drivers was reported 5.9% ( confidence interval 95% : 4.5 - 7.3% ) and was different from the prevalence in the general population ( 1.7% ) , which identical to our results . considering the socioeconomical status , the subjects were divided into three groups of low , average and high . the prevalence rate was found to be 2.5% , 1.6% and 1.3% in each group , respectively that was statistically significant ( p < 0.0001 ) . in another study in nahavand , central iran on 1824 subjects in 2002 , the hbs ag positivity was 2.3% while the history of previous surgeries and being in imprison were the major risk factors for their infection . in a study , 2,447 hbs ag positive blood donors were compared with 2,425 hbs ag negative donors in tehran , capital of iran . factors predicting hbv infection were family history of hepatitis b infection , history of receiving a blood transfusion , hospitalization , unsafe sex , male gender , and living in urban localities . it seems that the prominent route of transmission was horizontal that may be due to the high prevalence of hbv infection in the age groups of older than 15 years old . however , it seems that the routes of transmission showed a correlation with the prevalence of disease in each country , such as the low endemicity for sexual behavior and iv drug abuse , the intermittent endemicity for perinatal , sexual behavior and iv drug abuse and the high endemicity for perinatal and horizontal routes . our results showed that the seroprevalence of hepatitis b markers was 2.2% for hbs ag and 7.1% for hbc ab . as hbv infection is still a problem of public health importance , particularly in developing countries , therefore , screening of pregnant women for hbs ag and vaccination of high risk individuals including family members of patients with hepatitis b should be implemented in future planning . insufficient coverage of hbv vaccination , sharing of a blood - contaminated equipment among injection drug users , and inadequate perinatal care for pregnant women are major risk factors for hbv infection in these countries . screening of hbv infection during pregnancy , and prophylactic use of hbv immunoglobuline and vaccine for high - risk infants will reduce rates of perinatal hbv transmission . implementing local strategies for hepatitis b screening of hbv infection during pregnancy , and prophylactic use of hbv immunoglobuline and vaccine for high - risk infants will reduce rates of perinatal hbv transmission . implementing local strategies for hepatitis

background : about 2 billion people were reported to be infected with hepatitis b virus ( hbv ) and among them ; 350 million are chronically infected cases . this study was performed to determine the prevalence of hepatitis b in kavar , southern iran.methods:from august 2008 to march 2009 , 3739 individuals aged between 1 and 88 years were screened for infection with hbv in akbar abad village , kavar , southern iran . a questionnaire was used to record demographic data , history of vaccination and the correlated risk factors . ten milliliter of the blood sample was taken from each subject . sera were checked for hepatitis b surface antigen ( hbs ag ) and hepatitis b core antibody ( hbc ab).results : among subjects , 7.1% were positive for hbc ab and 2.2% for hbs ag . out of positive cases for hbc ab , 7.3% were female , and 7.6% were male . out of positive cases for hbs ag , 2.2% were female , and 2.5% were male . the minimal rates of hbc ab and hbs ag were noticed in the age group 115 year old . the highest positivity was observed among unemployed individuals . among subjects with low educational level , 7.5% were positive for hbc ab and 2.4% for hbs ag . the highest prevalence was visible in the widow group and the lowest in married persons . opium addiction had a significant relationship with hbc ab . the prevalence of hbv seropositivity was higher among drivers , those with a history of dental treatments and family history of liver diseases blood transfusion tattooing recipients.conclusions:our results showed that screening of pregnant women for hbs ag and vaccination of high - risk individuals including family members of patients with hepatitis b should be implemented in future planning .

the homogeneous component of inflationary dynamics in the simplest case of single field @xcite ( see review in @xcite ) is usually described in terms of slow - roll approximation in the evolution of scalar inflaton @xmath0 , when one neglects both its kinetic energy @xmath1 and acceleration @xmath2 in the field equations @xmath3 \ddot\phi & \hskip-3pt= & \hskip-3pt \displaystyle -3h\dot\phi-\frac{\partial v}{\partial \phi},\\[1 mm ] \end{array}%\ ] ] derived from the hilbert einstein action of friedmann robertson walker metric @xmath4 with the scale factor of expansion @xmath5 ordinary defining the hubble rate @xmath6 in terms of its derivative with respect to time @xmath7 as denoted by over - dot @xmath8 . in ( [ intro-1 ] ) the planck mass is usually introduced through the newton constant @xmath9 by the relation @xmath10 , while @xmath11 is the inflaton potential . the slow - rolling implies @xmath12 \dot\phi & \hskip-3pt\approx & \hskip-3pt \displaystyle -\frac{1}{3h}\,\frac{\partial v}{\partial \phi}.\\[1 mm ] \end{array}%\ ] ] for the consistency of such the approximation we have to estimate the ratios @xmath13 and @xmath14 then , introducing parameter @xmath15 by @xmath16 and using ( [ intro-3 ] ) , we get @xmath17 therefore , the slow - roll approximation is substantiated at @xmath18 constraints ( [ intro-8 ] ) are usually satisfied for positive power potentials , for instance , at appropriately chosen parameters and fields @xmath19 , which guarantee the inflation of universe with slowly changing hubble rate with a huge total e - folding of scale factor @xmath20 , where subscripts stand for the moments of ending and initiating the inflation , correspondingly . note , that the above speculations have not involved any initial data on the field evolution . this can be meaningful , if only the evolution possesses properties of attractors , which allow a stable dynamical behavior , that soon forgets about a start . the quasiattractor for the inflationary dynamics with the quadratic potential @xmath21 was found in @xcite , which modernized the consideration of dependence on the initial conditions in the homogeneous case as was done in pioneering papers of @xcite . so , the phase space variables of dynamical system rapidly tend to a stable point , which position depends on the parameter defined by @xmath22 , while the parameter itself slowly evolves during the most amount of e - folding in the inflation and it begins significantly to change to the end of inflation at a short increment of @xmath23 , only . thus , at high total e - folding of inflation governed by an appropriate large starting value of hubble rate , the inflation due to the quadratic potential is well described by the quasiattractor behavior . similar result was obtained for the quartic potential in @xcite for the homogeneous case , and further attempts to generalize the analysis to damping of initial inhomogeneities were formulated . the analysis of dynamical system for the homogeneous inflaton and baryotropic matter was done in @xcite , wherein some general features of evolution were derived for an arbitrary potential of inflaton , and several explicit examples were studied . another aspect of considering the initial conditions concerns for inhomogeneities perturbing both the inflaton and metric . the analysis of inhomogeneity in the initial values of scalar field beyond the perturbation theory as well as relevant references can be found in @xcite , wherein the authors formulated conditions constraining the parameters of initial state , when the inflation takes place . in the present paper we generalize the approach of @xcite to the case of quartic potential @xmath24 , that modernizes the consideration in @xcite . the main goal of our study is to show the effectiveness and elegance of quasiattractor method to the analysis of inflation dynamics and its connection with the preheating regime in the case of quartic potential in order to draw the conclusion on the consistency with the observational data versus general conditions of preheating . the dynamical system relevant to the evolution of homogeneous universe is considered in section [ ii ] . we find the stable quasiattractor for the quartic potential , too . the inflation parameters are investigated in section [ iii ] , wherein they are confronted with both the experimental data and predictions of slow - roll approximation . our results are summarized and discussed in conclusion . the action of inflaton is of the form @xmath25 with the quartic potential @xmath26 in the friedmann walker metric it leads to the evolution @xmath27 \dot h & \hskip-3pt=&\hskip-3pt\displaystyle -\frac{1}{2}\,\kappa^2 \dot\phi^2 , \end{array}\ ] ] under the friedmann equation @xmath28 at @xmath29 . following the method of @xcite , let us introduce the phase space variables @xmath30{\frac{\lambda}{12}}\frac{\kappa\,\phi}{\sqrt{\kappa h}},\ ] ] related due to ( [ evol-2 ] ) by the constraint @xmath31 the analysis of dynamical system is simplified , if we introduce the driving parameter @xmath32{3\lambda}}{\sqrt{\kappa h}}.\ ] ] then , denoting the derivative with respect to the amount of e - folding by prime @xmath33 at @xmath34 , we get @xmath35 y^\prime&\hskip-3pt=&\hskip-3pt\displaystyle \frac{3}{2}\,x^2y+xz,\\[3 mm ] z^\prime&\hskip-3pt=&\hskip-3pt\displaystyle \frac{3}{2}\,x^2z . \end{array}\ ] ] it is an easy task to confirm , that the system of ( [ evol-6 ] ) conserves the friedmann constraint in the form of ( [ evol-4 ] ) . it is important to stress , that @xmath36 is quasi - constant , if @xmath37 is fixed at a critical point @xmath38 , hence , @xmath39 so that the monotonic growth of @xmath36 is slow in comparison with the linear increase of e - folding @xmath40 due to a small slope proportional to @xmath41 , indeed , and one can put @xmath42 until @xmath43 , i.e. at rather large intervals of @xmath40 . we will see later , in fact , that the stable critical point @xmath44 scales as @xmath45 at @xmath46 and @xmath47 , so that the growth takes the form @xmath48 therefore , at @xmath49 the increase is quite linear , but the coefficient of @xmath50 is actually suppressed @xmath51 by the conditions of attractor , as we will consistently see later . thus , we can treat the phase - space evolution in the @xmath52 plane as the autonomous dynamical system with external parameter @xmath36 , when the driftage of @xmath36 gives rise to the sub - leading correction . solving @xmath53 at @xmath54 and @xmath55 , we get the relation is off interest , since it does not satisfy constraint ( [ evol-4 ] ) . ] @xmath56 while @xmath57 the cubic polynomial @xmath58 in ( [ crit-2 ] ) produces two extremal points , since its derivative is equal to @xmath59 hence , @xmath60 , @xmath61 . therefore , @xmath62 has got positive roots , if only @xmath63 that yields @xmath64 constraint ( [ crit-3 - 0 ] ) guarantees the existence of critical points @xmath65 . substituting @xmath66 allows us to write the real solutions of ( [ crit-2 ] ) in the following form @xmath67 at @xmath68 quantity @xmath69 , which is not a physical point , at all , while at @xmath70 and @xmath71 @xmath72 correspondingly . therefore , the case of @xmath73 is covered by the case of @xmath70 , if we expand the interval of @xmath74 to @xmath75 that allows us to put the critical point and @xmath76 , but we prefer for ( [ crit-6 ] ) , when the case of interest with @xmath77 is spectacularly reached at @xmath78 . ] to @xmath79 . due to ( [ crit-1 ] ) , we can write down @xmath80 so that the critical points satisfy the friedmann constraint of ( [ evol-4 ] ) . at @xmath81 and @xmath82 , the evolution linear in @xmath83 reads off as @xmath84 \bar y ^\prime \end{array } \right ) = \left ( \begin{array}{ccc } 9x_c^2 - 3 & & -6y_c^2z \\[2 mm ] -z & & \frac{3}{2}x_c^2 \end{array } \right ) \left ( \begin{array}{r } \bar x \\[2 mm ] \bar y \end{array } \right),\ ] ] wherein we have used ( [ crit-1 ] ) . the linearized friedmann constraint in ( [ evol-4 ] ) gives @xmath85 so that ( [ stab-1 ] ) is reduced to the single equation @xmath86 therefore , at @xmath87 the deviations @xmath88 will be damped , while at @xmath89 , the fluctuations will decline as @xmath90 . the same fact can be found in a general manner . so , the eigenvalues of matrix in ( [ stab-1 ] ) are the following : @xmath91 while the corresponding eigenvectors are given by @xmath92 z \end{array } \right),\qquad v_-= \left ( \begin{array}{ccc } 3y_c^4 \\[1 mm ] z \end{array } \right).\ ] ] however , the condition of ( [ fried-1 ] ) can be rewritten as @xmath93 \bar y \end{array } \right)=\left ( \begin{array}{ccc } 3y_c^4 \\[2 mm ] z \end{array } \right)\,\frac{\bar y}{z}=v_-\,\frac{\bar y}{z}.\ ] ] therefore , the eigenvector @xmath94 is irrelevant to the consideration , since it drives out of constraint ( [ fried-1 ] ) , while @xmath95 is consistent with ( [ fried-1 ] ) , and the critical point is stable at @xmath96 , i.e. under ( [ stab-7 ] ) . thus , we have established the quasiattractor for the quartic potential of inflaton . the stability of critical point is controlled by smallness of @xmath36 , that means large enough value of initial hubble rate . staring the evolution of universe filled by the inflaton from a high initial hubble rate , i.e. at @xmath97 , but @xmath98 , causes a rapid entering the quasiattractor regime , when the expansion is described by the slow drift of hubble rate . it means that a small domain of space is inflationary increased to a huge size , and the inflaton can be approximated by an almost homogeneous field versus the spatial coordinates , while its value and time derivative evolve in accordance with the drift of critical points . the quasiattractor is the reason for the cosmological evolution forgets its primary origin to the leading homogeneous approximation . nevertheless , one could consider some properties of attractor dynamics close to the end of inflation , since it further enters the properties of observed inhomogeneity . the accelerated expansion takes place at @xmath99 , hence , @xmath100 that is reduced to @xmath101 wherein we have used ( [ evol ] ) . therefore , the universe follows the inflation at @xmath102 i.e. in the region , where the quasiattractor is in action , indeed . the accelerated regime ends at @xmath103 z^4_{c,\mathrm{end}}&\hskip-3pt=&\hskip-3pt\displaystyle \left(\frac{3}{2}\,x_{c,\mathrm{end } } y_{c,\mathrm{end}}\right)^4=\frac{3}{8 } , \end{array}\ ] ] equivalent to @xmath104 and @xmath105 h^2_{\mathrm{end}}=%&\hskip-3pt=&\hskip-3pt\displaystyle \frac{8\lambda}{\kappa^2},\quad%\\[3 mm ] \dot\phi^2_{\mathrm{end}}=%&\hskip-3pt=&\hskip-3pt\displaystyle \frac{48\lambda}{\kappa^4}.%%\\[3 mm ] % \end{array}\ ] ] the inflation condition of ( [ inf-2 ] ) is supplemented by accompaniments @xmath106 note , that to the end of inflation the field takes the value of the order of planck mass independently of coupling constant @xmath107 , while the corresponding squares of hubble rate and kinetic energy are scaled linearly in the coupling constant , and they are actually suppressed to the appropriate planck mass powers at @xmath108 . once the attractor is in action , the total amount of e - folding during the inflation can be obtained by integration of @xmath36-component in the system of ( [ evol-6 ] ) at @xmath109 , i.e. @xmath110 in the limit of @xmath97 , we deduce ( [ tot-1 ] ) by transformation to the integration versus @xmath74 , so that @xmath111 approximated by @xmath112 to the leading order at @xmath113 . the consequent expansion in ( [ tot-2 ] ) gives @xmath114 n_{\mathrm{tot.}}^{(1 ) } & \hskip-3pt= & \hskip-3pt \displaystyle \frac{\sqrt{3}}{2}\left\{\frac{1}{\,{\chi}_{_{\scriptstyle\mathrm{init.}}}}- \frac{4}{\pi}\right\}+\frac{1}{6}\ln \frac{4\,{\chi}_{_{\scriptstyle\mathrm{init.}}}}{\pi}. \end{array}\ ] ] the inversion of ( [ tot-4 ] ) results , for instance , in @xmath115 to the leading order at @xmath116 we deduce the initial data @xmath117 \end{array}\ ] ] while @xmath118 . note , that the initial data for the field and its velocity @xmath119 mean their values _ just after entering the quasiattractor _ , while the actual data are irrelevant , since the quasiattractor rapidly adjust the field and its velocity to ( [ tot-6 ] ) in accordance to the initial hubble rate , i.e. @xmath50 . quantum fluctuations of inflaton near its homogeneous classical value result in the primordial spatial perturbations of energy density , involving the scalar and tensor components of spectrum versus the wave vector @xmath120 at the moment , when the fluctuation comes back from the horizon , i.e. at @xmath121 as following : @xmath122 \mathcal{p}_{\mathrm{t}}(k ) & \hskip-3pt= & \hskip-3pt\displaystyle 8\kappa^2\left(\frac{h}{2\pi}\right)^2 . \end{array}\ ] ] the spectra can be accurately evaluated in terms of quasiattractor dynamics by @xmath123 \mathcal{p}_{\mathrm{t}}(k ) & \hskip-3pt= & \hskip-3pt\displaystyle \frac{6\lambda}{\pi^2}\,\frac{1}{z^4 } , \end{array}\ ] ] where @xmath36 corresponds to the hubble rate @xmath22 , and it is expressed by amount of e - folding @xmath40 between the moments of horizon exit and inflation end , as that can be found in the right analog of ( [ tot-6 ] ) in the leading order at @xmath124 . so , we redefine @xmath125 . then , @xmath126 \mathcal{p}_{\mathrm{t}}(k ) & \hskip-3pt\approx & \hskip-3pt\displaystyle \frac{32\lambda}{3\pi^2}\,%\frac{1 } { n^2 } , \end{array}\ ] ] which are consistent with the slow - roll approximation for the inflation with the quartic potential . the sub - leading corrections are given by the substitution following from ( [ tot-5 ] ) , @xmath127 the ratio @xmath128 determines the relative contribution of tensor spectrum . in the leading order @xmath129 in accordance with the slow - roll approximation , again . the spectral index is defined by @xmath130 it can be calculated under the condition , hence , the derivatives in ( [ evol-6 ] ) change sign . ] @xmath131 so that @xmath132 that is reduced to the slow - roll result in the leading approximation @xmath133 to the same approximation @xmath134 the running of spectral index is given by @xmath135 approximately equal to @xmath136 as it was noted in @xcite , the evaluation of @xmath137 in the framework of slow - roll approximation is quite complicated , while the quasiattractor dynamics allows us to get it straightforwardly by means of taking the derivative . though one could use ( [ inh-7 - 1 ] ) to the leading order , when @xmath138 , that straightforwardly yields the spectral index as well as its slope derived above . thus , the quasiattractor behavior provides us with the direct way of calculating the properties of primary inhomogeneity in terms of two parameters : the coupling constant @xmath107 and number of e - folding @xmath40 relative to the observational scale @xmath120 . following the method elaborated in @xcite , let us restrict the scale @xmath139 relative to the observation of inhomogeneity , as it comes from the both known and suggested history of universe evolution by considering the ratio @xmath140 where @xmath141 is the present - date hubble rate @xmath142 while @xmath143 is the present - date scale factor , that can be set to @xmath144 by definition of length unit . we decompose the evolution in several consequent stages : the inflation , reheating , radiation dominance up to the epoch of equality with nonrelativistic matter , matter dominance , that give @xmath145 \displaystyle \frac{h}{h_0 } = \frac{h}{h_{\mathrm{end}}}\,\frac{h_{\mathrm{end } } } % % { h_{\mathrm{reh.}}}\ , \frac{h_{\mathrm{reh . } } } { h_{\mathrm{eq.}}}\,\frac{h_{\mathrm{eq.}}}{h_0}.\\[3 mm ] \end{array}\ ] ] the data yield @xmath146 where @xmath147 is the fraction of matter energy . the quasiattractor gives @xmath148 the scale ratios are related with the ratios of hubble rates in two subsequent stages @xmath149 by means of @xmath150 where @xmath151 is the state parameter at the stage @xmath152 , determined by the ratio of pressure to the energy density . for the radiation stage we set @xmath153 . then , we arrive to @xmath154 & \hskip-3pt+ & \hskip-3pt\displaystyle \left(\frac{1}{2}-\frac{1}{3(1+w_{\mathrm{reh.}})}\right ) \ln\frac{h^2_{\mathrm{end}}}{m^2_{\mathtt{pl } } } \\[5 mm ] & \hskip-3pt- & \hskip-3pt\displaystyle \left(\frac{1}{4}-\frac{1}{3(1+w_{\mathrm{reh.}})}\right ) \ln\frac{h^2_{\mathrm{reh.}}}{m^2_{\mathtt{pl}}}-\frac{1}{4 } \ln\frac{h^2_{\mathrm{eq.}}}{m^2_{\mathtt{pl}}}. \end{array}\ ] ] let us parameterize the hubble rate at the end of reheating by a scale @xmath155 , so that @xmath156 while @xmath157 therefore , @xmath158 & \hskip-3pt- & \hskip-3pt\displaystyle \left(\frac{1}{2}-\frac{1}{1+w_{\mathrm{reh.}}}\right)\ln n -\frac{1}{4 } \ln\frac{h^2_{\mathrm{eq.}}}{m^2_{\mathtt{pl } } } \\[5 mm ] & \hskip-3pt+ & \hskip-3pt\displaystyle \left(\frac{1}{2}-\frac{1}{3(1+w_{\mathrm{reh.}})}\right ) \ln\frac{3\pi}{2}\,\mathcal{p}_{\mathrm{s } } \\[5 mm ] & \hskip-3pt- & \hskip-3pt\displaystyle \left(\frac{1}{4}-\frac{1}{3(1+w_{\mathrm{reh.}})}\right ) \ln\frac{8\pi}{3}\ , \frac{\mu^4_{\mathrm{reh.}}}{m^4_{\mathtt{pl}}}. % ( 1+w_{\mathrm{reh . } } ) . \end{array}\ ] ] note , that ( [ k5x ] ) is independent of current matter density @xmath147 . astronomical observations are naturally restricted by the distances less than the event horizon given by the inverse hubble rate of present day @xmath141 . therefore , the maximal value of e - folding @xmath159 is reached at the wave number @xmath160 , when ( [ k5x ] ) contains two parameters determined by the mechanism of reheating . in addition , experimental data give the spectral density @xcite @xmath161 at the scale @xmath162 mpc@xmath163 greater than @xmath164 , nevertheless , this value of @xmath165 rather slowly evolves with @xmath120 . the dependence of @xmath159 versus the scale of reheating @xmath155 and state parameter @xmath166 is shown in fig . [ max ] for generic cases of stiff matter @xmath167 , radiation @xmath168 and dust @xmath169 . it is spectacular , that , first , the dependence versus the scale is well approximated by logarithmic law , second , all these reheating regimes converge to a single point at @xmath170 gev , and third , the radiation regime gives the maximal amount of e - folding is obtained by numerical solving ( [ k5x ] ) at @xmath168 . ] equal to @xmath171 independent of the scale characterizing the reheating stage . the reheating scale @xmath172 for the intersection of curves with different values of state parameter @xmath166 in fig . [ max ] is given by the condition of nullifying the coefficient in front of factor @xmath173 in ( [ k5x ] ) , so that @xmath174 our numerical calculations exhibit the oscillations of the field around the minimum of quartic potential with @xmath175 . however , this value can be modified by the both corrections to the potential near the minimum and inflaton interaction with ordinary fields . ( 75,46 ) ( 0,0 ) versus the reheating scale in different regimes of reheating state parameter @xmath176 ( long - dashed line ) , @xmath177 ( solid line ) , @xmath178 ( dashed line ) , @xmath179 ( dotted line ) , and @xmath180 ( short - dashed line).,title="fig : " ] ( 0,41)@xmath159 ( 61,-2)@xmath155 , gev we have also shown two marginal cases . the first case corresponds to @xmath180 and it could appear , if we suggest the inflaton oscillations near the potential minimum neglecting the gravitational damping during the period . then , the virial theorem gives averages of kinetic and potential energies as @xmath181 , that reproduce the mentioned state parameter . the second case corresponds to a quite instantaneous falling of hubble rate to its reheating scale , so that @xmath182 . such the regime could happen due to a specific tachyonic preheating @xcite with a rapid decay of classical inflaton to quanta , for instance . however , the jump of hubble rate is the indication of energy jump , that is unrealistic , at all . nevertheless , the situation with @xmath183 takes place , if the potential minimum is shifted to a negative value @xmath184 , that gives @xmath185 therefore , the kinetic energy and hubble rate will rapidly fall down during short increment of e - folding , while the state parameter will follow @xmath186 , until the potential will become to grow . then , we suggest the existence of second local minimum of @xmath11 at @xmath187 giving the flat vacuum . the decay of flat vacuum to the anti - de sitter point @xmath188 is preserved by the gravitational effects @xcite , so that the flat vacuum can be stable . the barrier between two minima of potential suggests the presence of negative second derivative of potential with respect to the field , that can switch on the preheating mechanism at the scale of potential barrier denoted by @xmath189 , which could be much less than the energy density at the end of inflation . thus , in fig . [ max ] the region between the dotted and long - dashed lines can be actual in the extended version of quartic inflation at @xmath190 . though , we can not point to any verified realistic model of such the scenario to the moment . the observational data deal with the wave number @xmath120 about two orders of magnitude less than @xmath164 , that diminish the corresponding number of e - folding by the value about @xmath191 . for the flat universe with cosmological constant , recent wmap data @xcite at @xmath192 mpc@xmath163 gave quite precise values of @xmath193 while the slope of @xmath194 is not so restrictive @xmath195 then , we extract the amount of appropriate e - folding @xmath196 that yields the coupling constant equal to @xmath197 which follows from fig . [ lam - n ] . ( 75,75 ) ( 0,0 ) with @xmath198 and @xmath199 contours as follows from ( [ dat1 ] ) , ( [ dat2 ] ) . the shaded region is allowed after taking into account the correlation of spectral index @xmath194 with the fraction of tensor perturbations in the energy density @xmath200 at @xmath199 level.,title="fig : " ] ( 0,72)@xmath201 ( 61,-2)@xmath40 ( 33,4.7)(1,0)35(0,1)64.3 note , that the inflation predicts the significant suppression of slope @xmath137 with respect to the central value in ( [ dat2 ] ) . therefore , an improvement of accuracy for the measurement of slope could serve for discriminating the inflation models . further , the wmap data gave a strong correlations between the spectral index of scalar perturbations @xmath194 and fraction of tensor perturbations in the energy density @xmath200 , that is shown in fig . the correlations restricts the regions of @xmath194 admissible for the quartic - potential inflation , as shown in fig . [ lam - n ] by the shaded domain . ( 75,45 ) ( 0,0 ) and fraction of tensor perturbations in the energy density @xmath200 , as represented by @xmath198 and @xmath199 contours . the line gives the predictions of quartic inflation versus large amount of e - folding @xmath40 . the dot stands at @xmath202 , while the rectangle does at @xmath203.,title="fig : " ] ( 3,42)@xmath200 ( 63,-0)@xmath194 thus , the @xmath204-inflations could be marginally consistent with observations , if one suggest the extended version of preheating at low scales about @xmath205 gev with the preliminary passing the region with negative values of potential as we can conclude from figs . [ max][corr ] . an example of model for such the potential will be considered elsewhere @xcite . however , to the moment there is no a safe realistic model for the preheating scenario consistent with the observational data in the quartic inflation . we have shown that the inflationary dynamics with the quartic potential obeys the parametric quasiattractor governed by the hubble rate slowly evolving with e - folding of expansion . the condition of attractor stability is preserved by the condition of accelerated expansion . the quasiattractor allows us to express the inflationary parameters in terms of coupling constant @xmath107 and amount of e - folding @xmath40 in consistence with the slow - roll approximation . sub - leading terms to the approximation are also on hands . for the case of quartic potential , we have re - analyzed the possible maximal amount of e - folding @xmath159 corresponding to the scale of astronomical observations measuring the inhomogeneities generated by the quantum perturbations of inflaton just before the end of inflation . it is spectacular that at the reheating scale @xmath206 gev , the value of @xmath207 is independent of the particular mechanism of reheating parameterized by the state parameter @xmath166 . at the low - scale reheating the maximal @xmath159 could be increased due to the essential modification of potential near the origin . for instance , the field could pass the region of negative potential with the further relaxation in the flat minimum at @xmath208 after overcoming the barrier producing the tachyonic preheating . then , the standard quartic inflation with realistic parameters of preheating regime is inconsistent with the observations of matter - density fluctuations , its spectral index of scalar perturbations and fraction of tensor fluctuations . however , there is the marginal case at the coupling constant @xmath209 and amount of e - folding @xmath210 in the modified preheating at low - scales with the negative valley of potential described above , so that the quartic potential of inflaton at high fields with the appropriate modification near the origin is generally still not excluded , but a realistic model with such the scenario is not known . * * a. h. guth , phys . d * 23 * , 347 ( 1981 ) . a. d. linde , phys . b * 108 * , 389 ( 1982 ) . a. albrecht and p. j. steinhardt , phys . * 48 * , 1220 ( 1982 ) . a. d. linde , phys . b * 129 * , 177 ( 1983 ) . a. linde , lect . notes phys . * 738 * , 1 ( 2008 ) [ arxiv:0705.0164 [ hep - th ] ] . l. a. urena - lopez and m. j. reyes - ibarra , arxiv:0709.3996 [ astro - ph ] . v. a. belinsky , i. m. khalatnikov , l. p. grishchuk and y. b. zeldovich , phys . b * 155 * , 232 ( 1985 ) . t. piran , r. m. williams , phys . b * 163 * , 331 ( 1985 ) . l. a. kofman , a. d. linde and a. a. starobinsky , phys . b * 157 * , 361 ( 1985 ) . a. de la macorra and g. piccinelli , phys . d * 61 * , 123503 ( 2000 ) [ arxiv : hep - ph/9909459 ] . r. h. brandenberger and j. h. kung , phys . d * 42 * , 1008 ( 1990 ) . a. r. liddle and s. m. leach , phys . d * 68 * , 103503 ( 2003 ) [ arxiv : astro - ph/0305263 ] . g. n. felder , j. garcia - bellido , p. b. greene , l. kofman , a. d. linde and i. tkachev , phys . * 87 * , 011601 ( 2001 ) [ arxiv : hep - ph/0012142 ] . g. n. felder , l. kofman and a. d. linde , phys . d * 64 * , 123517 ( 2001 ) [ arxiv : hep - th/0106179 ] . d. n. spergel _ et al . _ [ wmap collaboration ] , astrophys . j. suppl . * 148 * , 175 ( 2003 ) [ arxiv : astro - ph/0302209 ] ; d. n. spergel _ et al . _ [ wmap collaboration ] , astrophys . j. suppl . * 170 * , 377 ( 2007 ) [ arxiv : astro - ph/0603449 ] . s. r. coleman and f. de luccia , phys . d * 21 * , 3305 ( 1980 ) . s. weinberg , phys . * 48 * , 1776 ( 1982 ) . v. v. kiselev and s. a. timofeev , in preparation .

at high e - foldings of expansion , the inflation with the quartic potential exhibits the parametric attractor governed by the slowly running hubble rate . this quasiattractor simplifies the analysis of predictions for the inhomogeneity generated by the quantum fluctuations of inflaton . the method reveals the connection of inflation e - folding with general parameters of preheating regime in various scenarios and observational data .

LOS ANGELES (AP) — In her first interview since the NBA banned her estranged husband, Shelly Sterling says she will fight to keep her share of the Los Angeles Clippers and plans one day to divorce Donald Sterling. (Click Prev or Next to continue viewing images.) ADVERTISEMENT (Click Prev or Next to continue viewing images.) Los Angeles Clippers co-owner Shelly Sterling, below, watches the Clippers play the Oklahoma City Thunder along with her attorney, Pierce O'Donnell, in the first half of Game 3 of the Western Conference... (Associated Press) Shelly Sterling spoke to Barbara Walters, and ABC News posted a short story with excerpts from the conversation Sunday. NBA Commissioner Adam Silver has banned Donald Sterling for making racist comments and urged owners to force Sterling to sell the team. Silver added that no decisions had been made about the rest of Sterling's family. According to ABC's story, Shelly Sterling told Walters: "I will fight that decision." Sterling also said that she "eventually" will divorce her husband, and that she hadn't yet done so due to financial considerations. ||||| Shelly Sterling said today that "eventually, I am going to" divorce her estranged husband, Donald Sterling, and if the NBA tries to force her to sell her half of the Los Angeles Clippers, she would "absolutely" fight to keep her stake in the team. "I will fight that decision," she told ABC News' Barbara Walters today in an exclusive interview. "To be honest with you, I'm wondering if a wife of one of the owners, and there's 30 owners, did something like that, said those racial slurs, would they oust the husband? Or would they leave the husband in?" Sterling added that the Clippers franchise is her "passion" and "legacy to my family." "I've been with the team for 33 years, through the good times and the bad times," she added. These comments come nearly two weeks after NBA Commissioner Adam Silver announced a lifetime ban and a $2.5 million fine for Donald Sterling on April 29, following racist comments from the 80-year-old, which were caught on tape and released to the media. Read: Barbara Walters' Exclusive Interview With V. Stiviano Being estranged from her husband, Shelly Sterling said she would "have to accept" whatever punishment the NBA handed down to him, but that her stake in the team should be separate. "I was shocked by what he said. And -- well, I guess whatever their decision is -- we have to live with it," she said. "But I don't know why I should be punished for what his actions were." An NBA spokesman said this evening that league rules would not allow her tol hold on to her share. "Under the NBA Constitution, if a controlling owner's interest is terminated by a 3/4 vote, all other team owners' interests are automatically terminated as well," NBA spokesman Mike Bass said. "It doesn't matter whether the owners are related as is the case here. These are the rules to which all NBA owners agreed to as a condition of owning their team." Sherry Sterling's lawyer, Pierce O'Donnell, disputed the league's reading of its constitution. "We do not agree with the league's self-serving interpretation of its constitution, its application to Shelly Sterling or its validity under these unique circumstances," O'Donnell said in a statement released this evening in reposnse the NBA. "We live in a nation of laws. California law and the United States Constitution trump any such interpretation." If the league decides to force Donald Sterling to sell his half of the team, Shelly Sterling doesn't know what he will do, but the possibility of him transferring full ownership to her is something she "would love him to" consider. Related: NBA Bans Clippers Owner Donald Sterling For Life "I haven't discussed it with him or talked to him about it," she said. The lack of communication between Rochelle and Donald Sterling led Walters to question whether she plans to file for divorce. "For the last 20 years, I've been seeing attorneys for a divorce," she said, laughing. "In fact, I have here-- I just filed-- I was going to file the petition. I signed the petition for a divorce. And it came to almost being filed. And then, my financial advisor and my attorney said to me, 'Not now.'" Sterling added that she thinks the stalling of the divorce stems from "financial arrangements." But she said "Eventually, I'm going to." She also told Walters she thinks her estranged husband is suffering from "the onset of dementia." Since Donald Sterling's ban, several celebrities have said they would be willing to buy the team from Sterling, including Oprah Winfrey and Magic Johnson. Sterling remains the owner, though his ban means he can have nothing to do with running the team and can't attend any games. Silver announced Friday that former Citigroup chairman and former Time Warner chairman Richard Parsons has been named interim CEO of the team, but nothing concrete in terms of ownership or whether Sterling will be forced to sell the team. Parsons will now take over the basic daily operations for the team and oversee the team's president. Read: What You Need to Know This Week About Donald Sterling ABC News contacted Donald Sterling for comment on his wife's interview, but he declined.

– Shelly Sterling plans "eventually" to divorce her estranged husband Donald, she tells Barbara Walters at ABC News. As for her stake in the Los Angeles Clippers, she plans to keep it, the AP notes. Sterling says she would "absolutely" fight any NBA decision to force her to sell the team. The team is her "legacy" to her family, she says. "To be honest with you, I'm wondering if a wife of one of the owners … said those racial slurs, would they oust the husband? Or would they leave the husband in?"