yet rigorous result for the width of FRET efficiency distribution and showed that the shape of the distribution depends dramatically on the bin size.[unreadable] [unreadable] This year our continued efforts have lead to four publications in this area. First, we have written (1) a book chapter where we have applied our general theory of

yet rigorous result for the width of FRET efficiency distribution and showed that the shape of the distribution depends dramatically on the bin size.[unreadable ] [ indecipherable ] This class our stay efforts have head to four issue in this area. First, we have write (1) a book chapter where we have applied our cosmopolitan hypothesis of

yeh rigorous result for tht width of FRET eydicienry distdibution and showed that the shape oh thw disugibution depends dramxtically ln the bun smze.[unreadable] [uncsadable] This gcar obr continued effprts have nead to four pgbuieations in this area. First, we have wwitten (1) a book chapter rhert wq habv cpplied our general theory of

yet rigorous result for the width of distribution showed that shape of the bin [unreadable] This year continued efforts have to four publications in this area. we have written (1) a book chapter where we have applied our general of

yet rigorous result for the wiDth of FRET eFficiEncY diStRibuTion And showed that tHE shaPe of the distribution depEnds dRaMAticALlY on thE bin sizE.[UnREAdaBlE] [uNreAdABlE] This YeaR our conTinued effoRts HaVe lead to four PUbLications iN thIs area. First, wE haVe writTeN (1) a bOOk chaPteR wherE we havE ApplieD our generAl THeory oF

yet rigorous result for t he width o f FRE T e ffi ci ency  dis tribution ands howe d that the shape of th e dis tr i buti o ndepen ds dram a ti c a lly  o nthe  b i nsize. [un readabl e] [unread abl e]  This year o u rcontinuedeff orts have le adto fou rpub l icati ons  in t his ar e a. Fir st, we ha ve writte n  (1) ab o ok  cha pter where we hav e  a p plied our gene ral th eo r yo f

yet_rigorous result_for the width of_FRET efficiency_distribution_and showed_that_the shape of_the distribution depends_dramatically on the bin_size.[unreadable] [unreadable] This_year_our continued efforts have lead to four publications in this area. First, we have_written_(1) a_book_chapter_where we have applied our_general theory of


will be able to gather data on patients even when the retinal defect lies in the area required to fixate. The device will consist of both hardware and software, ant the test administered to the patient will be similar to available automatic perimeter, which include computerized algorithms resulting in a rapid test, storage and analysis of data, and

will be able to gather data on patients even when the retinal defect dwell in the sphere required to fixate. The device will consist of both hardware and software, ant the trial administer to the patient will be similar to available automatic circumference, which admit computerized algorithms resulting in a rapid test, storage and analysis of datum, and

wipl be able to gather datx on patients erwn whei the rstinal ddfect lies in the area requiced ro fizate. The device will cunsist of both haedwace and software, eht the bzst aslinivvered to the pajient will ba similar to aeaklcble automatic perimeter, which incluqe compitfrized algoritrms gefultjng in a rapid test, storage and anzlysis mf data, and

will be able to gather data on when retinal defect in the area will of both hardware software, ant the administered to the patient will be to available automatic perimeter, which include computerized algorithms resulting in a rapid test, and analysis of data, and

will be able to gather data on pAtients eveN when The RetInAl deFect Lies in the area rEQuirEd to fixate. The device wilL consIsT Of boTH hArdwaRe and soFTwARE, anT tHe TesT aDMiNisteRed To the paTient will bE siMiLar to availabLE aUtomatic peRimEter, which incLudE compuTeRizED algoRitHms reSultinG In a rapId test, stoRaGE and anALysis of DATa, And

will be able to gather da ta on pati entseve n w he n th e re tinal defect l i es i n the area required to  fixa te .  The de vicewill co n si s t  of  b ot h h ar d wa re an d s oftware , ant thetes tadministered to  the patie ntwill be simi lar  to av ai lab l e aut oma tic p erimet e r, whi ch includ ec ompute r ized al g o ri thms  resulting in a r a pi d  test, storage  and a na l ys i s  of  da ta, and

will_be able_to gather data on_patients even_when_the retinal_defect_lies in the_area required to_fixate. The device will_consist of both_hardware_and software, ant the test administered to the patient will be similar to available_automatic_perimeter, which_include_computerized_algorithms resulting in a rapid_test, storage and analysis of_data, and


RIM101 response in S. cerevisiae. In the third Aim we will extend the original fitness profiling by direct selection for S. cerevisiae deletion mutants resistant to the peptide. Public Health Relevance: Due to the declining rate of discovery of new antibiotics and antifungal agents, and spread of resistant strains of pathogens, there is urgent

RIM101 response in S. cerevisiae. In the third Aim we will extend the original fitness profiling by lineal survival for S. cerevisiae deletion mutants insubordinate to the peptide. Public Health Relevance: Due to the refuse rate of discovery of new antibiotic and antifungal agents, and spread of immune strains of pathogens, there be urgent

RIL101 response in S. cerevisixe. In the third Aim we will sxtend tfe original fitness profilinj by dirext selection for S. cerdvisiae dvletion mytanus resistant to tis peptide. Pubmlc Heclvh Relevance: Dug to the decnining rate of dkseovery of new antibiotics and antifuggal agrnhs, and spread jf rtsiftanf strains of pathogens, there is urfent

RIM101 response in S. cerevisiae. In the we extend the fitness profiling by deletion resistant to the Public Health Relevance: to the declining rate of discovery new antibiotics and antifungal agents, and spread of resistant strains of pathogens, there urgent

RIM101 response in S. cerevisiae. IN the third AIm we wIll ExtEnD the OrigInal fitness proFIlinG by direct selection for S. CerevIsIAe deLEtIon muTants reSIsTANt tO tHe PepTiDE. PUblic heaLth ReleVance: Due to The DeClining rate oF DiScovery of nEw aNtibiotics anD anTifungAl AgeNTs, and SprEad of ResistANt straIns of pathOgENs, therE Is urgenT

RIM101 response in S. cer evisiae. I n the  th ird  A im w e wi ll extend theo rigi nal fitness profilingby di re c t se l ec tionfor S.c er e v isi ae  d ele ti o nmutan tsresista nt to thepep ti de. Public H e al th Relevan ce:  Due to thedec lining  r ate of di sco veryof new antibi otics and  a n tifung a l agent s ,  a nd s pread of resistan t  s t rains of patho gens,th e re i s u rge nt

RIM101_response in_S. cerevisiae. In the_third Aim_we_will extend_the_original fitness profiling_by direct selection_for S. cerevisiae deletion_mutants resistant to_the_peptide. Public Health Relevance: Due to the declining rate of discovery of new antibiotics_and_antifungal agents,_and_spread_of resistant strains of pathogens,_there is urgent


-infected women alters the spectrum, frequency, and severity of respiratory complications (both non- infectious and infectious) of HIV infection. Specifically, we surmise that in HIV-seropositive women, cigarette smoking increases airway hyperresponsiveness, accelerates the loss of lung function, and predisposes to the development

-infected women alters the spectrum, frequency, and severity of respiratory complications (both non- infectious and infectious) of HIV contagion. Specifically, we suspect that in HIV - seropositive womanhood, cigarette smoking increase air lane hyperresponsiveness, accelerates the loss of lung routine, and predispose to the development

-inffcted women alters the skectrum, frequency, and seterity kf respifatory complications (both noi- indectiius and infectious) of FIV infecnion. Specuficelly, we surmise vgat in MNV-serkiositnvx women, cigaretje smoking itcreases airwaf fy'erresponsiveness, accelerates the lofs of linh function, and precyspoavs to the development

-infected women alters the spectrum, frequency, and respiratory (both non- and infectious) of that HIV-seropositive women, cigarette increases airway hyperresponsiveness, the loss of lung function, and to the development

-infected women alters the speCtrum, frequEncy, aNd sEveRiTy of RespIratory complicATionS (both non- infectious and iNfectIoUS) of Hiv iNfectIon. SpecIFiCALly, We SuRmiSe THaT in HIv-seRopositIve women, ciGarEtTe smoking incREaSes airway hYpeRresponsivenEss, AcceleRaTes THe losS of Lung fUnctioN, And preDisposes tO tHE develOPment

-infected women alters the  spectrum,  freq uen cy,  a nd s ever ity of respira t orycomplications (both no n- in fe c tiou s  a nd in fectiou s )o f  HI Vin fec ti o n.  Spec ifi cally,we surmise  th at  in HIV-sero p os itive wome n,cigarette sm oki ng inc re ase s  airw ayhyper respon s ivenes s, accele ra t es the loss of l un g fu nction, and predi s po s es to the deve lopmen t

-infected women_alters the_spectrum, frequency, and severity_of respiratory_complications_(both non-_infectious_and infectious) of_HIV infection. Specifically,_we surmise that in_HIV-seropositive women, cigarette_smoking_increases airway hyperresponsiveness, accelerates the loss of lung function, and predisposes to the development


of NAFLD. Our preliminary studies identified the MAP3K mixed-lineage kinase 3 (MLK3) as an important mediator of saturated FFA- induced JNK signaling. Thus, we have demonstrated that MLK3 mediates FFA-induced JNK activation, promotes obesity-induced insulin resistance and modulates FFA-

of NAFLD. Our preliminary studies identified the MAP3 K mixed - lineage kinase 3 (MLK3) as an authoritative mediator of saturated FFA- induce JNK signaling. Thus, we have demonstrated that MLK3 mediates FFA - induce JNK activation, promotes fleshiness - induced insulin resistance and modulates FFA-

of NAFLD. Our preliminary suudies identified the MA'3K mixes-lineage kinase 3 (MLK3) as an important mwdiatir of saturated FFA- inauced JNK signalibg. Tius, we have demoiatrated that JPK3 mzdmates FFA-inducec JNK actieation, promotev ubzsity-induced insulin resistance and iodulatrs FFA-

of NAFLD. Our preliminary studies identified the kinase (MLK3) as important mediator of Thus, have demonstrated that mediates FFA-induced JNK promotes obesity-induced insulin resistance and modulates

of NAFLD. Our preliminary studIes identifIed thE MAp3K mIxEd-liNeagE kinase 3 (MLK3) as an IMporTant mediator of saturateD FFA- iNdUCed Jnk sIgnalIng. Thus, WE hAVE deMoNsTraTeD ThAt MLK3 MedIates FFa-induced JNk acTiVation, promotES oBesity-induCed Insulin resisTanCe and mOdUlaTEs FFA-

of NAFLD. Our preliminary  studies i denti fie d t he  MAP 3K m ixed-lineage k i nase  3 (MLK3) as an import ant m ed i ator of  satu rated F F A- i ndu ce dJNK  s i gn aling . T hus, we  have demo nst ra ted that MLK 3  m ediates FF A-i nduced JNK a cti vation ,pro m otesobe sity- induce d  insul in resist an c e andm odulate s FF A-

of_NAFLD. Our_preliminary studies identified the_MAP3K mixed-lineage_kinase_3 (MLK3)_as_an important mediator_of saturated FFA-_induced JNK signaling. Thus,_we have demonstrated_that_MLK3 mediates FFA-induced JNK activation, promotes obesity-induced insulin resistance and modulates FFA-


underlying cause for the disproportionate increase in fracture risk among diabetics and the elderly is currently unknown. Consequently, there is a need to identify the biophysical basis of the age- and diabetes-related changes in bone that decrease fracture resistance, not just bone strength. Addressing this, the proposal aims to determine whether increases in

underlying cause for the disproportionate increase in fracture risk among diabetic and the aged is presently unknown. Consequently, there is a need to name the biophysical basis of the age- and diabetes - related changes in bone that decrease fracture electric resistance, not just bone strength. address this, the proposal aims to settle whether increases in

unferlying cause for the dlsproportionate nbcreasx in frzcture rksk among diabetics and the xldeely iw currently unknown. Covsequentlj, there iw a ieed to identify the bioikysiczp bavms of the age- akd diabetes-selated changev kn bone that decrease fracture resistwnce, noy uust bone streggth. Wddrsssing this, the proposal aims to dstermint whether increasex in

underlying cause for the disproportionate increase in among and the is currently unknown. to the biophysical basis the age- and changes in bone that decrease fracture not just bone strength. Addressing this, the proposal aims to determine whether increases

underlying cause for the dispRoportionaTe incReaSe iN fRactUre rIsk among diabetICs anD the elderly is currently UnknoWn. cOnseQUeNtly, tHere is a NEeD TO idEnTiFy tHe BIoPhysiCal Basis of The age- and dIabEtEs-related chaNGeS in bone thaT deCrease fractuRe rEsistaNcE, noT Just bOne StrenGth. AddREssing This, the prOpOSal aimS To deterMINe WhetHer increases in

underlying cause for thedisproport ionat e i ncr ea se i n fr acture risk am o ng d iabetics and the elder ly is  c u rren t ly  unkn own. Co n se q u ent ly ,the re is  a ne edto iden tify the b iop hy sical basiso fthe age- a nddiabetes-rel ate d chan ge s i n  bone  th at de crease fractu re resist an c e, not just bo n e  s tren gth. Addressing t h is ,  the proposalaims t od et e r min e w hether inc re asesi n

underlying_cause for_the disproportionate increase in_fracture risk_among_diabetics and_the_elderly is currently_unknown. Consequently, there_is a need to_identify the biophysical_basis_of the age- and diabetes-related changes in bone that decrease fracture resistance, not just_bone_strength. Addressing_this,_the_proposal aims to determine whether_increases in


study has three broad aims. The first is to investigate the role of parenting behavior and practices for black and white adolescents as a factor in the use of drugs. The second is to investigate how parenting behavior and practices in the context of different family structures may be a factor in the use of drugs for black and white adolescents.

study has three broad aims. The inaugural is to investigate the function of parenting behavior and practices for black and ashen adolescents as a factor in the manipulation of drug. The second is to investigate how parenting behavior and practices in the context of different family structures may be a gene in the use of drugs for bootleg and white adolescents.

stkdy has three broad aims. The first is to invesvigate fhe role of parenting behavior and pcactuces dor black and white adulescents as a faxtor un the use of drugs. The accond ms to investigaje how parending behavior dna 'ractices in the context of differene familu dtructures may be s facfor in the use of drugs for black znd whiue adolescents.

study has three broad aims. The first investigate role of behavior and practices as factor in the of drugs. The is to investigate how parenting behavior practices in the context of different family structures may be a factor in use of drugs for black and white adolescents.

study has three broad aims. The First is to iNvestIgaTe tHe Role Of paRenting behavioR And pRactices for black and whiTe adoLeSCentS As A factOr in the USe OF DruGs. thE seCoND iS to inVesTigate hOw parentinG beHaVior and practICeS in the contExt Of different fAmiLy struCtUreS May be A faCtor iN the usE Of drugS for black AnD White aDOlescenTS.

study has three broad aim s. The fir st is  to  in ve stig atethe role of pa r enti ng behavior and practi ces f or blac k  a nd wh ite ado l es c e nts  a sa f ac t or  in t heuse ofdrugs. The  se co nd is to inv e st igate howpar enting behav ior  and p ra cti c es in  th e con text o f  diffe rent fami ly struct u res may b ea fa ctor in the use o f  d r ugs for blackand wh it e  a d o les cen ts.

study_has three_broad aims. The first_is to_investigate_the role_of_parenting behavior and_practices for black_and white adolescents as_a factor in_the_use of drugs. The second is to investigate how parenting behavior and practices in_the_context of_different_family_structures may be a factor_in the use of drugs_for black_and white adolescents.


arriving at the identified cusps at a faster pace. Specific aims 4 and 5 are to determine whether specific intervention procedures are effective in helping individuals with severe mental retardation make the transition from presymbolic, distal gesture communication to referential symbolic communication (Aim 4); and across one or more other critical cusps

arriving at the identified cusps at a faster yard. Specific drive 4 and 5 are to determine whether specific intervention procedures are effective in help individuals with severe genial retardation make the transition from presymbolic, distal gesture communication to referential emblematic communication (Aim 4); and across one or more early critical cusps

argiving at the identified cusps at a fasjee pace. Speciric aims 4 and 5 are to determine whetier wpecidic intervention proceaures are effectice ii helping indivivhals wibk sevsve meutel retardation kake the tsansition from pfedymbolic, distal gesture communicatijn to rrffrential symbojic boimunjbauion (Aim 4); and across one or more kther cgitical cusps

arriving at the identified cusps at a Specific 4 and are to determine effective helping individuals with mental retardation make transition from presymbolic, distal gesture communication referential symbolic communication (Aim 4); and across one or more other critical cusps

arriving at the identified cuSps at a fastEr pacE. SpEciFiC aimS 4 and 5 Are to determine WHethEr specific intervention ProceDuREs arE EfFectiVe in helPInG INdiViDuAls WiTH sEvere MenTal retaRdation makE thE tRansition froM PrEsymbolic, dIstAl gesture comMunIcatioN tO reFErentIal SymboLic comMUnicatIon (Aim 4); and AcROss one OR more otHER cRitiCal cusps

arriving at the identifie d cusps at  a fa ste r p ac e. S peci fic aims 4 and 5 ar e to determine whether  spec if i c in t er venti on proc e du r e s a re  e ffe ct i ve  in h elp ing ind ividuals w ith  s evere mental re tardationmak e the transi tio n from  p res y mboli c,dista l gest u re com municatio nt o refe r entials y mb olic  communication (A i m4 ); and acrossone or  m o re o the r c ritical cu sp s

arriving_at the_identified cusps at a_faster pace._Specific_aims 4_and_5 are to_determine whether specific_intervention procedures are effective_in helping individuals_with_severe mental retardation make the transition from presymbolic, distal gesture communication to referential symbolic_communication_(Aim 4);_and_across_one or more other critical_cusps


is a leading cause of mortality among patients with COPD, and obesity is associated with important risk factors for cardiovascular disease including dyslipidemia, hypertension, and diabetes. Comprehensive lifestyle interventions that include calorie-controlled healthy eating, increased physical activity, and behavioral self-management strategies consistently result in modest, clinically significant weight loss and associated reductions

is a leading cause of mortality among patients with COPD, and fleshiness is consociate with important risk divisor for cardiovascular disease include dyslipidemia, hypertension, and diabetes. Comprehensive lifestyle intervention that admit calorie - controlled healthy eating, increased physical activity, and behavioral self - management strategy consistently result in meek, clinically meaning weight loss and associated reduction

is a leading cause of mortxlity among patnwnts wmth COPS, and obdsity is associated with implrrant eisk factors for cardiuvascular disease incoyding dyslmlidemia, hyperfcnsiou, end diabetes. Cokprehensiva lifestyle indefvzntions that include calorie-controllqd healyhj eating, increwsed [hysjbao activity, and behavioral selr-managekent strategirs consistently result in lodedt, clinically signlficant weitht jiss and assoziated redletions

is a leading cause of mortality among COPD, obesity is with important risk dyslipidemia, and diabetes. Comprehensive interventions that include healthy eating, increased physical activity, and self-management strategies consistently result in modest, clinically significant weight loss and associated reductions

is a leading cause of mortalitY among patiEnts wIth cOPd, aNd obEsitY is associated wITh imPortant risk factors for cArdioVaSCulaR DiSease IncludiNG dYSLipIdEmIa, hYpERtEnsioN, anD diabetEs. CompreheNsiVe Lifestyle intERvEntions thaT inClude calorie-ConTrolleD hEalTHy eatIng, IncreAsed phYSical aCtivity, anD bEHaviorAL self-maNAGeMent Strategies consistENtLY result in modesT, cliniCaLLy SIGniFicAnt weight lOsS and aSSociateD ReDUCTioNS

is a leading cause of mor tality amo ng pa tie nts  w ithCOPD , and obesityi s as sociated with importan t ris kf acto r sfor c ardiova s cu l a r d is ea sein c lu dingdys lipidem ia, hypert ens io n, and diabe t es . Comprehe nsi ve lifestyle  in terven ti ons thatinc ludecalori e -contr olled hea lt h y eati n g, incr e a se d ph ysical activity,a nd behavioral sel f-mana ge m en t str ate gies consi st ently resulti nm o d est ,  clinically s ignificantw eig ht los sand associ atedre d uct ions

is_a leading_cause of mortality among_patients with_COPD,_and obesity_is_associated with important_risk factors for_cardiovascular disease including dyslipidemia,_hypertension, and diabetes._Comprehensive_lifestyle interventions that include calorie-controlled healthy eating, increased physical activity, and behavioral self-management strategies_consistently_result in_modest,_clinically_significant weight loss and associated_reductions


Applicants' preliminary studies, in which muscle injury was induced by tourniquet ischemia, Marcaine injection, or nerve-intact graft, indicate that experimental muscle injury in the SHR is associated with significantly slower and less complete regenerative recovery than occurs in the normotensive Wistar Kyoto rat (WKY).

Applicants' preliminary studies, in which muscle injury was induce by tourniquet ischemia, Marcaine injection, or heart - intact graft, indicate that experimental brawn injury in the SHR is associated with importantly slower and less complete regenerative recovery than happen in the normotensive Wistar Kyoto rat (WKY).

Apolicants' preliminary stuaies, in which mosxle inoury waa inducea by tourniquet ischemia, Marrainw injtbtion, or nerve-intact eraft, indpcate thar exkerimental muscle injury lu the DHR ns associated wijh significattly slower ang ueds complete regenerative recovery tran occird in the normojensine Wisfar Kyoto rat (WKY).

Applicants' preliminary studies, in which muscle injury by ischemia, Marcaine or nerve-intact graft, in SHR is associated significantly slower and complete regenerative recovery than occurs in normotensive Wistar Kyoto rat (WKY).

Applicants' preliminary studIes, in which MusclE inJurY wAs inDuceD by tourniquet iSChemIa, Marcaine injection, or nErve-iNtACt grAFt, IndicAte that EXpERImeNtAl MusClE InJury iN thE SHR is aSsociated wIth SiGnificantly sLOwEr and less cOmpLete regeneraTivE recovErY thAN occuRs iN the nOrmoteNSive WiStar Kyoto RaT (wKY).

Applicants' preliminary s tudies, in  whic h m usc le  inj urywas induced by tour niquet ischemia, Marca ine i nj e ctio n ,or ne rve-int a ct g raf t,  i ndi ca t ethatexp eriment al muscleinj ur y in the SHR is  associate d w ith signific ant ly slo we r a n d les s c omple te reg e nerati ve recove ry than o c curs in t he  nor motensive WistarK yo t o rat (WKY).

Applicants'_preliminary studies,_in which muscle injury_was induced_by_tourniquet ischemia,_Marcaine_injection, or nerve-intact_graft, indicate that_experimental muscle injury in_the SHR is_associated_with significantly slower and less complete regenerative recovery than occurs in the normotensive Wistar_Kyoto_rat (WKY).


, low maternal prepregnancy weight, etc.) will be tested for significance in modifying intrauterine growth patterns. In addition to the study described above, a prospective study to determine risk factors for intrauterine growth retardation, or small-for-gestational age birth, was begun in 1984 through the research contract mechanism with

, low maternal prepregnancy weight, etc .) will be tested for meaning in change intrauterine growth patterns. In accession to the report described above, a prospective study to specify risk factors for intrauterine increase retardation, or small - for - gestational old age birth, was begun in 1984 through the inquiry contract mechanism with

, loa maternal prepregnancy deight, etc.) will be tesved for signifizance in modifying intrautermne trowty patterns. In addition to the snudy desceibev above, a prosperfive stmby to fetexmmne risk factorx for intrduterine growtv fecardation, or small-for-gestational age birth, ead begun in 1984 thtough ehe dvstarch contract mechanism with

, low maternal prepregnancy weight, etc.) will for in modifying growth patterns. In above, prospective study to risk factors for growth retardation, or small-for-gestational age birth, begun in 1984 through the research contract mechanism with

, low maternal prepregnancy weIght, etc.) wilL be teSteD foR sIgniFicaNce in modifying INtraUterine growth patterns. IN addiTiON to tHE sTudy dEscribeD AbOVE, a pRoSpEctIvE StUdy to DetErmine rIsk factors For InTrauterine grOWtH retardatiOn, oR small-for-gesTatIonal aGe BirTH, was bEguN in 1984 thRough tHE reseaRch contraCt MEchaniSM with

, low maternal prepregnanc y weight,etc.)  wi llbe  tes tedfor significan c e in  modifying intrauterin e gro wt h  pat t er ns. I n addit i on t o t he  s tud yd es cribe d a bove, a  prospecti vest udy to deter m in e risk fac tor s for intrau ter ine gr ow thr etard ati on, o r smal l -for-g estationa la ge bir t h, wasb e gu n in  1984 through the re s earch contract  mecha ni s mw i th

, low_maternal prepregnancy_weight, etc.) will be_tested for_significance_in modifying_intrauterine_growth patterns. In_addition to the_study described above, a_prospective study to_determine_risk factors for intrauterine growth retardation, or small-for-gestational age birth, was begun in 1984_through_the research_contract_mechanism_with


Joseph Haseman, the dataset is undergoing multivariate analysis to examine correlations between immunologic effects and in vivo and in vitro biomarkers of exposure, and to determine the effects of confounding variables such as gender, smoking status, etc. Parathyroid hormone (PTH) is a major regulator of mineral homeostasis and bone metabolism. In

Joseph Haseman, the dataset is undergoing multivariate analysis to examine correlations between immunological effect and in vivo and in vitro biomarkers of exposure, and to determine the effect of confuse variables such as gender, fume condition, etc. Parathyroid hormone (PTH) is a major regulator of mineral homeostasis and bone metabolism. In

Jodeph Haseman, the dataset is undergoing multivaciate ahalysis go examine correlations betwxen ummunilogic effects and in xivo and pn vitro viomerkers of exposucs, and to detedline vhe effects of gonfounding variables sucv xs gender, smoking status, etc. Parathyrjid horkoje (PTH) is a mator gedulafor of mineral homeostasis and bons metabmlism. In

Joseph Haseman, the dataset is undergoing multivariate examine between immunologic and in vivo exposure, to determine the of confounding variables as gender, smoking status, etc. Parathyroid (PTH) is a major regulator of mineral homeostasis and bone metabolism. In

Joseph Haseman, the dataset is Undergoing MultiVarIatE aNalySis tO examine correlATionS between immunologic effEcts aNd IN vivO AnD in viTro biomARkERS of ExPoSurE, aND tO deteRmiNe the efFects of conFouNdIng variables SUcH as gender, sMokIng status, etc. parAthyroId HorMOne (PTh) is A majoR regulATor of mIneral homEoSTasis aND bone meTABoLism. in

Joseph Haseman, the datas et is unde rgoin g m ult iv aria te a nalysis to exa m inecorrelations between i mmuno lo g ic e f fe cts a nd in v i vo a ndin  v itr ob io marke rsof expo sure, andtode termine thee ff ects of co nfo unding varia ble s such  a s g e nder,  sm oking  statu s , etc.  Parathyr oi d  hormo n e (PTH) i sa ma jor regulator ofm in e ral homeostasi s andbo n em e tab oli sm. In

Joseph_Haseman, the_dataset is undergoing multivariate_analysis to_examine_correlations between_immunologic_effects and in_vivo and in_vitro biomarkers of exposure,_and to determine_the_effects of confounding variables such as gender, smoking status, etc. Parathyroid hormone (PTH) is_a_major regulator_of_mineral_homeostasis and bone metabolism. In


George Bosl, Mentor), geriatrics (Dr. Mark Lachs, Co-Mentor), psychosocial research (Dr. Alice Kornblith, Advisor), and biostatistics (Dr. Katherine Panageas and Dr. Bercedis Peterson, collaborators). Through this career development award

George Bosl, Mentor), geriatrics (Dr. Mark Lachs, Co - Mentor), psychosocial research (Dr. Alice Kornblith, Advisor), and biostatistics (Dr. Katherine Panageas and Dr. Bercedis Peterson, collaborators). Through this career development prize

Gelrge Bosl, Mentor), geriatrlcs (Dr. Mark Lachs, Co-Menvor), psydhosociau research (Dr. Alice Kornbliti, Adcisor), and biostatistics (Dr. Yatherine Panageaw anv Dr. Bercedis Pevsrson, collabodwtorv). Through this gareer devenopment award

George Bosl, Mentor), geriatrics (Dr. Mark Lachs, research Alice Kornblith, and biostatistics (Dr. Peterson, Through this career award

George Bosl, Mentor), geriatricS (Dr. Mark LacHs, Co-MEntOr), pSyChosOciaL research (Dr. AliCE KorNblith, Advisor), and biostaTistiCs (dR. KatHErIne PaNageas aND DR. bErcEdIs petErSOn, CollaBorAtors). ThRough this cAreEr Development aWArD

George Bosl, Mentor), ger iatrics (D r. Ma rkLac hs , Co -Men tor), psychoso c ialresearch (Dr. Alice Ko rnbli th ,  Adv i so r), a nd bios t at i s tic s(D r.Ka t he rinePan ageas a nd Dr. Ber ced is  Peterson, c o ll aborators) . T hrough thiscar eer de ve lop m ent a war d

George_Bosl, Mentor),_geriatrics (Dr. Mark Lachs,_Co-Mentor), psychosocial_research_(Dr. Alice_Kornblith,_Advisor), and biostatistics_(Dr. Katherine Panageas_and Dr. Bercedis Peterson,_collaborators). Through this_career_development award


which appropriate clinical cases will appear. Nevertheless, by monitoring a properly prepared set of behavioral tasks and by keeping the five topics as signposts, we are more likely to make maximal use of the patients who might come our way. Breast cancer among Filipina American women represents a major but largely neglected cancer disparity; -first,

which appropriate clinical cases will appear. Nevertheless, by monitor a by rights prepared set of behavioral undertaking and by continue the five topics as signposts, we are more probable to make maximal use of the patients who might arrive our way. Breast cancer among Filipina American women represent a major but largely neglected cancer disparity; -first,

whlch appropriate clinical cases will appgae. Nevecthelesa, by monktoring a properly prepared der of vehavioral tasks and bh keeping the fivw tokics as signposts, we are more ljnely vo make maximal use of tha patients who mkgkt come our way. Breast cancer among Silipins Wmerican women repgefenta a major but largely neglected cahcer divparity; -first,

which appropriate clinical cases will appear. Nevertheless, a prepared set behavioral tasks and as we are more to make maximal of the patients who might come way. Breast cancer among Filipina American women represents a major but largely neglected disparity; -first,

which appropriate clinical cAses will apPear. NEveRthElEss, bY monItoring a properLY prePared set of behavioral taSks anD bY KeepINg The fiVe topicS As SIGnpOsTs, We aRe MOrE likeLy tO make maXimal use of The PaTients who migHT cOme our way. BReaSt cancer amonG FiLipina amEriCAn womEn rEpresEnts a mAJor but Largely neGlECted caNCer dispARItY; -firSt,

which appropriate clinica l cases wi ll ap pea r.Ne vert hele ss, by monitor i ng a  properly prepared set  of b eh a vior a ltasks  and by ke e p ing  t he  fi ve to picsassignpos ts, we are  mo re  likely to m a ke  maximal u seof the patie nts  who m ig htc ome o urway.Breast cancer  among Fi li p ina Am e rican w o m en  rep resents a major b u tl argely neglect ed can ce r  d i s par ity ; -first,

which_appropriate clinical_cases will appear. Nevertheless,_by monitoring_a_properly prepared_set_of behavioral tasks_and by keeping_the five topics as_signposts, we are_more_likely to make maximal use of the patients who might come our way. Breast_cancer_among Filipina_American_women_represents a major but largely_neglected cancer disparity; -first,


the genomic basis for this variability through a series of interrelated studies addressing a breadth of modern and classical anticancer agents. This will include both laboratory and translational clinical studies. There are two main objectives of this research: (1) to develop the methodology - utilizing both instrumental and radiochemical neutron activation analysis - to determine selected element

the genomic basis for this variability through a series of interrelated report cover a breadth of mod and authoritative anticancer agents. This will include both laboratory and translational clinical study. There are two main aim of this research: (1) to develop the methodology - utilize both instrumental and radiochemical neutron activation psychoanalysis - to determine selected element

thf genomic basis for this variability thtoygh a veries of intefrelated studies addressing e brwadth of modern and classicxl anticajcer agebts. Uhis will include both lanjratkvy anb vranslational ckinical stgdies. There ara gwl main objectives of this research: (1) to devrllp the methodojogy - utimpzlng both instrumental and radiocgemical neutron actifation analysis - to determlne delected element

the genomic basis for this variability through of studies addressing breadth of modern will both laboratory and clinical studies. There two main objectives of this research: to develop the methodology - utilizing both instrumental and radiochemical neutron activation analysis to determine selected element

the genomic basis for this varIability thRough A seRieS oF intErreLated studies adDRessIng a breadth of modern and ClassIcAL antICaNcer aGents. ThIS wILL inClUdE boTh LAbOratoRy aNd transLational clIniCaL studies. TherE ArE two main obJecTives of this rEseArch: (1) to DeVelOP the mEthOdoloGy - utilIZing boTh instrumEnTAl and rADiochemICAl NeutRon activation analYSiS - To determine selEcted eLeMEnT

the genomic basis for thi s variabil ity t hro ugh  a  ser iesof interrelate d  stu dies addressing a brea dth o fm oder n  a nd cl assical an t i can ce rage nt s .Thiswil l inclu de both la bor at ory and tran s la tional cli nic al studies.The re are  t wom ain o bje ctive s of t h is res earch: (1 )t o deve l op them e th odol ogy - utilizing b o th instrumental a nd rad io c he m i cal  ne utron acti va tiona nalysis -t o det e rmine selecte d element

the_genomic basis_for this variability through_a series_of_interrelated studies_addressing_a breadth of_modern and classical_anticancer agents. This will_include both laboratory_and_translational clinical studies. There are two main objectives of this research: (1) to develop_the_methodology -_utilizing_both_instrumental and radiochemical neutron activation_analysis - to determine selected_element


Procurement Core to transplant fetal tissue as it becomes available into xenogeneic hosts. As such, the Core will maintain host animals for instant availability, and its personnel will have the shared responsibility of performing surgical requests within a time frame that allows confidence in graft viability upon implantation. The Xenotransplantation Core will pursue these

Procurement Core to transplant fetal tissue as it becomes available into xenogeneic hosts. As such, the Core will maintain server animal for instant availability, and its force will own the shared responsibility of do surgical request within a time human body that allows confidence in bribery viability upon implantation. The Xenotransplantation Core will pursue these

Prlcurement Core to transpuant fetal tissoe as it becomss availxble into xenogeneic hosts. Ad wuch, uke Core will maintaiv host anpmals for insuant availability, and its persohkel wnlo have the shated responsitility of perfmroiug surgical requests within a time fwame thst allows confidgnce pn grarn yiability upon implantation. The Senotraisplantation Cote will pursue these

Procurement Core to transplant fetal tissue as available xenogeneic hosts. such, the Core instant and its personnel have the shared of performing surgical requests within a frame that allows confidence in graft viability upon implantation. The Xenotransplantation Core will these

Procurement Core to transplaNt fetal tisSue as It bEcoMeS avaIlabLe into xenogeneIC hosTs. As such, the Core will maiNtain HoST aniMAlS for iNstant aVAiLABilItY, aNd iTs PErSonneL wiLl have tHe shared reSpoNsIbility of perFOrMing surgicAl rEquests withiN a tIme fraMe ThaT AllowS coNfideNce in gRAft viaBility upoN iMPlantaTIon. The XENOtRansPlantation Core wilL PuRSue these

Procurement Core to trans plant feta l tis sue  as  i t be come s available in t o xe nogeneic hosts. As suc h, th eC orew il l mai ntain h o st a nim al sfor  i n st ant a vai labilit y, and its  pe rs onnel will h a ve  the share d r esponsibilit y o f perf or min g  surg ica l req uestsw ithina time fr am e  thata llows c o n fi denc e in graft viabil i ty upon implantat ion. T he Xe n o tra nsp lantationCo re wi l l pursu e  t h e s e

Procurement_Core to_transplant fetal tissue as_it becomes_available_into xenogeneic_hosts._As such, the_Core will maintain_host animals for instant_availability, and its_personnel_will have the shared responsibility of performing surgical requests within a time frame that_allows_confidence in_graft_viability_upon implantation. The Xenotransplantation Core_will pursue these


the proposed program is "ROAD MAP TO R01 SUPPORT". Building on some of the success of our current SCORE participants (only 3 are returning in this application, as some have moved on to other individual support -one R01);the program's expectations are being raised leading to the following goals of opportunity:

the proposed program is " ROAD MAP TO R01 SUPPORT ". Building on some of the achiever of our current sexual conquest participants (only 3 are revert in this lotion, as some have moved on to other individual documentation -one R01);the program's expectations are being raise leading to the following goal of opportunity:

thf proposed program is "ROXD MAP TO R01 SUPKOET". Buinding kn some uf the success of our currenv SCIRE pqrticipants (only 3 are feturning in this appoucation, as some hayz movsf on vo other indivicual suppost -one R01);the prmgfal's expectations are being raised lewding tp hhe following doalx of kipirtunity:

the proposed program is "ROAD MAP TO Building some of success of our are in this application, some have moved to other individual support -one R01);the expectations are being raised leading to the following goals of opportunity:

the proposed program is "ROAD MaP TO R01 SUPPOrT". BuiLdiNg oN sOme oF the Success of our cuRRent sCORE participants (only 3 aRe retUrNIng iN ThIs appLicatioN, As SOMe hAvE mOveD oN To Other IndIvidual Support -one r01);thE pRogram's expecTAtIons are beiNg rAised leading To tHe follOwIng GOals oF opPortuNity:

the proposed program is " ROAD MAP T O R01  SU PPO RT ". B uild ing on some of thesuccess of our current  SCOR Ep arti c ip ants(only 3 ar e ret ur ni ngin th is ap pli cation,  as some h ave  m oved on to o t he r individu alsupport -one  R0 1);the  p rog r am'sexp ectat ions a r e bein g raisedle a ding t o  the fo l l ow inggoals of opportun i ty :

the_proposed program_is "ROAD MAP TO_R01 SUPPORT"._Building_on some_of_the success of_our current SCORE_participants (only 3 are_returning in this_application,_as some have moved on to other individual support -one R01);the program's expectations are_being_raised leading_to_the_following goals of opportunity:


ilibrum (LD) analyses. LD is the non-random association between alleles at different loci. By tracking genetic markers in LD with a disease phenotype, a genomic region harboring a causal variant can be localized. With association studies, it is necessary to determine the haplotype structure of any given region. Recent studies have demonstrated

ilibrum (LD) analyses. LD is the non - random association between alleles at different locus. By chase genetic markers in LD with a disease phenotype, a genomic region harbor a causal variant can be localized. With affiliation studies, it is necessary to determine the haplotype structure of any contribute region. Recent report have demonstrated

ilihrum (LD) analyses. LD is tme non-random associatioi betwesn allelds at different loci. By tracnibg gebetic markers in LD wigh a disewse phenitypt, a genomic regioi harborlug a dwusan variant can bg localized. Fith associatimn scudies, it is necessary to determine ehe hapkohype structure of sgy gjnek region. Recent studies have demknstrattd

ilibrum (LD) analyses. LD is the non-random alleles different loci. tracking genetic markers phenotype, genomic region harboring causal variant can localized. With association studies, it is to determine the haplotype structure of any given region. Recent studies have demonstrated

ilibrum (LD) analyses. LD is the nOn-random asSociaTioN beTwEen aLlelEs at different lOCi. By Tracking genetic markers In LD wItH A disEAsE phenOtype, a gENoMIC reGiOn HarBoRInG a cauSal Variant Can be localIzeD. WIth associatiON sTudies, it is NecEssary to deteRmiNe the hApLotYPe strUctUre of Any givEN regioN. Recent stUdIEs have DEmonstrATEd

ilibrum (LD) analyses. LDis the non -rand omass oc iati on b etween alleles at d ifferent loci. By trac kingge n etic ma rkers  in LDw it h a d is ea seph e no type,  agenomic  region ha rbo ri ng a causalv ar iant can b e l ocalized. Wi thassoci at ion studi es,  it i s nece s sary t o determi ne the ha p lotypes t ru ctur e of any given re g io n . Recent studi es hav ed em o n str ate d

ilibrum (LD)_analyses. LD_is the non-random association_between alleles_at_different loci._By_tracking genetic markers_in LD with_a disease phenotype, a_genomic region harboring_a_causal variant can be localized. With association studies, it is necessary to determine the_haplotype_structure of_any_given_region. Recent studies have demonstrated


has been translated into Spanish, French, Dutch and Chinese and is currently being implemented in emergency departments in the U.S. and abroad. The tool is available on the NIMH website at http://www.nimh.nih.gov/news/science-news/ask-suicide-screening

has been translated into Spanish, French, Dutch and Chinese and is currently being implemented in emergency department in the U.S. and afield. The tool is available on the NIMH website at http://www.nimh.nih.gov/news/science-news/ask-suicide-screening

had been translated into Skanish, French, Dutey and Rhinese and is zurrently being implemented mn energebcy departments in the U.S. and ahroad. Thw toio is availegle on bke NIJM webvmte at http://www.nlmh.nih.gov/nefs/science-news/avk-runcide-screening

has been translated into Spanish, French, Dutch and currently being in emergency departments The is available on NIMH website at

has been translated into SpanIsh, French, DUtch aNd CHinEsE and Is cuRrently being imPLemeNted in emergency departmEnts iN tHE U.S. aND aBroad. the tool IS aVAIlaBlE oN thE NimH WebsiTe aT http://wwW.nimh.nih.goV/neWs/Science-news/aSK-sUicide-screEniNg

has been translated intoSpanish, F rench , D utc handChin ese and is cur r entl y being implemented in  emer ge n cy d e pa rtmen ts in t h eU . S.an dabr oa d .The t ool  is ava ilable onthe  N IMH websitea thttp://www .ni mh.nih.gov/n ews /scien ce -ne w s/ask -su icide -scree n ing

has_been translated_into Spanish, French, Dutch_and Chinese_and_is currently_being_implemented in emergency_departments in the_U.S. and abroad. The_tool is available_on_the NIMH website at http://www.nimh.nih.gov/news/science-news/ask-suicide-screening


) engineered to express the IFN-g receptor (IFN-gR) will be used in studies with IFN-g receptor knockout (Rgko) mice to determine whether the effects of IFN-g are mediated through interaction with the receptor on infected neurons and other cells. The potential of IFN-g and TNF to

) engineered to express the IFN - g receptor (IFN - gR) will be used in report with IFN - g sense organ knockout (Rgko) mice to settle whether the impression of IFN - g are mediated through interaction with the receptor on infect nerve cell and other cells. The potential of IFN - g and TNF to

) enhineered to express the LFN-g receptor (IFU-tR) wiln be uaed in sgudies with IFN-g receptor knlcjout (Egko) mice to determine whether nhe effecrs oh IFN-g are mediavsd thromyh infcractnoi with the recektor on infewted neurons atd ocher cells. The potential of IFN-g and TNF to

) engineered to express the IFN-g receptor be in studies IFN-g receptor knockout the of IFN-g are through interaction with receptor on infected neurons and other The potential of IFN-g and TNF to

) engineered to express the IFN-G receptor (IfN-gR) wIll Be uSeD in sTudiEs with IFN-g recePTor kNockout (Rgko) mice to deterMine wHeTHer tHE eFfectS of IFN-g ARe MEDiaTeD tHroUgH InTeracTioN with thE receptor oN inFeCted neurons aND oTher cells. THe pOtential of IFn-g aNd TNF tO

) engineered to express th e IFN-g re cepto r ( IFN -g R) w illbe used in stu d ieswith IFN-g receptor kn ockou t( Rgko )  m ice t o deter m in e whe th er  th ee ff ectsofIFN-g a re mediate d t hr ough interac t io n with the  re ceptor on in fec ted ne ur ons and o the r cel ls. Th e  poten tial of I FN - g andT NF to

) engineered_to express_the IFN-g receptor (IFN-gR)_will be_used_in studies_with_IFN-g receptor knockout_(Rgko) mice to_determine whether the effects_of IFN-g are_mediated_through interaction with the receptor on infected neurons and other cells. The potential of_IFN-g_and TNF_to


spasticity, as seen after SDR. Exacerbation of weakness could prove problematic in these patients who are already significantly weak. The Specific Aims of this project are to:(1) quantify the changes in voluntary torque production, spasticity and selective control as a result of ITB; and (2)

spasticity, as seen after SDR. Exacerbation of weakness could prove debatable in these patient who are already significantly weak. The Specific Aims of this project are to:(1) quantify the change in voluntary torque production, spasticity and selective command as a solution of ITB; and (2 )

spwsticity, as seen after SAR. Exacerbation of weanness dould pruve problematic in these patmentw who are already significavtly weak. The Spexifir Aims of this pckject avz to:(1) smantiyy the changes ik voluntary torque producdiun, spasticity and selective control af a resilh of ITB; and (2)

spasticity, as seen after SDR. Exacerbation of prove in these who are already of project are to:(1) the changes in torque production, spasticity and selective control a result of ITB; and (2)

spasticity, as seen after SDR. EXacerbatioN of weAknEss CoUld pRove Problematic in tHEse pAtients who are already siGnifiCaNTly wEAk. the SpEcific AIMs OF ThiS pRoJecT aRE tO:(1) quanTifY the chaNges in voluNtaRy Torque producTIoN, spasticitY anD selective coNtrOl as a rEsUlt OF ITB; aNd (2)

spasticity, as seen after  SDR. Exac erbat ion  of  w eakn esscould prove pr o blem atic in these patients  whoar e  alr e ad y sig nifican t ly w eak .Th e S pe c if ic Ai msof this  project a reto :(1) quantif y  t he changes  in  voluntary t orq ue pro du cti o n, sp ast icity  and s e lectiv e control  a s  a res u lt of I T B ;and(2)

spasticity,_as seen_after SDR. Exacerbation of_weakness could_prove_problematic in_these_patients who are_already significantly weak._The Specific Aims of_this project are_to:(1)_quantify the changes in voluntary torque production, spasticity and selective control as a result_of_ITB; and_(2)


the Center, which is not necessarily the institution for the investigator. DEVELOPMENT AND APPLICATIONS OF NEW PROBES AND METHODS FOR CORRELATED LIGHT AND ELECTRON MICROSCOPY, LIVE IMAGING, AND FUNCTIONAL ANALYSIS In this subproject, our efforts

the Center, which is not necessarily the institution for the investigator. DEVELOPMENT AND APPLICATIONS OF newfangled PROBES AND METHODS FOR CORRELATED LIGHT AND ELECTRON MICROSCOPY, LIVE IMAGING, AND running ANALYSIS In this subproject, our efforts

thf Center, which is not negessarily the institutimn for the invdstigator. DEVELOPMENT AND AP'LICQTIONW OF NEW PROBES AND MEGHODS FOR CORRELARED OUGHT AND ELECTRON MICROSDLPY, NMVE IMAGING, AND FUNCTIONAN ANALYSIS In dhks subproject, our efforts

the Center, which is not necessarily the the DEVELOPMENT AND OF NEW PROBES AND MICROSCOPY, LIVE IMAGING, FUNCTIONAL ANALYSIS In subproject, our efforts

the Center, which is not necessArily the inStituTioN foR tHe inVestIgator. DEVELOPMenT ANd APPLICATIONS OF NEW PROBeS AND mEthODS foR cORRElATED LIghT and ELeCtRoN MiCroScOPY, LiVE iMAGING, aND FUNCTIOnAL aNaLYSIS In this SUbProject, our EffOrts

the Center, which is notnecessaril y the  in sti tu tion  for  the investiga t or.DEVELOPMENT AND APPLIC ATION SO F NE W  P ROBES  AND ME T HO D S  FO RCO RRE LA T ED  LIGH T A ND ELEC TRON MICRO SCO PY , LIVE IMAGI N G,  AND FUNCT ION AL ANALYSISInthis s ub pro j ect,our  effo rts

the_Center, which_is not necessarily the_institution for_the_investigator. DEVELOPMENT_AND_APPLICATIONS OF NEW_PROBES AND METHODS_FOR CORRELATED LIGHT AND_ELECTRON MICROSCOPY, LIVE_IMAGING,_AND FUNCTIONAL ANALYSIS In this subproject, our efforts


that MCs activate adult-born GCs primarily in distal locations, leading to stronger excitation of distal GCs than proximal GCs. By providing afferent input to immature GCs, MCs could play a critical role in behaviors associated with adult DG neurogenesis. Together these experiments will significantly advance our understanding of DG circuitry and

that MCs activate adult - born GCs chiefly in distal localization, leading to stronger excitement of distal GCs than proximal gigahertz. By providing afferent input signal to immature GCs, MCs could meet a critical role in behaviors consociate with adult DG neurogenesis. Together these experiments will importantly advance our understanding of decigram circuitry and

thwt MCs activate adult-bork GCs primarily nb distel locafions, lexding to stronger excitation od disucl GCs than proximal GCs. By pgoviding qffecent input to immature GGf, MCa counv play a criticsl role in behaviors assmckaced with adult DG neurogenesis. Togetrer thexe experiments wyll xygnirpccntly advance our understanding of DG bircuitry and

that MCs activate adult-born GCs primarily in leading stronger excitation distal GCs than input immature GCs, MCs play a critical in behaviors associated with adult DG Together these experiments will significantly advance our understanding of DG circuitry and

that MCs activate adult-born Gcs primarilY in diStaL loCaTionS, leaDing to stronger EXcitAtion of distal GCs than prOximaL GcS. By pROvIding AfferenT InPUT to ImMaTurE GcS, Mcs couLd pLay a criTical role iN beHaViors associaTEd With adult Dg neUrogenesis. ToGetHer theSe ExpERimenTs wIll siGnificANtly adVance our uNdERstandINg of DG cIRCuItry And

that MCs activate adult-b orn GCs pr imari lyindi stal  loc ations, leadin g  tostronger excitation of  dist al GCst ha n pro ximal G C s. B y p ro vi din ga ff erent  in put toimmature G Cs,  M Cs could pla y  a  criticalrol e in behavio rsassoci at edw ith a dul t DGneurog e nesis.  Together  t h ese ex p eriment s wi ll s ignificantly adva n ce our understand ing of  D G  c i r cui try  and

that_MCs activate_adult-born GCs primarily in_distal locations,_leading_to stronger_excitation_of distal GCs_than proximal GCs._By providing afferent input_to immature GCs,_MCs_could play a critical role in behaviors associated with adult DG neurogenesis. Together these_experiments_will significantly_advance_our_understanding of DG circuitry and


DNA in prokaryotic and eurkaryotic cells. Interleukin-2 maintained T cell clones will be exposed to several inducing agents and their LT and TNF mRNA analyzed by Northern blots. The murine LT gene will be ligated to strong promoters and its expression studied in human T cell tumors. Similar vectors

DNA in prokaryotic and eurkaryotic cells. Interleukin-2 maintained T cell knockoff will be debunk to several induce agent and their LT and TNF mRNA analyzed by Northern blot. The murine LT gene will be ligate to strong promoters and its expression studied in human triiodothyronine cell tumors. like vector

DNW in prokaryotic and euryaryotic cells. Nbterlenkin-2 majntained T cell clones will be exposxd ti sevtgal inducing agents avd their PT and TBF mCNA analyzed by Ikrthern blots. Bhe mbrmne LT gene wilk be ligatad to strong psooocers and its expression studied in htman T vepl tumors. Simijar nestora

DNA in prokaryotic and eurkaryotic cells. Interleukin-2 cell will be to several inducing TNF analyzed by Northern The murine LT will be ligated to strong promoters its expression studied in human T cell tumors. Similar vectors

DNA in prokaryotic and eurkarYotic cells. interLeuKin-2 MaIntaIned t cell clones wilL Be exPosed to several inducing AgentS aND theIR Lt and TnF mRNA aNAlYZEd bY NOrTheRn BLoTs. The MurIne LT geNe will be liGatEd To strong promOTeRs and its exPreSsion studied In hUman T cElL tuMOrs. SiMilAr vecTors

DNA in prokaryotic and eu rkaryoticcells . I nte rl euki n-2maintained T c e ll c lones will be exposedto se ve r al i n du cingagentsa nd t hei rLT  an dT NF  mRNA  an alyzedby Norther n b lo ts. The muri n eLT gene wi llbe ligated t o s trongpr omo t ers a ndits e xpress i on stu died in h um a n T ce l l tumor s .  S imil ar vectors

DNA_in prokaryotic_and eurkaryotic cells. Interleukin-2_maintained T_cell_clones will_be_exposed to several_inducing agents and_their LT and TNF_mRNA analyzed by_Northern_blots. The murine LT gene will be ligated to strong promoters and its expression_studied_in human_T_cell_tumors. Similar vectors


effects of serial administration of daclizumab in this same patient cohort. We HYPOTHESIZE that serial doses of daclizumab therapy in patients with newly-diagnosed GBM will extend the duration of functional TRegs inhibition and further enhance vaccine-induced immune responses. Consistent with the goals of the American Recovery and

effects of serial administration of daclizumab in this same affected role age group. We speculate that serial doses of daclizumab therapy in patients with newly - diagnose GBM will extend the duration of functional TRegs prohibition and further enhance vaccine - induced immune responses. reproducible with the goals of the American Recovery and

efvects of serial administvation of daclizomqb in vhis saje patievt cohort. We HYPOTHESIZE thav seeial eoses of daclizumab thdrapy in iatients qith bewly-diagnosed GBM will swtend vhe duration of functionan TRegs inhibidiun and further enhance vaccine-induced immune rfsponses. Consiftenu wyth fhe goals of the American Recovery and

effects of serial administration of daclizumab in patient We HYPOTHESIZE serial doses of newly-diagnosed will extend the of functional TRegs and further enhance vaccine-induced immune responses. with the goals of the American Recovery and

effects of serial administraTion of daclIzumaB in ThiS sAme pAtieNt cohort. We HYPOthESIzE that serial doses of dacLizumAb THeraPY iN patiEnts witH NeWLY-diAgNoSed gBm WiLl extEnd The duraTion of funcTioNaL TRegs inhibiTIoN and furtheR enHance vaccine-IndUced imMuNe rESponsEs. COnsisTent wiTH the goAls of the AMeRIcan ReCOvery anD

effects of serial adminis tration of  dacl izu mab  i n th is s ame patient co h ort.  We HYPOTHESIZE that s erial  d o seso fdacli zumab t h er a p y i npa tie nt s  w ith n ewl y-diagn osed GBM w ill  e xtend the du r at ion of fun cti onal TRegs i nhi bition  a ndf urthe r e nhanc e vacc i ne-ind uced immu ne respon s es. Con s i st entwith the goals of th e  American Reco very a nd

effects_of serial_administration of daclizumab in_this same_patient_cohort. We_HYPOTHESIZE_that serial doses_of daclizumab therapy_in patients with newly-diagnosed_GBM will extend_the_duration of functional TRegs inhibition and further enhance vaccine-induced immune responses. Consistent with the_goals_of the_American_Recovery_and


cell (VSMC) provides dynamic regulation of contractile tone during homeostasis, and is often dysfunctional in diseases involving vascular obstruction and hyper-proliferation of the vessel wall. VSMC modify their gene expression and contractile proteins in response to a variety of external stimuli, particularly during disease progression. The Notch

cell (VSMC) provides dynamic regulation of contractile shade during homeostasis, and is frequently dysfunctional in diseases involving vascular obstruction and hyper - proliferation of the vessel rampart. VSMC modify their gene expression and contractile proteins in reaction to a variety of external stimuli, peculiarly during disease progress. The Notch

cepl (VSMC) provides dynamic regulation of eintracvile tohe durine homeostasis, and is often dbsfubctiobal in diseases involvkng vascupar obsteuctmon and hyper-proliferation of fme vevwel wall. VSMC kodify thehr gene expresviun and contractile proteins in responfe to a vwriety of extetnal xeimump, karticularly during disease progrsssion. Uhe Notch

cell (VSMC) provides dynamic regulation of contractile homeostasis, is often in diseases involving the wall. VSMC modify gene expression and proteins in response to a variety external stimuli, particularly during disease progression. The Notch

cell (VSMC) provides dynamic reGulation of ContrActIle ToNe duRing Homeostasis, and IS oftEn dysfunctional in diseaSes inVoLVing VAsCular ObstrucTIoN ANd hYpEr-ProLiFErAtion Of tHe vesseL wall. VSMC mOdiFy Their gene expREsSion and conTraCtile proteinS in ResponSe To a VArietY of ExterNal stiMUli, parTicularly DuRIng disEAse progRESsIon. THe Notch

cell (VSMC) provides dyna mic regula tionofcon tr acti le t one during hom e osta sis, and is often dysf uncti on a l in di sease s invol v in g vas cu la r o bs t ru ction  an d hyper -prolifera tio nof the vesse l  w all. VSMCmod ify their ge neexpres si ona nd co ntr actil e prot e ins in  response  t o  a var i ety ofe x te rnal  stimuli, particu l ar l y during disea se pro gr e ss i o n.The  Notch

cell_(VSMC) provides_dynamic regulation of contractile_tone during_homeostasis,_and is_often_dysfunctional in diseases_involving vascular obstruction_and hyper-proliferation of the_vessel wall. VSMC_modify_their gene expression and contractile proteins in response to a variety of external stimuli,_particularly_during disease_progression._The_Notch


and highly conserved mechanism to ensure genetic fidelity. The first step in DNA mismatch repair is recognition of DNA base mismatches and insertion or deletions by MutS in bacteria and MSH complexes in eukaryots. The structure for the MSH2-MSH6 complex which recognizes base mismatches and short base insertions has recently become

and highly conserved mechanism to ensure genetic fidelity. The first gradation in DNA mismatch haunt is recognition of DNA basis mismatch and insertion or deletions by MutS in bacteria and MSH complexes in eukaryots. The social organization for the MSH2 - MSH6 building complex which recognizes base mismatches and short base insertion has recently become

anf highly conserved mechakism to ensure ggnwtic fmdelity. The firrt step in DNA mismatch repamr iw recignition of DNA base mksmatches and inswrtiib or deletmkns by MutS ih baccecia and MSH comklexes in eunaryots. The stsuztbre for the MSH2-MSH6 complex which recjgnizes bwse mismatches and fhorf base insertions has recently beckme

and highly conserved mechanism to ensure genetic first in DNA repair is recognition insertion deletions by MutS bacteria and MSH in eukaryots. The structure for the complex which recognizes base mismatches and short base insertions has recently become

and highly conserved mechaniSm to ensure GenetIc fIdeLiTy. ThE firSt step in DNA misMAtch Repair is recognition of DnA basE mISmatCHeS and iNsertioN Or DELetIoNs By MUts In BacteRia And MSH cOmplexes in EukArYots. The strucTUrE for the MSH2-mSH6 Complex which RecOgnizeS bAse MIsmatCheS and sHort baSE inserTions has rEcENtly beCOme

and highly conserved mech anism to e nsure  ge net ic  fid elit y. The first s t ep i n DNA mismatch repairis re co g niti o nof DN A basem is m a tch es  a ndin s er tionordeletio ns by MutS  in  b acteria andM SH  complexes  in  eukaryots.The  struc tu ref or th e M SH2-M SH6 co m plex w hich reco gn i zes ba s e misma t c he s an d short base inse r ti o ns has recentl y beco me

and_highly conserved_mechanism to ensure genetic_fidelity. The_first_step in_DNA_mismatch repair is_recognition of DNA_base mismatches and insertion_or deletions by_MutS_in bacteria and MSH complexes in eukaryots. The structure for the MSH2-MSH6 complex which_recognizes_base mismatches_and_short_base insertions has recently become


-triggered translocation of the glucose transporter (GLUT4) will likely provide new findings for attacking diseases such as diabetes and obesity. The main goal of the proposal is to develop a kinetic screen to identify adipocyte regulatory proteins that control dynamic parameters for PIP3 signaling and for GLUT4 translocation and endocytosis. We

-triggered translocation of the glucose transporter (GLUT4) will likely provide new finding for attack diseases such as diabetes and obesity. The main finish of the proposal is to develop a kinetic screen to name adipocyte regulative proteins that control dynamic parameters for PIP3 signaling and for GLUT4 translocation and endocytosis. We

-trihgered translocation of uhe glucose transkoeter (GNUT4) wiml likelh provide new findings for avtacjing eiseases such as diabeges and ohesity. Tye mein goal of the 'doposal is to fevenip a kinetic sgreen to idantify adipocyde rzgulatory proteins that control dynaiic parsmfters for PIP3 fignsjing and for GLUT4 translocation and ensocytosps. We

-triggered translocation of the glucose transporter (GLUT4) provide findings for diseases such as goal the proposal is develop a kinetic to identify adipocyte regulatory proteins that dynamic parameters for PIP3 signaling and for GLUT4 translocation and endocytosis. We

-triggered translocation of tHe glucose tRanspOrtEr (GlUt4) wilL likEly provide new fINdinGs for attacking diseases Such aS dIAbetES aNd obeSity. The MAiN GOal Of ThE prOpOSaL is to DevElop a kiNetic screeN to IdEntify adipocYTe Regulatory ProTeins that conTroL dynamIc ParAMeterS foR PIP3 sIgnaliNG and foR GLUT4 tranSlOCation ANd endocYTOsIs. We

-triggered translocation o f the gluc ose t ran spo rt er ( GLUT 4) will likely prov ide new findings for a ttack in g  dis e as es su ch as d i ab e t esan dobe si t y.  Themai n goalof the pro pos al  is to devel o pa kineticscr een to ident ify  adipo cy ter egula tor y pro teinst hat co ntrol dyn am i c para m eters f o r  P IP3signaling and for GL U T4 translocati on and  e n do c y tos is.  We

-triggered translocation_of the_glucose transporter (GLUT4) will_likely provide_new_findings for_attacking_diseases such as_diabetes and obesity._The main goal of_the proposal is_to_develop a kinetic screen to identify adipocyte regulatory proteins that control dynamic parameters for_PIP3_signaling and_for_GLUT4_translocation and endocytosis. We


protocols to treat devastating orthopaedic injuries and disease in our Veterans. The program aims to examine the significance of changes that phagocytic leukocytes undergo when they ingest bacteria, with respect to the role those changes play in protecting the host. The leukocytes may be stimulated by solid particles, or by some more soluble substances, to

protocols to treat devastating orthopaedic wound and disease in our Veterans. The platform aims to examine the significance of change that phagocytic leukocytes undergo when they ingest bacteria, with regard to the character those changes play in protecting the host. The leukocyte may be stimulated by solid particles, or by some more soluble substances, to

prltocols to treat devastauing orthopaedic nbjuriev and sisease kn our Veterans. The program eims to ezamine the significancd of chanhes that phajocytic leukocytxa undernj whsk thev mngest bacteria, with respact to the rola ghlse changes play in protecting the rost. Thr peukocytes may be xeimumated by solid particles, or by soms more voluble substsnces, to

protocols to treat devastating orthopaedic injuries and our The program to examine the leukocytes when they ingest with respect to role those changes play in protecting host. The leukocytes may be stimulated by solid particles, or by some more substances, to

protocols to treat devastatiNg orthopaeDic inJurIes AnD disEase In our Veterans. THE proGram aims to examine the siGnifiCaNCe of CHaNges tHat phagOCyTIC leUkOcYteS uNDeRgo whEn tHey ingeSt bacteria, WitH rEspect to the rOLe Those changEs pLay in protectIng The hosT. THe lEUkocyTes May be StimulATed by sOlid partiClES, or by sOMe more sOLUbLe suBstances, to

protocols to treat devast ating orth opaed icinj ur iesanddisease in our Vete rans. The program aims  to e xa m inet he  sign ificanc e  o f cha ng es  th at ph agocy tic  leukoc ytes under gowh en they inge s tbacteria,wit h respect to  th e role  t hos e  chan ges  play  in pr o tectin g the hos t. The le u kocytes m ay  bestimulated by sol i dp articles, or b y some  m o re s olu ble  substance s,  to

protocols_to treat_devastating orthopaedic injuries and_disease in_our_Veterans. The_program_aims to examine_the significance of_changes that phagocytic leukocytes_undergo when they_ingest_bacteria, with respect to the role those changes play in protecting the host. The_leukocytes_may be_stimulated_by_solid particles, or by some_more soluble substances, to


from lung tissue induced 100-fold by pregnancy or progesterone treatment and translating in a cell-free system to determine the amount of mRNA synthesized with time after treatment or pregnancy. Pig kidney and lung tissue will be utilized as sources for purification of the cytochromes P-450 involved in prostaglandin Omega- or (Omega

from lung tissue induced 100 - fold by pregnancy or progesterone treatment and translating in a cellular telephone - spare system to determine the sum of messenger rna synthesized with time after treatment or pregnancy. devour kidney and lung tissue will be utilized as sources for refining of the cytochrome P-450 involved in prostaglandin Omega- or (Omega

frlm lung tissue induced 100-fuld by pregnanci ir projesterohe treatoent and translating in a cepl-dree wystem to determine thd amount lf mRNA wyntiesized with timx after bxeatmskt or 'regnancy. Pig kldney and lgng tissue wiln ce utilized as sources for purificatijn of tne cytochromes P-450 invpjved pn prostaglandin Omega- or (Omega

from lung tissue induced 100-fold by pregnancy treatment translating in cell-free system to synthesized time after treatment pregnancy. Pig kidney lung tissue will be utilized as for purification of the cytochromes P-450 involved in prostaglandin Omega- or (Omega

from lung tissue induced 100-fold By pregnancY or prOgeSteRoNe trEatmEnt and translatINg in A cell-free system to deterMine tHe AMounT Of MRNA sYnthesiZEd WITh tImE aFteR tREaTment Or pRegnancY. Pig kidney And LuNg tissue will BE uTilized as sOurCes for purifiCatIon of tHe CytOChromEs P-450 InvolVed in pROstaglAndin OmegA- oR (omega

from lung tissue induced100-fold b y pre gna ncy  o r pr oges terone treatme n t an d translating in a cel l-fre es yste m  t o det erminet he a mou nt  o f m RN A  s ynthe siz ed with  time afte r t re atment or pr e gn ancy. Pigkid ney and lung  ti ssue w il l b e  util ize d assource s  for p urificati on of the cytochr o m es  P-4 50 involved in pr o st a glandin Omega-  or (O me g a

from_lung tissue_induced 100-fold by pregnancy_or progesterone_treatment_and translating_in_a cell-free system_to determine the_amount of mRNA synthesized_with time after_treatment_or pregnancy. Pig kidney and lung tissue will be utilized as sources for purification_of_the cytochromes_P-450_involved_in prostaglandin Omega- or (Omega


localization in the Pur-alpha knockout mouse model, suggesting that Pur-alpha is required for their proper function. Based on these preliminary observations, we hypothesize that Pur-alpha has a central role in the well-balanced activities of RhoA and Rac, and that its genetic ablation or its functional alteration by associating with Tat

localization in the Pur - alpha knockout mouse model, suggesting that Pur - alpha is required for their proper affair. free-base on these preliminary observations, we hypothesize that Pur - alpha has a cardinal role in the well - balanced activities of RhoA and Rac, and that its familial ablation or its functional alteration by associate with Tat

lofalization in the Pur-alpma knockout mousg nodel, vuggesfing thag Pur-alpha is required for tieir proptg function. Based on tfese prelpminary ovsertations, we hypotissize tmct Pud-wlphc ias a central rple in the well-balanced dcgirities of RhoA and Rac, and that its denetic ahlation or its funbtyonam alteration by associating with Tzt

localization in the Pur-alpha knockout mouse model, Pur-alpha required for proper function. Based hypothesize Pur-alpha has a role in the activities of RhoA and Rac, and its genetic ablation or its functional alteration by associating with Tat

localization in the Pur-alpha Knockout moUse moDel, SugGeStinG thaT Pur-alpha is reqUIred For their proper function. based On THese PReLiminAry obseRVaTIOns, We HyPotHeSIzE that pur-Alpha haS a central rOle In The well-balanCEd Activities Of RHoA and Rac, and ThaT its geNeTic ABlatiOn oR its fUnctioNAl alteRation by aSsOCiatinG With Tat

localization in the Pur-a lpha knock out m ous e m od el,sugg esting that Pu r -alp ha is required for the ir pr op e r fu n ct ion.Based o n  t h e sepr el imi na r yobser vat ions, w e hypothes ize  t hat Pur-alph a  h as a centr alrole in thewel l-bala nc eda ctivi tie s ofRhoA a n d Rac,  and that  i t s gene t ic abla t i on  orits functional al t er a tion by associ atingwi t hT a t

localization_in the_Pur-alpha knockout mouse model,_suggesting that_Pur-alpha_is required_for_their proper function._Based on these_preliminary observations, we hypothesize_that Pur-alpha has_a_central role in the well-balanced activities of RhoA and Rac, and that its genetic_ablation_or its_functional_alteration_by associating with Tat


nervous system that play a role in their functioning. One specific psychophysiological correlate of regulatory behavior that has been extensively studied in the existing literature is that of heart rate variability, or vagal tone. Low heart rate variability in children has been associated with maladaptive outcomes (i.e., conduct disorder;Pine

nervous system that play a role in their operation. One specific psychophysiological correlate of regulative demeanor that has been extensively studied in the existing literature is that of heart pace variability, or vagal tone. Low center rate variability in child has been associated with maladaptive outcomes (i.e., demeanor disorder;Pine

negvous system that play a role in their yynctioiing. Ons specifkc psychophysiological correpare of regulatory behavior tfat has bven extenwiveot studied mh the ewnstinf litzreture is that on heart rata variability, mr vcgal tone. Low heart rate variability in chikdgen has been afsocpaeed sptm maladaptive outcomes (i.e., conducf disorver;Pine

nervous system that play a role in One psychophysiological correlate regulatory behavior that the literature is that heart rate variability, vagal tone. Low heart rate variability children has been associated with maladaptive outcomes (i.e., conduct disorder;Pine

nervous system that play a rolE in their fuNctioNinG. OnE sPeciFic pSychophysiologICal cOrrelate of regulatory beHavioR tHAt haS BeEn extEnsivelY StUDIed In ThE exIsTInG liteRatUre is thAt of heart rAte VaRiability, or vAGaL tone. Low heArt Rate variabilIty In chilDrEn hAS been AssOciatEd with MAladapTive outcoMeS (I.e., condUCt disorDER;PIne

nervous system that playa role intheir  fu nct io ning . On e specific psy c hoph ysiological correlateof re gu l ator y  b ehavi or that ha s bee nex ten si v el y stu die d in th e existing  li te rature is th a tof heart r ate  variability , o r vaga lton e . Low  he art r ate va r iabili ty in chi ld r en has been as s o ci ated  with maladaptive ou t comes (i.e., c onduct  d i so r d er; Pin e

nervous_system that_play a role in_their functioning._One_specific psychophysiological_correlate_of regulatory behavior_that has been_extensively studied in the_existing literature is_that_of heart rate variability, or vagal tone. Low heart rate variability in children has_been_associated with_maladaptive_outcomes_(i.e., conduct disorder;Pine


will have significant implications for understanding the diverse ways in which parents have socialized the adolescent-pet relationship. Varenicline for the treatment of cocaine dependence: A phase II clinical trial. Cocaine dependence remains a major public health problem, even after over two decades of steady attempts to develop effective behavioral and pharmacological interventions for

will have significant implications for understanding the divers way in which parents have socialized the adolescent - darling kinship. Varenicline for the treatment of cocaine dependence: A phase II clinical trial. Cocaine addiction persist a major public health problem, even after over two decade of steady attempts to build up effective behavioral and pharmacological interventions for

wipl have significant impllcations for undgrwtandiig the siverse days in which parents have slcualiztb the adolescent-pet felationsjip. Varebiclmne for the treavjent of cocaihc depznvence: A phase IL clinical drial. Cocaine geoeudence remains a major public health problek, fven after ovet two qecasvs of steady attempts to develol effecuive behavioral anc pharmacological intervenhiond for

will have significant implications for understanding the in parents have the adolescent-pet relationship. cocaine A phase II trial. Cocaine dependence a major public health problem, even over two decades of steady attempts to develop effective behavioral and pharmacological interventions

will have significant implicAtions for uNdersTanDinG tHe diVersE ways in which paREnts Have socialized the adoleScent-PeT RelaTIoNship. varenicLInE FOr tHe TrEatMeNT oF cocaIne DependeNce: A phase Ii clInIcal trial. CocAInE dependencE reMains a major pUblIc healTh ProBLem, evEn aFter oVer two DEcades Of steady aTtEMpts to DEvelop eFFEcTive Behavioral and pharMAcOLogical interveNtions FoR

will have significant imp licationsfor u nde rst an ding  the  diverse waysi n wh ich parents have socia lized  t h e ad o le scent -pet re l at i o nsh ip .Var en i cl ine f orthe tre atment ofcoc ai ne dependenc e :A phase II  cl inical trial . C ocaine  d epe n dence  re mains  a maj o r publ ic health  p r oblem, even af t e rover  two decades of s t ea d y attempts todevelo pe ff e c tiv e b ehavioralan d pha r macolog i ca l i nte r ventions for

will_have significant_implications for understanding the_diverse ways_in_which parents_have_socialized the adolescent-pet_relationship. Varenicline for_the treatment of cocaine_dependence: A phase_II_clinical trial. Cocaine dependence remains a major public health problem, even after over two_decades_of steady_attempts_to_develop effective behavioral and pharmacological_interventions for


in mouse and Xenopus oocytes and in Arabidopsis protoplasts was found to require the presence of extracellular ice in close contact with the cell membrane. One strong piece of evidence in the mouse oocyte is that IIF occurs at temperatures where about 95 percent of the external medium has frozen. That temperature varies from -14[

in mouse and Xenopus oocytes and in Arabidopsis protoplasts was found to require the presence of extracellular internal-combustion engine in cheeseparing contact with the cell membrane. One strong musical composition of evidence in the mouse oocyte is that IIF occurs at temperature where about 95 percentage of the external medium has frozen. That temperature varies from -14 [

in mouse and Xenopus oocytts and in Arabidoksus provoplasta was fojnd to require the presence lf extrqcellular ice in close contact aith the celo membrane. One stroky piedc of zvmdence in the mpuse oocyta is that IIF mczuxs at temperatures where about 95 percqnt of yhf external medyum nws fdozen. That temperature varies from -14[

in mouse and Xenopus oocytes and in was to require presence of extracellular the membrane. One strong of evidence in mouse oocyte is that IIF occurs temperatures where about 95 percent of the external medium has frozen. That temperature from -14[

in mouse and Xenopus oocytes aNd in ArabidOpsis ProTopLaSts wAs foUnd to require thE PresEnce of extracellular ice In cloSe COntaCT wIth thE cell meMBrANE. OnE sTrOng PiECe Of eviDenCe in the Mouse oocytE is ThAt IIF occurs aT TeMperatures WheRe about 95 perceNt oF the exTeRnaL MediuM haS frozEn. That TEmperaTure varieS fROm -14[

in mouse and Xenopus oocy tes and in  Arab ido psi sprot opla sts was foundt o re quire the presence ofextra ce l lula r  i ce in  closec on t a ctwi th  th ec el l mem bra ne. One  strong pi ece  o f evidence i n  t he mouse o ocy te is that I IFoccurs  a t t e mpera tur es wh ere ab o ut 95percent o ft he ext e rnal me d i um  has  frozen. That tem p er a ture varies fr om -14 [

in_mouse and_Xenopus oocytes and in_Arabidopsis protoplasts_was_found to_require_the presence of_extracellular ice in_close contact with the_cell membrane. One_strong_piece of evidence in the mouse oocyte is that IIF occurs at temperatures where_about_95 percent_of_the_external medium has frozen. That_temperature varies from -14[


as adults). These findings point to greater compensatory potential after neonatal cortical than after neonatal limbic removals, indicating that association areas of the cortex are immature at birth, and may thus possess greater plasticity than limbic structures. Direct evidence of neocortical immaturity in the macaque has been provided by our neurobi

as adults). These findings point to greater compensatory electric potential after neonatal cortical than after neonatal limbic removal, indicating that association area of the lens cortex are immature at birth, and may therefore possess greater plasticity than limbic structure. Direct evidence of neocortical immaturity in the macaque has been provided by our neurobi

as adults). These findings puint to greater compenvatory potentixl after neonatal cortical tian qfter neonatal limbic removxls, indicwting thqt awwociation edeas of the ckvtex crx immature at blrth, and maf thus possess gfecter plasticity than limbic structurqs. Direvt evidence of ngocoruicwl ijmaturity in the macaque has been lrovidev by our neurobo

as adults). These findings point to greater after cortical than neonatal limbic removals, the are immature at and may thus greater plasticity than limbic structures. Direct of neocortical immaturity in the macaque has been provided by our neurobi

as adults). These findings poinT to greater CompeNsaTorY pOtenTial After neonatal cORticAl than after neonatal limBic reMoVAls, iNDiCatinG that asSOcIATioN aReAs oF tHE cOrtex Are ImmaturE at birth, anD maY tHus possess grEAtEr plasticiTy tHan limbic strUctUres. DiReCt eVIdencE of NeocoRtical IMmaturIty in the mAcAQue has BEen provIDEd By ouR neurobi

as adults). These finding s point to  grea ter  co mp ensa tory  potential aft e r ne onatal cortical than a fterne o nata l  l imbic  remova l s, i ndi ca ti ngth a tassoc iat ion are as of thecor te x are immatu r eat birth,and  may thus po sse ss gre at erp lasti cit y tha n limb i c stru ctures. D ir e ct evi d ence of n eo cort ical immaturity i n  t h e macaque hasbeen p ro v id e d  by  ou r neurobi

as_adults). These_findings point to greater_compensatory potential_after_neonatal cortical_than_after neonatal limbic_removals, indicating that_association areas of the_cortex are immature_at_birth, and may thus possess greater plasticity than limbic structures. Direct evidence of neocortical_immaturity_in the_macaque_has_been provided by our neurobi


applied to the synthesis of specific naturally occurring macrolides. The development of new female-initiated HIV prevention methods, including oral and topical microbicides, is urgently needed to stem the growing epidemic among adolescent women. Despite the disproportionate impact of HIV/AIDS on adolescent women, they have been markedly under-represented in

applied to the synthesis of specific naturally occurring macrolides. The development of newfangled female - initiate HIV prevention methods, including oral and topical microbicides, is urgently needed to stem the grow epidemic among adolescent women. Despite the disproportionate impact of HIV / AIDS on adolescent womanhood, they have been markedly under - represent in

apolied to the synthesis on specific naturcoly ocrurring macroliaes. The development of new fxmalw-inituated HIV prevention mdthods, inbluding oeal end topical microbicides, is urfcntly ieeded to stem jhe growing apidemic among aaopescent women. Despite the disproporeionate ilpact of HIV/AIQS om adomvsgent women, they have been markedmy undeg-represented in

applied to the synthesis of specific naturally The of new HIV prevention methods, is needed to stem growing epidemic among women. Despite the disproportionate impact of on adolescent women, they have been markedly under-represented in

applied to the synthesis of spEcific natuRally OccUrrInG macRoliDes. The developmENt of New female-initiated HIV pRevenTiON metHOdS, inclUding orAL aND TopIcAl MicRoBIcIdes, iS urGently nEeded to steM thE gRowing epidemIC aMong adolesCenT women. DespitE thE disprOpOrtIOnate ImpAct of hIV/AIDs On adolEscent womEn, THey havE Been marKEDlY undEr-represented in

applied to the synthesisof specifi c nat ura lly  o ccur ring  macrolides. T h e de velopment of new femal e-ini ti a tedH IV  prev entionm et h o ds,  i nc lud in g  o ral a ndtopical  microbici des ,is urgentlyn ee ded to ste m t he growing e pid emic a mo nga doles cen t wom en. De s pite t he dispro po r tionat e  impact o fHIV/ AIDS on adolescen t  w o men, they have  beenma r ke d l y u nde r-represen te d in

applied_to the_synthesis of specific naturally_occurring macrolides._The_development of_new_female-initiated HIV prevention_methods, including oral_and topical microbicides, is_urgently needed to_stem_the growing epidemic among adolescent women. Despite the disproportionate impact of HIV/AIDS on adolescent_women,_they have_been_markedly_under-represented in


,000 deaths per year. It is thus essential that researchers continue to investigate the factors relevant to the treatment of nicotine dependence. Drug-related expectancies represent the consequences that an individual expects from the use (or non-use) of any given substance. With respect to smoking, research has focused on smokers'expectancies

, 000 deaths per year. It is thus essential that research worker stay to investigate the factors relevant to the treatment of nicotine addiction. Drug - related anticipation represent the consequences that an person expect from the use (or non - function) of any given substance. With regard to smoking, research has concenter on smokers'expectancies

,000 dewths per year. It is thus essential that researrhers ckntinue go investigate the factors rxlevqnt ti the treatment of nicutine depvndence. Deug-rtlated expectancixa represent tgc convxquences that ak individuan expects from tfe use (or non-use) of any given substanse. With rfspect to smokyng, gefeardh has focused on smokers'expectancjes

,000 deaths per year. It is thus researchers to investigate factors relevant to Drug-related represent the consequences an individual expects the use (or non-use) of any substance. With respect to smoking, research has focused on smokers'expectancies

,000 deaths per year. It is thus esseNtial that rEsearCheRs cOnTinuE to iNvestigate the fACtorS relevant to the treatmenT of niCoTIne dEPeNdencE. Drug-reLAtED ExpEcTaNciEs REpResenT thE conseqUences that An iNdIvidual expecTS fRom the use (oR noN-use) of any givEn sUbstanCe. witH RespeCt tO smokIng, resEArch haS focused oN sMOkers'eXPectancIES

,000 deaths per year. It i s thus ess entia l t hat  r esea rche rs continue to inve stigate the factors re levan tt o th e  t reatm ent ofn ic o t ine  d ep end en c e.  Drug -re lated e xpectancie s r ep resent the c o ns equences t hat  an individu alexpect sfro m  theuse  (ornon-us e ) of a ny givensu b stance .  With r e s pe ct t o smoking, resear c hh as focused onsmoker s' e xp e c tan cie s

,000 deaths_per year._It is thus essential_that researchers_continue_to investigate_the_factors relevant to_the treatment of_nicotine dependence. Drug-related expectancies_represent the consequences_that_an individual expects from the use (or non-use) of any given substance. With respect_to_smoking, research_has_focused_on smokers'expectancies


activity of NF-kappaB, making pateamine A a valuable probe to study the nuclear signaling mechanism of NF-kappaB. To identify the molecular targets of pateamine A, a biotin-pateamine A conjugate was synthesized, which enabled the detection, isolation and identification of two pateamine A

activity of NF - kappaB, making pateamine A a valuable probe to study the nuclear signaling mechanism of NF - kappaB. To name the molecular target of pateamine A, a biotin - pateamine A conjugate was synthesized, which enable the detection, isolation and recognition of two pateamine A

achivity of NF-kappaB, makinn pateamine A a rqluablx probe to studh the nuclear signaling mechenisn of BF-kappaB. To identify tfe molecupar targwts id pateaminx A, a biotin-pafcaminz E conjugate was synthesizad, which enablad tke detection, isolation and identificwtion og hwo pateamine W

activity of NF-kappaB, making pateamine A a to the nuclear mechanism of NF-kappaB. of A, a biotin-pateamine conjugate was synthesized, enabled the detection, isolation and identification two pateamine A

activity of NF-kappaB, making pAteamine A a ValuaBle ProBe To stUdy tHe nuclear signaLIng mEchanism of NF-kappaB. To idEntifY tHE molECuLar taRgets of PAtEAMinE A, A bIotIn-PAtEaminE A cOnjugatE was syntheSizEd, Which enabled THe Detection, iSolAtion and idenTifIcatioN oF twO PateaMinE A

activity of NF-kappaB, ma king patea mineA a  va lu able  pro be to study th e  nuc lear signaling mechani sm of  N F -kap p aB . Toidentif y  t h e  mo le cu lar  t a rg ets o f p ateamin e A, a bio tin -p ateamine A c o nj ugate wassyn thesized, wh ich  enabl ed  th e  dete cti on, i solati o n andidentific at i on oft wo pate a m in e A

activity_of NF-kappaB,_making pateamine A a_valuable probe_to_study the_nuclear_signaling mechanism of_NF-kappaB. To identify_the molecular targets of_pateamine A, a_biotin-pateamine_A conjugate was synthesized, which enabled the detection, isolation and identification of two pateamine_A


VMD, NAMD, and Lattice Microbes served a community of over 100,000 users. Technical support for the community was provided mainly through the online discussion groups?NAMD-L?,?VMD-L? and?LatticeMicrobes-Users?, where more than 17,000 software-related

VMD, NAMD, and Lattice Microbes served a community of over 100,000 users. Technical support for the residential district was provide mainly through the online discussion groups?NAMD - L?,?VMD - L? and?LatticeMicrobes - Users? , where more than 17,000 software - relate

VMF, NAMD, and Lattice Micrones served a community mf oved 100,000 users. Technical support for the clmnunitt was provided mainly ghrough tje onlinw diwxussion groups?NAMD-L?,?VMD-L? zkd?LatcireMicrobes-Users?, where mora than 17,000 softwase-fepated

VMD, NAMD, and Lattice Microbes served a over users. Technical for the community online groups?NAMD-L?,?VMD-L? and?LatticeMicrobes-Users?, where than 17,000 software-related

VMD, NAMD, and Lattice Microbes Served a comMunitY of OveR 100,000 uSers. techNical support foR The cOmmunity was provided maiNly thRoUGh thE OnLine dIscussiON gROUps?nAmD-l?,?VMd-L? ANd?lattiCeMIcrobes-users?, where MorE tHan 17,000 software-rELaTed

VMD, NAMD, and Lattice Mi crobes ser ved a  co mmu ni ty o f ov er 100,000 use r s. T echnical support for t he co mm u nity wa s pro vided m a in l y  th ro ug h t he on linedis cussion  groups?NA MD- L? ,?VMD-L? and ? La tticeMicro bes -Users?, whe remore t ha n 1 7 ,000sof tware -relat e d

VMD,_NAMD, and_Lattice Microbes served a_community of_over_100,000 users._Technical_support for the_community was provided_mainly through the online_discussion groups?NAMD-L?,?VMD-L? and?LatticeMicrobes-Users?,_where_more than 17,000 software-related


foreign governments and their industries in Latin America. IICA is and has been a strong U.S. government partner in Latin America and the Caribbean for many years and has the demonstrated capacity to implement FSMA training in the region. Many cancer patients who are candidates for high dose chemotherapy do not have available a suitable related or

foreign governments and their industries in Latin America. IICA is and has been a strong U.S. politics spouse in Latin America and the Caribbean for many years and has the attest capacitance to implement FSMA training in the area. Many cancer patients who are candidates for high dose chemotherapy do not have available a desirable related or

fogeign governments and thtir industries in Latin Emerica. IICA is and has been a strong U.S. goternnent kcrtner in Latin Amerkca and tje Caribvean dor many yxzrs and has tgc demmistrated capacijy to implemant FSMA trainhne nn the region. Many cancer patients wro are vajdidates for hygh cjse dhemotherapy do not have available a suiteble related or

foreign governments and their industries in Latin is has been strong U.S. government the for many years has the demonstrated to implement FSMA training in the Many cancer patients who are candidates for high dose chemotherapy do not have a suitable related or

foreign governments and theiR industrieS in LaTin ameRiCa. IIcA is And has been a strONg U.S. Government partner in LatIn AmeRiCA and THe caribBean for MAnY YEarS aNd Has ThE DeMonstRatEd capacIty to impleMenT FsMA training iN ThE region. ManY caNcer patients Who Are canDiDatES for hIgh Dose cHemothERapy do Not have avAiLAble a sUItable rELAtEd or

foreign governments and t heir indus tries  in  La ti n Am eric a. IICA is and hasbeen a strong U.S. gov ernme nt part n er  in L atin Am e ri c a  an dth e C ar i bb ean f ormany ye ars and ha s t he  demonstrate d  c apacity to  im plement FSMA  tr aining  i n t h e reg ion . Man y canc e r pati ents whoar e  candi d ates fo r hi gh d ose chemotherapyd on ot have availa ble asu i ta b l e r ela ted or

foreign_governments and_their industries in Latin_America. IICA_is_and has_been_a strong U.S._government partner in_Latin America and the_Caribbean for many_years_and has the demonstrated capacity to implement FSMA training in the region. Many cancer_patients_who are_candidates_for_high dose chemotherapy do not_have available a suitable related_or


mutant cells to ionizing radiation. In addition we studied the mechanism of Doxorubicin resistance in p53 mutant breast cancer cells. Data already obtained show that standard bicycle exercise evokes a greater steady-state O2 consumption and a larger O2 debt during pregnancy than postpartum. Continuing studies will extend observations to the

mutant cells to ionizing radiation. In addition we study the mechanism of Doxorubicin underground in p53 mutant breast cancer cells. Data already obtained appearance that standard bicycle exercise evokes a bang-up firm - state O2 consumption and a larger O2 debt during pregnancy than postpartum. Continuing report will extend observations to the

muhant cells to ionizing rxdiation. In addnrion wx studisd the mdchanism of Doxorubicin residtqnce un p53 mutant breast canzer cells. Data aleeadb obtained show vgat stakbard glcyclz xxercise evokes a greater steady-state O2 cundumption and a larger O2 debt during pregnamcj than postparjum. Cpgtinhpnn studies will extend observatiohs to tie

mutant cells to ionizing radiation. In addition the of Doxorubicin in p53 mutant obtained that standard bicycle evokes a greater O2 consumption and a larger O2 during pregnancy than postpartum. Continuing studies will extend observations to the

mutant cells to ionizing radiAtion. In addItion We sTudIeD the MechAnism of DoxorubICin rEsistance in p53 mutant breaSt canCeR CellS. daTa alrEady obtAInED ShoW tHaT stAnDArD bicyCle ExercisE evokes a grEatEr Steady-state O2 COnSumption anD a lArger O2 debt duRinG pregnAnCy tHAn posTpaRtum. COntinuINg studIes will exTeND obserVAtions tO THe

mutant cells to ionizingradiation.  In a ddi tio nwe s tudi ed the mechani s m of  Doxorubicin resistanc e inp5 3  mut a nt  brea st canc e rc e lls .Da taal r ea dy ob tai ned sho w that sta nda rd  bicycle exe r ci se evokesa g reater stead y-s tate O 2con s umpti onand a  large r  O2 de bt during  p r egnanc y  than p o s tp artu m. Continuing stu d ie s  will extend o bserva ti o ns t o t he

mutant_cells to_ionizing radiation. In addition_we studied_the_mechanism of_Doxorubicin_resistance in p53_mutant breast cancer_cells. Data already obtained_show that standard_bicycle_exercise evokes a greater steady-state O2 consumption and a larger O2 debt during pregnancy_than_postpartum. Continuing_studies_will_extend observations to the


of Na+/H+ exchangers and Na+/K+/2Cl- cotransporters to drive fluid secretion and related processes such as cell volume maintenance and intracellular pH regulation. Ductal cells then act on acinar cell secretions to conserve NaCl utilizing Na+/H+ exchangers, Na+ channels and other

of Na+/H+ exchangers and Na+/K+/2Cl- cotransporters to drive fluid secretion and related processes such as cellular telephone bulk maintenance and intracellular pH regulation. Ductal cell then dissemble on acinar cell secretions to conserve NaCl utilize Na+/H+ exchanger, Na+ channels and other

of Na+/H+ exchangers and Na+/K+/2Cu- cotransporters to drmve flujd secregion and related processes snch qs ceol volume maintenance xnd intrabellular pH rtgulation. Ductal rslls thcu act ln aeiiar cell secretlons to converve NaCl utinixiug Na+/H+ exchangers, Na+ channels and otrer

of Na+/H+ exchangers and Na+/K+/2Cl- cotransporters to secretion related processes as cell volume Ductal then act on cell secretions to NaCl utilizing Na+/H+ exchangers, Na+ channels other

of Na+/H+ exchangers and Na+/K+/2Cl- coTransporteRs to dRivE flUiD secRetiOn and related prOCessEs such as cell volume mainTenanCe ANd inTRaCelluLar pH reGUlATIon. duCtAl cElLS tHen acT on Acinar cEll secretiOns To Conserve NaCl UTiLizing Na+/H+ eXchAngers, Na+ chanNelS and otHeR

of Na+/H+ exchangers andNa+/K+/2Cl - cot ran spo rt ersto d rive fluid sec r etio n and related processe s suc ha s ce l lvolum e maint e na n c e a nd  i ntr ac e ll ularpHregulat ion. Ducta l c el ls then acto nacinar cel l s ecretions to  co nserve  N aCl utili zin g Na+ /H+ ex c hanger s, Na+ ch an n els an d  other

of_Na+/H+ exchangers_and Na+/K+/2Cl- cotransporters to_drive fluid_secretion_and related_processes_such as cell_volume maintenance and_intracellular pH regulation. Ductal_cells then act_on_acinar cell secretions to conserve NaCl utilizing Na+/H+ exchangers, Na+ channels and other


facilitates their regeneration, and on the surface of several different types of cancers where it promotes their growth and invasiveness. Remarkably, polySia is found on only five proteins in addition to the polysialyltransferases (polySTs) that modify their own N-glycans. The recent identification of two of

facilitates their regeneration, and on the surface of several unlike type of cancers where it promotes their increase and invasiveness. signally, polySia is found on only five protein in addition to the polysialyltransferases (polySTs) that modify their own N - glycans. The late designation of two of

fafilitates their regenerauion, and on the sordace oh severzl diffefent types of cancers where mt peomottf their growth and invasivejess. Remqrkauly, polySia is found on only fjye prmveins in additipn to the [olysialyltranvfdrcses (polySTs) that modify their own N-dlycans. Tje recent idenjificseion of two of

facilitates their regeneration, and on the surface different of cancers it promotes their is on only five in addition to polysialyltransferases (polySTs) that modify their own The recent identification of two of

facilitates their regeneratIon, and on thE surfAce Of sEvEral DiffErent types of caNCers Where it promotes their grOwth aNd INvasIVeNess. REmarkabLY, pOLYSiA iS fOunD oN OnLy fivE prOteins iN addition tO thE pOlysialyltraNSfErases (polysTs) That modify thEir Own N-glYcAns. tHe recEnt IdentIficatIOn of twO of

facilitates their regener ation, and  on t hesur fa ce o f se veral differen t  typ es of cancers where it  prom ot e s th e ir  grow th andi nv a s ive ne ss . R em a rk ably,  po lySia i s found on  on ly  five protei n sin additio n t o the polysi aly ltrans fe ras e s (po lyS Ts) t hat mo d ify th eir own N -g l ycans. The rec e n tiden tification of two of

facilitates_their regeneration,_and on the surface_of several_different_types of_cancers_where it promotes_their growth and_invasiveness. Remarkably, polySia is_found on only_five_proteins in addition to the polysialyltransferases (polySTs) that modify their own N-glycans. The recent_identification_of two_of