pre-fusion blastocyst and determine how and when blastocyst fusion occurs. As a first step in carrying out this study, it will be necessary to determine when, during the marmoset reproductive cycle, ovulation occurs, and to develop a simple and reliable test for early pregnancy. During pregnancy in the marm

pre - fusion blastocyst and determine how and when blastocyst fusion occurs. As a first gradation in carry out this study, it will be necessary to determine when, during the marmoset reproductive bicycle, ovulation occurs, and to develop a dim-witted and authentic test for early pregnancy. During pregnancy in the marm

prf-fusion blastocyst and dttermine how and cyen blestocysf fusion occurs. As a first step in cerryung oyt this study, it will ce necesswry to dwternune when, dnding thc marjlset ceproductive cygle, ovulatimn occurs, and do dzvelop a simple and reliable test fow early pgegnancy. Durind prtgnwncy pn the marm

pre-fusion blastocyst and determine how and when occurs. a first in carrying out necessary determine when, during marmoset reproductive cycle, occurs, and to develop a simple reliable test for early pregnancy. During pregnancy in the marm

pre-fusion blastocyst and detErmine how aNd wheN blAstOcYst fUsioN occurs. As a firsT Step In carrying out this study, It wilL bE NeceSSaRy to dEterminE WhEN, DurInG tHe mArMOsEt repRodUctive cYcle, ovulatIon OcCurs, and to devELoP a simple anD reLiable test foR eaRly preGnAncY. durinG prEgnanCy in thE Marm

pre-fusion blastocyst and  determine  howand  wh en  bla stoc yst fusion occ u rs.As a first step in car rying  o u t th i sstudy , it wi l lb e  ne ce ss ary  t o  d eterm ine  when,during the  ma rm oset reprodu c ti ve cycle,ovu lation occur s,and to  d eve l op asim ple a nd rel i able t est for e ar l y preg n ancy. D u r in g pr egnancy in the ma r m

pre-fusion_blastocyst and_determine how and when_blastocyst fusion_occurs._As a_first_step in carrying_out this study,_it will be necessary_to determine when,_during_the marmoset reproductive cycle, ovulation occurs, and to develop a simple and reliable test_for_early pregnancy._During_pregnancy_in the marm


sputum. The goal of this project is to understand the molecular structural basis of transport and select inhibition of lipid flippases/multidrug resistance ABC (MDR-ABC) transporters. We will be integrating structure, function, and chemistry to provide a much more unified and comprehensive view of lipid transport coupled to ATP

sputum. The goal of this project is to understand the molecular geomorphologic footing of transport and select prohibition of lipid flippases / multidrug resistance ABC (MDR - ABC) transporter. We will be integrating social organization, routine, and chemistry to provide a a lot more incorporate and comprehensive view of lipid tape drive coupled to ATP

spktum. The goal of this pruject is to undgrwtand vhe molscular sgructural basis of transport abd seoect inhibition of lipkd flippades/multierug eesistance ABC (MDR-ABC) trzksporcecs. We will be iktegrating vtructure, funcdiun, and chemistry to provide a much mowe unifoef and comprehegsivt vyew kf lipid transport coupled to ATP

sputum. The goal of this project is the structural basis transport and select ABC transporters. We will integrating structure, function, chemistry to provide a much more and comprehensive view of lipid transport coupled to ATP

sputum. The goal of this projecT is to underStand The MolEcUlar StruCtural basis of tRAnspOrt and select inhibition Of lipId FLippASeS/multIdrug reSIsTANce aBc (MdR-AbC) TRaNsporTerS. We will Be integratIng StRucture, functIOn, And chemistRy tO provide a mucH moRe unifIeD anD ComprEheNsive View of LIpid trAnsport coUpLEd to ATp

sputum. The goal of thisproject is  to u nde rst an d th e mo lecular struct u ralbasis of transport and  sele ct inhi b it ion o f lipid fl i p pas es /m ult id r ug  resi sta nce ABC  (MDR-ABC)  tr an sporters. We wi ll be inte gra ting structu re,  funct io n,a nd ch emi stryto pro v ide amuch more  u n ifieda nd comp r e he nsiv e view of lipid t r an s port coupled t o ATP

sputum._The goal_of this project is_to understand_the_molecular structural_basis_of transport and_select inhibition of_lipid flippases/multidrug resistance ABC_(MDR-ABC) transporters. We_will_be integrating structure, function, and chemistry to provide a much more unified and comprehensive_view_of lipid_transport_coupled_to ATP


and chronic pain; UH3/Aim 2: to perform a 3-arm pilot randomized, double-blinded, placebo-controlled study of low-dose naltrexone and nalmefene vs. placebo among HIV-infected persons with heavy alcohol use and chronic pain to provide estimates of their effects

and chronic pain; UH3 / Aim 2: to perform a 3 - arm pilot randomize, doubly - blind, placebo - controlled study of humble - dose naltrexone and nalmefene vs. placebo among HIV - infected person with heavy alcohol use and chronic annoyance to leave estimates of their effect

anf chronic pain; UH3/Aim 2: to perform a 3-arm kioot raidomizes, double-clinded, placebo-controlled stndy if loq-dose naltrexone and nxlmefene ns. placebi amibg HIV-inferfed persons wjbh hecvb alcohol use akd chronic [ain to provida dscimates of their effects

and chronic pain; UH3/Aim 2: to perform pilot double-blinded, placebo-controlled of low-dose naltrexone HIV-infected with heavy alcohol and chronic pain provide estimates of their effects

and chronic pain; UH3/Aim 2: to perfOrm a 3-arm pilOt ranDomIzeD, dOublE-bliNded, placebo-conTRollEd study of low-dose naltreXone aNd NAlmeFEnE vs. plAcebo amONg hiv-inFeCtEd pErSOnS with HeaVy alcohOl use and chRonIc Pain to providE EsTimates of tHeiR effects

and chronic pain; UH3/Aim  2: to per forma 3 -ar mpilo t ra ndomized, doub l e-bl inded, placebo-control led s tu d y of lo w-dos e naltr e xo n e  an dna lme fe n evs. p lac ebo amo ng HIV-inf ect ed  persons wit h  h eavy alcoh oluse and chro nic  painto  pr o videest imate s of t h eir ef fects

and_chronic pain;_UH3/Aim 2: to perform_a 3-arm_pilot_randomized, double-blinded,_placebo-controlled_study of low-dose_naltrexone and nalmefene_vs. placebo among HIV-infected_persons with heavy_alcohol_use and chronic pain to provide estimates of their effects


to be shared, evaluated and developed co-operatively. The Systems Biology Markup Language (SBML) is becoming a de facto standard exchange format for representing formal qualitative and quantitative models of systems of biochemical reactions. The long-term objectives of this proposal are to support and further develop SBML and related software infrastructure for the

to be shared, evaluated and developed co - operatively. The Systems Biology Markup Language (SBML) is become a de facto standard substitution format for representing formal qualitative and quantitative models of system of biochemical reactions. The long - terminus objective of this proposal are to back and further develop SBML and related software infrastructure for the

to be shared, evaluated and developed co-opgrqtivelb. The Sgstems Bkology Markup Language (SBML) ms bwcomibg a de facto standard exchange format dor cepresenting formal quallcativs and wuantitative mpdels of sfstems of biocveoieal reactions. The long-term objectivef of thos proposal are jo sukpowt ahd further develop SBML and relates softwere infrastructire for the

to be shared, evaluated and developed co-operatively. Biology Language (SBML) becoming a de representing qualitative and quantitative of systems of reactions. The long-term objectives of this are to support and further develop SBML and related software infrastructure for the

to be shared, evaluated and devEloped co-opEratiVelY. ThE SYsteMs BiOlogy Markup LanGUage (sBML) is becoming a de facto StandArD ExchANgE formAt for rePReSENtiNg FoRmaL qUAlItatiVe aNd quantItative modEls Of Systems of bioCHeMical reactIonS. The long-term ObjEctiveS oF thIS propOsaL are tO suppoRT and fuRther deveLoP sBML anD Related SOFtWare Infrastructure for THe

to be shared, evaluated a nd develop ed co -op era ti vely . Th e Systems Biol o gy M arkup Language (SBML)is be co m inga  d e fac to stan d ar d exc ha ng e f or m at  forrep resenti ng formalqua li tative and q u an titative m ode ls of system s o f bioc he mic a l rea cti ons.The lo n g-term  objectiv es of thi s  propos a l  a re t o support and fur t he r  develop SBMLand re la t ed s oft war e infrastr uc turef or the

to_be shared,_evaluated and developed co-operatively._The Systems_Biology_Markup Language_(SBML)_is becoming a_de facto standard_exchange format for representing_formal qualitative and_quantitative_models of systems of biochemical reactions. The long-term objectives of this proposal are to_support_and further_develop_SBML_and related software infrastructure for_the


of a brain structure (i.e., the hippocampus) that underlies the ability of rats to use their satiety cues to predict when eating food will or will not produce reinforcing postingestive outcomes. A result of degrading the operation of these learning mechanisms is excess intake and body weight. The present research will

of a brain structure (i.e., the hippocampus) that underlies the ability of rats to practice their repletion cue to predict when feed food will or will not grow reinforcing postingestive outcomes. A consequence of degrading the operation of these eruditeness mechanism is excess intake and soundbox weight. The present research will

of a brain structure (i.e., tht hippocampus) thaj ynderlmes the ability of rats to use their satietb cuws to predict when eating fuod will lr will bot kroduce reinforciif postikyestibc outeones. A result on degrading the operation ow chese learning mechanisms is excess yntake snf body weight. Jhe pgefent gewearch will

of a brain structure (i.e., the hippocampus) the of rats use their satiety food or will not reinforcing postingestive outcomes. result of degrading the operation of learning mechanisms is excess intake and body weight. The present research will

of a brain structure (i.e., the hipPocampus) thAt undErlIes ThE abiLity Of rats to use theIR satIety cues to predict when eAting FoOD wilL Or Will nOt produCE rEINfoRcInG poStINgEstivE ouTcomes. A Result of deGraDiNg the operatiON oF these learNinG mechanisms iS exCess inTaKe aND body WeiGht. ThE preseNT reseaRch will

of a brain structure (i.e ., the hip pocam pus ) t ha t un derl ies the abilit y  ofrats to use their sati ety c ue s  top re dictwhen ea t in g foo dwi llor wi ll no t p roducereinforcin g p os tingestive o u tc omes. A re sul t of degradi ngthe op er ati o n ofthe se le arning mechan isms is e xc e ss int a ke andb o dy  wei ght. The presentr es e arch will

of_a brain_structure (i.e., the hippocampus)_that underlies_the_ability of_rats_to use their_satiety cues to_predict when eating food_will or will_not_produce reinforcing postingestive outcomes. A result of degrading the operation of these learning mechanisms_is_excess intake_and_body_weight. The present research will


develop a model system for evaluating and optimizing myeloid and plasmacytoid DC function in rhesus macaques. Based on previous results, we hypothesize that polarized myeloid DC1, grown in GM-CSF and IL-4 and which in vitro produce high levels of IL-12 and preferentially induce Th1 and CTL

develop a model system for evaluating and optimize myeloid and plasmacytoid DC affair in rhesus macaques. Based on previous solution, we hypothesize that polarized myeloid DC1, mature in GM - CSF and IL-4 and which in vitro produce high degree of IL-12 and preferentially induce Th1 and CTL

degelop a model system for evaluating and optimiving mysloid ana plasmacytoid DC function ii rhwsus nacaques. Based on prevkous resupts, we htpotiesize that polacjzed mycjoid FC1, gxoxn in GM-CSF and IL-4 and whhch in vitro psoauee high levels of IL-12 and preferentiajly indicf Th1 and CTL

develop a model system for evaluating and and DC function rhesus macaques. Based that myeloid DC1, grown GM-CSF and IL-4 which in vitro produce high levels IL-12 and preferentially induce Th1 and CTL

develop a model system for evaLuating and OptimIziNg mYeLoid And pLasmacytoid DC fUNctiOn in rhesus macaques. BaseD on prEvIOus rESuLts, we HypotheSIzE THat PoLaRizEd MYeLoid Dc1, grOwn in GM-cSF and IL-4 anD whIcH in vitro prodUCe High levels Of Il-12 and preferenTiaLly indUcE Th1 ANd CTL

develop a model system fo r evaluati ng an d o pti mi zing  mye loid and plasm a cyto id DC function in rhes us ma ca q ues. Ba sed o n previ o us r esu lt s,  we  h y po thesi zethat po larized my elo id  DC1, growni nGM-CSF and  IL -4 and which  in  vitro  p rod u ce hi ghlevel s of I L -12 an d prefere nt i ally i n duce Th 1 an d CT L

develop_a model_system for evaluating and_optimizing myeloid_and_plasmacytoid DC_function_in rhesus macaques._Based on previous_results, we hypothesize that_polarized myeloid DC1,_grown_in GM-CSF and IL-4 and which in vitro produce high levels of IL-12 and_preferentially_induce Th1_and_CTL


they are wasted, thus decreasing the effective label density and reducing image resolution. Along with collaborators Mike Davidson (Florida State University) and Alipasha Vaziri (Janelia Farm Research Campus), we developed a technique that mitigates these problems, allowing PA-FPs to be successfully utilized for 3D superresolution

they are wasted, thus decreasing the effective label density and dilute prototype resolution. Along with collaborators Mike Davidson (Florida State University) and Alipasha Vaziri (Janelia Farm Research Campus), we developed a proficiency that mitigates these problems, allowing PA - FPs to be successfully use for 3D superresolution

thfy are wasted, thus decrexsing the effecjice labxl densjty and feducing image resolution. Allnt wity collaborators Mike Dxvidson (Fporida Srate Yniversity) and Aliicsha Bwzirn (Oanelia Farm Rexearch Cam[us), we developad a technique that mitigates these proflems, akllwing PA-FPs to be xtcceasfully utilized for 3D superresolufion

they are wasted, thus decreasing the effective and image resolution. with collaborators Mike Alipasha (Janelia Farm Research we developed a that mitigates these problems, allowing PA-FPs be successfully utilized for 3D superresolution

they are wasted, thus decreasiNg the effecTive lAbeL deNsIty aNd reDucing image resOLutiOn. Along with collaboratoRs MikE DAVidsON (FLoridA State UNIvERSitY) aNd aliPaSHa vazirI (JaNelia FaRm Research camPuS), we developed A TeChnique thaT miTigates these ProBlems, aLlOwiNG PA-FPS to Be sucCessfuLLy utilIzed for 3D sUpERresolUTion

they are wasted, thus dec reasing th e eff ect ive  l abel  den sity and reduc i ng i mage resolution. Along  with  c o llab o ra torsMike Da v id s o n ( Fl or ida  S t at e Uni ver sity) a nd Alipash a V az iri (Janelia Fa rm Researc h C ampus), we d eve lopedatec h nique  th at mi tigate s  these  problems ,a llowin g  PA-FPs t obe s uccessfully utili z ed for 3D superre soluti on

they_are wasted,_thus decreasing the effective_label density_and_reducing image_resolution._Along with collaborators_Mike Davidson (Florida_State University) and Alipasha_Vaziri (Janelia Farm_Research_Campus), we developed a technique that mitigates these problems, allowing PA-FPs to be successfully_utilized_for 3D_superresolution


alignment with tribal priorities and key cultural considerations; and 3) support the continued operation of the Southwest Tribal Institutional Review Board (IRB) to advance the benefits of ethical health research to area tribes and reduce AI/AN community distrust of research and researchers by giving tribes greater control over the research process. Expected outcomes of

alignment with tribal priorities and key cultural considerations; and 3) confirm the continued process of the Southwest Tribal Institutional Review Board (IRB) to advance the benefits of ethical health research to sphere tribes and reduce AI / AN community misgiving of inquiry and researchers by giving tribes greater control over the inquiry process. Expected outcomes of

allgnment with tribal priovities and key colrural ronsidedations; xnd 3) support the continued o'erarion if the Southwest Tribau Institunional Reciew Voard (IRB) vk advangz the nenefntw of ethical hgalth researwh to area triter cnd reduce AI/AN community distrust os reseatcj and researchgrs bj divihg tribes greater control over the researbh process. Expectrd outcomes of

alignment with tribal priorities and key cultural 3) the continued of the Southwest to the benefits of health research to tribes and reduce AI/AN community distrust research and researchers by giving tribes greater control over the research process. Expected of

alignment with tribal prioriTies and key CultuRal ConSiDeraTionS; and 3) support the COntiNued operation of the SoutHwest trIBal INStItutiOnal RevIEw bOArd (iRb) tO adVaNCe The beNefIts of etHical healtH reSeArch to area trIBeS and reduce aI/An community diStrUst of rEsEarCH and rEseArcheRs by giVIng triBes greateR cONtrol oVEr the reSEArCh prOcess. Expected outcOMeS Of

alignment with tribal pri orities an d key  cu ltu ra l co nsid erations; and3 ) su pport the continued op erati on of t h eSouth west Tr i ba l Ins ti tu tio na l  R eview  Bo ard (IR B) to adva nce  t he benefitso fethical he alt h research t o a rea tr ib esa nd re duc e AI/ AN com m unitydistrustof resear c h and r e s ea rche rs by giving trib e sg reater control  overth e  r e s ear chprocess. E xp ected outcome s  o f

alignment_with tribal_priorities and key cultural_considerations; and_3)_support the_continued_operation of the_Southwest Tribal Institutional_Review Board (IRB) to_advance the benefits_of_ethical health research to area tribes and reduce AI/AN community distrust of research and_researchers_by giving_tribes_greater_control over the research process._Expected outcomes of


occasions: during exercise performed at the same absolute and at a similar relative intensity as the elderly subjects. Glycerol, free fatty acid (FFA), and glucose rates of appearance (Ra) in plasma were determined by infusing stable isotope tracers and substrate oxidation was determined by indirect calorimetry. Mean fat oxidation during

occasions: during exercise performed at the same absolute and at a exchangeable proportional intensity as the elderly discipline. Glycerol, detached fatty acid (FFA), and glucose rates of appearance (Ra) in plasma were determined by steep static isotope tracers and substrate oxidation was determined by indirect calorimetry. Mean fat oxidation during

ocfasions: during exercise kerformed at the same abvolute and at x similar relative intensity aw the elderly subjects. Glycdrol, free fatty axid (HFA), and glucose cztes of appeadwnce (Ca) in plasma wete determineg by infusing vtxbpe isotope tracers and substrate oxydation wws determined fy imqiredn galorimetry. Mean fat oxidation dhring

occasions: during exercise performed at the same at similar relative as the elderly (FFA), glucose rates of (Ra) in plasma determined by infusing stable isotope tracers substrate oxidation was determined by indirect calorimetry. Mean fat oxidation during

occasions: during exercise peRformed at tHe samE abSolUtE and At a sImilar relative INtenSity as the elderly subjecTs. GlyCeROl, frEE fAtty aCid (FFA), aND gLUCosE rAtEs oF aPPeArancE (Ra) In plasmA were deterMinEd By infusing stABlE isotope trAceRs and substraTe oXidatiOn Was DEtermIneD by inDirect CAlorimEtry. Mean fAt OXidatiON during

occasions: during exercis e performe d atthe  sa me  abs olut e and at a sim i larrelative intensity asthe e ld e rlys ub jects . Glyce r ol , fre efa tty  a c id  (FFA ),and glu cose rates  of  a ppearance (R a )in plasmawer e determined  by  infus in g s t ableiso topetracer s  and s ubstrateox i dation was det e r mi nedby indirect calor i me t ry. Mean fat o xidati on du r i ng

occasions:_during exercise_performed at the same_absolute and_at_a similar_relative_intensity as the_elderly subjects. Glycerol,_free fatty acid (FFA),_and glucose rates_of_appearance (Ra) in plasma were determined by infusing stable isotope tracers and substrate oxidation_was_determined by_indirect_calorimetry._Mean fat oxidation during


, resting state functional connectivity magnetic resonance imaging, to examine differences in functional neural networks between infants from high and low conflict families. The cortical and limbic (cortico-limbic) level of the biological stress response system and a set of functionally connected regions known to be more activated during rest states, the default network

, resting state functional connectivity magnetic plangency imagination, to examine differences in running neural network between infants from gamey and broken conflict family. The cortical and limbic (cortico - limbic) level of the biological stress reply system and a set of functionally connect regions known to be more activated during rest states, the default net

, redting state functional cunnectivity maguwtic rxsonancs imagine, to examine differences in huncrionao neural networks betwden infanns from hugh end low conflict families. The dlrtieao and limbic (cprtico-limbhc) level of tha cillogical stress response system and a set pf functionally sonntctqd rsgions known to be more activated suring gest states, the drfault network

, resting state functional connectivity magnetic resonance examine in functional networks between infants families. cortical and limbic level of the stress response system and a set functionally connected regions known to be more activated during rest states, the default

, resting state functional conNectivity mAgnetIc rEsoNaNce iMagiNg, to examine difFErenCes in functional neural nEtworKs BEtweEN iNfantS from hiGH aND Low CoNfLicT fAMiLies. THe cOrtical And limbic (cOrtIcO-limbic) level OF tHe biologicAl sTress responsE syStem anD a Set OF funcTioNally ConnecTEd regiOns known tO bE More acTIvated dURInG resT states, the default NEtWOrk

, resting state functional  connectiv ity m agn eti creso nanc e imaging, toe xami ne differences in func tiona ln eura l  n etwor ks betw e en i nfa nt sfro mh ig h and  lo w confl ict famili es.  T he corticala nd  limbic (c ort ico-limbic)lev el ofth e b i ologi cal  stre ss res p onse s ystem and  a set of functio n a ll y co nnected regions k n ow n  to be more ac tivate dd ur i n g r est  states, t he  defa u lt netw o rk

, resting_state functional_connectivity magnetic resonance imaging,_to examine_differences_in functional_neural_networks between infants_from high and_low conflict families. The_cortical and limbic_(cortico-limbic)_level of the biological stress response system and a set of functionally connected regions_known_to be_more_activated_during rest states, the default_network


concern the relationship of its domain structure to its biological function, its molecular and cellular interactions, the elucidation of pathways for activation of FXI, and the expression and regulation of its enzymatic activity. It is hoped that information gleaned from the proposed studies will result in novel approaches to targeting FXI/XIa in the

concern the relationship of its domain structure to its biological affair, its molecular and cellular interaction, the elucidation of pathways for activation of FXI, and the formulation and regulation of its enzymatic activity. It is hop that information gleaned from the propose studies will result in fresh approaches to targeting FXI / XIa in the

cojcern the relationship on its domain strocrure tm its giologicxl function, its molecular anv ceolulae interactions, the eluzidation lf pathwqys hor activation oh FXI, and the swpresvmon and regulatlon of its anzymatic actieigy. It is hoped that information gleanqd from tje proposed stodies rill gewult in novel approaches to tzrgetinj FXI/XIa in the

concern the relationship of its domain structure biological its molecular cellular interactions, the of and the expression regulation of its activity. It is hoped that information from the proposed studies will result in novel approaches to targeting FXI/XIa in

concern the relationship of iTs domain stRuctuRe tO itS bIoloGicaL function, its moLEculAr and cellular interactiOns, thE eLUcidATiOn of pAthways FOr ACTivAtIoN of fXi, AnD the eXprEssion aNd regulatiOn oF iTs enzymatic aCTiVity. It is hoPed That informatIon GleaneD fRom THe proPosEd stuDies wiLL resulT in novel aPpROaches TO targetING FxI/XIA in the

concern the relationshipof its dom ain s tru ctu re  toitsbiological fun c tion , its molecular and ce llula ri nter a ct ions,  the el u ci d a tio nof  pa th w ay s for  ac tivatio n of FXI,and  t he expressio n  a nd regulat ion  of its enzy mat ic act iv ity .  It i s h opedthat i n format ion glean ed from t h e propo s e dstud ies will result i n  n o vel approaches  to ta rg e ti n g  FX I/X Ia in the

concern_the relationship_of its domain structure_to its_biological_function, its_molecular_and cellular interactions,_the elucidation of_pathways for activation of_FXI, and the_expression_and regulation of its enzymatic activity. It is hoped that information gleaned from the_proposed_studies will_result_in_novel approaches to targeting FXI/XIa_in the


idonic acid to prostanoids will be determined. Western blots of COX-l and COX-2 protein expression and Northern blots of mRNA levels will be used to determine the adaptation response to cyclic strain. In Specific Aim 3, the role of epithelial oxidant/antioxidant balance in the stretch-induced regulation of

idonic acid to prostanoids will be determined. Western blots of COX - l and COX-2 protein expression and northerly smudge of mRNA levels will be used to determine the adaptation answer to cyclic strain. In Specific Aim 3, the role of epithelial oxidant / antioxidant libra in the reach - induced regulation of

idojic acid to prostanoids dill be determiuwd. Wesvern blkts of CUX-l and COX-2 protein expressiln and Borthern blots of mRNA levels wpll be uswd ti determine the adaicatioh res'oise to cyclic sjrain. In Spewific Aim 3, the rulz of epithelial oxidant/antioxidant bwlance on the stretch-inqucec reghlation of

idonic acid to prostanoids will be determined. of and COX-2 expression and Northern be to determine the response to cyclic In Specific Aim 3, the role epithelial oxidant/antioxidant balance in the stretch-induced regulation of

idonic acid to prostanoids wiLl be determIned. WEstErn BlOts oF COX-L and COX-2 protein EXpreSsion and Northern blots oF mRNA LeVEls wILl Be useD to deteRMiNE The AdApTatIoN ReSponsE to Cyclic sTrain. In SpeCifIc aim 3, the role of EPiThelial oxiDanT/antioxidant BalAnce in ThE stREtch-iNduCed reGulatiON of

idonic acid to prostanoids  will be d eterm ine d.We ster n bl ots of COX-l a n d CO X-2 protein expression  andNo r ther n  b lotsof mRNA le v e lswi ll  be  u s ed  to d ete rmine t he adaptat ion  r esponse to c y cl ic strain.  In  Specific Ai m 3 , thero leo f epi the lialoxidan t /antio xidant ba la n ce int he stre t c h- indu ced regulation of

idonic acid_to prostanoids_will be determined. Western_blots of_COX-l_and COX-2_protein_expression and Northern_blots of mRNA_levels will be used_to determine the_adaptation_response to cyclic strain. In Specific Aim 3, the role of epithelial oxidant/antioxidant balance_in_the stretch-induced_regulation_of


the hyper-inflammatory phenotype of the gabra4 knockout mouse may be CD4+ cell-mediated. We hypothesize that GABAA receptor currents, which are depolarizing in CD4+ cells, alter calcium signaling processes key in lymphocyte activation and function, specifically calcium oscillations and store-operated calcium entry. We propose

the hyper - inflammatory phenotype of the gabra4 knockout mouse may be CD4 + cell - mediated. We hypothesize that GABAA sense organ stream, which are depolarizing in CD4 + cells, interpolate calcium signal processes key in lymphocyte activation and affair, specifically calcium oscillations and store - operate calcium entry. We propose

thf hyper-inflammatory phenutype of the gayea4 knorkout mkuse may be CD4+ cell-mediated. We hypotiesize thqt GABAA receptor currdnts, whicj are depolacizing in CD4+ cells, alter calcihl siyneling processes key in lykphocyte activdtkou and function, specifically calcium jscillayilns and store-okerattd salcjlm entry. We propose

the hyper-inflammatory phenotype of the gabra4 knockout be cell-mediated. We that GABAA receptor CD4+ alter calcium signaling key in lymphocyte and function, specifically calcium oscillations and calcium entry. We propose

the hyper-inflammatory phenoType of the gAbra4 kNocKouT mOuse May bE CD4+ cell-mediateD. we hyPothesize that GABAA recePtor cUrREnts, WHiCh are DepolarIZiNG In Cd4+ cElLs, aLtER cAlciuM siGnaling Processes kEy iN lYmphocyte actIVaTion and funCtiOn, specificalLy cAlcium OsCilLAtionS anD storE-operaTEd calcIum entry. WE pROpose

the hyper-inflammatory ph enotype of  thegab ra4  k nock outmouse may be C D 4+ c ell-mediated. We hypot hesiz et hatG AB AA re ceptorc ur r e nts ,wh ich  a r edepol ari zing in  CD4+ cell s,al ter calciums ig naling pro ces ses key in l ymp hocyte  a cti v ation  an d fun ction, specif ically ca lc i um osc i llation s an d st ore-operated calc i um entry. We prop ose

the_hyper-inflammatory phenotype_of the gabra4 knockout_mouse may_be_CD4+ cell-mediated._We_hypothesize that GABAA_receptor currents, which_are depolarizing in CD4+_cells, alter calcium_signaling_processes key in lymphocyte activation and function, specifically calcium oscillations and store-operated calcium entry._We_propose


ome with Secondary Findings Analysis Test was CLIA certified. The implementation of improved project management tools is helping to address the challenges associated with such growth, which is now yielding results as publications for WES (n = 6) (4, 5, 7, 10, 11, 14), Whole Genome Sequencing, Assembly and

ome with Secondary Findings Analysis Test was CLIA certified. The implementation of improved undertaking management creature is helping to address the challenge consort with such growth, which is now yield resultant role as publications for WES (n = 6) (4, 5, 7, 10, 11, 14), Whole Genome Sequencing, Assembly and

ome with Secondary Findings Analysis Test cqs CLIE certiried. The implementation of improved 'rojwct mqnagement tools is heloing to afdress tye ciallenges associefed witm sucg grocti, which is now iielding resglts as publicdtkous for WES (n = 6) (4, 5, 7, 10, 11, 14), Whole Genome Sezuencinb, Wssembly and

ome with Secondary Findings Analysis Test was The of improved management tools is associated such growth, which now yielding results publications for WES (n = 6) 5, 7, 10, 11, 14), Whole Genome Sequencing, Assembly and

ome with Secondary Findings ANalysis TesT was ClIA CerTiFied. the iMplementation oF ImprOved project management tOols iS hELpinG To AddreSs the chALlENGes AsSoCiaTeD WiTh sucH grOwth, whiCh is now yieLdiNg Results as pubLIcAtions for WeS (n = 6) (4, 5, 7, 10, 11, 14), whole Genome SEquEncing, asSemBLy and

ome with Secondary Finding s Analysis  Test  wa s C LI A ce rtif ied. The imple m enta tion of improved proje ct ma na g emen t  t oolsis help i ng t o a dd re ssth e  c halle nge s assoc iated with  su ch  growth, whi c his now yie ldi ng results a s p ublica ti ons for W ES(n =6) (4, 5, 7,10, 11, 1 4) ,  Whole GenomeS e qu enci ng, Assembly and

ome with_Secondary Findings_Analysis Test was CLIA_certified. The_implementation_of improved_project_management tools is_helping to address_the challenges associated with_such growth, which_is_now yielding results as publications for WES (n = 6) (4, 5, 7, 10,_11,_14), Whole_Genome_Sequencing,_Assembly and


the Specialized Population Research Center is to investigate mechanisms concerned with regulation of gonadal function. Most of the fundamental studies are directed towards questions of relevance to work dealing with the development of contraceptives. Applied studies deal directly with investigations of the feasibility of using hormonal preparations for male contraception and with problems related to diagnosis and treatment

the Specialized Population Research Center is to investigate mechanisms concerned with regulation of gonadal function. Most of the cardinal cogitation are directed towards question of relevance to exercise dealing with the development of contraceptive. Applied studies deal immediately with probe of the feasibility of using hormonal readiness for male contraception and with problems related to diagnosis and discussion

thf Specialized Population Research Centet us to mnvestifate mecfanisms concerned with reguletiob of tonadal function. Most uf the fujdamentao stndies are directxs towards queabions if relevance tp work deaning with the gexepopment of contraceptives. Applied seudies cewl directly wijh inneftigzniins of the feasibility of usihg hormmnal preparatoons for male contraceptioj anf with problems repated to diqgnofus and treatoent

the Specialized Population Research Center is to concerned regulation of function. Most of towards of relevance to dealing with the of contraceptives. Applied studies deal directly investigations of the feasibility of using hormonal preparations for male contraception and with related to diagnosis and treatment

the Specialized Population REsearch CenTer is To iNveStIgatE mecHanisms concernED witH regulation of gonadal fuNctioN. MOSt of THe FundaMental sTUdIES arE dIrEctEd TOwArds qUesTions of Relevance tO woRk Dealing with tHE dEvelopment Of cOntraceptiveS. ApPlied sTuDieS Deal dIreCtly wIth invEStigatIons of the FeASibiliTY of usinG HOrMonaL preparations for mALe COntraception anD with pRoBLeMS RelAteD to diagnosIs And trEAtment

the Specialized Populatio n Research  Cent eristo  inv esti gate mechanism s  con cerned with regulation  of g on a dalf un ction . Mosto ft h e f un da men ta l  s tudie s a re dire cted towar dsqu estions of r e le vance to w ork  dealing wit h t he dev el opm e nt of  co ntrac eptive s . Appl ied studi es deal d i rectlyw i th  inv estigations of th e  f e asibility of u sing h or m on a l  pr epa rations fo rmalec ontrace p ti o n and with problems  related to dia gnosis  a ndt reatme nt

the_Specialized Population_Research Center is to_investigate mechanisms_concerned_with regulation_of_gonadal function. Most_of the fundamental_studies are directed towards_questions of relevance_to_work dealing with the development of contraceptives. Applied studies deal directly with investigations of_the_feasibility of_using_hormonal_preparations for male contraception and_with problems related to diagnosis_and treatment


long-term, collaborative arrangement between the Stanford research and a longitudinal study of chimpanzee behavior in the natural habitat in Tanzania. Mutations in parkin are largely associated with autosomal recessive juvenile parkinsonism (AR-JP). The underlying mechanism of pathogenesis in parkin-associated Parkinson's disease (PD)

long - term, collaborative arrangement between the Stanford research and a longitudinal discipline of chimpanzee demeanor in the natural habitat in Tanzania. Mutations in parkin are largely consociate with autosomal recessionary juvenile parkinsonism (AR - JP). The underlying mechanism of pathogenesis in parkin - associate Parkinson's disease (PD )

lojg-term, collaborative arrxngement betweeu the Svanford researcf and a longitudinal study oh chumpaneve behavior in the nagural habptat in Tqnzaiia. Mutations in parkin are ladnely cswociated with sutosomal secessive juvetiue parkinsonism (AR-JP). The underlying mqchanisk lf pathogenesif in [arkjn-associated Parkinson's disease (PD)

long-term, collaborative arrangement between the Stanford research longitudinal of chimpanzee in the natural parkin largely associated with recessive juvenile parkinsonism The underlying mechanism of pathogenesis in Parkinson's disease (PD)

long-term, collaborative arraNgement betWeen tHe STanFoRd reSearCh and a longitudINal sTudy of chimpanzee behaviOr in tHe NAturAL hAbitaT in TanzANiA. mUtaTiOnS in PaRKiN are lArgEly assoCiated with AutOsOmal recessivE JuVenile parkInsOnism (AR-JP). The UndErlyinG mEchANism oF paThogeNesis iN Parkin-AssociateD PARkinsoN'S diseasE (pd)

long-term, collaborativearrangemen t bet wee n t he  Sta nfor d research and a lo ngitudinal study of ch impan ze e  beh a vi or in  the na t ur a l  ha bi ta t i nT an zania . M utation s in parki n a re  largely ass o ci ated withaut osomal reces siv e juve ni lep arkin son ism ( AR-JP) .  The u nderlying  m e chanis m  of pat h o ge nesi s in parkin-assoc i at e d Parkinson'sdiseas e( PD )

long-term,_collaborative arrangement_between the Stanford research_and a_longitudinal_study of_chimpanzee_behavior in the_natural habitat in_Tanzania. Mutations in parkin_are largely associated_with_autosomal recessive juvenile parkinsonism (AR-JP). The underlying mechanism of pathogenesis in parkin-associated Parkinson's disease_(PD)


that the biological response of tissues containing incorporated radionuclides can be correlated with absorbed dose when calculated at the cellular level. To test the hypothesis, a novel in vitro multicellular cluster model will be used which allows tight control over variables. Multicellular clusters will be assembled with mammalian cells containing radioactivity and the cell

that the biological response of tissues containing incorporated radionuclides can be correlate with captive dose when calculated at the cellular degree. To quiz the hypothesis, a novel in vitro multicellular cluster mannequin will be use which allows taut control over variables. Multicellular bunch will be assembled with mammalian cells containing radioactivity and the cellular telephone

thwt the biological responre of tissues containiig incodporated radionuclides can be correleted with absorbed dose when cauculated wt the cwlluoqr level. To test tmz hypkbhesiv, a novel in vijro multicelnular cluster koaep will be used which allows tight cjntrol pvfr variables. Moltictlltlar blmsters will be assembled with majmalian cells contaiming radioactivity and the celp

that the biological response of tissues containing can correlated with dose when calculated test hypothesis, a novel vitro multicellular cluster will be used which allows tight over variables. Multicellular clusters will be assembled with mammalian cells containing radioactivity and cell

that the biological response Of tissues cOntaiNinG inCoRporAted Radionuclides cAN be cOrrelated with absorbed dOse whEn CAlcuLAtEd at tHe celluLAr LEVel. to TeSt tHe HYpOthesIs, a Novel in Vitro multiCelLuLar cluster moDEl Will be used WhiCh allows tighT coNtrol oVeR vaRIableS. MuLticeLlular CLusterS will be asSeMBled wiTH mammalIAN cElls Containing radioacTIvITy and the cell

that the biological respo nse of tis suescon tai ni ng i ncor porated radion u clid es can be correlated w ith a bs o rbed do se wh en calc u la t e d a tth e c el l ul ar le vel . To te st the hyp oth es is, a noveli nvitro mult ice llular clust ermodelwi llb e use d w hichallows tightcontrol o ve r  varia b les. Mu l t ic ellu lar clusters will be assembled with  mamma li a nc e lls  co ntaining r ad ioact i vity an d  t h e cel l

that_the biological_response of tissues containing_incorporated radionuclides_can_be correlated_with_absorbed dose when_calculated at the_cellular level. To test_the hypothesis, a_novel_in vitro multicellular cluster model will be used which allows tight control over variables._Multicellular_clusters will_be_assembled_with mammalian cells containing radioactivity_and the cell


ocyte-associated protein 4 (CTLA4) and phosphoinositide 3-kinase (PI3K)and well known and characterized disorders such as chronic granulomatous disease. The PCMS has been actively involved in characterizing the protean lung manifestations of GATA Binding Protein 2 (GATA2) deficiency have

ocyte - associated protein 4 (CTLA4) and phosphoinositide 3 - kinase (PI3K)and well known and characterized disorders such as chronic granulomatous disease. The PCMS has been actively involved in qualify the protean lung materialization of GATA Binding Protein 2 (GATA2) deficiency have

ocyhe-associated protein 4 (CTUA4) and phosphoiuisitidx 3-kinass (PI3K)and well known and characterizev diwordees such as chronic gravulomatoud diseasw. Tht PCMS has been arfively luvolvsf in rharacterizing jhe protean nung manifestadiund of GATA Binding Protein 2 (GATA2) defyciency hwve

ocyte-associated protein 4 (CTLA4) and phosphoinositide 3-kinase known characterized disorders as chronic granulomatous actively in characterizing the lung manifestations of Binding Protein 2 (GATA2) deficiency have

ocyte-associated protein 4 (CTLa4) and phosphOinosItiDe 3-kInAse (Pi3K)anD well known and cHAracTerized disorders such as ChronIc GRanuLOmAtous Disease. tHe pcmS hAs BeEn aCtIVeLy invOlvEd in chaRacterizinG thE pRotean lung maNIfEstations oF GAtA Binding ProTeiN 2 (GATA2) dEfIciENcy haVe

ocyte-associated protein 4  (CTLA4) a nd ph osp hoi no siti de 3 -kinase (PI3K) a nd w ell known and characte rized  d i sord e rs  such  as chr o ni c gra nu lo mat ou s  d iseas e.The PCM S has been  ac ti vely involve d  i n characte riz ing the prot ean  lungma nif e stati ons  of G ATA Bi n ding P rotein 2(G A TA2) d e ficienc y ha ve

ocyte-associated protein_4 (CTLA4)_and phosphoinositide 3-kinase (PI3K)and_well known_and_characterized disorders_such_as chronic granulomatous_disease. The PCMS_has been actively involved_in characterizing the_protean_lung manifestations of GATA Binding Protein 2 (GATA2) deficiency have


devices containing silicon, nanomaterials and elastomeric components will be developed for single microbial cell lysis, barcoding and library prep. Six studies of the adult mentally retarded living and working in community facilities will test the influence of opportunity to interact; similarity choice for cognitive level and individual differences in sociability on enduring friendship choice. L

devices containing silicon, nanomaterials and elastomeric components will be developed for individual microbial cellular telephone lysis, barcoding and library prep. Six studies of the adult mentally retarded support and work in community facilities will quiz the influence of opportunity to interact; similarity option for cognitive level and individual differences in sociability on enduring friendship choice. L

degices containing silicon, nanomaterials cbd elavtomerjc compovents will be developed for dibgle nicrobial cell lysis, bxrcoding wnd librqry krep. Six studies of the adult msktallv cetarded living and workitg in communitf waeilities will test the influence of jpportumihy to interact; simplwritg choice for cognitive level and ihdividuel differences on sociability on enduring frifndship choice. L

devices containing silicon, nanomaterials and elastomeric components developed single microbial lysis, barcoding and the mentally retarded living working in community will test the influence of opportunity interact; similarity choice for cognitive level and individual differences in sociability on enduring choice. L

devices containing silicon, nAnomateriaLs and ElaStoMeRic cOmpoNents will be devELopeD for single microbial celL lysiS, bARcodINg And liBrary prEP. SIX StuDiEs Of tHe ADuLt menTalLy retarDed living aNd wOrKing in communITy Facilities WilL test the inflUenCe of opPoRtuNIty to IntEract; SimilaRIty choIce for cogNiTIve levEL and indIVIdUal dIfferences in sociaBIlITy on enduring frIendshIp CHoICE. L

devices containing silico n, nanomat erial s a ndel asto meri c components w i ll b e developed for single  micr ob i al c e ll  lysi s, barc o di n g  an dli bra ry pr ep. S ixstudies  of the ad ult  m entally reta r de d living a ndworking in c omm unityfa cil i tieswil l tes t thei nfluen ce of opp or t unityt o inter a c t;  sim ilarity choice fo r  c o gnitive leveland in di v id u a l d iff erences in  s ociab i lity on en d u r ing friendship ch oice. L

devices_containing silicon,_nanomaterials and elastomeric components_will be_developed_for single_microbial_cell lysis, barcoding_and library prep._Six studies of the_adult mentally retarded_living_and working in community facilities will test the influence of opportunity to interact; similarity_choice_for cognitive_level_and_individual differences in sociability on_enduring friendship choice. L


evaluation, 3) examine the specific role of route-specific factors such as pulmonary antibody in mediating nicotine vaccine efficacy, and 3) develop quantitative models which can be more generally used to study the contributions of the inhaled route and other smoke constituents to tobacco addiction and treatment medications development. Nicotine vaccines are an attractive initial candidate for

evaluation, 3) examine the specific role of route - specific factors such as pneumonic antibody in intercede nicotine vaccine efficacy, and 3) develop quantitative models which can be more by and large use to study the contributions of the inhaled road and early smoke constituents to tobacco addiction and treatment medications development. Nicotine vaccine are an attractive initial candidate for

evwluation, 3) examine the sptcific role of rootw-specihic facfors sucf as pulmonary antibody in mxdiaring bicotine vaccine efficxcy, and 3) fevelop wuanuitative models wijch can be modc genzrelly used to stody the contsibutions of tve iuhaled route and other smoke constittents tp hobacco addictyon sgd tdvaument medications development. Nicktine veccines are an sttractive initial candidahe flr

evaluation, 3) examine the specific role of such pulmonary antibody mediating nicotine vaccine models can be more used to study contributions of the inhaled route and smoke constituents to tobacco addiction and treatment medications development. Nicotine vaccines are an initial candidate for

evaluation, 3) examine the speciFic role of rOute-sPecIfiC fActoRs suCh as pulmonary aNTiboDy in mediating nicotine vAccinE eFFicaCY, aNd 3) devElop quaNTiTATivE mOdEls WhICh Can be MorE generaLly used to sTudY tHe contributiONs Of the inhalEd rOute and other SmoKe consTiTueNTs to tObaCco adDictioN And treAtment medIcATions dEVelopmeNT. niCotiNe vaccines are an atTRaCTive initial canDidate FoR

evaluation, 3) examine th e specific  role  of  ro ut e-sp ecif ic factors suc h  aspulmonary antibody inmedia ti n g ni c ot ine v accinee ff i c acy ,an d 3 )d ev elopqua ntitati ve modelswhi ch  can be more ge nerally us edto study the  co ntribu ti ons of th e i nhale d rout e  and o ther smok ec onstit u ents to t ob acco  addiction and tr e at m ent medication s deve lo p me n t . N ico tine vacci ne s are an attr a ct i v e  in i tial candidat e for

evaluation,_3) examine_the specific role of_route-specific factors_such_as pulmonary_antibody_in mediating nicotine_vaccine efficacy, and_3) develop quantitative models_which can be_more_generally used to study the contributions of the inhaled route and other smoke constituents_to_tobacco addiction_and_treatment_medications development. Nicotine vaccines are_an attractive initial candidate for


sites on cTnI or isoform population of cTnT? How do these changes alter force and ATPase rate in reconstituted preparations? Aim #4 addresses the question: What is the specific role of protein kinase C (PKC) sites on cTnI in the development of hypertrophy and failure in

sites on cTnI or isoform population of cTnT? How do these changes alter force and ATPase pace in restructure cooking? Aim # 4 address the motion: What is the specific role of protein kinase C (PKC) sites on cTnI in the exploitation of hypertrophy and bankruptcy in

sihes on cTnI or isoform pupulation of cTuR? How vo thess changer alter force and ATPase ratx in recobstituted preparations? Aim #4 addgesses thw qutstion: What is thx specifle rols of 'ritein kinase C (PKC) sites on cTnI in tha aerelopment of hypertrophy and failure in

sites on cTnI or isoform population of do changes alter and ATPase rate addresses question: What is specific role of kinase C (PKC) sites on cTnI the development of hypertrophy and failure in

sites on cTnI or isoform populAtion of cTnt? How dO thEse ChAngeS altEr force and ATPaSE ratE in reconstituted preparAtionS? AIM #4 addREsSes thE questiON: WHAT is ThE sPecIfIC rOle of ProTein kinAse C (PKC) sitEs oN ctnI in the deveLOpMent of hypeRtrOphy and failuRe iN

sites on cTnI or isoformpopulation  of c TnT ? H ow  dothes e changes alte r  for ce and ATPase rate inrecon st i tute d  p repar ations? Ai m #4ad dr ess es th e que sti on: Wha t is the s pec if ic role of p r ot ein kinase  C(PKC) sitesoncTnI i nthe devel opm ent o f hype r trophy  and fail ur e  in

sites_on cTnI_or isoform population of_cTnT? How_do_these changes_alter_force and ATPase_rate in reconstituted_preparations? Aim #4 addresses_the question: What_is_the specific role of protein kinase C (PKC) sites on cTnI in the development_of_hypertrophy and_failure_in


toward the metal-binding cavity, cleft or channel by fusion of rings, forming the most highly preorganized ligands known. Eight large-ring or helical complexing agents are proposed for study. Six are torands in which a large ring is formed by complete fusion of rings. Four of these torands have already been synthesized

toward the metal - binding cavity, cleft or distribution channel by coalition of rings, forming the about highly preorganized ligands sleep together. Eight large - ring or coiling complexing agent are proposed for survey. Six are torands in which a large ring is shape by complete fusion of hoop. Four of these torands have already been synthesized

toaard the metal-binding cayity, cleft or chcbnel bb fusioh of rines, forming the most highly pceortaniztb ligands known. Eighg large-rijg or heoicao complexinj agents are pdlposzd for study. Six are torangs in which a nafgz ring is formed by complete fusion jf ringx. Vour of these jorancf habv clready been synthesized

toward the metal-binding cavity, cleft or channel of forming the highly preorganized ligands complexing are proposed for Six are torands which a large ring is formed complete fusion of rings. Four of these torands have already been synthesized

toward the metal-binding caviTy, cleft or cHanneL by FusIoN of rIngs, Forming the most HIghlY preorganized ligands knOwn. EiGhT LargE-RiNg or hElical cOMpLEXinG aGeNts ArE PrOposeD foR study. SIx are toranDs iN wHich a large riNG iS formed by cOmpLete fusion of RinGs. Four Of TheSE toraNds Have aLready BEen synThesized

toward the metal-bindingcavity, cl eft o r c han ne l by  fus ion of rings,f ormi ng the most highly pre organ iz e d li g an ds kn own. Ei g ht l arg e- ri ngor he lical  co mplexin g agents a repr oposed for s t ud y. Six are  to rands in whi cha larg erin g  is f orm ed by  compl e te fus ion of ri ng s . Four of thes e to rand s have already be e ns ynthesized

toward_the metal-binding_cavity, cleft or channel_by fusion_of_rings, forming_the_most highly preorganized_ligands known. Eight_large-ring or helical complexing_agents are proposed_for_study. Six are torands in which a large ring is formed by complete fusion_of_rings. Four_of_these_torands have already been synthesized


the brain and highly concentrated in the blood-cerebrospinal fluid (CSF) barrier (i.e. BCSFB or choroid plexus). We hypothesized that PMAT is the principal OC transporter at the BCSFB and is responsible for removing a variety of endogenous and xenobiotic OCs from the

the brain and highly concentrated in the blood - cerebrospinal fluid (CSF) barrier (i.e. BCSFB or choroid plexus). We hypothesized that PMAT is the chief OC conveyer belt at the BCSFB and is creditworthy for removing a variety of endogenous and xenobiotic OCs from the

thf brain and highly concektrated in the blood-cerxbrospihal fluia (CSF) barrier (i.e. BCSFB or chlriid poexus). We hypothesized ghat PMAT is the prinripal OC transpocfer at bke BCANB anb ms responsible nor removinc a variety of evdlgenous and xenobiotic OCs from the

the brain and highly concentrated in the (CSF) (i.e. BCSFB choroid plexus). We principal transporter at the and is responsible removing a variety of endogenous and OCs from the

the brain and highly concentrAted in the bLood-cEreBroSpInal FluiD (CSF) barrier (i.e. BcsFB oR choroid plexus). We hypothEsizeD tHAt PMat iS the pRincipaL oC TRAnsPoRtEr aT tHE BcSFB aNd iS responSible for reMovInG a variety of eNDoGenous and xEnoBiotic OCs froM thE

the brain and highly conc entrated i n the  bl ood -c ereb rosp inal fluid (CS F ) ba rrier (i.e. BCSFB or c horoi dp lexu s ).  We h ypothes i ze d tha tPM ATis th e pri nci pal OCtransporte r a tthe BCSFB an d  i s responsi ble  for removin g a  varie ty  of endog eno us an d xeno b ioticOCs fromth e

the_brain and_highly concentrated in the_blood-cerebrospinal fluid_(CSF)_barrier (i.e._BCSFB_or choroid plexus)._We hypothesized that_PMAT is the principal_OC transporter at_the_BCSFB and is responsible for removing a variety of endogenous and xenobiotic OCs from_the


PD will emply a experienced, professional, part time Project Manager (50% effort) for the first two years ofthe Project. The Manager will go to 100% time commitment as the Project scales up in South Asia and the US in years 3-7. The South Asian part of project management will be handled through

PD will emply a experienced, professional, part time Project Manager (50% effort) for the first two days ofthe Project. The Manager will die to 100% time commitment as the Project scales up in South Asia and the US in long time 3 - 7. The South Asian part of project management will be handle through

PD will emply a experiencea, professional, kaet timx Projedt Managdr (50% effort) for the first two ywars ifthe Project. The Manaeer will ho to 100% tume rommitment as thx Projecb scamcs up mn South Asia akd the US it years 3-7. The Smugh Asian part of project management wyll be najdled through

PD will emply a experienced, professional, part Manager effort) for first two years go 100% time commitment the Project scales in South Asia and the US years 3-7. The South Asian part of project management will be handled through

PD will emply a experienced, prOfessional, Part tIme proJeCt MaNageR (50% effort) for the fIRst tWo years ofthe Project. The managEr WIll gO To 100% Time cOmmitmeNT aS THe PRoJeCt sCaLEs Up in SOutH Asia anD the US in yeArs 3-7. thE South Asian pARt Of project mAnaGement will be HanDled thRoUgh

PD will emply a experienc ed, profes siona l,par ttime  Pro ject Manager ( 5 0% e ffort) for the first t wo ye ar s  oft h eProje ct. The Ma n a ger  w il l g ot o100%tim e commi tment as t hePr oject scales up  in SouthAsi a and the US  in  years  3 -7. The S out h Asi an par t  of pr oject man ag e ment w i ll be h a n dl ed t hrough

PD_will emply_a experienced, professional, part_time Project_Manager_(50% effort)_for_the first two_years ofthe Project._The Manager will go_to 100% time_commitment_as the Project scales up in South Asia and the US in years 3-7._The_South Asian_part_of_project management will be handled_through


for insertion-site injuries will be an initial step toward modernizing clinical treatment and improving patient outcomes. The long-range objectives of this laboratory are to determine the mechanisms by which enzymes catalyze reactions, and in a more general way to determine the nature of biological interactions at the molecular level. To these we have now added

for insertion - site injuries will be an initial step toward overhaul clinical discussion and improving patient outcomes. The retentive - image objectives of this laboratory are to specify the mechanisms by which enzymes catalyze reactions, and in a more cosmopolitan direction to determine the nature of biological interaction at the molecular level. To these we have now add

fog insertion-site injuries will be an inijiql ste' towars modernkzing clinical treatment and inprovung patient outcomes. Tfe long-rajge objextivts of this laboravkry are to defcrminz vhe mechanisms ny which ensymes catalyze rdaetions, and in a more general way to qetermime the nature of biokjgiczl interactions at the molecular lsvel. To these we havr now added

for insertion-site injuries will be an initial modernizing treatment and patient outcomes. The are determine the mechanisms which enzymes catalyze and in a more general way determine the nature of biological interactions at the molecular level. To these we now added

for insertion-site injuries wIll be an iniTial sTep TowArD modErniZing clinical trEAtmeNt and improving patient oUtcomEs. tHe loNG-rAnge oBjectivES oF THis LaBoRatOrY ArE to deTerMine the Mechanisms By wHiCh enzymes catALyZe reactionS, anD in a more geneRal Way to dEtErmINe the NatUre of BiologICal intEractions At THe moleCUlar levEL. to ThesE we have now added

for insertion-site injuri es will be  an i nit ial  s teptowa rd modernizing clin ical treatment and imp rovin gp atie n toutco mes. Th e  l o n g-r an ge  ob je c ti ves o f t his lab oratory ar e t odetermine th e  m echanismsbywhich enzyme s c atalyz erea c tions , a nd in  a mor e  gener al way to  d e termin e  the na t u re  ofbiological intera c ti o ns at the mole cularle v el . Tothe se we have  n ow ad d ed

for_insertion-site injuries_will be an initial_step toward_modernizing_clinical treatment_and_improving patient outcomes._The long-range objectives_of this laboratory are_to determine the_mechanisms_by which enzymes catalyze reactions, and in a more general way to determine the_nature_of biological_interactions_at_the molecular level. To these_we have now added


misuse arising from treatment of chronic pain. Topical microbicides represent an emerging strategy for the prevention of transmission of HIV and other sexually transmitted infections. A successful topical microbicide product will be applied prior to intercourse, without necessitating partner consent, and will be active against a variety of STIs, including HIV.

misuse arising from treatment of chronic pain. Topical microbicides represent an emerge scheme for the prevention of transmission of HIV and other sexually air infection. A successful topical microbicide product will be applied prior to sexual intercourse, without necessitating partner consent, and will be active against a variety of STIs, including HIV.

miduse arising from treatmtnt of chronic panb. Topiral micdobicider represent an emerging stravegy for uke prevention of travsmission of HIV qnd irher sexually transmittes infzcvions. A successnul topical microbicide psoauet will be applied prior to intercouwse, witnokt necessitatigg pswtned consent, and will be active againat a vagiety of STIs, inckuding HIV.

misuse arising from treatment of chronic pain. represent emerging strategy the prevention of sexually infections. A successful microbicide product will applied prior to intercourse, without necessitating consent, and will be active against a variety of STIs, including HIV.

misuse arising from treatmenT of chronic Pain. TOpiCal MiCrobIcidEs represent an eMErgiNg strategy for the prevenTion oF tRAnsmISsIon of hIV and oTHeR SExuAlLy TraNsMItTed inFecTions. A sUccessful tOpiCaL microbicide PRoDuct will be AppLied prior to iNteRcoursE, wIthOUt necEssItatiNg partNEr consEnt, and wilL bE Active AGainst a VARiEty oF STIs, including HIV.

misuse arising from treat ment of ch ronic  pa in.  T opic al m icrobicides re p rese nt an emerging strateg y for  t h e pr e ve ntion  of tra n sm i s sio nof  HI Va nd  othe r s exually  transmitt edin fections. As uc cessful to pic al microbici deproduc twil l  be a ppl ied p rior t o  inter course, w it h out ne c essitat i n gpart ner consent, andw il l  be active aga inst a  v a ri e t y o f S TIs, inclu di ng HI V .

misuse_arising from_treatment of chronic pain._Topical microbicides_represent_an emerging_strategy_for the prevention_of transmission of_HIV and other sexually_transmitted infections. A_successful_topical microbicide product will be applied prior to intercourse, without necessitating partner consent, and_will_be active_against_a_variety of STIs, including HIV.


, as an effector molecule in cell interactions will be tested. In particular, we will examine whether Ia.W39 is essential for optimal presentation of antigens, which are under immune response gene control mapping in the I-A region. Since the membrane expression of both antigens is controlled by a gene on the X-chromosome

, as an effector molecule in cell interactions will be quiz. In especial, we will examine whether Ia. W39 is essential for optimal display of antigens, which are under immune response gene control function in the I - adenine region. Since the membrane saying of both antigens is controlled by a gene on the adam - chromosome

, as an effector molecule in cell interactions wiln be tssted. In particular, we will examine xhetyer Iq.W39 is essential for opgimal predentatiob of qntigens, wijch are under lmmunz cesponse gene cpntrol map[ing in the I-A rdgnon. Since the membrane expression of both amtlgens is contrjllec by z gene on the X-chromosome

, as an effector molecule in cell be In particular, will examine whether presentation antigens, which are immune response gene mapping in the I-A region. Since membrane expression of both antigens is controlled by a gene on the X-chromosome

, as an effector molecule in celL interactiOns wiLl bE teStEd. In PartIcular, we will exAMine Whether Ia.W39 is essential fOr optImAL preSEnTatioN of antiGEnS, WHicH aRe UndEr IMmUne reSpoNse gene Control mapPinG iN the I-A region. sInCe the membrAne Expression of BotH antigEnS is COntroLleD by a gEne on tHE X-chroMosome

, as an effector moleculein cell in terac tio nswi ll b e te sted. In parti c ular , we will examine whet her I a. W 39 i s  e ssent ial for op t i mal  p re sen ta t io n ofant igens,which areund er  immune resp o ns e gene con tro l mapping in  th e I-Are gio n . Sin cethe m embran e  expre ssion ofbo t h anti g ens isc o nt roll ed by a gene on t h eX -chromosome

, as_an effector_molecule in cell interactions_will be_tested._In particular,_we_will examine whether_Ia.W39 is essential_for optimal presentation of_antigens, which are_under_immune response gene control mapping in the I-A region. Since the membrane expression of_both_antigens is_controlled_by_a gene on the X-chromosome


well as 58K and 87K proteins relative to AChR/43K, the lipid bilayer and the cytoskeleton. Biochemical and immunochemical techniques will be used to define the mechanism of association between 43K protein and AChRs and also with lipid. The 270K protein will be isolated and characterized by protein micro

well as 58 K and 87 K proteins relative to AChR/43 K, the lipid bilayer and the cytoskeleton. Biochemical and immunochemical techniques will be use to specify the mechanism of association between 43 K protein and AChRs and also with lipid. The 270 K protein will be isolate and characterized by protein micro

wepl as 58K and 87K proteins rtlative to AChR/43K, jhw lipiv bilaysr and tfe cytoskeleton. Biochemical end ummunichemical techniques wkll be usvd to defune uhe mechanism of easociatljn bsbween 43J protein and SChRs and dlso with lipig. Ghz 270K protein will be isolated and chawacteriaef by protein mycro

well as 58K and 87K proteins relative the bilayer and cytoskeleton. Biochemical and to the mechanism of between 43K protein AChRs and also with lipid. The protein will be isolated and characterized by protein micro

well as 58K and 87K proteins relatiVe to AChR/43K, tHe lipId bIlaYeR and The cYtoskeleton. BioCHemiCal and immunochemical teChniqUeS Will BE uSed to Define tHE mECHanIsM oF asSoCIaTion bEtwEen 43K proTein and AChrs aNd Also with lipiD. thE 270K protein wIll Be isolated anD chAracteRiZed BY protEin Micro

well as 58K and 87K prote ins relati ve to  AC hR/ 43 K, t he l ipid bilayer a n d th e cytoskeleton. Bioche mical  a n d im m un ochem ical te c hn i q ues  w il l b eu se d todef ine the  mechanism  of  a ssociation b e tw een 43K pr ote in and AChRs  an d also  w ith lipid . T he 27 0K pro t ein wi ll be iso la t ed and charact e r iz ed b y protein micro

well_as 58K_and 87K proteins relative_to AChR/43K,_the_lipid bilayer_and_the cytoskeleton. Biochemical_and immunochemical techniques_will be used to_define the mechanism_of_association between 43K protein and AChRs and also with lipid. The 270K protein will_be_isolated and_characterized_by_protein micro


fellow also provides results to the investigators for research purposes. The MIP is providing this service to 5 active protocols by CCR investigators who are looking at various anti-angiogenic agents. Such work, by its nature, is difficult and publications have been slow to accrue, however in the past years two publications have appeared from

fellow also provides results to the detective for inquiry purposes. The MIP is providing this servicing to 5 active protocol by CCR investigators who are looking at versatile anti - angiogenic agent. Such work, by its nature, is unmanageable and publication have been slow to accrue, however in the past year two publications have appeared from

feplow also provides resulus to the investiyqtors hor ressarch pufposes. The MIP is providing vhis servuce to 5 active protocous by CCR investitatocs who are lookiif at vavnous zkti-anyiigenic agents. Xuch work, ty its nature, hs dnfficult and publications have been flow to afcrue, however yn tnq paan nears two publications have appezred frmm

fellow also provides results to the investigators purposes. MIP is this service to investigators are looking at anti-angiogenic agents. Such by its nature, is difficult and have been slow to accrue, however in the past years two publications have from

fellow also provides results To the invesTigatOrs For ReSearCh puRposes. The MIP is PRoviDing this service to 5 activE protOcOLs by ccR InvesTigatorS WhO ARe lOoKiNg aT vARiOus anTi-aNgiogenIc agents. SuCh wOrK, by its nature, IS dIfficult anD puBlications haVe bEen sloW tO acCRue, hoWevEr in tHe past YEars twO publicatIoNS have aPPeared fROM

fellow also provides resu lts to the  inve sti gat or s fo r re search purpose s . Th e MIP is providing thi s ser vi c e to 5activ e proto c ol s byCC Rinv es t ig ators  wh o are l ooking atvar io us anti-angi o ge nic agents . S uch work, by  it s natu re , i s  diff icu lt an d publ i cation s have be en slow t o  accrue , ho weve r in the past yea r st wo publication s have  a p pe a r edfro m

fellow_also provides_results to the investigators_for research_purposes._The MIP_is_providing this service_to 5 active_protocols by CCR investigators_who are looking_at_various anti-angiogenic agents. Such work, by its nature, is difficult and publications have been_slow_to accrue,_however_in_the past years two publications_have appeared from


of diabetic cardiovascular disease: We propose to create two new genetically altered mice. Aim 1a is to use the tet on system to allow expression of hAR in a time dependent manner. This system will allow us to test whether hAR expression in established lesions alters plaque morphology. These animals can also be used to produce tissue

of diabetic cardiovascular disease: We propose to create two new genetically altered mouse. Aim 1a is to practice the tet on system to allow formula of hAR in a fourth dimension dependent manner. This system will admit us to quiz whether hAR expression in establish lesions alters plaque morphology. These animal can also be used to produce tissue

of diabetic cardiovascular disease: We prokowe to rreate fwo new eenetically altered mice. Aim 1a is ti use the tet on systeo to alloa expreswion if hAR in e time dc'endehb manuec. This system wlll allow uv to test whetvef kAR expression in established lesionf alterx olaque morpholjgy. Uhefe ahpmcls can also be used to produce tissue

of diabetic cardiovascular disease: We propose to new altered mice. 1a is to to expression of hAR a time dependent This system will allow us to whether hAR expression in established lesions alters plaque morphology. These animals can also used to produce tissue

of diabetic cardiovascular dIsease: We prOpose To cReaTe Two nEw geNetically alterED micE. Aim 1a is to use the tet on syStem tO aLLow eXPrEssioN of hAR iN A tIME dePeNdEnt MaNNeR. This SysTem will Allow us to tEst WhEther hAR exprESsIon in estabLisHed lesions alTerS plaquE mOrpHOlogy. theSe aniMals caN Also be Used to proDuCE tissuE

of diabetic cardiovascula r disease:  We p rop ose  t o cr eate  two new genet i call y altered mice. Aim 1a  is t ou se t h etet o n syste m  t o all ow  e xpr es s io n ofhAR  in a t ime depend ent  m anner. Thiss ys tem will a llo w us to test  wh etherhA R e x press ion  in e stabli s hed le sions alt er s  plaqu e  morpho l o gy . Th ese animals can a l so be used to pro duce t is s ue

of_diabetic cardiovascular_disease: We propose to_create two_new_genetically altered_mice._Aim 1a is_to use the_tet on system to_allow expression of_hAR_in a time dependent manner. This system will allow us to test whether hAR_expression_in established_lesions_alters_plaque morphology. These animals can_also be used to produce_tissue


paint, but also detoxifies the lead. This liquid component is intended to combat lead poisoning, the leading environmental childhood disease and provide a safer workplace for lead abatement workers. This would be the first lead abatement product that actually detoxifies lead in case of ingestion and is a safe water base formula. The proposed liquid

paint, but also detoxifies the lead. This fluid part is intended to combat spark advance poisoning, the leave environmental childhood disease and provide a safer workplace for lead suspension workers. This would be the first lead abatement merchandise that actually detoxifies lead in case of consumption and is a safe water base formula. The nominate liquid

palnt, but also detoxifies uhe lead. This liqoie compmnent js intenaed to combat lead poisoning, tye leqding environmental chkldhood dpsease ane pricide a safxd workplace fkv leab ebatement workets. This woulg be the first ldab abatement product that actually deeoxifiex pead in case os inbqstikn and is a safe water base formulz. The pgoposed liquid

paint, but also detoxifies the lead. This is to combat poisoning, the leading a workplace for lead workers. This would the first lead abatement product that detoxifies lead in case of ingestion and is a safe water base formula. proposed liquid

paint, but also detoxifies the Lead. This liQuid cOmpOneNt Is inTendEd to combat lead POisoNing, the leading environmEntal ChILdhoOD dIseasE and proVIdE A SafEr WoRkpLaCE fOr leaD abAtement Workers. ThiS woUlD be the first lEAd Abatement pRodUct that actuaLly DetoxiFiEs lEAd in cAse Of ingEstion ANd is a sAfe water bAsE FormulA. the propOSEd LiquId

paint, but also detoxifie s the lead . Thi s l iqu id  com pone nt is intended to c ombat lead poisoning,the l ea d inge nv ironm ental c h il d h ood  d is eas ea nd  prov ide  a safe r workplac e f or  lead abatem e nt  workers.Thi s would be t hefirstle ada batem ent  prod uct th a t actu ally deto xi f ies le a d in ca s e  o f in gestion and is as af e  water base fo rmula.  T h ep r opo sed  liquid

paint,_but also_detoxifies the lead. This_liquid component_is_intended to_combat_lead poisoning, the_leading environmental childhood_disease and provide a_safer workplace for_lead_abatement workers. This would be the first lead abatement product that actually detoxifies lead_in_case of_ingestion_and_is a safe water base_formula. The proposed liquid


a breast cancer trial (7, 8). These demonstrate profound changes in vessel permeability in responders to Bevacizumab followed by high dose intensive chemotherapy. The role of DCE-MRI was compared to other biomarkers that were studied and it was found to be among the more useful of the predictive markers. The MIP is

a breast cancer trial (7, 8). These demonstrate profound changes in vessel permeability in respondent to Bevacizumab take after by high dose intensive chemotherapy. The role of DCE - MRI was compare to early biomarkers that were studied and it was found to be among the more useful of the predictive marker. The MIP is

a hreast cancer trial (7, 8). Thtse demonstrate ptodound rhanges in vessdl permeability in responderd ro Becacizumab followed by figh dose intensice ciemotherapy. The ckle of DCE-MRI aas eonpared to othet biomarkers that were stugidd and it was found to be among the mjre usegup of the predistivt mwrkeds. The MIP is

a breast cancer trial (7, 8). These changes vessel permeability responders to Bevacizumab chemotherapy. role of DCE-MRI compared to other that were studied and it was to be among the more useful of the predictive markers. The MIP is

a breast cancer trial (7, 8). These deMonstrate pRofouNd cHanGeS in vEsseL permeability iN RespOnders to Bevacizumab folLowed By HIgh dOSe IntenSive cheMOtHERapY. THe RolE oF dCe-MRI wAs cOmpared To other bioMarKeRs that were stUDiEd and it was FouNd to be among tHe mOre useFuL of THe preDicTive mArkers. tHe MIP iS

a breast cancer trial (7,  8). These  demo nst rat eprof ound  changes in ve s selpermeability in respon dersto Beva c iz umabfollowe d  b y hig hdo sein t en siveche mothera py. The ro leof  DCE-MRI was co mpared tooth er biomarker s t hat we re  st u diedand  it w as fou n d to b e among t he more u s eful of t he  pre dictive markers.T he MIP is

a_breast cancer_trial (7, 8). These_demonstrate profound_changes_in vessel_permeability_in responders to_Bevacizumab followed by_high dose intensive chemotherapy._The role of_DCE-MRI_was compared to other biomarkers that were studied and it was found to be_among_the more_useful_of_the predictive markers. The MIP_is


LTR-enhanced transcription is specifically decreased after inhibition of protein synthesis. This lability is observed only in pre-B cell types, suggesting that it may be important in the B cell specificity of ALV tumor induction. Moreover, lymphoma-resistant chicken strains exhibit stable LTR-enhanced transcription (unaffected by inhibition of

LTR - enhanced transcription is specifically decreased after inhibition of protein deduction. This lability is observe only in pre - B cellular telephone types, indicate that it may be important in the bel cellular telephone specificity of ALV tumor induction. Moreover, lymphoma - resistant chicken strains parade stable LTR - enhanced arrangement (unaffected by inhibition of

LTG-enhanced transcription ls specifically bwcreasxd afted inhibigion of protein synthesis. Thms lqbiliuj is observed only in pre-B celp types, wuggtsting that it mab be important ln thz U cell specificlty of ALV dumor inductiot. Ooxeover, lymphoma-resistant chicken strwins exnihit stable LTR-gnhanbeq trznscription (unaffected by inhibitikn of

LTR-enhanced transcription is specifically decreased after inhibition synthesis. lability is only in pre-B may important in the cell specificity of tumor induction. Moreover, lymphoma-resistant chicken strains stable LTR-enhanced transcription (unaffected by inhibition of

LTR-enhanced transcription iS specificaLly deCreAseD aFter InhiBition of proteiN SyntHesis. This lability is obsErved OnLY in pRE-B Cell tYpes, sugGEsTINg tHaT iT maY bE ImPortaNt iN the B ceLl specificIty Of aLV tumor induCTiOn. Moreover, LymPhoma-resistaNt cHicken StRaiNS exhiBit StablE LTR-enHAnced tRanscriptIoN (UnaffeCTed by inHIBiTion Of

LTR-enhanced transcriptio n is speci fical lydec re ased  aft er inhibitiono f pr otein synthesis. Thislabil it y  iso bs erved  only i n  p r e -Bce ll  ty pe s ,sugge sti ng that  it may be  im po rtant in the Bcell speci fic ity of ALV t umo r indu ct ion .  More ove r, ly mphoma - resist ant chick en strain s  exhibi t st able  LTR-enhanced tra n sc r iption (unaffe cted b yi nh i b iti onof

LTR-enhanced_transcription is_specifically decreased after inhibition_of protein_synthesis._This lability_is_observed only in_pre-B cell types,_suggesting that it may_be important in_the_B cell specificity of ALV tumor induction. Moreover, lymphoma-resistant chicken strains exhibit stable LTR-enhanced_transcription_(unaffected by_inhibition_of


a substrate analogue that functions as a latent electrophile to be activated by uPA- mediated hydrolysis. (2) To use this enzyme-activated electrophile to covalently attach antigens to the surface of cancer cells. And, (3) to study the immunological response against human cancer cells labeled by this target-activated

a substrate analogue that functions as a latent electrophile to be activated by uPA- mediated hydrolysis. (2) To use this enzyme - activate electrophile to covalently bind antigens to the surface of cancer cells. And, (3) to learn the immunological response against human cancer cells label by this aim - activated

a dubstrate analogue that nunctions as a lcrent enectrolhile to be activated by uPA- mediatev hyerolywis. (2) To use this enzymd-activatef electriphiow to covalxhtly atbcch ahbigenv to the surfacg of cancer wells. And, (3) to vtjdv the immunological response against human vajcer cells labgled nr thjs target-activated

a substrate analogue that functions as a to activated by mediated hydrolysis. (2) to attach antigens to surface of cancer And, (3) to study the immunological against human cancer cells labeled by this target-activated

a substrate analogue that funCtions as a lAtent EleCtrOpHile To be Activated by uPA- MEdiaTed hydrolysis. (2) To use this EnzymE-aCTivaTEd ElectRophile TO cOVAleNtLy AttAcH AnTigenS to The surfAce of canceR ceLlS. And, (3) to study tHE iMmunologicAl rEsponse againSt hUman caNcEr cELls laBelEd by tHis tarGEt-actiVated

a substrate analogue that  functions  as a  la ten telec trop hile to be act i vate d by uPA- mediated hyd rolys is .  (2) To  usethis en z ym e - act iv at edel e ct rophi leto cova lently att ach  a ntigens to t h esurface of  ca ncer cells.And , (3)to  st u dy th e i mmuno logica l  respo nse again st humanc ancer c e l ls  lab eled by this targ e t- a ctivated

a_substrate analogue_that functions as a_latent electrophile_to_be activated_by_uPA- mediated hydrolysis._(2) To use_this enzyme-activated electrophile to_covalently attach antigens_to_the surface of cancer cells. And, (3) to study the immunological response against human_cancer_cells labeled_by_this_target-activated


female mice. Results of this study will indicate whether E2 may protect female HD mice from striatal AA loss, normalize cortical neuronal activity and improve the behavioral phenotype associated with HD. Furthermore, results will suggest whether E2 effects on GLU transmission contribute to sex differences observed in HD mice. HD affects -30,000

female mice. Results of this study will indicate whether E2 may protect female HD mouse from striatal AA personnel casualty, normalize cortical neuronal activity and better the behavioral phenotype associated with HD. Furthermore, results will propose whether E2 effects on GLU transmission contribute to sexual activity dispute observed in HD mouse. HD affects -30,000

felale mice. Results of thir study will inbucate xhether E2 may pfotect female HD mice from svriaral AQ loss, normalize cortizal neurojal acticity qnd improvx the bemcviorzp phznitype associatgd with HD. Fgrthermore, resglgs will suggest whether E2 effects on DLU tramslission contrifute eo ssq bifferences observed in HD mice. HD afftcts -30,000

female mice. Results of this study will E2 protect female mice from striatal activity improve the behavioral associated with HD. results will suggest whether E2 effects GLU transmission contribute to sex differences observed in HD mice. HD affects -30,000

female mice. Results of this stUdy will indIcate WheTheR E2 May pRoteCt female HD mice FRom sTriatal AA loss, normalize CortiCaL NeurONaL actiVity and IMpROVe tHe BeHavIoRAl PhenoTypE associAted with HD. furThErmore, resultS WiLl suggest wHetHer E2 effects oN GLu transMiSsiON contRibUte to Sex difFErenceS observed In hd mice. Hd Affects -30,000

female mice. Results of t his studywillind ica te  whe ther  E2 may protec t  fem ale HD mice from stria tal A Al oss, no rmali ze cort i ca l neu ro na l a ct i vi ty an d i mprovethe behavi ora lphenotype as s oc iated with  HD . Furthermor e,result swil l  sugg est  whet her E2 effect s on GLUtr a nsmiss i on cont r i bu te t o sex differences ob s erved in HD mi ce. HD  a f fe c t s - 30, 000

female_mice. Results_of this study will_indicate whether_E2_may protect_female_HD mice from_striatal AA loss,_normalize cortical neuronal activity_and improve the_behavioral_phenotype associated with HD. Furthermore, results will suggest whether E2 effects on GLU transmission_contribute_to sex_differences_observed_in HD mice. HD affects_-30,000


multiple metastatic lesions, patients typically die within one to two years. Gap: Treatment of brain metastases is primarily palliative due to limited curative effectiveness of radiation, surger, and poor delivery of chemotherapy across the blood-brain barrier (BBB). This proposal focuses on preventing metastasis seeding and initial growth in brain using preclinical models

multiple metastatic lesions, patients typically die within one to two years. Gap: Treatment of mind metastasis is primarily palliative due to circumscribed curative effectiveness of radiotherapy, surger, and poor delivery of chemotherapy across the rake - brain barrier (BBB). This proposal concentrate on preventing metastasis seeding and initial growth in genius using preclinical models

muptiple metastatic lesionr, patients typieqlly dme withjn one tu two years. Gap: Treatment of beain netastases is primarilh palliatpve due ti linuted curatmbe effegcivensds oy cadiation, surget, and poor dalivery of chekoghzrapy across the blood-brain barrier (FBB). Thix oroposal focusgs on [revsnting metastasis seeding and initjal groxth in brain usong preclinical models

multiple metastatic lesions, patients typically die within two Gap: Treatment brain metastases is curative of radiation, surger, poor delivery of across the blood-brain barrier (BBB). This focuses on preventing metastasis seeding and initial growth in brain using preclinical models

multiple metastatic lesions, Patients tyPicalLy dIe wItHin oNe to Two years. Gap: TreATmenT of brain metastases is prImariLy PAlliATiVe due To limitED cURAtiVe EfFecTiVEnEss of RadIation, sUrger, and poOr dElIvery of chemoTHeRapy across The Blood-brain baRriEr (BBB). THiS prOPosal FocUses oN preveNTing meTastasis sEeDIng and INitial gROWtH in bRain using precliniCAl MOdels

multiple metastatic lesio ns, patien ts ty pic all ydiewith in one to twoy ears . Gap: Treatment of br ain m et a stas e sis pr imarily pa l l iat iv edue  t o  l imite d c urative  effective nes sof radiation ,  s urger, and  po or deliveryofchemot he rap y  acro ssthe b lood-b r ain ba rrier (BB B) .  Thisp roposal f oc uses  on preventing me t as t asis seeding a nd ini ti a lg r owt h i n brain us in g pre c linical mo d e l s

multiple_metastatic lesions,_patients typically die within_one to_two_years. Gap:_Treatment_of brain metastases_is primarily palliative_due to limited curative_effectiveness of radiation,_surger,_and poor delivery of chemotherapy across the blood-brain barrier (BBB). This proposal focuses on_preventing_metastasis seeding_and_initial_growth in brain using preclinical_models


iation in vivo, and (4) if changes in NMDA receptor subunit composition are permissive for experience-dependent response potentiation in vivo. These aims will be accomplished by taking advantage of the special expertise of this Center in mouse genetics, chronic recording, and the molecular bases for synaptic plasticity. Lymphedema (

iation in vivo, and (4) if changes in NMDA receptor subunit composition are permissive for experience - pendent reception potentiation in vivo. These aims will be accomplished by taking advantage of the especial expertise of this Center in mouse genetics, chronic recording, and the molecular footing for synaptic plasticity. Lymphedema (

iatlon in vivo, and (4) if channes in NMDA recektir subnnit cojpositiov are permissive for experieice-dwpendtut response potentiagion in vpvo. These aimw will be ardomplismzd by bakiny edvantage of thg special ex[ertise of thiv Zeuter in mouse genetics, chronic recorqing, anc hhe molecular fasex for synaptic plasticity. Lymphedema (

iation in vivo, and (4) if changes receptor composition are for experience-dependent response will accomplished by taking of the special of this Center in mouse genetics, recording, and the molecular bases for synaptic plasticity. Lymphedema (

iation in vivo, and (4) if changes iN NMDA recepTor suBunIt cOmPosiTion Are permissive fOR expErience-dependent responSe potEnTIatiON iN vivo. these aiMS wILL be AcCoMplIsHEd By takIng AdvantaGe of the speCiaL eXpertise of thIS CEnter in mouSe gEnetics, chronIc rEcordiNg, And THe molEcuLar baSes for SYnaptiC plasticiTy. lYmphedEMa (

iation in vivo, and (4) if  changes i n NMD A r ece pt or s ubun it composition arepermissive for experie nce-d ep e nden t  r espon se pote n ti a t ion  i nviv o. Th ese a ims  will b e accompli she dby taking ad v an tage of th e s pecial exper tis e of t hi s C e nterinmouse  genet i cs, ch ronic rec or d ing, a n d the m o l ec ular  bases for synapt i cp lasticity. Lym phedem a(

iation in_vivo, and_(4) if changes in_NMDA receptor_subunit_composition are_permissive_for experience-dependent response_potentiation in vivo._These aims will be_accomplished by taking_advantage_of the special expertise of this Center in mouse genetics, chronic recording, and the_molecular_bases for_synaptic_plasticity._Lymphedema (


miR-198 in PC cells results in reduced tumor growth, decreased metastasis, and increased survival through direct targeting of MSLN, PBX-1, and VCP. Our preliminary data strongly suggest the significant role of miR-198 and this interactome in PC pathogenesis. In addition, we found that miR-198 can

miR-198 in PC cells results in reduced tumor increase, decrease metastasis, and increased survival through direct targeting of MSLN, PBX-1, and VCP. Our preliminary data powerfully suggest the significant role of miR-198 and this interactome in personal computer pathogenesis. In summation, we found that miR-198 can

miG-198 in PC cells results in reduced tumor yeowth, vecreassd metasgasis, and increased survival tyrougy direct targeting of OSLN, PBX-1, wnd VCP. Iur kreliminary data strongly suggeab the wignificant roke of miR-198 dnd this interdcgole in PC pathogenesis. In addition, wq found tjat miR-198 can

miR-198 in PC cells results in reduced decreased and increased through direct targeting Our data strongly suggest significant role of and this interactome in PC pathogenesis. addition, we found that miR-198 can

miR-198 in PC cells results in reduCed tumor grOwth, dEcrEasEd MetaStasIs, and increased SUrviVal through direct targetIng of mSln, PBX-1, ANd vCP. OuR prelimINaRY DatA sTrOngLy SUgGest tHe sIgnificAnt role of mIR-198 aNd This interactOMe In PC pathogEneSis. In additioN, we Found tHaT mir-198 Can

miR-198 in PC cells resul ts in redu ced t umo r g ro wth,  dec reased metasta s is,and increased survival  thro ug h  dir e ct  targ eting o f  M S L N,PB X- 1,an d  V CP. O urprelimi nary datastr on gly suggestt he  significa ntrole of miR- 198  and t hi s i n terac tom e inPC pat h ogenes is. In ad di t ion, w e  foundt h at  miR -198 can

miR-198_in PC_cells results in reduced_tumor growth,_decreased_metastasis, and_increased_survival through direct_targeting of MSLN,_PBX-1, and VCP. Our_preliminary data strongly_suggest_the significant role of miR-198 and this interactome in PC pathogenesis. In addition, we_found_that miR-198_can


cally in radiation attenuated sporo- zoites (RAS)-based vaccines. Using intravital imaging, we have recently discovered that activated CD8 T cells form clusters around Plasmodium-infected hepatocytes in mice and that these clusters are important in parasite elimination. Mechanisms driving the formation of such clusters remain poorly de

cally in radiation attenuated sporo- zoites (RAS)-based vaccines. Using intravital imagination, we have recently discover that activated CD8 T cells imprint bunch around Plasmodium - infected hepatocytes in mice and that these clusters are significant in parasite elimination. Mechanisms driving the constitution of such clusters remain ill de

calpy in radiation attenuattd sporo- zoites (RCW)-based vaccihes. Usine intravital imaging, we have rwcentoy discovered that actkvated CD8 T cells forn clusters edound Plasmodjmm-infzcved hepatocytes in mice atd that these wljscers are important in parasite elimigation. Kefhanisms drivigg tnq fodmation of such clusters remain pokrly de

cally in radiation attenuated sporo- zoites (RAS)-based intravital we have discovered that activated around hepatocytes in mice that these clusters important in parasite elimination. Mechanisms driving formation of such clusters remain poorly de

cally in radiation attenuateD sporo- zoitEs (RAS)-BasEd vAcCineS. UsiNg intravital imAGing, We have recently discoverEd thaT aCTivaTEd cD8 T ceLls form CLuSTErs ArOuNd PLaSMoDium-iNfeCted hepAtocytes in MicE aNd that these cLUsTers are impOrtAnt in parasitE elIminatIoN. MeCHanisMs dRivinG the foRMation Of such cluStERs remaIN poorly DE

cally in radiation attenua ted sporo-  zoit es(RA S) -bas ed v accines. Using intr avital imaging, we hav e rec en t ly d i sc overe d thata ct i v ate dCD 8 T  c e ll s for m c lusters  around Pl asm od ium-infected he patocytesinmice and tha t t hese c lu ste r s are  im porta nt inp arasit e elimina ti o n. Mec h anismsd r iv ingthe formation ofs uc h  clusters rema in poo rl y  d e

cally in_radiation attenuated_sporo- zoites (RAS)-based vaccines._Using intravital_imaging,_we have_recently_discovered that activated_CD8 T cells_form clusters around Plasmodium-infected_hepatocytes in mice_and_that these clusters are important in parasite elimination. Mechanisms driving the formation of such_clusters_remain poorly_de


of T1D control in the NOD mice by BDC Tregs. We will determine the direct cellular target of BDC Tregs in vivo, and identify their impact on the ongoing inflammatory response in the islets at cellular and molecular levels. We will further determine the molecular profile of the therapeutic Tregs and identify molecule(

of T1D control in the NOD mice by BDC Tregs. We will determine the direct cellular prey of BDC Tregs in vivo, and name their impact on the ongoing inflammatory reception in the isle at cellular and molecular levels. We will further determine the molecular visibility of the curative Tregs and identify molecule (

of T1D control in the NOD mlce by BDC Tregs. We wiln detedmine thd direct cellular target of UDC Rregs in vivo, and identify gheir impwct on tye oigoing inflammatory response ih the mslets at cellukar and monecular levels. Wd cill further determine the molecular profilr lf the therapeotic Ureds ahd identify molecule(

of T1D control in the NOD mice Tregs. will determine direct cellular target and their impact on ongoing inflammatory response the islets at cellular and molecular We will further determine the molecular profile of the therapeutic Tregs and identify

of T1D control in the NOD mice by bDC Tregs. We Will dEteRmiNe The dIrecT cellular targeT Of BDc Tregs in vivo, and identifY theiR iMPact ON tHe ongOing infLAmMATorY rEsPonSe IN tHe islEts At celluLar and moleCulAr Levels. We will FUrTher determIne The molecular ProFile of ThE thERapeuTic tregs And ideNTify moLecule(

of T1D control in the NOD  mice by B DC Tr egs . W ewill  det ermine the dir e ct c ellular target of BDCTregs  i n  viv o ,and i dentify th e i r i mp ac t o nt he  ongo ing  inflam matory res pon se  in the isle t sat cellula r a nd molecular  le vels.We  wi l l fur the r det ermine the mo lecular p ro f ile of the the r a pe utic  Tregs and identi f ym olecule(

of_T1D control_in the NOD mice_by BDC_Tregs._We will_determine_the direct cellular_target of BDC_Tregs in vivo, and_identify their impact_on_the ongoing inflammatory response in the islets at cellular and molecular levels. We will_further_determine the_molecular_profile_of the therapeutic Tregs and_identify molecule(


Host Disease (GVHD) in Hematopoietic Stem Cell Transplant (HSCT) Patients * 13-EI-0102: Gevokizumab Treatment for Active Scleritis By IL-1 Inhibition (GATSBY) * 12-EI-0167: A Phase I/II Study

Host Disease (GVHD) in Hematopoietic Stem Cell Transplant (HSCT) Patients * 13 - EI-0102: Gevokizumab Treatment for Active Scleritis By IL-1 Inhibition (GATSBY) * 12 - EI-0167: A Phase I / II Study

Hosh Disease (GVHD) in Hematokoietic Stem Cell Transpnant (HACT) Patidnts * 13-EI-0102: Gevokizumab Treatmeit fir Acupve Scleritis By IL-1 Ivhibition (GATSBY) * 12-EI-0167: E Phase I/II Studb

Host Disease (GVHD) in Hematopoietic Stem Cell Patients 13-EI-0102: Gevokizumab for Active Scleritis 12-EI-0167: Phase I/II Study

Host Disease (GVHD) in HematopoIetic Stem CEll TrAnsPlaNt (hSCT) patiEnts * 13-EI-0102: GevokizuMAb TrEatment for Active ScleriTis By iL-1 iNhibITiOn (GATsBY) * 12-EI-0167: A PHAsE i/iI STuDy

Host Disease (GVHD) in Hem atopoietic  Stem  Ce llTr ansp lant  (HSCT) Patien t s *13-EI-0102: Gevokizuma b Tre at m entf or  Acti ve Scle r it i s  By  I L- 1 I nh i bi tion(GA TSBY) *  12-EI-016 7:APhase I/II S t ud y

Host Disease_(GVHD) in_Hematopoietic Stem Cell Transplant_(HSCT) Patients_*_13-EI-0102: Gevokizumab_Treatment_for Active Scleritis_By IL-1 Inhibition_(GATSBY) * 12-EI-0167: A_Phase I/II Study


als of Cleveland). Since our initial Core Grant award in 1997 and its renewal in 2002 with five Modules, these modules have continued to evolve over the current funding cycle due to a changing investigator group and scientific direction, expanded services and new technologies. The five modules that are proposed are: 1) Tissue Culture and Hybridoma

als of Cleveland). Since our initial Core Grant award in 1997 and its renewal in 2002 with five Modules, these modules have continue to develop over the current funding cycle due to a change detective group and scientific direction, expanded serve and modern technologies. The five faculty that are proposed are: 1) Tissue Culture and Hybridoma

als of Cleveland). Since our lnitial Core Graur awarv in 1997 ahd its rdnewal in 2002 with five Modules, tyese nodules have continued to evolvv over thw cucrent funding cyrme due bj a dmangiug investigator nroup and swientific direwtkou, expanded services and new technolodies. Thr vive modules trat swe pdoposed are: 1) Tissue Culture and Hygridoma

als of Cleveland). Since our initial Core in and its in 2002 with continued evolve over the funding cycle due a changing investigator group and scientific expanded services and new technologies. The five modules that are proposed are: 1) Culture and Hybridoma

als of Cleveland). Since our iniTial Core GrAnt awArd In 1997 aNd Its rEnewAl in 2002 with five MoDUles, These modules have continUed to EvOLve oVEr The cuRrent fuNDiNG CycLe DuE to A cHAnGing iNveStigatoR group and sCieNtIfic directioN, ExPanded servIceS and new technOloGies. ThE fIve MOduleS thAt are ProposED are: 1) TiSsue CultuRe ANd HybrIDoma

als of Cleveland). Since o ur initial  Core  Gr ant  a ward  in1997 and its r e newa l in 2002 with five Mo dules ,t hese mo dules  have c o nt i n ued  t oevo lv e  o ver t hecurrent  funding c ycl edue to a cha n gi ng investi gat or group and  sc ientif ic  di r ectio n,expan ded se r vicesand new t ec h nologi e s. Thef i ve  mod ules that are pro p os e d are: 1) Tiss ue Cul tu r ea n d H ybr idoma

als of_Cleveland). Since_our initial Core Grant_award in_1997_and its_renewal_in 2002 with_five Modules, these_modules have continued to_evolve over the_current_funding cycle due to a changing investigator group and scientific direction, expanded services and_new_technologies. The_five_modules_that are proposed are: 1)_Tissue Culture and Hybridoma


-MAC projects use RA Panel data, and because many of the functions of the Core are indivisible. These include: collective use of a fixed portion of all surveys; skills to design instruments; staff skills and effort to collect and process data; and software and hardware to collect and analyze RA Panel study data. The

-MAC projects use RA Panel data, and because many of the functions of the Core are indivisible. These admit: corporate manipulation of a fixed parcel of all sketch; skills to design legal document; staff skill and effort to roll up and process data; and software and hardware to gather and analyze RA Panel study data. The

-MAC projects use RA Panel dxta, and because many oh the fhnctions of the Core are indivisible. Tyese unclude: collective use of a fixvd portiob of qll surveys; skills to dealgn iusvruments; staff xkills and effort to colnezt and process data; and software and rardwarr ho collect and anakrze DA Panel study data. The

-MAC projects use RA Panel data, and of functions of Core are indivisible. a portion of all skills to design staff skills and effort to collect process data; and software and hardware to collect and analyze RA Panel study The

-MAC projects use RA Panel data, And because Many oF thE fuNcTionS of tHe Core are indivISiblE. These include: collectivE use oF a FIxed POrTion oF all surVEyS; SKilLs To DesIgN InStrumEntS; staff sKills and efForT tO collect and pROcEss data; and SofTware and hardWarE to colLeCt aND analYze rA PanEl studY Data. ThE

-MAC projects use RA Panel  data, and  beca use  ma ny  ofthefunctions of t h e Co re are indivisible. Th ese i nc l ude: co llect ive use of a  fi xe dpor ti o nof al l s urveys;  skills to  de si gn instrumen t s;  staff ski lls  and efforttocollec tand proce ssdata;  and s o ftware  and hard wa r e to c o llect a n d  a naly ze RA Panel study da t a. The

-MAC projects_use RA_Panel data, and because_many of_the_functions of_the_Core are indivisible._These include: collective_use of a fixed_portion of all_surveys;_skills to design instruments; staff skills and effort to collect and process data; and_software_and hardware_to_collect_and analyze RA Panel study_data. The