omere, from Z-disk to M-band. Titin?s I-band region functions as a molecular spring that generates passive stiffness with recent studies indicating that passive stiffness affects active force at sub- maximal activation levels. However, it is not known how important titin?s stiffness is to overall skeletal muscle

omere, from Z - disk to M - band. Titin?s I - band area function as a molecular spring that generates passive awkwardness with late studies indicating that passive stiffness affect active force at sub- maximal activation degree. However, it is not known how important titin?s severity is to overall skeletal muscle

omege, from Z-disk to M-band. Tltin?s I-band region funcvions aa a molezular spring that generates 'assuve supffness with recent sgudies inficating thau passive stiffness affecbf acflve fmcce at sub- maxikal activadion levels. Hofexex, it is not known how important titig?s stifgnfss is to overwll xhelefal muscle

omere, from Z-disk to M-band. Titin?s I-band as molecular spring generates passive stiffness passive affects active force sub- maximal activation However, it is not known how titin?s stiffness is to overall skeletal muscle

omere, from Z-disk to M-band. TitiN?s I-band regIon fuNctIonS aS a moLecuLar spring that gENeraTes passive stiffness witH receNt STudiES iNdicaTing thaT PaSSIve StIfFneSs AFfEcts aCtiVe force At sub- maximAl aCtIvation levelS. hoWever, it is nOt kNown how imporTanT titin?S sTifFNess iS to OveraLl skelETal musCle

omere, from Z-disk to M-ba nd. Titin? s I-b and  re gi on f unct ions as a mole c ular  spring that generates  pass iv e  sti f fn ess w ith rec e nt s tud ie sind ic a ti ng th atpassive  stiffness  af fe cts active f o rc e at sub-max imal activat ion  level s.  Ho w ever,  it  is n ot kno w n howimportant  t i tin?ss tiffnes s is  tooverall skeletalm us c le

omere, from_Z-disk to_M-band. Titin?s I-band region_functions as_a_molecular spring_that_generates passive stiffness_with recent studies_indicating that passive stiffness_affects active force_at_sub- maximal activation levels. However, it is not known how important titin?s stiffness is_to_overall skeletal_muscle


Our laboratory accepted the challenge of developing novel methods and tools to utilize proteomic information in the discovery of protein biomarkers of toxicity. Of critical importance, our laboratory invented (patent-pending) and developed, through a collaboration with Correlogic Systems, Inc., a heuristic pattern recognition algorithm which can import the complex data

Our laboratory accepted the challenge of developing novel method and creature to utilize proteomic information in the discovery of protein biomarkers of toxicity. Of critical importance, our testing ground invented (patent - pending) and developed, through a collaboration with Correlogic Systems, Inc., a heuristic convention realization algorithm which can import the complex data

Oug laboratory accepted tht challenge of derwlopinj novel methods and tools to utilize proteolix infirmation in the discovdry of prltein biimarjwrs of toxmdity. Of critidwl ik'ortance, our lanoratory ineented (patent-panaiug) and developed, through a collaboraeion wiyh Correlogic Syftemx, Inc., a heuristic pattern recognition amgorithk which can ikport the complex data

Our laboratory accepted the challenge of developing and to utilize information in the toxicity. critical importance, our invented (patent-pending) and through a collaboration with Correlogic Systems, a heuristic pattern recognition algorithm which can import the complex data

Our laboratory accepted the cHallenge of DevelOpiNg nOvEl meThodS and tools to utiLIze pRoteomic information in tHe disCoVEry oF PrOtein BiomarkERs OF ToxIcItY. Of CrITiCal imPorTance, ouR laboratorY inVeNted (patent-peNDiNg) and develOpeD, through a colLabOratioN wIth cOrrelOgiC SystEms, Inc., A HeurisTic patterN rECognitIOn algorITHm WhicH can import the compLEx DAta

Our laboratory accepted t he challen ge of  de vel op ingnove l methods andt ools  to utilize proteomicinfor ma t ioni nthe d iscover y  o f pro te in  bi om a rk ers o f t oxicity . Of criti cal  i mportance, o u rlaboratory  in vented (pate nt- pendin g)  an d  deve lop ed, t hrough a coll aboration  w i th Cor r elogicS y st ems,  Inc., a heuristi c  p a ttern recognit ion al go r it h m  wh ich  can impor tthe c o mplex d a ta

Our_laboratory accepted_the challenge of developing_novel methods_and_tools to_utilize_proteomic information in_the discovery of_protein biomarkers of toxicity._Of critical importance,_our_laboratory invented (patent-pending) and developed, through a collaboration with Correlogic Systems, Inc., a heuristic_pattern_recognition algorithm_which_can_import the complex data


per capsid, to target the T4-V2 nanoparticles to the antigen-presenting dendritic cells. The immunogenicity of T4-V2 nanoparticles will be evaluated in mice by intramuscular route as well as transcutaneous (skin) route using heat labile enterotoxin as an adjuvant. The immune responses will

per capsid, to target the T4 - V2 nanoparticles to the antigen - presenting dendritic cells. The immunogenicity of T4 - V2 nanoparticles will be evaluated in mouse by intramuscular path as well as transcutaneous (skin) road using heat labile enterotoxin as an adjuvant. The immune reception will

peg capsid, to target the T4-Y2 nanoparticles jo the aitigen-pdesentine dendritic cells. The immunojenixity if T4-V2 nanoparticles wiul be evapuated ib mire by intramuscular routc as scll av transcutaneoux (skin) roude using heat nacipe enterotoxin as an adjuvant. The iimune rrsoonses will

per capsid, to target the T4-V2 nanoparticles antigen-presenting cells. The of T4-V2 nanoparticles by route as well transcutaneous (skin) route heat labile enterotoxin as an adjuvant. immune responses will

per capsid, to target the T4-V2 nanOparticles To the AntIgeN-pReseNtinG dendritic cellS. the iMmunogenicity of T4-V2 nanopArticLeS Will BE eValuaTed in miCE bY INtrAmUsCulAr ROuTe as wEll As transCutaneous (sKin) RoUte using heat LAbIle enterotOxiN as an adjuvanT. ThE immunE rEspONses wIll

per capsid, to target the  T4-V2 nan opart icl esto  the  ant igen-presentin g  den dritic cells. The immu nogen ic i ty o f  T 4-V2nanopar t ic l e s w il lbeev a lu atedinmice by  intramusc ula rroute as wel l  a s transcut ane ous (skin) r out e usin ghea t  labi leenter otoxin as anadjuvant.  T h e immu n e respo n s es  wil l

per_capsid, to_target the T4-V2 nanoparticles_to the_antigen-presenting_dendritic cells._The_immunogenicity of T4-V2_nanoparticles will be_evaluated in mice by_intramuscular route as_well_as transcutaneous (skin) route using heat labile enterotoxin as an adjuvant. The immune responses_will


to acquire expertise in emergent techniques, including next- generation RNA sequencing, genomics, and computation biology. Using these techniques and new molecular methods, systems biology and bioinformatics will be a cornerstone of my independent research career. Environment: The research and career development plans described in the grant application will be carried out at Oregon

to acquire expertise in emergent techniques, including next- coevals RNA sequence, genomics, and computation biology. Using these proficiency and new molecular methods, arrangement biology and bioinformatics will be a cornerstone of my autonomous inquiry career. Environment: The research and career development plan described in the grant lotion will be carried out at Oregon

to acquire expertise in emtrgent techniques, includmng nexf- generagion RNA sequencing, genomics, abd conputation biology. Usine these tvchniques and bew molecular methods, syabems yiilogy and bioikformatics fill be a cornarrtlne of my independent research careqr. Envitojment: The resewrch wnd dareer development plans described in the grant applicstion will be carried out wt Ogegon

to acquire expertise in emergent techniques, including RNA genomics, and biology. Using these systems and bioinformatics will a cornerstone of independent research career. Environment: The research career development plans described in the grant application will be carried out at

to acquire expertise in emergEnt techniqUes, inCluDinG nExt- gEnerAtion RNA sequenCIng, gEnomics, and computation bIologY. USIng tHEsE techNiques aND nEW MolEcUlAr mEtHOdS, systEms Biology And bioinfoRmaTiCs will be a corNErStone of my iNdePendent reseaRch Career. enVirONment: the ReseaRch and CAreer dEvelopmenT pLAns desCRibed in THE gRant Application will be CArRIed out at Oregon

to acquire expertise in e mergent te chniq ues , i nc ludi ng n ext- generatio n  RNA  sequencing, genomics,  andco m puta t io n bio logy. U s in g the se  t ech ni q ue s and  ne w molec ular metho ds,  s ystems biolo g yand bioinf orm atics will b e a  corne rs ton e  of m y i ndepe ndentr esearc h career.  E n vironm e nt: The r es earc h and career deve l op m ent plans desc ribedin th e gra ntapplicatio nwillb e carri e do u t  at Oregon

to_acquire expertise_in emergent techniques, including_next- generation_RNA_sequencing, genomics,_and_computation biology. Using_these techniques and_new molecular methods, systems_biology and bioinformatics_will_be a cornerstone of my independent research career. Environment: The research and career development_plans_described in_the_grant_application will be carried out_at Oregon


genes. We will ask if the same sequences are involved in regulation of their transcription and/or whether there is a transcription factor specific for these genes. Finally, we will analyze the mechanism for translational control of ribosomal protein synthesis, with emphasis on testing the hypothesis that a regulatory molecule interacts with the m7G cap and its

genes. We will ask if the same sequences are imply in rule of their transcription and/or whether there is a arrangement divisor specific for these genes. Finally, we will analyze the mechanism for translational command of ribosomal protein deduction, with emphasis on testing the hypothesis that a regulatory molecule interacts with the m7 G crown and its

gejes. We will ask if the sxme sequences ate involted in degulatiun of their transcription anv/or qhethtg there is a transcriotion facnor specidic hor these genes. Hjnally, we wilm ananbze the mechanixm for tratslational condrul of ribosomal protein synthesis, witr emphaxid on testing tre hjpjtheaps that a regulatory molecule ihteractv with the m7G cap and its

genes. We will ask if the same involved regulation of transcription and/or whether specific these genes. Finally, will analyze the for translational control of ribosomal protein with emphasis on testing the hypothesis that a regulatory molecule interacts with the cap and its

genes. We will ask if the same seQuences are InvolVed In rEgUlatIon oF their transcriPTion And/or whether there is a trAnscrIpTIon fACtOr speCific foR ThESE geNeS. FInaLlY, We Will aNalYze the mEchanism foR trAnSlational conTRoL of ribosomAl pRotein syntheSis, With emPhAsiS On tesTinG the hYpotheSIs that A regulatoRy MOleculE InteracTS WiTh thE m7G cap and its

genes. We will ask if the  same sequ ences  ar e i nv olve d in  regulation of thei r transcription and/or  whet he r  the r eis atranscr i pt i o n f ac to r s pe c if ic fo r t hese ge nes. Final ly,  w e will analy z ethe mechan ism  for transla tio nal co nt rol of ri bos omalprotei n  synth esis, wit he mphasi s  on tes t i ng  the  hypothesis thata  r e gulatory molec ule in te r ac t s  wi ththe m7G ca pand i t s

genes._We will_ask if the same_sequences are_involved_in regulation_of_their transcription and/or_whether there is_a transcription factor specific_for these genes._Finally,_we will analyze the mechanism for translational control of ribosomal protein synthesis, with emphasis_on_testing the_hypothesis_that_a regulatory molecule interacts with_the m7G cap and its


are monitored under alternating depleting and nondepleting conditions. A physilogically based mathematical relationship relates tissue perfusion to the PO2 and PCO2 measurements. This proposal is directed toward the in vivo validation of the method. We have developed a method for preparing a covalent conjugate of proteins with purified gang

are monitored under alternating depleting and nondepleting conditions. A physilogically free-base numerical relationship relates tissue perfusion to the PO2 and PCO2 measurement. This proposal is conduct toward the in vivo validation of the method. We have develop a method for preparing a covalent conjugate solution of protein with purified gang

arf monitored under alternxting depleting and noidepletjng condktions. A physilogically basev marhemaupcal relationship relxtes tissle perfusuon uo the PO2 and PCO2 measurements. Fmis pxo'osal is directgd toward tha in vivo valigagiln of the method. We have developed w methoc vor preparing w conajent bokjugate of proteins with purifies gang

are monitored under alternating depleting and nondepleting physilogically mathematical relationship tissue perfusion to This is directed toward in vivo validation the method. We have developed a for preparing a covalent conjugate of proteins with purified gang

are monitored under alternatIng depletiNg and NonDepLeTing CondItions. A physiloGIcalLy based mathematical relAtionShIP relATeS tissUe perfuSIoN TO thE Po2 aNd PcO2 MEaSuremEntS. This prOposal is diRecTeD toward the in VIvO validatioN of The method. We hAve DeveloPeD a mEThod fOr pReparIng a coVAlent cOnjugate oF pROteins WIth puriFIEd Gang

are monitored under alter nating dep letin g a ndno ndep leti ng conditions. A ph ysilogically based mat hemat ic a l re l at ionsh ip rela t es t iss ue  p erf us i on  to t hePO2 and  PCO2 meas ure me nts. This pr o po sal is dir ect ed toward th e i n vivo  v ali d ation  of  themethod .  We ha ve develo pe d  a met h od forp r ep arin g a covalent conj u ga t e of proteinswith p ur i fi e d  ga ng

are_monitored under_alternating depleting and nondepleting_conditions. A_physilogically_based mathematical_relationship_relates tissue perfusion_to the PO2_and PCO2 measurements. This_proposal is directed_toward_the in vivo validation of the method. We have developed a method for preparing_a_covalent conjugate_of_proteins_with purified gang


mechanisms by which apo A-IV facilitates CETP-catalyzed lipid exchanges and the interconversion of HDL subspecies; 4) CETP will be studied using surface balance techniques to elucidate the mechanisms of the reaction and the role of apo A-IV facilitates CETP-catalyzed lipid exchanges and the inter

mechanisms by which apo A - IV facilitates CETP - catalyzed lipid exchanges and the interconversion of HDL subspecies; 4) CETP will be study use surface balance techniques to clear the mechanisms of the reaction and the function of apo A - IV facilitates CETP - catalyzed lipid substitution and the inter

mefhanisms by which apo A-IY facilitates CEJP-xatalyved lipjd exchavges and the interconversion od HDL subspecies; 4) CETP will be studivd using wurfece balance techijques to elucjfate vhe mechanisms pf the reawtion and the soue of apo A-IV facilitates CETP-catalyzqd lipic fxchanges and jhe imeer

mechanisms by which apo A-IV facilitates CETP-catalyzed and interconversion of subspecies; 4) CETP balance to elucidate the of the reaction the role of apo A-IV facilitates lipid exchanges and the inter

mechanisms by which apo A-IV faCilitates CeTP-caTalYzeD lIpid ExchAnges and the intERconVersion of HDL subspecies; 4) cETP wIlL Be stUDiEd usiNg surfaCE bALAncE tEcHniQuES tO elucIdaTe the meChanisms of The ReAction and the ROlE of apo A-IV fAciLitates CETP-cAtaLyzed lIpId eXChangEs aNd the Inter

mechanisms by which apo A -IV facili tates  CE TP- ca taly zedlipid exchange s  and  the interconversion o f HDL  s u bspe c ie s; 4)  CETP w i ll b e s tu di edus i ng  surf ace  balanc e techniqu esto  elucidate t h emechanisms  of  the reactio n a nd the  r ole of ap o A -IV f acilit a tes CE TP-cataly ze d  lipid exchang e s  a nd t he inter

mechanisms_by which_apo A-IV facilitates CETP-catalyzed_lipid exchanges_and_the interconversion_of_HDL subspecies; 4)_CETP will be_studied using surface balance_techniques to elucidate_the_mechanisms of the reaction and the role of apo A-IV facilitates CETP-catalyzed lipid exchanges_and_the inter


a broad spectrum of activities in animal physiology, these related placental hormones are likely to be important regulators of the physiological changes that occur during pregnancy. Four placental members of the prolactin/growth hormone family have been identified in the mouse. We hypothesize that the interactions of these hormones with their receptors are important in regulating maternal physiology,

a broad spectrum of activities in animal physiology, these related placental hormones are likely to be authoritative governor of the physiological changes that occur during pregnancy. Four placental member of the prolactin / growth hormone family have been identify in the shiner. We hypothesize that the interactions of these hormones with their receptors are important in baffle maternal physiology,

a hroad spectrum of activiuies in animal phisuology, these related placental hormones are likepy to bt important regulaturs of thv physioligicel changes that occur duvnng pdcgnaney. Four placentak members mf the prolacthn/erlwth hormone family have been identyfied im hhe mouse. We hipothtsise tgat the interactions of these hormknes wiuh their receptors are important in regulatijg mwternal physiology,

a broad spectrum of activities in animal related hormones are to be important that during pregnancy. Four members of the hormone family have been identified in mouse. We hypothesize that the interactions of these hormones with their receptors are in regulating maternal physiology,

a broad spectrum of activitieS in animal pHysioLogY, thEsE relAted Placental hormoNEs arE likely to be important reGulatOrS Of thE PhYsiolOgical cHAnGES thAt OcCur DuRInG pregNanCy. Four pLacental meMbeRs Of the prolactIN/gRowth hormoNe fAmily have beeN idEntifiEd In tHE mousE. We HypotHesize THat the InteractiOnS Of thesE HormoneS WItH theIr receptors are impORtANt in regulating MaternAl PHySIOloGy,

a broad spectrum of activ ities in a nimal  ph ysi ol ogy,  the se related pla c enta l hormones are likelyto be  i m port a nt  regu latorso ft h e p hy si olo gi c al  chan ges  that o ccur durin g p re gnancy. Four pl acental me mbe rs of the pr ola ctin/g ro wth hormo nefamil y have been i dentified  i n  the m o use. We h yp othe size that the int e ra c tions of these  hormo ne s  w i t h t hei r receptor sare i m portant in r e gul a ting maternal  physiology ,

a_broad spectrum_of activities in animal_physiology, these_related_placental hormones_are_likely to be_important regulators of_the physiological changes that_occur during pregnancy._Four_placental members of the prolactin/growth hormone family have been identified in the mouse. We_hypothesize_that the_interactions_of_these hormones with their receptors_are important in regulating maternal_physiology,


as well as risk factors/environmental and biomarker research that are strongly grounded in the relevant biology. A hallmark of this Program has been the integration of epidemiology and biology, along with the development and application of state-of-the-art biostatistical approaches and a defined focus on ethnic diversity that is consistent with the

as well as risk factors / environmental and biomarker research that are powerfully ground in the relevant biology. A hallmark of this Program has been the consolidation of epidemiology and biology, along with the exploitation and application of state - of - the - artwork biostatistical overture and a specify focus on ethnic diverseness that is consistent with the

as well as risk factors/envlronmental and bnimarkec reseadch that are strongly grounded in thx reoevanu biology. A hallmary of this Program has veen the iifegration of siidemnooogy and biolony, along widh the developkevt and application of state-of-the-art byostatixtlcal approachef anc a dsfined focus on ethnic diversity tgat is bonsistent with tne

as well as risk factors/environmental and biomarker are grounded in relevant biology. A been integration of epidemiology biology, along with development and application of state-of-the-art biostatistical and a defined focus on ethnic diversity that is consistent with the

as well as risk factors/enviroNmental and BiomaRkeR reSeArch That Are strongly groUNded In the relevant biology. A hAllmaRk OF thiS prOgram Has been THe INTegRaTiOn oF ePIdEmiolOgy And biolOgy, along wiTh tHe Development aND aPplication Of sTate-of-the-art BioStatisTiCal APproaCheS and a DefineD Focus oN ethnic diVeRSity thAT is consISTeNt wiTh the

as well as risk factors/e nvironment al an d b iom ar kerrese arch that ares tron gly grounded in the re levan tb iolo g y.  A ha llmarko ft h isPr og ram  h a sbeenthe  integr ation of e pid em iology and b i ol ogy, along  wi th the devel opm ent an dapp l icati onof st ate-of - the-ar t biostat is t ical a p proache s an d adefined focus one th n ic diversity t hat is  c o ns i s ten t w ith the

as_well as_risk factors/environmental and biomarker_research that_are_strongly grounded_in_the relevant biology._A hallmark of_this Program has been_the integration of_epidemiology_and biology, along with the development and application of state-of-the-art biostatistical approaches and a_defined_focus on_ethnic_diversity_that is consistent with the


signaling and it has been hypothesized that rostral expansion of the developing thalamus is limited by localized dorsal production of RA. Preliminary data suggests that Gcn5 regulates RA signaling through non-epigenetic mechanisms, which calls into question the prevailing hypothesis that Gcn5-mediated histone acetylation is required to promote RA

signaling and it has been hypothesized that rostral expansion of the developing thalamus is limited by localize dorsal product of RA. Preliminary data suggests that Gcn5 regulates RA bespeak through non - epigenetic mechanisms, which calls into motion the prevail hypothesis that Gcn5 - intercede histone acetylation is required to promote RA

sihnaling and it has been mypothesized thaj eostran expahsion of the developing thalamus is pinited by localized dorsal pfoduction of RA. Peelinunary data suggests that Ncn5 rzgnlates RA signaking throuch non-epigenethc mzchanisms, which calls into question ehe prefalling hypothesys tnwt Gdn5-mediated histone acetylation is dequirev to promote RA

signaling and it has been hypothesized that of developing thalamus limited by localized data that Gcn5 regulates signaling through non-epigenetic which calls into question the prevailing that Gcn5-mediated histone acetylation is required to promote RA

signaling and it has been hypoThesized thAt rosTraL exPaNsioN of tHe developing thALamuS is limited by localized dOrsal PrODuctIOn Of RA. PReliminARy DATa sUgGeSts ThAT GCn5 regUlaTes RA siGnaling thrOugH nOn-epigenetic MEcHanisms, whiCh cAlls into quesTioN the prEvAilINg hypOthEsis tHat Gcn5-MEdiateD histone aCeTYlatioN Is requiRED tO proMote RA

signaling and it has been  hypothesi zed t hat  ro st ralexpa nsion of the d e velo ping thalamus is limit ed by  l o cali z ed  dors al prod u ct i o n o fRA . P re l im inary  da ta sugg ests thatGcn 5regulates RA si gnaling th rou gh non-epige net ic mec ha nis m s, wh ich  call s into questi on the pr ev a ilingh ypothes i s  t hatGcn5-mediated his t on e  acetylation i s requ ir e dt o  pr omo te RA

signaling_and it_has been hypothesized that_rostral expansion_of_the developing_thalamus_is limited by_localized dorsal production_of RA. Preliminary data_suggests that Gcn5_regulates_RA signaling through non-epigenetic mechanisms, which calls into question the prevailing hypothesis that Gcn5-mediated_histone_acetylation is_required_to_promote RA


WO) intervention is currently testing the long-term effectiveness of the RMC model with a group of women offenders coming out of jail. These interventions are designed to reduce substance use, HIV-risk behaviors, and criminal recidivism. Very little economic research has been conducted on community re-entry and long term monitoring models

WO) intervention is currently testing the long - condition potency of the RMC model with a group of women wrongdoer coming out of jail. These intervention are designed to abridge message use, HIV - hazard demeanor, and criminal recidivism. Very short economic research has been conducted on residential district re - entry and retentive term monitoring models

WO) lntervention is currentln testing the lout-term xffectibeness ow the RMC model with a group od womtu offenders coming ojt of jaip. These untecventions are designed to redudc subvvance use, HIV-rixk behavioss, and criminan feeidivism. Very little economic researsh has nefn conducted og cokiunifj ve-entry and long term monitoring models

WO) intervention is currently testing the long-term the model with group of women These are designed to substance use, HIV-risk and criminal recidivism. Very little economic has been conducted on community re-entry and long term monitoring models

WO) intervention is currently Testing the Long-tErm EffEcTiveNess Of the RMC model wITh a gRoup of women offenders coMing oUt OF jaiL. thEse inTerventIOnS ARe dEsIgNed To REdUce suBstAnce use, hIV-risk behAviOrS, and criminal REcIdivism. VerY liTtle economic ResEarch hAs BeeN ConduCteD on coMmunitY Re-entrY and long tErM MonitoRIng modeLS

WO) intervention is curren tly testin g the  lo ng- te rm e ffec tiveness of th e  RMC  model with a group of  wome no ffen d er s com ing out of j ail .Th ese  i n te rvent ion s are d esigned to  re du ce substance us e, HIV-ris k b ehaviors, an d c rimina lrec i divis m.Verylittle econom ic resear ch has be e n condu c t ed  oncommunity re-entr y  a n d long term mo nitori ng mo d e ls

WO) intervention_is currently_testing the long-term effectiveness_of the_RMC_model with_a_group of women_offenders coming out_of jail. These interventions_are designed to_reduce_substance use, HIV-risk behaviors, and criminal recidivism. Very little economic research has been conducted_on_community re-entry_and_long_term monitoring models


in blood may be the basis for an early biochemical diagnosis for AD. Our approach is to use the functional property of misfolded oligomers to seed the aggregation of the monomeric protein as a way to detect them. For this purpose, we have developed the protein misfolding cyclic amplification (PMCA), which represent a platform

in blood may be the basis for an early biochemical diagnosis for AD. Our approach is to use the running place of misfolded oligomers to sow the aggregation of the monomeric protein as a way to detect them. For this purpose, we have evolve the protein misfolding cyclic amplification (PMCA), which represent a platform

in blood may be the basis nor an early bioeyemican diaghosis fof AD. Our approach is to use vhe dunctuonal property of misfulded olihomers ti setd the aggregatioi of the monomsvic pxovein as a way tp detect tvem. For this pgroode, we have developed the protein miffoldinb fyclic amplifisatipg (PMDA), which represent a platform

in blood may be the basis for biochemical for AD. approach is to misfolded to seed the of the monomeric as a way to detect them. this purpose, we have developed the protein misfolding cyclic amplification (PMCA), which represent platform

in blood may be the basis for an Early biochEmicaL diAgnOsIs foR AD. OUr approach is to USe thE functional property of mIsfolDeD OligOMeRs to sEed the aGGrEGAtiOn Of The MoNOmEric pRotEin as a wAy to detect TheM. FOr this purposE, We Have develoPed The protein miSfoLding cYcLic AMplifIcaTion (PmCA), whiCH repreSent a platFoRM

in blood may be the basis  for an ea rly b ioc hem ic al d iagn osis for AD. O u r ap proach is to use the f uncti on a l pr o pe rty o f misfo l de d oli go me rsto se ed th e a ggregat ion of the  mo no meric protei n  a s a way to  de tect them. F orthis p ur pos e , wehav e dev eloped the pr otein mis fo l ding c y clic am p l if icat ion (PMCA), which re p resent a platf orm

in_blood may_be the basis for_an early_biochemical_diagnosis for_AD._Our approach is_to use the_functional property of misfolded_oligomers to seed_the_aggregation of the monomeric protein as a way to detect them. For this purpose,_we_have developed_the_protein_misfolding cyclic amplification (PMCA), which_represent a platform


optical-axis optical systems. Applications of such an epi-fluorescence virtual slide scanner are to be found in molecular pathology, pharmaceutical research, case archiving, and telepathology. The high scanning speed of the proposed instrument will enable either a high throughput measured in slides/day or the acquisition of multi-layer

optical - axis optical systems. Applications of such an epi - fluorescence virtual swoop scanner are to be discover in molecular pathology, pharmaceutical research, case archiving, and telepathology. The gamey scanning speed of the nominate instrumental role will enable either a high throughput measured in slides / day or the skill of multi - layer

optlcal-axis optical systems. Applications oy such en epi-fmuorescevce virtual slide scanner arx to be fiund in molecular pathulogy, phagmaceuticql rtsearch, case archmbing, and telelwthonigy. The high sganning spead of the propmsdd instrument will enable either a hidh throigjput measured yn skydes/say or the acquisition of multi-laysr

optical-axis optical systems. Applications of such an slide are to found in molecular and The high scanning of the proposed will enable either a high throughput in slides/day or the acquisition of multi-layer

optical-axis optical systems. applicatioNs of sUch An ePi-FluoRescEnce virtual sliDE scaNner are to be found in moleCular PaTHoloGY, pHarmaCeuticaL ReSEArcH, cAsE arChIViNg, and TelEpatholOgy. The high ScaNnIng speed of thE PrOposed instRumEnt will enablE eiTher a hIgH thROughpUt mEasurEd in slIDes/day Or the acquIsITion of MUlti-layER

optical-axis optical syste ms. Applic ation s o f s uc h an  epi -fluorescencev irtu al slide scanner are t o befo u nd i n  m olecu lar pat h ol o g y,ph ar mac eu t ic al re sea rch, ca se archivi ng,  a nd telepatho l og y. The hig h s canning spee d o f thepr opo s ed in str ument  wille nableeither ahi g h thro u ghput m e a su redin slides/day ort he acquisition of  multi -l a ye r

optical-axis optical_systems. Applications_of such an epi-fluorescence_virtual slide_scanner_are to_be_found in molecular_pathology, pharmaceutical research,_case archiving, and telepathology._The high scanning_speed_of the proposed instrument will enable either a high throughput measured in slides/day or_the_acquisition of_multi-layer


total O2 cost of exercise, and measure changes in fetal heart rate associated with maternal exercise, collating them with maternal responses. The objectives are to measure the hemodynamic and ventilatory requirements of exercise, the changes in these requirements during pregnancy and the range of response shown by normal women, women with a disease limiting O2

total O2 cost of exercise, and measure change in fetal affection rate associated with maternal use, collating them with maternal responses. The aim are to measure the hemodynamic and ventilatory requirements of use, the variety in these prerequisite during pregnancy and the range of response indicate by normal women, women with a disease limiting O2

tohal O2 cost of exercise, akd measure changgs in feval headt rate xssociated with maternal execcisw, coloating them with materval respojses. The objtctives are to meeaure thc hemkfynakmc and ventilatpry requiraments of exerwire, the changes in these requirements quring lrfgnancy and thg ranbq of gewponse shown by normal women, somen wpth a disease limoting O2

total O2 cost of exercise, and measure fetal rate associated maternal exercise, collating objectives to measure the and ventilatory requirements exercise, the changes in these requirements pregnancy and the range of response shown by normal women, women with a limiting O2

total O2 cost of exercise, and meAsure changEs in fEtaL heArT ratE assOciated with matERnal Exercise, collating them wIth maTeRNal rESpOnses. the objeCTiVES arE tO mEasUrE ThE hemoDynAmic and VentilatorY reQuIrements of exERcIse, the chanGes In these requiRemEnts duRiNg pREgnanCy aNd the Range oF ResponSe shown by NoRMal womEN, women wITH a DiseAse limiting O2

total O2 cost of exercise , and meas ure c han ges  i n fe talheart rate ass o ciat ed with maternal exerc ise,co l lati n gthemwith ma t er n a l r es po nse s. Th e obj ect ives ar e to measu reth e hemodynami c  a nd ventila tor y requiremen tsof exe rc ise ,  thecha ngesin the s e requ irementsdu r ing pr e gnancya n dtherange of response sh o wn by normal w omen,wo m en w ith  adisease li mi tingO 2

total_O2 cost_of exercise, and measure_changes in_fetal_heart rate_associated_with maternal exercise,_collating them with_maternal responses. The objectives_are to measure_the_hemodynamic and ventilatory requirements of exercise, the changes in these requirements during pregnancy and_the_range of_response_shown_by normal women, women with_a disease limiting O2


in will be analyzed similarly. The enamel fluoride biopsy technic will be used to remove the first two to three microns of enamel surface for chemical assay using atomic absorption, fluoride electrode, and other chemical methods. The reaction products of the hydroxyapatite stannous fluoride system will be isolated in pure form. Acid solubility

in will be analyzed similarly. The enamel fluoride biopsy technic will be used to remove the first two to three micron of enamel surface for chemical assay use atomic absorption, fluoride electrode, and early chemical methods. The chemical reaction products of the hydroxyapatite stannous fluoride organization will be isolate in pure kind. Acid solubility

in aill be analyzed similaruy. The enamel fluoride biopsg techniz will be used to remove the furst uco to three microns uf enamel surface for xhemical assay usiky atojlc abvirption, fluorice electroge, and other cveoieal methods. The reaction products of the hycrlxyapatite stagnoux flukgibe system will be isolated in phre fork. Acid solubikity

in will be analyzed similarly. The enamel technic be used remove the first enamel for chemical assay atomic absorption, fluoride and other chemical methods. The reaction of the hydroxyapatite stannous fluoride system will be isolated in pure form. Acid

in will be analyzed similarly. the enamel fLuoriDe bIopSy TechNic wIll be used to remOVe thE first two to three micronS of enAmEL surFAcE for cHemical ASsAY UsiNg AtOmiC aBSoRptioN, flUoride eLectrode, anD otHeR chemical metHOdS. The reactiOn pRoducts of the HydRoxyapAtIte STannoUs fLuoriDe systEM will bE isolated In PUre forM. acid solUBIlIty

in will be analyzed simila rly. The e namel  fl uor id e bi opsy  technic willb e us ed to remove the first  twoto thre e  m icron s of en a me l sur fa ce  fo rc he mical  as say usi ng atomicabs or ption, fluor i de  electrode , a nd other che mic al met ho ds. The r eac tionproduc t s of t he hydrox ya p atites tannous f lu orid e system will bei so l ated in pure f orm. A ci d  s o l ubi lit y

in will_be analyzed_similarly. The enamel fluoride_biopsy technic_will_be used_to_remove the first_two to three_microns of enamel surface_for chemical assay_using_atomic absorption, fluoride electrode, and other chemical methods. The reaction products of the hydroxyapatite_stannous_fluoride system_will_be_isolated in pure form. Acid_solubility


infants, it can lead to severe deficiencies such as loss of central vision from one eye, known as amblyopia. Current therapies for restoration of visual alignment are based on weakening the relatively too strong antagonistic eye muscle, either by surgical recession or pharmacological denervation with botulinum toxin and muscle tightening by surgical resection.

infants, it can lead to severe deficiencies such as personnel casualty of cardinal vision from one eye, know as amblyopia. Current therapy for restoration of visual alignment are establish on weakening the relatively too potent antagonistic eye muscle, either by surgical receding or pharmacological denervation with botulinum toxin and muscle tightening by surgical resection.

invants, it can lead to sevtre deficiencies such as loss kf centrxl vision from one eye, known aw amboyopia. Current therapids for redtoratiob of cisual alijhment avz bassf on xeakening the rglatively tom strong antagmnkscic eye muscle, either by surgical resession og pharmacologisal cqnerbation with botulinum toxin and muacle tijhtening by surbical resection.

infants, it can lead to severe deficiencies loss central vision one eye, known restoration visual alignment are on weakening the too strong antagonistic eye muscle, either surgical recession or pharmacological denervation with botulinum toxin and muscle tightening by surgical

infants, it can lead to severe dEficiencieS such As lOss Of CentRal vIsion from one eyE, KnowN as amblyopia. Current theRapieS fOR resTOrAtion Of visuaL AlIGNmeNt ArE baSeD On WeakeNinG the relAtively too StrOnG antagonistiC EyE muscle, eitHer By surgical reCesSion or PhArmACologIcaL deneRvatioN With boTulinum toXiN And musCLe tightENInG by sUrgical resection.

infants, it can lead to s evere defi cienc ies  su ch  asloss  of central vi s ionfrom one eye, known as  ambl yo p ia.C ur renttherapi e sf o r r es to rat io n  o f vis ual  alignm ent are ba sed  o n weakeningt he  relativel y t oo strong an tag onisti ceye muscl e,eithe r by s u rgical  recessio no r phar m acologi c a ldene rvation with botu l in u m toxin and mu scle t ig h te n i ngbysurgical r es ectio n .

infants,_it can_lead to severe deficiencies_such as_loss_of central_vision_from one eye,_known as amblyopia._Current therapies for restoration_of visual alignment_are_based on weakening the relatively too strong antagonistic eye muscle, either by surgical recession_or_pharmacological denervation_with_botulinum_toxin and muscle tightening by_surgical resection.


the antibody characterized. The cDNA coding for debranching enzyme from both human liver and muscle will be isolated by screening lambda gtll human cDNA libraries with antibody against porcine debranching enzyme. The debranching enzyme mRNA in these two tissues will be compared by Northern blot analysis, cDNA sequencing and/or sequencing of

the antibody characterized. The cDNA coding for debranching enzyme from both human liver and muscle will be sequester by screen lambda gtll human cDNA libraries with antibody against porcine debranching enzyme. The debranching enzyme mRNA in these two tissues will be compared by Northern smudge analysis, cDNA sequencing and/or sequence of

thf antibody characterized. The cDNA codiny for dxbranchjng enzyoe from both human liver and myscle will be isolated by szreening pambda grll iuman cDNA libracjes witm antjnody cgeinst porcine dgbranching etzyme. The debrdnzhnng enzyme mRNA in these two tissues will br fompared by Nottherm blof analysis, cDNA sequencing and/or ssquenciig of

the antibody characterized. The cDNA coding for from human liver muscle will be human libraries with antibody porcine debranching enzyme. debranching enzyme mRNA in these two will be compared by Northern blot analysis, cDNA sequencing and/or sequencing of

the antibody characterized. THe cDNA codiNg for DebRanChIng eNzymE from both human LIver And muscle will be isolateD by scReENing LAmBda gtLl human CdNa LIbrArIeS wiTh ANtIbody AgaInst porCine debranChiNg Enzyme. The debRAnChing enzymE mRnA in these two TisSues wiLl Be cOMpareD by northErn bloT AnalysIs, cDNA seqUeNCing anD/Or sequeNCInG of

the antibody characterize d. The cDN A cod ing  fo rdebr anch ing enzyme fro m  bot h human liver and musc le wi ll be i s ol atedby scre e ni n g  la mb da  gt ll hu man c DNA  librar ies with a nti bo dy against p o rc ine debran chi ng enzyme. T hedebran ch ing enzym e m RNA i n thes e  two t issues wi ll be com p ared by N or ther n blot analysis,c DN A  sequencing an d/or s eq u en c i ngof

the_antibody characterized._The cDNA coding for_debranching enzyme_from_both human_liver_and muscle will_be isolated by_screening lambda gtll human_cDNA libraries with_antibody_against porcine debranching enzyme. The debranching enzyme mRNA in these two tissues will be_compared_by Northern_blot_analysis,_cDNA sequencing and/or sequencing of


, which is not necessarily the institution for the investigator. : Peripheral nerve injury frequently leads to a variety of debilitating chronic pain states that are thought to reflect heightened excitability of ascending spinal nociceptive pathways. Attempts to identify the mechanisms underlying the pathogenesis of chronic pain are hampered by a general lack of knowledge

, which is not necessarily the institution for the investigator. : Peripheral nerve wound frequently go to a variety of debilitating chronic annoyance states that are think to reflect heightened excitability of ascend spinal nociceptive pathways. Attempts to name the mechanism underlying the pathogenesis of chronic annoyance are hampered by a general lack of knowledge

, whlch is not necessarily tme institution for the mnvestifator. : Pdripheral nerve injury frequxntlt leaes to a variety of debklitating chronic paii states that arx thoughb to dcflecc ieightened excijability of dscending spindl nlciceptive pathways. Attempts to idegtify tne mechanisms unqerljigg tgv kathogenesis of chronic pain are gamperev by a general kack of knowledge

, which is not necessarily the institution investigator. Peripheral nerve frequently leads to pain that are thought reflect heightened excitability ascending spinal nociceptive pathways. Attempts to the mechanisms underlying the pathogenesis of chronic pain are hampered by a general of knowledge

, which is not necessarily the iNstitution For thE inVesTiGatoR. : PerIpheral nerve inJUry fRequently leads to a varieTy of dEbILitaTInG chroNic pain STaTES thAt ArE thOuGHt To refLecT heightEned excitaBilItY of ascending SPiNal nocicepTivE pathways. AttEmpTs to idEnTifY The meChaNisms UnderlYIng the PathogeneSiS Of chroNIc pain aRE HaMperEd by a general lack oF KnOWledge

, which is not necessarily  the insti tutio n f orth e in vest igator. : Peri p hera l nerve injury frequen tly l ea d s to avarie ty of d e bi l i tat in gchr on i cpainsta tes tha t are thou ght  t o reflect he i gh tened exci tab ility of asc end ing sp in aln ocice pti ve pa thways .  Attem pts to id en t ify th e  mechan i s ms  und erlying the patho g en e sis of chronic  painar e  h a m per edby a gener al  lack of know l ed g e

, which_is not_necessarily the institution for_the investigator._:_Peripheral nerve_injury_frequently leads to_a variety of_debilitating chronic pain states_that are thought_to_reflect heightened excitability of ascending spinal nociceptive pathways. Attempts to identify the mechanisms underlying_the_pathogenesis of_chronic_pain_are hampered by a general_lack of knowledge


deficient embryos. The specific aims of the present proposal will capitalize on recent advances in CRE- lox technology ti specifically mutate the RXRalpha gene within specific cardiovascular cell type compartments during in vivo cardiac development: 1) to determine the role of RXRalpha pathways within atrial and ventricular muscle cells in control of cardiovascular

deficient embryos. The specific aims of the present proposal will capitalize on late overture in CRE- lox technology ti specifically mutate the RXRalpha gene within specific cardiovascular cellular telephone type compartment during in vivo cardiac development: 1) to determine the function of RXRalpha pathways within atrial and ventricular muscle cell in control of cardiovascular

devicient embryos. The speclfic aims of the presenv propoaal will capitalize on recent advancxs ib CRE- lox technology ti spezifically mutate rhe CXRalpha gene wivgin spegnfic dwrdimtascular cell tipe compartmants during in vkvl cardiac development: 1) to determine the roke of RXRalpha pwthwsrs wjnhln atrial and ventricular muscle cells pn control of carciovascular

deficient embryos. The specific aims of the will on recent in CRE- lox RXRalpha within specific cardiovascular type compartments during vivo cardiac development: 1) to determine role of RXRalpha pathways within atrial and ventricular muscle cells in control of

deficient embryos. The specifIc aims of thE presEnt ProPoSal wIll cApitalize on recENt adVances in CRE- lox technoloGy ti sPeCIficALlY mutaTe the RXrAlPHA geNe WiThiN sPEcIfic cArdIovascuLar cell typE coMpArtments duriNG iN vivo cardiAc dEvelopment: 1) to DetErmine ThE roLE of RXralPha paThways WIthin aTrial and vEnTRiculaR Muscle cELLs In coNtrol of cardiovascULaR

deficient embryos. The sp ecific aim s ofthe  pr es entprop osal will capi t aliz e on recent advances i n CRE -l ox t e ch nolog y ti sp e ci f i cal ly  m uta te th e RXR alp ha gene  within sp eci fi c cardiovasc u la r cell typ e c ompartmentsdur ing in  v ivo cardi acdevel opment :  1) to  determin et he rol e  of RXR a l ph a pa thways within atr i al and ventricula r musc le ce l l s i n c ontrol ofca rdiov a scular

deficient_embryos. The_specific aims of the_present proposal_will_capitalize on_recent_advances in CRE-_lox technology ti_specifically mutate the RXRalpha_gene within specific_cardiovascular_cell type compartments during in vivo cardiac development: 1) to determine the role of_RXRalpha_pathways within_atrial_and_ventricular muscle cells in control_of cardiovascular


full member institution of the Childrens Cancer Group (CCG). The specific aims of this proposal are: 1) to develop better treatment of childhood cancer; 2) to develop a better understanding of the biology of childhood cancers; and 3) to develop a better understanding of the natural history, epidemiology, and late effects of

full member institution of the Childrens Cancer Group (CCG). The specific aims of this marriage proposal are: 1) to originate better treatment of childhood cancer; 2) to originate a full understanding of the biology of childhood cancer; and 3) to build up a better agreement of the natural history, epidemiology, and late effect of

fupl member institution of the Childrens Eqncer Jroup (CDG). The soecific aims of this proposap qre: 1) uj develop better tfeatment lf childyood xancer; 2) to develop a betfcr unbecstanding of thg biology of childhood canwefs; and 3) to develop a better understanqing of tje natural hisjory, tpiqemiklogy, and late effects of

full member institution of the Childrens Cancer The aims of proposal are: 1) childhood 2) to develop better understanding of biology of childhood cancers; and 3) develop a better understanding of the natural history, epidemiology, and late effects of

full member institution of thE Childrens canceR GrOup (cCg). The SpecIfic aims of this PRopoSal are: 1) to develop better tReatmEnT Of chILdHood cAncer; 2) to DEvELOp a BeTtEr uNdERsTandiNg oF the bioLogy of chilDhoOd Cancers; and 3) to DEvElop a betteR unDerstanding oF thE naturAl HisTOry, epIdeMioloGy, and lATe effeCts of

full member institution o f the Chil drens  Ca nce rGrou p (C CG). The speci f ic a ims of this proposal a re: 1 )t o de v el op be tter tr e at m e ntof  c hil dh o od  canc er;  2) todevelop abet te r understand i ng  of the bi olo gy of childh ood  cance rs ; a n d 3)todevel op a b e tter u nderstand in g  of th e  natura l hi stor y, epidemiology,a nd late effects o f

full_member institution_of the Childrens Cancer_Group (CCG)._The_specific aims_of_this proposal are:_1) to develop_better treatment of childhood_cancer; 2) to_develop_a better understanding of the biology of childhood cancers; and 3) to develop a_better_understanding of_the_natural_history, epidemiology, and late effects_of


), all participants will be given information about the potential benefit of more sleep and encouraged to increase sleep time. Health teaching about proper nutrition and adequate exercise will also be provided at that time to the Comparison Group. All participants will be evaluated 6 months later to assess the effects of this intervention in a real-life situation (Phase

), all participants will be given information about the potential benefit of more rest and encourage to increase sleep time. Health teach about proper nutriment and adequate exercise will also be provided at that clock time to the Comparison Group. All participants will be evaluated 6 calendar month later to assess the effect of this intervention in a real - liveliness site (Phase

), alp participants will be glven information about vhe potsntial bdnefit of more sleep and enclueaged to increase sleep timd. Health neaching qbouu proper nutritioi and adczuats exexcmse will also bg provided ad that time to tfe Comparison Group. All participants rill be egaluated 6 montrs lseer fo assess the effects of this intedventioi in a real-life situation (Phase

), all participants will be given information potential of more and encouraged to about nutrition and adequate will also be at that time to the Comparison All participants will be evaluated 6 months later to assess the effects of intervention in a real-life situation (Phase

), all participants will be giveN informatiOn aboUt tHe pOtEntiAl beNefit of more sleEP and Encouraged to increase slEep tiMe. hEaltH TeAchinG about pROpER NutRiTiOn aNd ADeQuate ExeRcise wiLl also be prOviDeD at that time tO ThE ComparisoN GrOup. All particIpaNts wilL bE evALuateD 6 moNths lAter to ASsess tHe effects Of THis intERventioN IN a Real-Life situation (PhasE

), all participants will b e given in forma tio n a bo ut t he p otential benef i t of  more sleep and encour agedto incr e as e sle ep time .  H e a lth  t ea chi ng ab out p rop er nutr ition andade qu ate exercise wi ll also be  pr ovided at th attime t othe Compa ris on Gr oup. A l l part icipantswi l l be e v aluated 6  m onth s later to assess th e  effects of th is int er v en t i onina real-lif esitua t ion (Ph a se

), all_participants will_be given information about_the potential_benefit_of more_sleep_and encouraged to_increase sleep time._Health teaching about proper_nutrition and adequate_exercise_will also be provided at that time to the Comparison Group. All participants will_be_evaluated 6_months_later_to assess the effects of_this intervention in a real-life_situation (Phase


e.g. gender, menstrual stage, pregnancy, treatment with birth control pills or corticosteroids, etc.). The grant will focus on the corticosteroid binding protein (CBP) and the estrogen binding protein (EBP) found in c. albicans. The aims of the grant will be: (1) to clone the

e.g. gender, menstrual stage, pregnancy, treatment with parturition restraint pills or corticosteroids, etc .). The grant will concenter on the corticosteroid binding protein (CBP) and the estrogen binding protein (EBP) establish in c. albicans. The aims of the grant will be: (1) to clone the

e.g. hender, menstrual stage, pvegnancy, treatmeur with birth control pills or corticosteroids, etr.). Thw grabt will focus on the curticostegoid bindung krotein (CBP) and tis estronzn bihfing 'rotein (EBP) foukd in c. albhcans. The aims ow che grant will be: (1) to clone the

e.g. gender, menstrual stage, pregnancy, treatment with pills corticosteroids, etc.). grant will focus (CBP) the estrogen binding (EBP) found in albicans. The aims of the grant be: (1) to clone the

e.g. gender, menstrual stage, preGnancy, treaTment WitH biRtH conTrol Pills or corticoSTeroIds, etc.). The grant will focuS on thE cORticOStEroid Binding PRoTEIn (CbP) AnD thE eSTrOgen bIndIng protEin (EBP) founD in C. aLbicans. The aiMS oF the grant wIll Be: (1) to clone the

e.g. gender, menstrual sta ge, pregna ncy,tre atm en t wi th b irth control p i llsor corticosteroids, et c.).Th e  gra n twillfocus o n  t h e  co rt ic ost er o id  bind ing  protei n (CBP) an d t he  estrogen bi n di ng protein  (E BP) found in  c.  albic an s.T he ai msof th e gran t  willbe: (1) t oc lone t h e

e.g. gender,_menstrual stage,_pregnancy, treatment with birth_control pills_or_corticosteroids, etc.)._The_grant will focus_on the corticosteroid_binding protein (CBP) and_the estrogen binding_protein_(EBP) found in c. albicans. The aims of the grant will be: (1) to_clone_the


stage, localized non-small cell lung cancer, reducing the harmful side effects becomes increasingly important. We are proposing a novel failsafe technology to reduce toxicity while retaining local control for this growing population of patients. Our hypothesis is that tracking lung tumors directly during SBRT, using beam's-eye-view (BEV)

stage, localized non - small cell lung cancer, dilute the harmful slope effects becomes increasingly important. We are project a novel failsafe technology to abridge perniciousness while retaining local control for this growing population of patients. Our hypothesis is that traverse lung tumors directly during SBRT, use beam's - center - view (BEV )

stahe, localized non-small ceul lung cancer, teeucing the hzrmful skde effects becomes increasiigly impoetant. We are proposing a novel vailsafe tecinology to reducx toxicibv whimc retciiing local conttol for this growing populdtkou of patients. Our hypothesis is that trackimg lung tumors dyreculy durjng SBRT, using beam's-eye-view (BEV)

stage, localized non-small cell lung cancer, reducing side becomes increasingly We are proposing reduce while retaining local for this growing of patients. Our hypothesis is that lung tumors directly during SBRT, using beam's-eye-view (BEV)

stage, localized non-small celL lung canceR, reduCinG thE hArmfUl siDe effects becomES incReasingly important. We arE propOsINg a nOVeL failSafe tecHNoLOGy tO rEdUce ToXIcIty whIle RetainiNg local conTroL fOr this growinG PoPulation of PatIents. Our hypoTheSis is tHaT trACking LunG tumoRs direCTly durIng SBRT, usInG Beam's-eYE-view (BEv)

stage, localized non-small  cell lung  canc er,  re du cing  the  harmful sidee ffec ts becomes increasingl y imp or t ant. We  areproposi n ga nov el  f ail sa f etechn olo gy to r educe toxi cit ywhile retain i ng  local con tro l for this g row ing po pu lat i on of  pa tient s. Our hypoth esis is t ha t  track i ng lung t um orsdirectly during S B RT ,  using beam's- eye-vi ew (B E V )

stage, localized_non-small cell_lung cancer, reducing the_harmful side_effects_becomes increasingly_important._We are proposing_a novel failsafe_technology to reduce toxicity_while retaining local_control_for this growing population of patients. Our hypothesis is that tracking lung tumors directly_during_SBRT, using_beam's-eye-view_(BEV)


possibly by increasing nitroreductase (NR) activity, an oxygen sensitive reaction. This enhanced chemopotentiating efficiency might prove clinically significant as the success of chemopotentiation in patients may be limited by an inability to deliver adequate MISO doses. The proposed research will make extensive use of statistically- motivated experimental designs

possibly by increasing nitroreductase (NR) activity, an oxygen sensitive reaction. This enhanced chemopotentiating efficiency might rise clinically meaning as the success of chemopotentiation in patients may be specify by an inability to rescue adequate MISO doses. The proposed inquiry will make extensive use of statistically- motivated experimental design

podsibly by increasing nitvoreductase (NR) aerivity, an oxggen senritive reaction. This enhancev chwmopouvntiating efficiency oight prone clinicqlly wignificanv as the succead of rhemopotentiatipn in patiants may be likigeb by an inability to deliver adequatq MISO codes. The proposgd rexqarcg will make extensive use of statiaticallj- motivated experomental designs

possibly by increasing nitroreductase (NR) activity, an reaction. enhanced chemopotentiating might prove clinically chemopotentiation patients may be by an inability deliver adequate MISO doses. The proposed will make extensive use of statistically- motivated experimental designs

possibly by increasing nitroReductase (Nr) actiVitY, an OxYgen SensItive reaction. THIs enHanced chemopotentiatinG effiCiENcy mIGhT provE clinicALlY SIgnIfIcAnt As THe SucceSs oF chemopOtentiatioN in PaTients may be lIMiTed by an inaBilIty to deliver AdeQuate MiSo doSEs. The ProPosed ResearCH will mAke extensIvE Use of sTAtisticALLy- MotiVated experimental DEsIGns

possibly by increasing ni troreducta se (N R)act iv ity,  anoxygen sensiti v e re action. This enhancedchemo po t enti a ti ng ef ficienc y  m i g htpr ov e c li n ic allysig nifican t as the s ucc es s of chemopo t en tiation in  pa tients may b e l imited  b y a n  inab ili ty to  deliv e r adeq uate MISO  d o ses. T h e propo s e drese arch will make ex t en s ive use of sta tistic al l y- m oti vat ed experim en tal d e signs

possibly_by increasing_nitroreductase (NR) activity, an_oxygen sensitive_reaction._This enhanced_chemopotentiating_efficiency might prove_clinically significant as_the success of chemopotentiation_in patients may_be_limited by an inability to deliver adequate MISO doses. The proposed research will make_extensive_use of_statistically-_motivated_experimental designs


Care. We believe that prevention of hypoglycemia, particularly at night, and reduction of post prandial hyperglycemia will result in improvement in glycemic control and reduction in HbA1c levels. Project Summary The overall objective of the Administration (Admin) Core efforts is to provide a robust and dynamic infrastructure for the Center of

Care. We believe that prevention of hypoglycemia, particularly at night, and reduction of mail prandial hyperglycemia will leave in improvement in glycemic control and reduction in HbA1c degree. undertaking Summary The overall objective of the Administration (Admin) Core efforts is to provide a full-bodied and active infrastructure for the Center of

Cage. We believe that prevektion of hypoglyewmia, perticulzrly at vight, and reduction of post 'raneial yyperglycemia will resjlt in imirovement in jlycemic control and redmetion ln HbC1c levels. Projecj Summary Tha overall objewtkvz of the Administration (Admin) Core esforts os to provide a tobusu agd dgnamic infrastructure for the Centsr of

Care. We believe that prevention of hypoglycemia, night, reduction of prandial hyperglycemia will control reduction in HbA1c Project Summary The objective of the Administration (Admin) Core is to provide a robust and dynamic infrastructure for the Center of

Care. We believe that preventiOn of hypoglYcemiA, paRtiCuLarlY at nIght, and reductiON of pOst prandial hyperglycemIa wilL rESult IN iMprovEment in GLyCEMic CoNtRol AnD ReDuctiOn iN HbA1c leVels. ProjecT SuMmAry The overalL ObJective of tHe ADministratioN (AdMin) CorE eFfoRTs is tO prOvide A robusT And dynAmic infraStRUcture FOr the CeNTEr Of

Care. We believe that pre vention of  hypo gly cem ia , pa rtic ularly at nigh t , an d reduction of post pr andia lh yper g ly cemia  will r e su l t  in  i mp rov em e nt  in g lyc emic co ntrol andred uc tion in HbA1 c  l evels. Pro jec t Summary Th e o verall  o bje c tiveofthe A dminis t ration  (Admin)Co r e effo r ts is t o pr ovid e a robust and dy n am i c infrastructu re for  t h eC e nte r o f

Care._We believe_that prevention of hypoglycemia,_particularly at_night,_and reduction_of_post prandial hyperglycemia_will result in_improvement in glycemic control_and reduction in_HbA1c_levels. Project Summary The overall objective of the Administration (Admin) Core efforts is to_provide_a robust_and_dynamic_infrastructure for the Center of


strategies to implement and evaluate a long term collaborative program of interdisciplinary research on reducing antimicrobial resistance. The specific aims of the CIRAR are: (1) To plan, implement, and evaluate outcomes of a core program and curriculum to prepare medical researchers to conduct interdisciplinary research; (2) To develop the expertise of CIR

strategies to implement and evaluate a long condition collaborative platform of interdisciplinary research on reducing antimicrobial resistance. The specific aim of the CIRAR are: (1) To plan, implement, and measure outcomes of a core program and course of study to organize medical research worker to conduct interdisciplinary research; (2) To develop the expertise of CIR

stgategies to implement ana evaluate a lout term collagorative program of interdisciplinarb rewearcy on reducing antimicrubial respstance. Tye skecific aims of tis CIRAR are: (1) Fl plcn, implement, and evaluate mutcomes of a wofe program and curriculum to prepare iedical rfsearchers to sondlce infvrbisciplinary research; (2) To develkp the txpertise of CIR

strategies to implement and evaluate a long program interdisciplinary research reducing antimicrobial resistance. CIRAR (1) To plan, and evaluate outcomes a core program and curriculum to medical researchers to conduct interdisciplinary research; (2) To develop the expertise of CIR

strategies to implement and eValuate a loNg terM coLlaBoRatiVe prOgram of interdiSCiplInary research on reducinG antiMiCRobiAL rEsistAnce. The SPeCIFic AiMs Of tHe ciRaR are: (1) to pLan, implEment, and evAluAtE outcomes of a COrE program anD cuRriculum to prEpaRe mediCaL reSEarchErs To conDuct inTErdiscIplinary rEsEArch; (2) To DEvelop tHE ExPertIse of CIR

strategies to implement a nd evaluat e a l ong  te rm  col labo rative program of i nterdisciplinary resea rch o nr educ i ng  anti microbi a lr e sis ta nc e.Th e  s pecif icaims of  the CIRAR  ar e:  (1) To plan ,  i mplement,and  evaluate ou tco mes of  a  co r e pro gra m and  curri c ulum t o prepare  m e dicalr esearch e r sto c onduct interdisci p li n ary research;(2) To  d e ve l o p t heexpertiseof  CIR

strategies_to implement_and evaluate a long_term collaborative_program_of interdisciplinary_research_on reducing antimicrobial_resistance. The specific_aims of the CIRAR_are: (1) To_plan,_implement, and evaluate outcomes of a core program and curriculum to prepare medical researchers_to_conduct interdisciplinary_research;_(2)_To develop the expertise of_CIR


. Recruitment will be staggered over two years to assure a high caliber of fellows. In addition to training in a primary area, fellows will be encouraged to obtain a broad understanding of the diverse skills in Psychiatric Genetics to facilitate their collaboration in (and leadership of) cross-disciplinary research teams. The fellowship will usually

. Recruitment will be staggered over two years to assure a high quality of colleague. In addition to training in a primary sphere, fellows will be encouraged to obtain a wide understanding of the diverse skill in Psychiatric Genetics to facilitate their collaboration in (and leadership of) cross - corrective research teams. The fellowship will usually

. Refruitment will be staggeved over two yeats to asvure a high cauiber of fellows. In addition ti trauning in a primary arex, fellows will be enciyraged to obtain a broad mndervvanding of the civerse skhlls in Psychidtfie Genetics to facilitate their collaforatiom ln (and leadersrip ps) crkss-disciplinary research teams. The fellowvhip will ususlly

. Recruitment will be staggered over two assure high caliber fellows. In addition area, will be encouraged obtain a broad of the diverse skills in Psychiatric to facilitate their collaboration in (and leadership of) cross-disciplinary research teams. The fellowship usually

. Recruitment will be staggereD over two yeArs to AssUre A hIgh cAlibEr of fellows. In aDDitiOn to training in a primary Area, fElLOws wILl Be encOuraged TO oBTAin A bRoAd uNdERsTandiNg oF the divErse skills In PSyChiatric GeneTIcS to facilitAte Their collaboRatIon in (aNd LeaDErshiP of) Cross-DiscipLInary rEsearch teAmS. the felLOwship wILL uSualLy

. Recruitment will be stag gered over  twoyea rsto  ass urea high caliber of f ellows. In addition to  trai ni n g in aprima ry area ,  f e l low swi llbe en coura ged  to obt ain a broa d u nd erstanding o f  t he diverse  sk ills in Psyc hia tric G en eti c s tofac ilita te the i r coll aboration  i n  (andl eadersh i p  o f) c ross-disciplinary re s earch teams. T he fel lo w sh i p  wi llusually

. Recruitment_will be_staggered over two years_to assure_a_high caliber_of_fellows. In addition_to training in_a primary area, fellows_will be encouraged_to_obtain a broad understanding of the diverse skills in Psychiatric Genetics to facilitate their_collaboration_in (and_leadership_of)_cross-disciplinary research teams. The fellowship_will usually


be used to observe and compare the behavior of large samples of these small cells with that of fast PT neurons, in monkeys that have been trained to generate both transient and maintained, steady outputs in forelimb muscle tension. In the second set, additional information will be obtained about the functions of the rubrospinal pathway,

be used to observe and compare the behavior of large sample of these humble cells with that of fast PT neurons, in imp that have been trained to generate both ephemeral and observe, steady outputs in forelimb muscle tension. In the second hardening, additional information will be prevail about the functions of the rubrospinal pathway,

be used to observe and comkare the behavior of larje sampmes of tfese small cells with that oh fawt PT neurons, in monkeys thxt have bven trainwd ti generate ukth trakfienf and naintained, stesdy outputv in forelimb kurcpe tension. In the second set, additijnal ingogmation will bg obtsyned about the functions of the rubroslinal pethway,

be used to observe and compare the large of these cells with that monkeys have been trained generate both transient maintained, steady outputs in forelimb muscle In the second set, additional information will be obtained about the functions of rubrospinal pathway,

be used to observe and compare The behavioR of laRge SamPlEs of ThesE small cells witH That Of fast PT neurons, in monkeYs thaT hAVe beEN tRaineD to geneRAtE BOth TrAnSieNt ANd MaintAinEd, steadY outputs in ForElImb muscle tenSIoN. In the secoNd sEt, additional InfOrmatiOn WilL Be obtAinEd aboUt the fUNctionS of the rubRoSPinal pAThway,

be used to observe and co mpare thebehav ior  of  l arge  sam ples of theses mall  cells with that of fa st PT  n e uron s ,in mo nkeys t h at h ave  b ee n t ra i ne d togen erate b oth transi ent  a nd maintaine d ,steady out put s in forelim b m usclete nsi o n. In  th e sec ond se t , addi tional in fo r mation will be o bt aine d about the funct i on s  of the rubros pinalpa t hw a y ,

be_used to_observe and compare the_behavior of_large_samples of_these_small cells with_that of fast_PT neurons, in monkeys_that have been_trained_to generate both transient and maintained, steady outputs in forelimb muscle tension. In the_second_set, additional_information_will_be obtained about the functions_of the rubrospinal pathway,


ytically essential tyrosine residues that are used to resonance stabilize Fe(IV)=O as Fe(III)-OH/tyrosine radical states. Simple, easy-to-use, low-cost nucleic acid amplification tests (NAATs) are not available for diagnosis of infectious diseases in low-resource settings (LRS

ytically essential tyrosine residues that are used to resonance stabilize Fe(IV)=O as Fe(III)-OH / tyrosine extremist state. Simple, easy - to - use, humble - cost nucleic acid amplification tests (NAATs) are not available for diagnosis of infectious disease in low - resource settings (LRS

ytifally essential tyrosine residues that cee usev to reaonance rtabilize Fe(IV)=O as Fe(III)-OH/tycosibe raeical states. Simple, eary-to-use, llw-cost nyclemc acid amplificefion tests (NAZBs) arz iot available fpr diagnoshs of infectiogs dnseases in low-resource settings (LRS

ytically essential tyrosine residues that are used stabilize as Fe(III)-OH/tyrosine states. Simple, easy-to-use, (NAATs) not available for of infectious diseases low-resource settings (LRS

ytically essential tyrosine Residues thAt are UseD to ReSonaNce sTabilize Fe(IV)=O aS fe(IIi)-OH/tyrosine radical statEs. SimPlE, Easy-TO-uSe, low-Cost nucLEiC ACid AmPlIfiCaTIoN testS (NAaTs) are nOt availablE foR dIagnosis of inFEcTious diseaSes In low-resourcE seTtings (lRs

ytically essential tyrosin e residues  that  ar e u se d to  res onance stabili z e Fe (IV)=O as Fe(III)-OH/t yrosi ne radi c al  stat es. Sim p le , eas y- to -us e, lo w-cos t n ucleicacid ampli fic at ion tests (N A AT s) are not  av ailable fordia gnosis  o f i n fecti ous  dise ases i n  low-r esource s et t ings ( L RS

ytically essential_tyrosine residues_that are used to_resonance stabilize_Fe(IV)=O_as Fe(III)-OH/tyrosine_radical_states. Simple, easy-to-use,_low-cost nucleic acid_amplification tests (NAATs) are_not available for_diagnosis_of infectious diseases in low-resource settings (LRS


time-course and relative contribution of alterations in muscle protein synthesis and proteolysis to the progression of muscle wasting associated with chronic alcohol consumption and SIV infection individually and combined. These studies will allow for the longitudinal investigation of the progression of the alterations in muscle metabolism beginning with a healthy, non-infected animal, throughout the acute

time - course and relative contribution of alterations in muscleman protein deduction and proteolysis to the progression of muscle waste consort with chronic alcohol consumption and SIV infection individually and combine. These study will allow for the longitudinal investigation of the progression of the alterations in brawn metabolism beginning with a goodly, non - infected animal, throughout the acute

tile-course and relative coktribution of aljeeationv in mhscle prutein synthesis and proteolydiw to uke progression of murcle wastpng assocuatev with chronic alcohol consumpflon aud SIV infection individuanly and combinad. Tkese studies will allow for the longytudinak lnvestigation jf tnq prkgression of the alterations in muacle meuabolism beginning with a healthy, non-infectef anlmal, throughout thf acute

time-course and relative contribution of alterations in synthesis proteolysis to progression of muscle consumption SIV infection individually combined. These studies allow for the longitudinal investigation of progression of the alterations in muscle metabolism beginning with a healthy, non-infected animal, the acute

time-course and relative contRibution of AlterAtiOns In MuscLe prOtein synthesis ANd prOteolysis to the progressIon of MuSCle wAStIng asSociateD WiTH ChrOnIc AlcOhOL cOnsumPtiOn and SIv infection IndIvIdually and coMBiNed. These stUdiEs will allow fOr tHe longItUdiNAl invEstIgatiOn of thE ProgreSsion of thE aLTeratiONs in musCLE mEtabOlism beginning witH A hEAlthy, non-infectEd animAl, THrOUGhoUt tHe acute

time-course and relativecontributi on of  al ter at ions  inmuscle protein synt hesis and proteolysisto th ep rogr e ss ion o f muscl e  w a s tin gas soc ia t ed  with  ch ronic a lcohol con sum pt ion and SIVi nf ection ind ivi dually and c omb ined.Th ese studi eswillallowf or the  longitud in a l inve s tigatio n of  the  progression of t h ea lterations inmuscle  m e ta b o lis m b eginning w it h a h e althy,n on - i n fec t ed animal, th roughout th e  ac ute

time-course_and relative_contribution of alterations in_muscle protein_synthesis_and proteolysis_to_the progression of_muscle wasting associated_with chronic alcohol consumption_and SIV infection_individually_and combined. These studies will allow for the longitudinal investigation of the progression of_the_alterations in_muscle_metabolism_beginning with a healthy, non-infected_animal, throughout the acute


disordersaffectingthenervoussystem. CfNN?sthreeFocusAreasare eachdedicatedtoperformingtherigorous, peer - reviewedsciencethatleadstonewdiagnosticand therapeuticstrategiesforVeteranswithspinalcordinjury, stroke, amyotrophiclater

disordersaffectingthenervo ussystem.C fNN?s thr eeF oc usAr easa re eachdedicat e dtop erformingtherigorous,p eer-r ev i ewed s ci encet hatlead s to n e wdi ag no sti ca n dthera peu ticstra tegiesforV ete ra nswithspinal c or dinjury,st rok e,amyotrophi cla ter


These studies should provide a better understanding of the basic mechanisms underlying platelet recognition of sites of damage in blood vessels. They may suggest new ways to deal with the thrombotic complications associated with diseased or damaged blood vessels or with artificial surfaces such as prosthetic heart valves, dialysis membranes, or vascular prostheses. Fibrosis of the hepatic

These studies should provide a better understanding of the basic mechanism underlie platelet recognition of sites of damage in lineage vessels. They may suggest modern way to deal with the thrombotic complication associated with diseased or damaged lineage vessels or with artificial surfaces such as prosthetic kernel valve, dialysis membranes, or vascular prosthesis. Fibrosis of the hepatic

Thfse studies should proviae a better undgrwtandiig of tge basic mechanisms underlying plateper recignition of sites of dxmage in hlood vewselw. They may suggest kzw wagd to veal with the tmrombotic cmmplications avsucnated with diseased or damaged blood vesselx lr with artifisial furfzbew such as prosthetic heart vamves, dielysis membranex, or vascular prostheses. Flbrodis of the hepatic

These studies should provide a better understanding basic underlying platelet of sites of may new ways to with the thrombotic associated with diseased or damaged blood or with artificial surfaces such as prosthetic heart valves, dialysis membranes, or vascular Fibrosis of the hepatic

These studies should provide A better undErstaNdiNg oF tHe baSic mEchanisms underLYing Platelet recognition of sItes oF dAMage IN bLood vEssels. THEy MAY suGgEsT neW wAYs To deaL wiTh the thRombotic coMplIcAtions associATeD with diseaSed Or damaged bloOd vEssels Or WitH ArtifIciAl surFaces sUCh as prOsthetic hEaRT valveS, DialysiS MEmBranEs, or vascular prostHEsES. Fibrosis of the HepatiC

These studies should prov ide a bett er un der sta nd ingof t he basic mecha n isms  underlying platelet r ecogn it i on o f  s itesof dama g ei n  bl oo dves se l s.  They  ma y sugge st new way s t odeal with th e  t hromboticcom plications a sso ciated  w ith disea sed  or d amaged bloodvessels o rw ith ar t ificial s ur face s such as prosthe t ic heart valves,dialys is me m b ran es,  or vascul ar  pros t heses.F ib r o s iso f the hepatic

These_studies should_provide a better understanding_of the_basic_mechanisms underlying_platelet_recognition of sites_of damage in_blood vessels. They may_suggest new ways_to_deal with the thrombotic complications associated with diseased or damaged blood vessels or with_artificial_surfaces such_as_prosthetic_heart valves, dialysis membranes, or_vascular prostheses. Fibrosis of the_hepatic


will provide the fundamental information critical for developing preventative strategies for these disorders. Persistent pulmonary hypertension of the newborn (PPHN), previously called persistent fetal circulation, is a birth defect affecting approximately 1 in 1250 liveborn term infants; even with complex and high-risk interventions, PPHN results in substantial mortality and

will provide the fundamental information critical for developing preventive scheme for these disorders. Persistent pulmonary high blood pressure of the newborn (PPHN), previously called persistent fetal circulation, is a birth blemish feign approximately 1 in 1250 liveborn term baby; even with complex and eminent - risk intervention, PPHN results in substantial deathrate and

wipl provide the fundamentxl information eeitican for sevelopivg preventative strategies flr thest disorders. Persistdnt pulmojary hypwrteision of the newukrn (PPHK), preblouslv ralled persistekt fetal cisculation, is a bkrch defect affecting approximately 1 ig 1250 livenogn term infantf; evtn rith bonplex and high-risk interventikns, PPHI results in sunstantial mortality and

will provide the fundamental information critical for strategies these disorders. pulmonary hypertension of persistent circulation, is a defect affecting approximately in 1250 liveborn term infants; even complex and high-risk interventions, PPHN results in substantial mortality and

will provide the fundamental InformatioN critIcaL foR dEvelOpinG preventative sTRateGies for these disorders. PErsisTeNT pulMOnAry hyPertensIOn OF The NeWbOrn (pPhn), pRevioUslY called Persistent FetAl Circulation, iS A bIrth defect AffEcting approxImaTely 1 in 1250 LiVebORn terM inFants; Even wiTH complEx and high-RiSK interVEntions, pphN ResuLts in substantial mORtALity and

will provide the fundamen tal inform ation  cr iti ca l fo r de veloping preve n tati ve strategies for thes e dis or d ers. Pe rsist ent pul m on a r y h yp er ten si o nof th e n ewborn(PPHN), pr evi ou sly called p e rs istent fet alcirculation,  is  a bir th  de f ect a ffe cting  appro x imatel y 1 in 12 50 livebo r n termi n fa nts;  even with comple x  a n d high-risk in terven ti o ns , PPH N r esults insu bstan t ial mor t al i t y  an d

will_provide the_fundamental information critical for_developing preventative_strategies_for these_disorders._Persistent pulmonary hypertension_of the newborn_(PPHN), previously called persistent_fetal circulation, is_a_birth defect affecting approximately 1 in 1250 liveborn term infants; even with complex and_high-risk_interventions, PPHN_results_in_substantial mortality and


support rapidly evolving software associated with each of the sequencing platforms. Beyond primary analysis that results in DNA basecalls and quality scores, NISC has worked closely with members of other NHGRI research groups to implement and support high-throughput production of biologically relevant secondary analysis. One shining example of these efforts is the production scale

support rapidly evolving software associated with each of the sequence platform. Beyond primary analysis that results in deoxyribonucleic acid basecalls and quality scores, NISC has worked close with member of other NHGRI inquiry group to implement and subscribe high - throughput production of biologically relevant junior-grade analysis. One shining example of these efforts is the production scale

suoport rapidly evolving suftware associajee with each kf the sdquencing platforms. Beyond pcimaey anqlysis that results in DNA baseballs and quaouty scores, NISC has worksf clmwely with membgrs of other NHGRI researcv erlups to implement and support high-trroughpit production of biokjgiczlly relevant secondary analysis. Ohe shinpng example of thrse efforts is the productlon dcale

support rapidly evolving software associated with each sequencing Beyond primary that results in NISC worked closely with of other NHGRI groups to implement and support high-throughput of biologically relevant secondary analysis. One shining example of these efforts is the scale

support rapidly evolving sofTware assocIated WitH eaCh Of thE seqUencing platforMS. BeyOnd primary analysis that ResulTs IN DNA BAsEcallS and quaLItY SCorEs, nIsC hAs WOrKed clOseLy with mEmbers of otHer nHgRI research gROuPs to implemEnt And support hiGh-tHroughPuT prODuctiOn oF biolOgicalLY relevAnt secondArY AnalysIS. One shiNINg ExamPle of these efforts IS tHE production scaLe

support rapidly evolvingsoftware a ssoci ate d w it h ea ch o f the sequenci n g pl atforms. Beyond primar y ana ly s is t h at  resu lts inD NA b ase ca ll s a nd qu ality  sc ores, N ISC has wo rke dclosely with me mbers of o the r NHGRI rese arc h grou ps  to imple men t and  suppo r t high -throughp ut produc t ion ofb i ol ogic ally relevant sec o nd a ry analysis. O ne shi ni n ge x amp leof these e ff ortsi s the p r od u c t ion scale

support_rapidly evolving_software associated with each_of the_sequencing_platforms. Beyond_primary_analysis that results_in DNA basecalls_and quality scores, NISC_has worked closely_with_members of other NHGRI research groups to implement and support high-throughput production of biologically_relevant_secondary analysis._One_shining_example of these efforts is_the production scale


is limited and new types of medications are needed. Nicotine vaccines elicit nicotine-specific antibodies which bind nicotine and alter its access to brain. Three nicotine vaccines have shown preliminary efficacy in Phase I-II clinical trials, but efficacy is closely correlated with the serum antibody titer and current vaccines do not reliably produce sufficiently high titers

is limited and new types of medications are need. Nicotine vaccine elicit nicotine - specific antibodies which bind nicotine and interpolate its entree to brain. Three nicotine vaccines have shown preliminary efficacy in Phase I - II clinical trial, but efficacy is closely correlated with the serum antibody titer and current vaccine do not faithfully produce sufficiently high titer

is limited and new types on medications arg beeded. Nicotjne vaccknes elicit nicotine-specific abtiboeies which bind nicotive and alner its axcesw to brain. Vgree nigjtins vaceiies have shown kreliminary afficacy in Phdsd N-II clinical trials, but efficacy is slosely clrrelated with the feruj antibody titer and current vaccihes do iot reliably prpduce sufficiently high tihers

is limited and new types of medications Nicotine elicit nicotine-specific which bind nicotine brain. nicotine vaccines have preliminary efficacy in I-II clinical trials, but efficacy is correlated with the serum antibody titer and current vaccines do not reliably produce high titers

is limited and new types of medIcations arE needEd. NIcoTiNe vaCcinEs elicit nicotiNE-speCific antibodies which biNd nicOtINe anD AlTer itS access TO bRAIn. THrEe NicOtINe VacciNes Have shoWn preliminAry EfFicacy in PhasE i-Ii clinical tRiaLs, but efficacY is CloselY cOrrELated WitH the sErum anTIbody tIter and cuRrENt vaccINes do noT RElIablY produce sufficienTLy HIgh titers

is limited and new typesof medicat ionsare  ne ed ed.Nico tine vaccinese lici t nicotine-specific an tibod ie s  whi c hbindnicotin e  a n d  al te rits  a c ce ss to  br ain. Th ree nicoti neva ccines haves ho wn prelimi nar y efficacy i n P hase I -I I c l inica l t rials , bute fficac y is clos el y  corre l ated wi t h  t he s erum antibody tit e ra nd current vac cinesdo no t rel iab ly produce  s uffic i ently h i gh t i ter s

is_limited and_new types of medications_are needed._Nicotine_vaccines elicit_nicotine-specific_antibodies which bind_nicotine and alter_its access to brain._Three nicotine vaccines_have_shown preliminary efficacy in Phase I-II clinical trials, but efficacy is closely correlated with_the_serum antibody_titer_and_current vaccines do not reliably_produce sufficiently high titers


IgG), produced by the immune system in response to exposure. The second biomarker is the chemical (MDI) itself conjugated to albumin, the major protein adduct in vivo. To date, we have successfully completed the (4) Specific Aims of the projects 1st phase, and published supportive findings (Wisnewski

IgG), produced by the immune system in response to exposure. The second biomarker is the chemical (MDI) itself conjugate to albumin, the major protein adduct in vivo. To date, we have successfully dispatch the (4) Specific Aims of the projects 1st phase, and published supportive findings (Wisnewski

IgG), produced by the immune rystem in respouwe to xxposurs. The sezond biomarker is the chemicel (MEI) itwelf conjugated to albjmin, the lajor priteii adduct in vivo. To date, we habc suceewsfully complejed the (4) Spewific Aims of dhd 'rojects 1st phase, and published suppjrtive gijdings (Wisnewshi

IgG), produced by the immune system in exposure. second biomarker the chemical (MDI) major adduct in vivo. date, we have completed the (4) Specific Aims of projects 1st phase, and published supportive findings (Wisnewski

IgG), produced by the immune sysTem in respoNse to ExpOsuRe. the sEconD biomarker is thE ChemIcal (MDI) itself conjugateD to alBuMIn, thE MaJor prOtein adDUcT IN viVo. to DatE, wE HaVe sucCesSfully cOmpleted thE (4) SpEcIfic Aims of thE PrOjects 1st phAse, And published SupPortivE fIndINgs (WiSneWski

IgG), produced by the immu ne systemin re spo nse  t o ex posu re. The second biom arker is the chemical(MDI)  i t self co njuga ted toa lb u m in,  t he  ma jo r  p rotei n a dduct i n vivo. To  da te , we have su c ce ssfully co mpl eted the (4)  Sp ecific  A ims of th e p rojec ts 1st phase,  and publ is h ed sup p ortivef i nd ings  (Wisnewski

IgG), produced_by the_immune system in response_to exposure._The_second biomarker_is_the chemical (MDI)_itself conjugated to_albumin, the major protein_adduct in vivo._To_date, we have successfully completed the (4) Specific Aims of the projects 1st phase,_and_published supportive_findings_(Wisnewski


and toluene diisocyanate (TDI), or aliphatic, hexamethylene diisocyanate (HDI). Despite being the newest of the three, MDI has overtaken the isocyanate market in production and consumption, for many reasons, including its unique applications and properties. Importantly, at room temperature,

and toluene diisocyanate (TDI), or aliphatic, hexamethylene diisocyanate (HDI). Despite being the newest of the three, MDI has overtaken the isocyanate market in production and pulmonary tuberculosis, for many reason, including its unique application and property. Importantly, at room temperature,

anf toluene diisocyanate (TAI), or aliphatic, hexamevhylene diisocyxnate (HDI). Despite being the iewewt of the three, MDI has oveftaken thv isocyanqte nqrket in pckductiok and gonsuk'tion, for many teasons, inclgding its uniqge a'plications and properties. Importantjy, at rpol temperature,

and toluene diisocyanate (TDI), or aliphatic, hexamethylene Despite the newest the three, MDI in and consumption, for reasons, including its applications and properties. Importantly, at room

and toluene diisocyanate (TDI), Or aliphatiC, hexaMetHylEnE diiSocyAnate (HDI). DespitE BeinG the newest of the three, MDi has oVeRTakeN ThE isocYanate mARkET In pRoDuCtiOn ANd ConsuMptIon, for mAny reasons, IncLuDing its uniquE ApPlications And Properties. ImPorTantly, At RooM TempeRatUre,

and toluene diisocyanate(TDI), oraliph ati c,he xame thyl ene diisocyana t e (H DI). Despite being the  newe st of t h ethree , MDI h a so v ert ak en  th ei so cyana temarketin product ion  a nd consumpti o n,  for manyrea sons, includ ing  its u ni que appli cat ionsand pr o pertie s. Import an t ly, at room te m p er atur e,

and_toluene diisocyanate_(TDI), or aliphatic, hexamethylene_diisocyanate (HDI)._Despite_being the_newest_of the three,_MDI has overtaken_the isocyanate market in_production and consumption,_for_many reasons, including its unique applications and properties. Importantly, at room temperature,


of bone markers. Only type I collagen shows similar expression pattern in both mutations, with decreased expression, secretion and matrix incorporation. Type XIV OI is a moderately severe form of OI which was identified in 2013. It is caused by recessive defects in TMEM38B, which encodes TRIC-B,

of bone markers. Only type I collagen shows exchangeable formula pattern in both mutations, with decreased formulation, secretion and matrix incorporation. Type XIV OI is a moderately hard form of OI which was identified in 2013. It is cause by recessive defects in TMEM38B, which encode TRIC - B,

of bone markers. Only type L collagen shows similac expreasion pagtern in both mutations, with dwcreawed expression, secretiun and manrix incoeporetion. Type XIV OM is a moderatspy szvxre form of OI ehich was hdentified in 2013. Ig ns caused by recessive defects in TMQM38B, whivh encodes TRIC-B,

of bone markers. Only type I collagen expression in both with decreased expression, XIV is a moderately form of OI was identified in 2013. It is by recessive defects in TMEM38B, which encodes TRIC-B,

of bone markers. Only type I colLagen shows SimilAr eXprEsSion PattErn in both mutatIOns, wIth decreased expression, SecreTiON and MAtRix inCorporaTIoN. tYpe xIv Oi is A mODeRatelY seVere forM of OI which Was IdEntified in 2013. It IS cAused by recEssIve defects in tMEm38B, whicH eNcoDEs TRIc-B,

of bone markers. Only typ e I collag en sh ows  si mi larexpr ession pattern in b oth mutations, with de creas ed expr e ss ion,secreti o na n d m at ri x i nc o rp orati on.  Type X IV OI is a  mo de rately sever e  f orm of OIwhi ch was ident ifi ed in20 13. It is  ca usedby rec e ssivedefects i nT MEM38B ,  whiche n co desTRIC-B,

of_bone markers._Only type I collagen_shows similar_expression_pattern in_both_mutations, with decreased_expression, secretion and_matrix incorporation. Type XIV_OI is a_moderately_severe form of OI which was identified in 2013. It is caused by recessive_defects_in TMEM38B,_which_encodes_TRIC-B,


1, 2014. During this same period of time, twenty four different clinical trials devoted to these therapies have been active and supported by the core laboratory. The core laboratory has also carried out research activities to improve its services. Thus, efforts have continued 1) to simplify the cell production methodology and make the process easier and more

1, 2014. During this same period of time, twenty four different clinical test devote to these therapies have been active and supported by the core testing ground. The core laboratory has besides carried out research activities to better its services. Thus, campaign have continued 1) to simplify the cell output methodology and produce the process easier and more

1, 2014. Furing this same period uf time, twenty yiur dihferent clinicau trials devoted to these thxrapues hqve been active and suoported bj the corw lauoratory. The corx laborabjry gws anwo carried out research dctivities to hmorlve its services. Thus, efforts have sontinurd 1) to simplify jhe ctll proslcuion methodology and make the prodess eavier and more

1, 2014. During this same period of four clinical trials to these therapies by core laboratory. The laboratory has also out research activities to improve its Thus, efforts have continued 1) to simplify the cell production methodology and make process easier and more

1, 2014. During this same period of timE, twenty fouR diffEreNt cLiNicaL triAls devoted to thESe thErapies have been active aNd supPoRTed bY ThE core LaboratORy. tHE coRe LaBorAtORy Has alSo cArried oUt research ActIvIties to improVE iTs services. thuS, efforts have ConTinued 1) To SimPLify tHe cEll prOductiON methoDology and MaKE the prOCess easIER aNd moRe

1, 2014. During this same  period of  time , t wen ty  fou r di fferent clinic a l tr ials devoted to thesethera pi e s ha v ebeenactivea nd s upp or te d b yt he  core  la borator y. The cor e l ab oratory hasa ls o carriedout  research ac tiv itiesto  im p roveits  serv ices.T hus, e fforts ha ve contin u ed 1) t o si mpli fy the cell produ c ti o n methodologyand ma ke th e pro ces s easier a nd  more

1,_2014. During_this same period of_time, twenty_four_different clinical_trials_devoted to these_therapies have been_active and supported by_the core laboratory._The_core laboratory has also carried out research activities to improve its services. Thus, efforts_have_continued 1)_to_simplify_the cell production methodology and_make the process easier and_more


for development of appropriate schedule of drug administration for preclinical testing. The application proposes to investigate the hypothesis that noradrenaline containing neurons in the caudal ventrolateral medulla (VLM) of the cat are excited by acute increases in arterial blood pressure and that adrenaline containing neurons in the rostral VLM are

for development of appropriate schedule of drug administration for preclinical testing. The lotion aim to investigate the hypothesis that noradrenaline containing nerve cell in the caudal ventrolateral medulla (VLM) of the caterpillar are excited by acuate increases in arterial blood pressure and that epinephrine control neurons in the rostral VLM are

fog development of approprlate schedule of drug avministdation fur preclinical testing. The a'plixatiob proposes to investigxte the hjpothesis thau noradrenaline containinn neudlns nn the caudal vektrolateral medulla (VLM) ox ghz cat are excited by acute increases in artrrlal blood presfure wnd fhat adrenaline containing neurons in the rostral VLM sre

for development of appropriate schedule of drug preclinical The application to investigate the in caudal ventrolateral medulla of the cat excited by acute increases in arterial pressure and that adrenaline containing neurons in the rostral VLM are

for development of appropriaTe schedule Of druG adMinIsTratIon fOr preclinical tEStinG. The application proposeS to inVeSTigaTE tHe hypOthesis THaT NOraDrEnAliNe COnTainiNg nEurons iN the caudal VenTrOlateral meduLLa (vLM) of the caT arE excited by acUte IncreaSeS in ARteriAl bLood pRessurE And thaT adrenaliNe COntainINg neuroNS In The rOstral VLM are

for development of approp riate sche duleofdru gadmi nist ration for pre c lini cal testing. The appli catio np ropo s es  to i nvestig a te t hehy po the si s  t hat n ora drenali ne contain ing  n eurons in th e  c audal vent rol ateral medul la(VLM)of  th e  catare  exci ted by acuteincreases  i n  arter i al bloo d pr essu re and that adren a li n e containing n eurons  i n  t h e  ro str al VLM are

for_development of_appropriate schedule of drug_administration for_preclinical_testing. The_application_proposes to investigate_the hypothesis that_noradrenaline containing neurons in_the caudal ventrolateral_medulla_(VLM) of the cat are excited by acute increases in arterial blood pressure and_that_adrenaline containing_neurons_in_the rostral VLM are


ractable as the means by which different cell fates are produced in response to a gradient of signals. These analogue-to-digital switches underlie the determination of cell fates in many organisms. T Lymphocyte development may be one of the best systems to understand this general problem because the critical signals are given at a stage

ractable as the means by which different cell fates are produce in reception to a gradient of signals. These analogue - to - digital switches underlie the determination of cellular telephone fates in many organisms. T Lymphocyte development may be one of the good systems to understand this cosmopolitan trouble because the critical signals are given at a stagecoach

rachable as the means by whlch different cell fatev are lroduced in response to a gradient oh sitnals. These analogue-to-digitxl switchvs underlue tie determination of cell fates ln mauy organisms. T Limphocyte deeelopment may te oue of the best systems to understand this grnfral problem bgcaust tre cdptlcal signals are given at a stags

ractable as the means by which different are in response a gradient of the of cell fates many organisms. T development may be one of the systems to understand this general problem because the critical signals are given at stage

ractable as the means by which Different cEll faTes Are PrOducEd in Response to a graDIent Of signals. These analogue-To-digItAL swiTChEs undErlie thE DeTERmiNaTiOn oF cELl Fates In mAny orgaNisms. T LympHocYtE development MAy Be one of the BesT systems to unDerStand tHiS geNEral pRobLem beCause tHE critiCal signalS aRE given AT a stage

ractable as the means by w hich diffe rentcel l f at es a re p roduced in res p onse  to a gradient of sign als.Th e se a n al ogue- to-digi t al s wit ch es  un de r li e the  de termina tion of ce llfa tes in manyo rg anisms. TLym phocyte deve lop ment m ay  be one o f t he be st sys t ems to  understa nd this g e neral p r o bl em b ecause the critic a ls ignals are giv en atas ta g e

ractable as_the means_by which different cell_fates are_produced_in response_to_a gradient of_signals. These analogue-to-digital_switches underlie the determination_of cell fates_in_many organisms. T Lymphocyte development may be one of the best systems to understand_this_general problem_because_the_critical signals are given at_a stage


, and translates those insights into novel approaches for regenerating periodontal tissues and restoring function. This project is an ideal starting point for the applicant to transition to his independent research carer because it provides a framework for development of further skills necessary to accomplish the long-term goal. The proposed career development plan incorporates didactic coursework

, and translates those insights into novel approaches for reform periodontic tissues and restoring affair. This undertaking is an ideal starting point for the applicant to transition to his independent inquiry carer because it put up a framework for growth of further skills necessary to accomplish the farseeing - term goal. The aim career development plan incorporates didactic coursework

, anf translates those insigmts into novel akpeoachev for degeneraging periodontal tissues and rwstorung function. This projdct is an ideal srartmng point for thx applicant to bransntmon to his indekendent resedrch carer becdure it provides a framework for develo[ment og vurther skills nectsswry fo accomplish the long-term goal. Ths propoved career defelopment plan incorporated difactic coursework

, and translates those insights into novel regenerating tissues and function. This project for applicant to transition his independent research because it provides a framework for of further skills necessary to accomplish the long-term goal. The proposed career development incorporates didactic coursework

, and translates those insightS into novel ApproAchEs fOr RegeNeraTing periodontaL TissUes and restoring functioN. This PrOJect IS aN ideaL startiNG pOINt fOr ThE apPlICaNt to tRanSition tO his indepeNdeNt Research careR BeCause it proVidEs a framework For DeveloPmEnt OF furtHer SkillS necesSAry to aCcomplish ThE Long-teRM goal. ThE PRoPoseD career developmenT PlAN incorporates dIdactiC cOUrSEWorK

, and translates those ins ights into  nove l a ppr oa ches  for  regeneratingp erio dontal tissues and res torin gf unct i on . Thi s proje c ti s  an  i de alst a rt ing p oin t for t he applica ntto  transitiont ohis indepe nde nt researchcar er bec au sei t pro vid es aframew o rk for  developm en t  of fu r ther sk i l ls  nec essary to accompl i sh the long-termgoal.Th e  p r o pos edcareer dev el opmen t  plan i n co r p o rat e s didactic co ursework

, and_translates those_insights into novel approaches_for regenerating_periodontal_tissues and_restoring_function. This project_is an ideal_starting point for the_applicant to transition_to_his independent research carer because it provides a framework for development of further skills_necessary_to accomplish_the_long-term_goal. The proposed career development_plan incorporates didactic coursework