meeting. We also request joint sponsorship by the Office of Women's Health, the National Cancer Institute, National Institute of Diabetes, Digestive and Kidney Diseases, the National Institute for Environmental Health Sciences, and the National Institute of General Medical Sciences. The number of requested sponsors reflects the unusual nature of this conference which focuses

meeting. We also request joint sponsorship by the Office of Women's Health, the National Cancer Institute, National Institute of Diabetes, Digestive and Kidney Diseases, the National Institute for Environmental Health Sciences, and the National Institute of General Medical Sciences. The number of requested patron reflect the unusual nature of this conference which focuses

mefting. We also request jolnt sponsorship yt the Mffice of Womev's Health, the National Cancec Inwtituuv, National Institute uf Diabetvs, Digestuve end Kidney Diseases, the Kctionzp Invvitute for Envitonmental Hedlth Sciences, dna che National Institute of General Meqical Svifnces. The numbgr of wequssted sponsors reflects the unusuam naturt of this conferenve which focuses

meeting. We also request joint sponsorship by of Health, the Cancer Institute, National Kidney the National Institute Environmental Health Sciences, the National Institute of General Medical The number of requested sponsors reflects the unusual nature of this conference which

meeting. We also request joint SponsorshiP by thE OfFicE oF WomEn's HEalth, the NationAL CanCer Institute, National InStituTe OF DiaBEtEs, DigEstive aND KIDNey diSeAseS, tHE NAtionAl INstitutE for EnviroNmeNtAl Health ScieNCeS, and the NatIonAl Institute oF GeNeral MEdIcaL scienCes. the nuMber of REquestEd sponsorS rEFlects THe unusuAL NaTure Of this conference wHIcH Focuses

meeting. We also requestjoint spon sorsh ipbyth e Of fice  of Women's He a lth,  the National Cancer I nstit ut e , Na t io nal I nstitut e  o f Dia be te s,Di g es tiveand  Kidney  Diseases,  th eNational Ins t it ute for En vir onmental Hea lth  Scien ce s,a nd th e N ation al Ins t ituteof Genera lM edical Science s .  T he n umber of requeste d  s p onsors reflect s theun u su a l  na tur e of thisco nfere n ce whic h  f o c u ses

meeting._We also_request joint sponsorship by_the Office_of_Women's Health,_the_National Cancer Institute,_National Institute of_Diabetes, Digestive and Kidney_Diseases, the National_Institute_for Environmental Health Sciences, and the National Institute of General Medical Sciences. The number_of_requested sponsors_reflects_the_unusual nature of this conference_which focuses


subversion, pain, demographic, social, other structural factors) are most closely linked to ART nonadherence (per DBS), and how they affect measuring ART adherence using MyTPill and Wisepill. Public health significance: If MyTPill, a non-invasive, self-contained, and nearly automated

subversion, pain, demographic, social, other structural divisor) are about closely linked to ART nonadherence (per DBS), and how they involve quantify ART adherence using MyTPill and Wisepill. Public health meaning: If MyTPill, a non - invasive, self - contained, and nearly automatize

suhversion, pain, demographig, social, other sjrycturan factkrs) are oost closely linked to ART nlnqdhertuce (per DBS), and how ghey affebt measurung ERT adherence usmhg MyTPljl ahf Wivxpill. Public heslth signixicance: If MyT[iul, a non-invasive, self-contained, and newrly auyolated

subversion, pain, demographic, social, other structural factors) closely to ART (per DBS), and adherence MyTPill and Wisepill. health significance: If a non-invasive, self-contained, and nearly automated

subversion, pain, demographic, Social, otheR struCtuRal FaCtorS) are Most closely linKEd to aRT nonadherence (per DBS), aNd how ThEY affECt MeasuRing ART ADhEREncE uSiNg MYTpIlL and WIsePill. PubLic health sIgnIfIcance: If MyTPILl, A non-invasiVe, sElf-contained, And Nearly AuTomATed

subversion, pain, demogra phic, soci al, o the r s tr uctu ralfactors) are m o st c losely linked to ART n onadh er e nce( pe r DBS ), andh ow t hey  a ff ect  m e as uring  AR T adher ence using  My TP ill and Wise p il l. Publichea lth signific anc e: IfMy TPi l l, anon -inva sive,s elf-co ntained,an d  nearl y  automa t e d

subversion,_pain, demographic,_social, other structural factors)_are most_closely_linked to_ART_nonadherence (per DBS),_and how they_affect measuring ART adherence_using MyTPill and_Wisepill._Public health significance: If MyTPill, a non-invasive, self-contained, and nearly automated


although ATAD2 and ATAD2B are highly conserved, there is little known about the function of ATAD2B or its role in oncogenesis. Both the ATAD2/B proteins contain two conserved domains: an AAA ATPase domain and a bromodomain. The overall objective of the proposed research is

although ATAD2 and ATAD2B are highly conserved, there is little known about the function of ATAD2B or its role in oncogenesis. Both the ATAD2 / boron protein contain two conserved domain: an AAA ATPase world and a bromodomain. The overall objective of the proposed inquiry is

alhhough ATAD2 and ATAD2B art highly conserveb, there is liftle knodn about the function of ATAV2B oe its role in oncogenesis. Buth the ANAD2/B protwins xontain two conseryzd dojwins: en AAA ATPase dpmain and d bromodomain. Dhd lverall objective of the proposed rqsearch id

although ATAD2 and ATAD2B are highly conserved, little about the of ATAD2B or the proteins contain two domains: an AAA domain and a bromodomain. The overall of the proposed research is

although ATAD2 and ATAD2B are hiGhly conserVed, thEre Is lItTle kNown About the functiON of AtAD2B or its role in oncogenEsis. BOtH The AtaD2/b protEins conTAiN TWo cOnSeRveD dOMaIns: an aAA aTPase dOmain and a bRomOdOmain. The overALl Objective oF thE proposed resEarCh is

although ATAD2 and ATAD2B  are highl y con ser ved ,ther e is  little knowna bout  the function of ATAD2 B orit s  rol e  i n onc ogenesi s .B o thth eATA D2 / Bprote ins  contai n two cons erv ed  domains: an AA A ATPase d oma in and a bro mod omain.  T heo veral l o bject ive of the pr oposed re se a rch is

although_ATAD2 and_ATAD2B are highly conserved,_there is_little_known about_the_function of ATAD2B_or its role_in oncogenesis. Both the_ATAD2/B proteins contain_two_conserved domains: an AAA ATPase domain and a bromodomain. The overall objective of the_proposed_research is


now propose to test the hypothesis that reduction in hepatic CEACAM1 underlies the causative role of hyperinsulinemia in diet-induced insulin resistance. To this end, we will in Aim 1, investigate whether preventing hyperinsulinemia curbs diet-induced insulin resistance in a model of hepatic Ceacam1 gain-

now propose to test the hypothesis that decrease in hepatic CEACAM1 underlie the causative role of hyperinsulinemia in diet - induced insulin underground. To this conclusion, we will in Aim 1, investigate whether preventing hyperinsulinemia curbs diet - induce insulin resistor in a model of hepatic Ceacam1 gain-

noa propose to test the hykothesis that redocrion ii hepatjc CEACAO1 underlies the causative rope of htperinsulinemia in dieg-induced pnsulin rwsisuance. To this end, we will in Aij 1, inrewtigate whethet preventing hyperinsulinekix eurbs diet-induced insulin resistance in a mpdfl of hepatic Seacsi1 gajn-

now propose to test the hypothesis that hepatic underlies the role of hyperinsulinemia this we will in 1, investigate whether hyperinsulinemia curbs diet-induced insulin resistance in model of hepatic Ceacam1 gain-

now propose to test the hypothEsis that reDuctiOn iN hePaTic CeACAm1 underlies the cAUsatIve role of hyperinsulineMia in DiET-indUCeD insuLin resiSTaNCE. To ThIs End, We WIlL in AiM 1, inVestigaTe whether pRevEnTing hyperinsULiNemia curbs DieT-induced insuLin ResistAnCe iN A modeL of HepatIc CeacAM1 gain-

now propose to test the h ypothesisthatred uct io n in  hep atic CEACAM1 u n derl ies the causative role  of h yp e rins u li nemia  in die t -i n d uce din sul in re sista nce . To th is end, we  wi ll  in Aim 1, i n ve stigate wh eth er preventin g h yperin su lin e mia c urb s die t-indu c ed ins ulin resi st a nce in a model o fhepa tic Ceacam1 gain-

now_propose to_test the hypothesis that_reduction in_hepatic_CEACAM1 underlies_the_causative role of_hyperinsulinemia in diet-induced_insulin resistance. To this_end, we will_in_Aim 1, investigate whether preventing hyperinsulinemia curbs diet-induced insulin resistance in a model of_hepatic_Ceacam1 gain-


after global ischemia is still unknown. Our hypotheses is that oxidative stress induced by mild ischemia and reperfusion causes the delayed hippocampal neuronal injury and death through pathways involving both necrosis and apoptosis, and that the latter is exacerbated when mitochondrial dysfunction occurs during reperfusion. It is our aim to test our hypothesis using transgenic mice overexpressing Sod1

after global ischemia is still unknown. Our hypotheses is that oxidative tension induce by mild ischemia and reperfusion causes the stay hippocampal neural injury and death through pathways involve both necrosis and apoptosis, and that the latter is exacerbated when mitochondrial dysfunction occurs during reperfusion. It is our purpose to test our hypothesis use transgenic mice overexpressing Sod1

afher global ischemia is suill unknown. Our ktpotheves is that oxkdative stress induced by mipd ischtiia and reperfusiov causes nhe delaywd hmppocampal neuroizl injuvv and featk vhrough pathwayx involvinc both necrosiv xnb apoptosis, and that the latter is evacerbayef when mitochogdrisj dyafunction occurs during reperfusioh. It is our aim to trst our hypothesis using tganshenic mice overexpgessing Sod1

after global ischemia is still unknown. Our that stress induced mild ischemia and neuronal and death through involving both necrosis apoptosis, and that the latter is when mitochondrial dysfunction occurs during reperfusion. It is our aim to test our using transgenic mice overexpressing Sod1

after global ischemia is stilL unknown. OuR hypoTheSes Is That OxidAtive stress indUCed bY mild ischemia and reperfUsion CaUSes tHE dElayeD hippocAMpAL NeuRoNaL inJuRY aNd deaTh tHrough pAthways invOlvInG both necrosiS AnD apoptosis, And That the latteR is ExacerBaTed WHen miTocHondrIal dysFUnctioN occurs duRiNG reperFUsion. It IS OuR aim To test our hypothesIS uSIng transgenic mIce oveReXPrESSinG SoD1

after global ischemia isstill unkn own.Our  hy po thes es i s that oxidati v e st ress induced by mild i schem ia andr ep erfus ion cau s es t hede la yed  h i pp ocamp alneurona l injury a ndde ath throughp at hways invo lvi ng both necr osi s andap opt o sis,and  that  the l a tter i s exacerb at e d when mitocho n d ri al d ysfunction occurs du r ing reperfusio n. Itis ou r aim  to  test ourhy pothe s is usin g  t r a n sge n ic mice overe xpressing S o d1

after_global ischemia_is still unknown. Our_hypotheses is_that_oxidative stress_induced_by mild ischemia_and reperfusion causes_the delayed hippocampal neuronal_injury and death_through_pathways involving both necrosis and apoptosis, and that the latter is exacerbated when mitochondrial_dysfunction_occurs during_reperfusion._It_is our aim to test_our hypothesis using transgenic mice_overexpressing Sod1


efforts designed to prevent and alleviate distress in partners and relationships. Identifying protective factors that encourage some spouses and marriages to thrive and endure in middle adulthood is critical to understanding the determinants of healthy aging and promoting public health. Psychophysical methods will be used to study perception of temporally ordered visual stimulation. Two novel techniques have been

efforts designed to prevent and alleviate distress in partners and relationship. identify protective factors that encourage some spouses and marriage to thrive and endure in center adulthood is critical to understand the determinants of goodly ripening and promoting public health. Psychophysical methods will be use to study perception of temporally ordered ocular stimulation. Two novel techniques have been

efvorts designed to prevenu and alleviate dnwtress in padtners avd relationships. Identifying peotecupve factors that encojrage somv spouses and narriages vk thrivc and cndurz mn middle adultmood is cridical to undervtxnbing the determinants of healthy agigg and lrlmoting public heakeh. Pajcmophysical methods will be used fo studj perception of trmporally ordered visual shimupation. Two novel tfchniques hqve fwen

efforts designed to prevent and alleviate distress and Identifying protective that encourage some and in middle adulthood critical to understanding determinants of healthy aging and promoting health. Psychophysical methods will be used to study perception of temporally ordered visual Two novel techniques have been

efforts designed to prevent aNd alleviatE distResS in PaRtneRs anD relationships. iDentIfying protective factorS that EnCOuraGE sOme spOuses anD MaRRIagEs To ThrIvE AnD enduRe iN middle Adulthood iS crItIcal to undersTAnDing the detErmInants of healThy Aging aNd ProMOting PubLic heAlth. PsYChophySical methOdS Will be USed to stUDY pErcePtion of temporally ORdERed visual stimuLation. twO NoVEL teChnIques have bEeN

efforts designed to preve nt and all eviat e d ist re ss i n pa rtners and rel a tion ships. Identifying pro tecti ve fact o rs  that  encour a ge s ome  s po use sa nd  marr iag es to t hrive andend ur e in middlea du lthood iscri tical to und ers tandin gthe deter min antsof hea l thy ag ing and p ro m otingp ublic h e a lt h. P sychophysical met h od s  will be usedto stu dy pe r c ept ion  of tempor al ly or d ered vi s ua l s tim u lation. Two n ovel techni q ues  havebe en

efforts_designed to_prevent and alleviate distress_in partners_and_relationships. Identifying_protective_factors that encourage_some spouses and_marriages to thrive and_endure in middle_adulthood_is critical to understanding the determinants of healthy aging and promoting public health. Psychophysical_methods_will be_used_to_study perception of temporally ordered_visual stimulation. Two novel techniques_have been


Ps (microbe-associated molecular patterns) from microorganisms and microbial products have significant influence on the suppression of allergic response. This suppressive response was implicated to the induction of regulatory T cells (Treg) by recent revisions of the Hygiene Hypothesis. Therefore we propose to explore and determine how combined airway exposures to

Ps (microbe - associated molecular patterns) from microorganisms and microbial products get meaning influence on the suppression of allergic response. This suppressive reception was entail to the induction of regulatory triiodothyronine cell (Treg) by recent revision of the Hygiene Hypothesis. Therefore we propose to research and determine how combined airway exposures to

Ps (licrobe-associated molecuuar patterns) from micrmorganjsms and microbial products have sigiifixant unfluence on the supprdssion of allergix rewponse. This suppressive rsdponvx was implicatec to the itduction of recuuacory T cells (Treg) by recent revisionf of thr Jygiene Hypothgsis. Uhewefodv ce propose to explore and deterjine hox combined airwsy exposures to

Ps (microbe-associated molecular patterns) from microorganisms and have influence on suppression of allergic implicated the induction of T cells (Treg) recent revisions of the Hygiene Hypothesis. we propose to explore and determine how combined airway exposures to

Ps (microbe-associated molecuLar patternS) from MicRooRgAnisMs anD microbial prodUCts hAve significant influencE on thE sUPpreSSiOn of aLlergic REsPONse. thIs SupPrESsIve reSpoNse was iMplicated tO thE iNduction of reGUlAtory T cellS (TrEg) by recent reVisIons of ThE HyGIene HYpoThesiS. ThereFOre we pRopose to eXpLOre and DEterminE HOw CombIned airway exposurES tO

Ps (microbe-associated mol ecular pat terns ) f rom  m icro orga nisms and micr o bial  products have signifi cantin f luen c eon th e suppr e ss i o n o fal ler gi c  r espon se.  This s uppressive  re sp onse was imp l ic ated to th e i nduction ofreg ulator yT c e lls ( Tre g) by  recen t  revis ions of t he Hygien e  Hypoth e s is . Th erefore we propos e  t o  explore and d etermi ne ho w com bin ed airwayex posur e s to

Ps (microbe-associated_molecular patterns)_from microorganisms and microbial_products have_significant_influence on_the_suppression of allergic_response. This suppressive_response was implicated to_the induction of_regulatory_T cells (Treg) by recent revisions of the Hygiene Hypothesis. Therefore we propose to_explore_and determine_how_combined_airway exposures to


use with an isolated perfused hindlimb preparation. We will determine the energy contribution of branched-chain amino acid oxidation, the extent of oxidative deamination of glutarate, and the mode of amine nitrogen elimination from the working muscle. A major adaptation induced in skeletal muscle by training is an increase in the capacity for ATP

use with an isolated perfused hindlimb readiness. We will settle the energy contribution of branched - chain amino acid oxidation, the extent of oxidative deamination of glutarate, and the modality of amine nitrogen elimination from the working muscle. A major adaptation induced in bony muscle by training is an increase in the capability for ATP

usf with an isolated perfured hindlimb prgpqratioi. We wiml deteroine the energy contribution od brabched-chain amino acid uxidation, the extwnt id oxidativx deamination kn glucacate, and the moce of amina nitrogen elikivacion from the working muscle. A major adaptayiln induced in fkelttaj muablt by training is an increase in tge capabity for ATP

use with an isolated perfused hindlimb preparation. determine energy contribution branched-chain amino acid deamination glutarate, and the of amine nitrogen from the working muscle. A major induced in skeletal muscle by training is an increase in the capacity for

use with an isolated perfused Hindlimb prEparaTioN. We WiLl deTermIne the energy coNTribUtion of branched-chain amIno acId OXidaTIoN, the eXtent of OXiDATivE dEaMinAtIOn Of gluTarAte, and tHe mode of amIne NiTrogen eliminATiOn from the wOrkIng muscle. A maJor AdaptaTiOn iNDuced In sKeletAl muscLE by traIning is an InCRease iN The capaCITy For AtP

use with an isolated perf used hindl imb p rep ara ti on.We w ill determinet he e nergy contribution ofbranc he d -cha i namino  acid o x id a t ion ,th e e xt e nt  of o xid ative d eamination  of  g lutarate, an d  t he mode of  am ine nitrogen  el iminat io n f r om th e w orkin g musc l e. A m ajor adap ta t ion in d uced in s ke leta l muscle by train i ng is an increase  in th ec ap a c ity  fo r ATP

use_with an_isolated perfused hindlimb preparation._We will_determine_the energy_contribution_of branched-chain amino_acid oxidation, the_extent of oxidative deamination_of glutarate, and_the_mode of amine nitrogen elimination from the working muscle. A major adaptation induced in_skeletal_muscle by_training_is_an increase in the capacity_for ATP


and other cytokines, immunologic and virologic parameters. This study will address the mechanisms of HIV-induced wasting and investigate the role of two potential medical treatments. Injection drug use is a serious public health problem, leading to blood-borne infections including HBC, HCV, and HIV. In spite of advances in

and other cytokines, immunologic and virologic parameters. This discipline will cover the mechanisms of HIV - induced cachexia and investigate the character of two potential medical discussion. Injection drug manipulation is a serious public health trouble, go to blood - hold infections including HBC, HCV, and HIV. In cattiness of progress in

anf other cytokines, immunouogic and virologic pacametera. This sgudy will address the mechanmsms of HUV-induced wasting and knvestigane the rooe oh two potential medical bxeatmskts. Iujxction drug use is a serimus public heantf 'roblem, leading to blood-borne infectyons invlkding HBC, HCV, wnd NYV. Ih spite of advances in

and other cytokines, immunologic and virologic parameters. will the mechanisms HIV-induced wasting and potential treatments. Injection drug is a serious health problem, leading to blood-borne infections HBC, HCV, and HIV. In spite of advances in

and other cytokines, immunoloGic and viroLogic ParAmeTeRs. ThIs stUdy will address THe meChanisms of HIV-induced waSting AnD InveSTiGate tHe role oF TwO POteNtIaL meDiCAl TreatMenTs. InjecTion drug usE is A sErious public HEaLth problem, LeaDing to blood-bOrnE infecTiOns INcludIng hBC, HCv, and HIv. in spitE of advancEs IN

and other cytokines, immu nologic an d vir olo gic  p aram eter s. This studyw illaddress the mechanisms  of H IV - indu c ed  wast ing and in v e sti ga te  th er ol e oftwo  potent ial medica l t re atments. Inj e ct ion drug u seis a serious  pu blic h ea lth probl em,  lead ing to blood- borne inf ec t ions i n cluding H BC , HC V, and HIV. In sp i te of advances in

and_other cytokines,_immunologic and virologic parameters._This study_will_address the_mechanisms_of HIV-induced wasting_and investigate the_role of two potential_medical treatments. Injection_drug_use is a serious public health problem, leading to blood-borne infections including HBC, HCV,_and_HIV. In_spite_of_advances in


long-term work in a particular occupation and the onset of chronic disease later in life. A secondary aim is to test the utility o that process for assessing the relationship between long-term exposure to various job characteristics and activities (e.g., handling materials and objects) and subsequent chronic disease outcomes (e.g.,

long - term work in a particular occupation and the attack of chronic disease subsequently in life. A secondary purpose is to quiz the utility o that summons for assess the relationship between retentive - term exposure to versatile job characteristics and activeness (for example, handling materials and object) and subsequent chronic disease outcomes (e.g.,

lojg-term work in a particuuar occupation cbd the onset of chrovic disease later in life. A dexondaey aim is to test the jtility o that pricesw for assessing the relatjlnshnp between long-tgrm exposure to various jot zhcracteristics and activities (e.g., handjing mayegials and objests) sgd shbsequent chronic disease outcomes (e.g.,

long-term work in a particular occupation and of disease later life. A secondary utility that process for the relationship between exposure to various job characteristics and (e.g., handling materials and objects) and subsequent chronic disease outcomes (e.g.,

long-term work in a particular Occupation And thE onSet Of ChroNic dIsease later in lIFe. A sEcondary aim is to test the UtiliTy O That PRoCess fOr assesSInG THe rElAtIonShIP bEtweeN loNg-term eXposure to vAriOuS job characteRIsTics and actIviTies (e.g., handliNg mAteriaLs And OBjectS) anD subsEquent CHronic Disease ouTcOMes (e.g.,

long-term work in a parti cular occu patio n a ndth e on setof chronic dis e aselater in life. A secon daryai m  ist otestthe uti l it y o t ha tpro ce s sfor a sse ssing t he relatio nsh ip  between lon g -t erm exposu reto various j obcharac te ris t ics a ndactiv ities( e.g.,handlingma t erials and obj e c ts ) an d subsequent chro n ic disease outcom es (e. g. ,

long-term_work in_a particular occupation and_the onset_of_chronic disease_later_in life. A_secondary aim is_to test the utility_o that process_for_assessing the relationship between long-term exposure to various job characteristics and activities (e.g., handling_materials_and objects)_and_subsequent_chronic disease outcomes (e.g.,


research is to develop new therapies that will increase the number of patients who are non-diabetic following islet autotransplant. Such therapies may also benefit recipients of islet allotransplant for type 1 diabetes. Following islet transplantation, the islets must acutely survive the stress of the procedure, and then they must

research is to develop new therapies that will increase the numeral of patient who are non - diabetic following islet autotransplant. Such therapies may besides benefit recipients of islet allotransplant for character 1 diabetes. trace islet transplant, the islets must acutely outlive the stress of the procedure, and then they must

redearch is to develop new therapies that will iicrease the numcer of patients who are non-dmaberic fillowing islet autotravsplant. Slch therapies nay also bxhefit rceipiehbs of mslet allotransklant for ty[e 1 diabetes. Fmluocing islet transplantation, the isletf must scktely survive jhe surefs or the procedure, and then they must

research is to develop new therapies that the of patients are non-diabetic following also recipients of islet for type 1 Following islet transplantation, the islets must survive the stress of the procedure, and then they must

research is to develop new theRapies that Will iNcrEasE tHe nuMber Of patients who aRE non-Diabetic following islet AutotRaNSplaNT. SUch thErapies MAy ALSo bEnEfIt rEcIPiEnts oF isLet alloTransplant For TyPe 1 diabetes. FoLLoWing islet tRanSplantation, tHe iSlets mUsT acUTely sUrvIve thE stresS Of the pRocedure, aNd THen theY Must

research is to develop ne w therapie s tha t w ill  i ncre asethe number ofp atie nts who are non-diabet ic fo ll o wing is let a utotran s pl a n t.Su ch  th er a pi es ma y a lso ben efit recip ien ts  of islet al l ot ransplantfor  type 1 diab ete s. Fol lo win g  isle t t ransp lantat i on, th e isletsmu s t acut e ly surv i v ethestress of the pro c ed u re, and then t hey mu st

research_is to_develop new therapies that_will increase_the_number of_patients_who are non-diabetic_following islet autotransplant._Such therapies may also_benefit recipients of_islet_allotransplant for type 1 diabetes. Following islet transplantation, the islets must acutely survive the_stress_of the_procedure,_and_then they must


several gaps in our knowledge. The first concerns the role of topoisomerase I in DNA repair. How are DNA repair processes dependent upon the type of initial lesion? Is topoisomerase I involved in the repair of all kinds of DNA lesions? From a practical point of view, the combination of topoisomerase I inhibitors

several gaps in our knowledge. The first concern the function of topoisomerase I in DNA repair. How are DNA repair process dependent upon the type of initial wound? Is topoisomerase I involved in the repair of all kinds of deoxyribonucleic acid lesion? From a practical compass point of view, the combination of topoisomerase I inhibitors

segeral gaps in our knowleage. The first concerns the rkle of tupoisomerase I in DNA repair. Hiw art DNA repair procesres depenfent upob tht type of initial lesion? Lf tollisokxrase I involvec in the rapair of all khnas of DNA lesions? From a practical poynt of fifw, the combinajion ps toloisomerase I inhibitors

several gaps in our knowledge. The first role topoisomerase I DNA repair. How upon type of initial Is topoisomerase I in the repair of all kinds DNA lesions? From a practical point of view, the combination of topoisomerase I

several gaps in our knowledge. the first coNcernS thE roLe Of toPoisOmerase I in DNA rEPair. how are DNA repair processEs depEnDEnt uPOn The tyPe of iniTIaL LEsiOn? is TopOiSOmErase i inVolved iN the repair Of aLl Kinds of DNA leSIoNs? From a praCtiCal point of viEw, tHe combInAtiON of toPoiSomerAse I inHIbitorS

several gaps in our knowl edge. Thefirst  co nce rn s th e ro le of topoisom e rase  I in DNA repair. Howare D NA repa i rproce sses de p en d e ntup on  th et yp e ofini tial le sion? Is t opo is omerase I in v ol ved in the  re pair of allkin ds ofDN A l e sions ? F rom a  pract i cal po int of vi ew ,  the c o mbinati o n  o f to poisomerase I inh i bi t ors

several_gaps in_our knowledge. The first_concerns the_role_of topoisomerase_I_in DNA repair._How are DNA_repair processes dependent upon_the type of_initial_lesion? Is topoisomerase I involved in the repair of all kinds of DNA lesions?_From_a practical_point_of_view, the combination of topoisomerase_I inhibitors


-led group program, Combating Prejudice and Discrimination through Photovoice Empowerment, which blends Photovoice, a novel public health participatory action research methodology, with psychoeducation and teaching proactive coping strategies to empower individuals with serious mental illnesses to resist public prejudice and discrimination, and participate in the community

-led group program, Combating Prejudice and Discrimination through Photovoice Empowerment, which blends Photovoice, a novel public health participatory legal action inquiry methodology, with psychoeducation and teaching proactive coping scheme to endow individuals with serious mental illness to protest public prejudice and discrimination, and enter in the residential district

-led group program, Combating Prejudice and Buscrimmnation through Photovoice Empowerment, whici blwnds Kkotovoice, a novel puclic healnh particupatiey action cssearch methosllogv, xith psychoeducstion and deaching proacdixe coping strategies to empower indivyduals eihh serious menjal ikjnesavs to resist public prejudice ahd discgimination, and patticipate in the community

-led group program, Combating Prejudice and Discrimination Empowerment, blends Photovoice, novel public health psychoeducation teaching proactive coping to empower individuals serious mental illnesses to resist public and discrimination, and participate in the community

-led group program, Combating PRejudice anD DiscRimInaTiOn thRougH Photovoice EmpOWermEnt, which blends PhotovoiCe, a noVeL PublIC hEalth ParticiPAtORY acTiOn ResEaRCh MethoDolOgy, with PsychoeducAtiOn And teaching pROaCtive copinG stRategies to emPowEr indiViDuaLS with SerIous mEntal iLLnesseS to resist PuBLic preJUdice anD DIsCrimInation, and particiPAtE In the community

-led group program, Combat ing Prejud ice a ndDis cr imin atio n through Phot o voic e Empowerment, which b lends  P h otov o ic e, anovel p u bl i c  he al th  pa rt i ci pator y a ction r esearch me tho do logy, with p s yc hoeducatio n a nd teachingpro active  c opi n g str ate giesto emp o wer in dividuals  w i th ser i ous men t a lilln esses to resist p u bl i c prejudice an d disc ri m in a t ion , a nd partici pa te in the com m un i t y

-led group_program, Combating_Prejudice and Discrimination through_Photovoice Empowerment,_which_blends Photovoice,_a_novel public health_participatory action research_methodology, with psychoeducation and_teaching proactive coping_strategies_to empower individuals with serious mental illnesses to resist public prejudice and discrimination, and_participate_in the_community


The Urokinase is supplied by the National Heart and Lung Institute, and is derived from the stockpile of the Urokinase subcommittee which approved of this protocol and hence released the amount of urokinase sufficient for this project. We aim to compare anticoagulant therapy and the use of Urokinase therapy. All

The Urokinase is supplied by the National Heart and Lung Institute, and is derived from the stockpile of the Urokinase subcommittee which approved of this protocol and therefore release the amount of plasminogen activator sufficient for this project. We draw a bead on to compare anticoagulant therapy and the use of Urokinase therapy. All

Thf Urokinase is supplied ny the National Kwart aid Lung Instituge, and is derived from the svockpile if the Urokinase subcoomittee wjich appeovev of this protocol and hcuce rspeaszd the amount of urokinase sufficient fos ghns project. We aim to compare anticoadulant yhfrapy and the ose og Uroipncse therapy. All

The Urokinase is supplied by the National Lung and is from the stockpile approved this protocol and released the amount urokinase sufficient for this project. We to compare anticoagulant therapy and the use of Urokinase therapy. All

The Urokinase is supplied by tHe National heart And lunG INstiTute, And is derived frOM the Stockpile of the UrokinasE subcOmMItteE WhIch apProved oF ThIS ProToCoL anD hENcE releAseD the amoUnt of urokiNasE sUfficient for THiS project. We Aim To compare antIcoAgulanT tHerAPy and The Use of urokinASe therApy. All

The Urokinase is supplied  by the Na tiona l H ear tandLung  Institute, an d  isderived from the stock pileof theU ro kinas e subco m mi t t eewh ic h a pp r ov ed of  th is prot ocol and h enc ereleased the am ount of ur oki nase suffici ent  for t hi s p r oject . W e aim  to co m pare a nticoagul an t  thera p y and t h e  u se o f Urokinase thera p y. All

The_Urokinase is_supplied by the National_Heart and_Lung_Institute, and_is_derived from the_stockpile of the_Urokinase subcommittee which approved_of this protocol_and_hence released the amount of urokinase sufficient for this project. We aim to compare_anticoagulant_therapy and_the_use_of Urokinase therapy. All


osome in the nucleolus. We propose to study in Saccharomyces cerevisiae the mechanisms controlling both the transcription of ribosomal RNA and the synthesis of ribosomal proteins. Ribosomal RNA: We have identified a sequence in the rDNA repeat with many of the properties of an enhancer element. We plan to identify the precise sequences involved

osome in the nucleolus. We propose to study in Saccharomyces cerevisiae the mechanisms controlling both the arrangement of ribosomal RNA and the deduction of ribosomal proteins. Ribosomal RNA: We have identified a succession in the rDNA repeat with many of the properties of an foil element. We plan to name the precise sequences involved

osole in the nucleolus. We pvopose to study nb Sacciaromycss cerevksiae the mechanisms controlpibg bouk the transcription uf ribosolal RNA qnd uhe synthesis of cjbosomal protslns. Rnbisomal RNA: We mave identixied a sequenca kn the rDNA repeat with many of the pwopertirs of an enhancet elekqnt. Sv klan to identify the precise sequsnces iivolved

osome in the nucleolus. We propose to Saccharomyces the mechanisms both the transcription synthesis ribosomal proteins. Ribosomal We have identified sequence in the rDNA repeat with of the properties of an enhancer element. We plan to identify the precise involved

osome in the nucleolus. We propOse to study In SacChaRomYcEs ceReviSiae the mechaniSMs coNtrolling both the transcRiptiOn OF ribOSoMal RNa and the SYnTHEsiS oF rIboSoMAl ProteIns. ribosomAl RNA: We havE idEnTified a sequeNCe In the rDNA rEpeAt with many of The ProperTiEs oF An enhAncEr eleMent. We PLan to iDentify thE pREcise sEQuences INVoLved

osome in the nucleolus. We  propose t o stu dyinSa ccha romy ces cerevisiae themechanisms controlling  both  t h e tr a ns cript ion ofr ib o s oma lRN A a nd th e syn the sis ofribosomalpro te ins. Ribosom a lRNA: We ha veidentified a  se quence  i n t h e rDN A r epeat  withm any of  the prop er t ies of an enha n c er  ele ment. We plan toi de n tify the preci se seq ue n ce s inv olv ed

osome in_the nucleolus._We propose to study_in Saccharomyces_cerevisiae_the mechanisms_controlling_both the transcription_of ribosomal RNA_and the synthesis of_ribosomal proteins. Ribosomal_RNA:_We have identified a sequence in the rDNA repeat with many of the properties_of_an enhancer_element._We_plan to identify the precise_sequences involved


as realize the scientific goals of the Center. The ACE Administrative Core will accomplish four Specific Aims during this funding period: Aim 1 Create and maintain a knowledgeable, skilled, and interdisciplinary leadership team that is connected to the research and the wider network; Aim 2 Design and implement a clear and effective communication plan across the Center

as realize the scientific goals of the Center. The ACE Administrative Core will accomplish four Specific Aims during this funding time period: Aim 1 make and maintain a knowledgeable, skilled, and interdisciplinary leadership team that is connected to the inquiry and the wider network; Aim 2 Design and implement a clean and effective communication plan across the Center

as realize the scientific noals of the Cenjee. The ECE Admjnistratkve Core will accomplish fouc Spwcifix Aims during this funaing perild: Aim 1 Xreaue and maintain a knowlednzable, dkilnxd, and interdisgiplinary laadership team tfac is connected to the research and tre widet jetwork; Aim 2 Dgsign wnd jmplement a clear and effective cojmunicauion plan across tne Center

as realize the scientific goals of the ACE Core will four Specific Aims 1 and maintain a skilled, and interdisciplinary team that is connected to the and the wider network; Aim 2 Design and implement a clear and effective plan across the Center

as realize the scientific goaLs of the CenTer. ThE ACe AdMiNistRatiVe Core will accoMPlisH four Specific Aims durinG this FuNDing PErIod: AiM 1 Create ANd MAIntAiN a KnoWlEDgEable, SkiLled, and InterdisciPliNaRy leadership TEaM that is conNecTed to the reseArcH and thE wIdeR NetwoRk; AIm 2 DesIgn and IMplemeNt a clear aNd EFfectiVE communICAtIon pLan across the CenteR

as realize the scientific  goals ofthe C ent er.  T he A CE A dministrativeC orewill accomplish four S pecif ic Aims du ringthis fu n di n g  pe ri od : A im 1Creat e a nd main tain a kno wle dg eable, skill e d,  and inter dis ciplinary le ade rshipte amt hat i s c onnec ted to the re search an dt he wid e r netwo r k ;Aim2 Design and impl e me n t a clear andeffect iv e  c o m mun ica tion planac rosst he Cent e r

as_realize the_scientific goals of the_Center. The_ACE_Administrative Core_will_accomplish four Specific_Aims during this_funding period: Aim 1_Create and maintain_a_knowledgeable, skilled, and interdisciplinary leadership team that is connected to the research and the_wider_network; Aim_2_Design_and implement a clear and_effective communication plan across the_Center


, the KSPXK peptide showed a mainly extended conformation with beta-turns. These differences revealed a structural specificity for the substrate of this kinase. using two dimensional NMR methods and molecular modeling. We are also studying the mechanism of cdk5 activation. Though, cdk5 is similar to other cdc2

, the KSPXK peptide showed a mainly extended conformation with beta - turn. These dispute revealed a structural specificity for the substrate of this kinase. using two dimensional NMR method acting and molecular modeling. We are also learn the mechanism of cdk5 energizing. Though, cdk5 is similar to other cdc2

, thf KSPXK peptide showed a mainly extendeb confocmation with bega-turns. These differences retealwd a wtructural specificity for the dubstratw of rhis kinasx. using bco dijcnsiouao NMR methods snd molecunar modeling. Wa xrz also studying the mechanism of cdk5 activayiln. Though, cdk5 ys spmylar no other cdc2

, the KSPXK peptide showed a mainly with These differences a structural specificity kinase. two dimensional NMR and molecular modeling. are also studying the mechanism of activation. Though, cdk5 is similar to other cdc2

, the KSPXK peptide showed a maiNly extendeD confOrmAtiOn With Beta-Turns. These diffERencEs revealed a structural sPecifIcITy foR ThE subsTrate of THiS KInaSe. UsIng TwO DiMensiOnaL NMR metHods and molEcuLaR modeling. We aRE aLso studyinG thE mechanism of Cdk5 ActivaTiOn. THOugh, cDk5 iS simiLar to oTHer cdc2

, the KSPXK peptide showed  a mainlyexten ded  co nf orma tion  with beta-tur n s. T hese differences revea led a  s t ruct u ra l spe cificit y  f o r  th esu bst ra t eof th iskinase.  using two  di me nsional NMRm et hods and m ole cular modeli ng.  We ar eals o  stud yin g the  mecha n ism of  cdk5 act iv a tion.T hough,c d k5  issimilar to otherc dc 2

, the_KSPXK peptide_showed a mainly extended_conformation with_beta-turns._These differences_revealed_a structural specificity_for the substrate_of this kinase. using_two dimensional NMR_methods_and molecular modeling. We are also studying the mechanism of cdk5 activation. Though, cdk5_is_similar to_other_cdc2


, various novel imaging characteristics that may prove to be better predictors of breast cancer risk than standard mammographic density. We have published the first formal method for enumerating cells in breast duct lavage (BDL) fluid, described the results of BDL in the largest cohort of BRCA mutation carriers yet reported, and quantified the

, various novel imaging characteristics that may prove to be good predictor of breast cancer risk than standard mammographic density. We have published the beginning formal method for count cell in breast duct lavage (BDL) fluid, described the consequence of BDL in the largest cohort of BRCA mutant carriers yet reported, and quantified the

, vagious novel imaging charxcteristics thaj nay prmve to be bettdr predictors of breast cancxr rusk tyan standard mammograpfic densiny. We havw puulished the firsv formal methos for xnumerating celks in breavt duct lavage (BAL) fluid, described the results of BDL in the lwrgest cohort jf BGCW mufation carriers yet reported, and qhantifitd the

, various novel imaging characteristics that may be predictors of cancer risk than published first formal method enumerating cells in duct lavage (BDL) fluid, described the of BDL in the largest cohort of BRCA mutation carriers yet reported, and the

, various novel imaging characTeristics tHat maY prOve To Be beTter Predictors of brEAst cAncer risk than standard mAmmogRaPHic dENsIty. We Have pubLIsHED thE fIrSt fOrMAl MethoD foR enumerAting cells In bReAst duct lavagE (bDl) fluid, descRibEd the results Of BdL in thE lArgESt cohOrt Of BRCa mutatIOn carrIers yet rePoRTed, and QUantifiED ThE

, various novel imaging ch aracterist ics t hat  ma yprov e to  be better pre d icto rs of breast cancer ri sk th an stan d ar d mam mograph i cd e nsi ty .Weha v epubli she d the f irst forma l m et hod for enum e ra ting cells  in  breast duct  la vage ( BD L)f luid,  de scrib ed the result s of BDLin the la r gest co h o rt  ofBRCA mutation car r ie r s yet reported , andqu a nt i f ied  th e

, various_novel imaging_characteristics that may prove_to be_better_predictors of_breast_cancer risk than_standard mammographic density._We have published the_first formal method_for_enumerating cells in breast duct lavage (BDL) fluid, described the results of BDL in_the_largest cohort_of_BRCA_mutation carriers yet reported, and_quantified the


a requirement for each of 8 cysteine codons within the region for proper folding of the v-sis gene project. These studies have also predicted three testable models for the active conformation of this protein are represent an important step in identifying the receptor binding domain of this oncogenic growth factor. The BLAST family of protein and DNA

a requirement for each of 8 cysteine codons within the region for proper folding of the five - systeme international d'unites gene project. These studies have besides predicted three testable mannequin for the active conformation of this protein are represent an significant step in identifying the sense organ constipate knowledge domain of this oncogenic growth factor. The good time family of protein and DNA

a gequirement for each of 8 cysteine codons withii the rsgion fof proper folding of the v-sis gwne peoject. These studies hxve also iredicted thrte testable models for thc actjye coufirmation of thls protein dre represent dn ilportant step in identifying the reseptor nijding domain os thps onckgenic growth factor. The BLAST famjly of krotein and DNA

a requirement for each of 8 cysteine the for proper of the v-sis also three testable models the active conformation this protein are represent an important in identifying the receptor binding domain of this oncogenic growth factor. The BLAST of protein and DNA

a requirement for each of 8 cystEine codons WithiN thE reGiOn foR proPer folding of thE V-sis Gene project. These studieS have AlSO preDIcTed thRee testABlE MOdeLs FoR thE aCTiVe conForMation oF this proteIn aRe Represent an iMPoRtant step iN idEntifying the RecEptor bInDinG DomaiN of This oNcogenIC growtH factor. ThE BlaST famILy of proTEIn And DnA

a requirement for each of  8 cystein e cod ons  wi th in t he r egion for prop e r fo lding of the v-sis gen e pro je c t. T h es e stu dies ha v ea l sopr ed ict ed th ree t est able mo dels for t heac tive conform a ti on of this  pr otein are re pre sent a nimp o rtant  st ep in  ident i fyingthe recep to r  bindi n g domai n of  thi s oncogenic growt h  f a ctor. The BLAS T fami ly of p rot ein  and DNA

a_requirement for_each of 8 cysteine_codons within_the_region for_proper_folding of the_v-sis gene project._These studies have also_predicted three testable_models_for the active conformation of this protein are represent an important step in identifying_the_receptor binding_domain_of_this oncogenic growth factor. The_BLAST family of protein and_DNA


The proposed experiments are aimed at the discovery of drug-like compounds that can target Shp2?s unique allosteric site, potentially providing highly selective Shp2 inhibitors that have not been realized through active-site- directed efforts. Also proposed are small-molecule-discovery efforts targeting two disease- causing Sh

The proposed experiments are aimed at the discovery of drug - like compound that can target Shp2?s alone allosteric site, potentially providing highly selective Shp2 inhibitors that have not been understand through active - site- directed efforts. besides proposed are small - molecule - discovery attempt targeting two disease- causing Sh

Thf proposed experiments ave aimed at the buscovecy of ddug-like zompounds that can target Sh'2?s ubique allosteric site, potengially prlviding yighot selectivx Shp2 inmnbitodd thct have not been realized dhrough active-vige- directed efforts. Also proposed are small-mplfcule-discovery effpwts fargeting two disease- causing Sh

The proposed experiments are aimed at the drug-like that can Shp2?s unique allosteric Shp2 that have not realized through active-site- efforts. Also proposed are small-molecule-discovery efforts two disease- causing Sh

The proposed experiments are Aimed at the DiscoVerY of DrUg-liKe coMpounds that can TArgeT Shp2?s unique allosteric sIte, poTeNTialLY pRovidIng highLY sELEctIvE SHp2 iNhIBiTors tHat Have not Been realizEd tHrOugh active-siTE- dIrected effOrtS. Also proposeD arE small-MoLecULe-disCovEry efForts tARgetinG two diseaSe- CAusing sH

The proposed experimentsare aimedat th e d isc ov eryof d rug-like compo u ndsthat can target Shp2?s  uniq ue allo s te ric s ite, po t en t i all ypr ovi di n ghighl y s electiv e Shp2 inh ibi to rs that have no t been rea liz ed through a cti ve-sit e-  di r ected  ef forts . Also propos ed are sm al l -molec u le-disc o v er y ef forts targeting t w od isease- causin g Sh

The_proposed experiments_are aimed at the_discovery of_drug-like_compounds that_can_target Shp2?s unique_allosteric site, potentially_providing highly selective Shp2_inhibitors that have_not_been realized through active-site- directed efforts. Also proposed are small-molecule-discovery efforts targeting two disease-_causing_Sh


discoveries regarding well-being over the lifespan. The goal of the final specific aim will be to evaluate how previous aging- related well-being findings obtained with evaluative measures generalize to experiential methods. More importantly, the data from this longitudinal study will be made publicly available so that other researchers can advance the science of

discoveries regarding well - being over the lifespan. The finish of the concluding specific bearing will be to evaluate how former aging- related good - being findings obtained with appraising measures generalize to experiential methods. More importantly, the datum from this longitudinal discipline will be made publicly available so that early researchers can advance the science of

didcoveries regarding well-neing over the lndespan. The gkal of tfe final specific aim will bx to evalyate how previous agine- related well-beibg fmndings obtained with evaluatibc meavnres generalize to experiantial methods. Murz importantly, the data from this londitudinsl study will be madt ptblidly available so that other researdhers cen advance the xcience of

discoveries regarding well-being over the lifespan. The the specific aim be to evaluate findings with evaluative measures to experiential methods. importantly, the data from this longitudinal will be made publicly available so that other researchers can advance the science

discoveries regarding well-bEing over thE lifeSpaN. ThE gOal oF the Final specific aIM wilL be to evaluate how previoUs agiNg- RElatED wEll-beIng findINgS OBtaInEd WitH eVAlUativE meAsures gEneralize tO exPeRiential methODs. more importAntLy, the data froM thIs longItUdiNAl stuDy wIll be Made puBLicly aVailable sO tHAt otheR ResearcHERs Can aDvance the science oF

discoveries regarding wel l-being ov er th e l ife sp an.Thegoal of the fi n al s pecific aim will be to  eval ua t e ho w  p revio us agin g -r e lat ed  w ell -b e in g fin din gs obta ined witheva lu ative measur e sgeneralize  to  experientia l m ethods .Mor e  impo rta ntly,  the d a ta fro m this lo ng i tudina l  studyw i ll  bemade publicly ava i la b le so that oth er res ea r ch e r s c anadvance th escien c e of

discoveries_regarding well-being_over the lifespan. The_goal of_the_final specific_aim_will be to_evaluate how previous_aging- related well-being findings_obtained with evaluative_measures_generalize to experiential methods. More importantly, the data from this longitudinal study will be_made_publicly available_so_that_other researchers can advance the_science of


maturation of GCs. PKA accomplishes this integrating function by phosphorylating substrates that directly regulate transcription or by regulating pathways whose targets regulate transcription. The co-activator beta-catenin is emerging as one potential PKA substrate necessary for activation of a subset of FSH target genes. PKA also phosphorylates

maturation of GCs. PKA accomplishes this integrating function by phosphorylating substrate that immediately regulate transcription or by determine pathway whose targets regulate recording. The colorado - activator beta - catenin is emerging as one likely PKA substrate necessary for energizing of a subset of FSH target genes. PKA besides phosphorylates

mahuration of GCs. PKA accooplishes this iuregratmng fundtion by phosphorylating substrates vhat dirextly regulate transcriotion or hy regulqtinj pathways whose targets regulzbe trcnwcription. The go-activator beta-catenin iv dmzrging as one potential PKA substratq necesxagy for activatyon ps a albwet of FSH target genes. PKA amso phovphorylates

maturation of GCs. PKA accomplishes this integrating phosphorylating that directly transcription or by transcription. co-activator beta-catenin is as one potential substrate necessary for activation of a of FSH target genes. PKA also phosphorylates

maturation of GCs. PKA accomplIshes this iNtegrAtiNg fUnCtioN by pHosphorylating SUbstRates that directly regulAte trAnSCripTIoN or by RegulatINg PAThwAyS wHosE tARgEts reGulAte tranScription. THe cO-aCtivator beta-CAtEnin is emerGinG as one potentIal pKA subStRatE NecesSarY for aCtivatIOn of a sUbset of FSh tARget geNEs. PKA alSO PhOsphOrylates

maturation of GCs. PKA ac complishes  this  in teg ra ting  fun ction by phosp h oryl ating substrates thatdirec tl y  reg u la te tr anscrip t io n orby  r egu la t in g pat hwa ys whos e targetsreg ul ate transcri p ti on. The co -ac tivator beta -ca teninis  em e rging  as  onepotent i al PKA  substrat en ecessa r y for a c t iv atio n of a subset ofF SH target genes.PKA al so ph o s pho ryl ates

maturation_of GCs._PKA accomplishes this integrating_function by_phosphorylating_substrates that_directly_regulate transcription or_by regulating pathways_whose targets regulate transcription._The co-activator beta-catenin_is_emerging as one potential PKA substrate necessary for activation of a subset of FSH_target_genes. PKA_also_phosphorylates


high density range by a receptor-mediated process not associated with lipoprotein endocytosis and lysosomal degradation. These observations raise two major questions which our proposal is designed to answer: (1) What properties of the lipoprotein are responsible for "HDL receptor" recognition and cholesterol uptake? (2) What is the mechanism by which adren

high density range by a receptor - intercede procedure not associated with lipoprotein endocytosis and lysosomal degradation. These observations rear two major questions which our proposal is design to suffice: (1) What properties of the lipoprotein are responsible for " HDL receptor " recognition and cholesterol uptake? (2) What is the mechanism by which adren

hihh density range by a regeptor-mediated ptoxess nmt asskciated dith lipoprotein endocytosis abd lywosomal degradation. Thdse obsernations rqise rwo major questions whicg our 'roposal is deslgned to anvwer: (1) What pro[eftnes of the lipoprotein are responsibje for "NDP receptor" recjgniuiog ans cholesterol uptake? (2) What is the jechanivm by which acren

high density range by a receptor-mediated process with endocytosis and degradation. These observations our is designed to (1) What properties the lipoprotein are responsible for "HDL recognition and cholesterol uptake? (2) What is the mechanism by which adren

high density range by a receptOr-mediated ProceSs nOt aSsOciaTed wIth lipoprotein ENdocYtosis and lysosomal degrAdatiOn. tHese OBsErvatIons raiSE tWO MajOr QuEstIoNS wHich oUr pRoposal Is designed To aNsWer: (1) What propeRTiEs of the lipOprOtein are respOnsIble foR "HdL rECeptoR" reCogniTion anD CholesTerol uptaKe? (2) wHat is tHE mechanISM bY whiCh adren

high density range by a r eceptor-me diate d p roc es s no t as sociated withl ipop rotein endocytosis and  lyso so m al d e gr adati on. The s eo b ser va ti ons  r a is e two  ma jor que stions whi chou r proposal i s  d esigned to  an swer: (1) Wh atproper ti eso f the  li popro tein a r e resp onsible f or "HDL r e ceptor" r ec ogni tion and choleste r ol uptake? (2) Wh at isth e  m e c han ism  by whichad ren

high_density range_by a receptor-mediated process_not associated_with_lipoprotein endocytosis_and_lysosomal degradation. These_observations raise two_major questions which our_proposal is designed_to_answer: (1) What properties of the lipoprotein are responsible for "HDL receptor" recognition and_cholesterol_uptake? (2)_What_is_the mechanism by which adren


abnormal protrusion of the facial nuclei into the 4th ventricle, premature arrest of the pontine migrational stream, and slowed migration of cerebellar granule cells. This study provides evidence that NMHC II-B is required for migration of certain groups of neuronal cells. Removal of the Neo cassette from B-R/

abnormal protrusion of the facial nuclei into the 4th ventricle, premature apprehension of the pontine migrational flow, and slowed migration of cerebellar granule cells. This discipline provide evidence that NMHC II - B is required for migration of certain group of neuronal cells. Removal of the Neo cassette from bacillus - R/

abjormal protrusion of the facial nuclei nbto thx 4th vehtricle, oremature arrest of the pontmne nigrauponal stream, and slowdd migratpon of ceeebeooar granulx cells. Bkis sfmdy pxotides evidence jhat NMHC II-T is required xof ligration of certain groups of neurjnal cekld. Removal of tre Nto sasssntt from B-R/

abnormal protrusion of the facial nuclei into ventricle, arrest of pontine migrational stream, granule This study provides that NMHC II-B required for migration of certain groups neuronal cells. Removal of the Neo cassette from B-R/

abnormal protrusion of the faCial nuclei Into tHe 4tH veNtRiclE, preMature arrest of THe poNtine migrational stream, And slOwED migRAtIon of CerebelLAr GRAnuLe CeLls. thIS sTudy pRovIdes eviDence that NmHC iI-b is required fOR mIgration of CerTain groups of NeuRonal cElLs. REMoval Of tHe Neo CassetTE from B-r/

abnormal protrusion of th e facial n uclei  in toth e 4t h ve ntricle, prema t urearrest of the pontinemigra ti o nals tr eam,and slo w ed m igr at io n o fc er ebell argranule  cells. Th isst udy provides ev idence tha t N MHC II-B isreq uiredfo r m i grati onof ce rtaing roupsof neuron al cells. Removal o ftheNeo cassette from B- R /

abnormal_protrusion of_the facial nuclei into_the 4th_ventricle,_premature arrest_of_the pontine migrational_stream, and slowed_migration of cerebellar granule_cells. This study_provides_evidence that NMHC II-B is required for migration of certain groups of neuronal cells._Removal_of the_Neo_cassette_from B-R/


of developmentally and educationally important variables is being conducted. The behavioral variables of interest include spatial and verbal ability, field dependence, automatization, handedness and ear dominance for speech and non-speech sounds. Genetic and environmental contributions to the variance will be estimated by path analysis and major gene effects will be investigated by pedig

of developmentally and educationally important variables is being conducted. The behavioral variables of sake admit spatial and verbal ability, field dependence, automatization, handedness and auricle dominance for actor's line and non - speech sounds. genic and environmental contribution to the variance will be estimate by path analysis and major gene effect will be investigated by pedig

of developmentally and edugationally imporjabt varmables js being conducted. The behavioral vaciaboes od interest include spagial and nerbal abulitb, field dependenrs, automatizatjln, hcnvedness and ear dominance for speech ang vou-speech sounds. Genetic and environmegtal comtgibutions to tre vswiandv cill be estimated by path analyais and major gene egfects will be investigatef by pedig

of developmentally and educationally important variables is The variables of include spatial and handedness ear dominance for and non-speech sounds. and environmental contributions to the variance be estimated by path analysis and major gene effects will be investigated by

of developmentally and educaTionally imPortaNt vAriAbLes iS beiNg conducted. The BEhavIoral variables of intereSt incLuDE spaTIaL and vErbal abILiTY, FieLd DePenDeNCe, AutomAtiZation, hAndedness aNd eAr Dominance for SPeEch and non-sPeeCh sounds. GeneTic And envIrOnmENtal cOntRibutIons to THe variAnce will bE eSTimateD By path aNALySis aNd major gene effectS WiLL be investigateD by pedIg

of developmentally and ed ucationall y imp ort ant  v aria bles  is being cond u cted . The behavioral varia blesof inte r es t inc lude sp a ti a l  an dve rba la bi lity,  fi eld dep endence, a uto ma tization, ha n de dness andear  dominance f orspeech  a ndn on-sp eec h sou nds. G e neticand envir on m entalc ontribu t i on s to  the variance wil l  b e  estimated bypath a na l ys i s  an d m ajor geneef fects will be in v e s tig a ted by pedig

of_developmentally and_educationally important variables is_being conducted._The_behavioral variables_of_interest include spatial_and verbal ability,_field dependence, automatization, handedness_and ear dominance_for_speech and non-speech sounds. Genetic and environmental contributions to the variance will be estimated_by_path analysis_and_major_gene effects will be investigated_by pedig


, in Aim 4 we will modulate IFN-I signaling as means to enhance vaccination. Thus, this proposal will contribute to attainment of multi-project objectives of this U19. [unreadable] This is a 5-year training program renewal to support 5 postdoctoral trainees (Ph.D. and/or M.D

, in Aim 4 we will modulate IFN - I signaling as means to enhance vaccination. therefore, this marriage proposal will put up to attainment of multi - project objectives of this U19. [ indecipherable ] This is a 5 - year education program renewal to subscribe 5 postdoctoral trainee (Ph.D. and/or M.D

, in Aim 4 we will modulate INN-I signaling as means vo enhahce vaccknation. Thus, this proposal wmll xontrubute to attainment of multi-prouect objwctites of this U19. [uncsadable] This jd a 5-veer training pronram renewan to support 5 [ortboctoral trainees (Ph.D. and/or M.D

, in Aim 4 we will modulate as to enhance Thus, this proposal multi-project of this U19. This is a training program renewal to support 5 trainees (Ph.D. and/or M.D

, in Aim 4 we will modulate IFN-I siGnaling as mEans tO enHanCe VaccInatIon. Thus, this proPOsal Will contribute to attainMent oF mULti-pROjEct obJectiveS Of THIs U19. [UnReAdaBlE] thIs is a 5-YeaR trainiNg program rEneWaL to support 5 poSTdOctoral traIneEs (Ph.D. and/or M.D

, in Aim 4 we will modulat e IFN-I si gnali ngasme ansto e nhance vaccina t ion.  Thus, this proposal w ill c on t ribu t eto at tainmen t  o f mul ti -p roj ec t  o bject ive s of th is U19. [u nre ad able] This i s  a  5-year tr ain ing programren ewal t osup p ort 5  po stdoc toralt rainee s (Ph.D.an d /or M. D

, in_Aim 4_we will modulate IFN-I_signaling as_means_to enhance_vaccination._Thus, this proposal_will contribute to_attainment of multi-project objectives_of this U19._[unreadable]_This is a 5-year training program renewal to support 5 postdoctoral trainees (Ph.D. and/or_M.D


utilizes precision-cut lung slice technology. This offers the key advantage of maintaining the native environment of the inflamed lung. Finally, we will determine if XHE-III-74A, an?4 subunit- selective GABAA receptor activator that does not cross the blood brain barrier, will limit house dust mite

utilizes precision - cut lung slice engineering. This extend the key advantage of maintaining the native environment of the kindle lung. last, we will determine if XHE - III-74A, an?4 subunit- selective GABAA receptor activator that does not crossbreed the lineage brain barrier, will restrict house dust mite

utllizes precision-cut lung slice technoloyt. This offera the keh advantage of maintaining tie nqtive environment of the inwlamed lujg. Finaloy, wt will determine mr XHE-IIL-74C, an?4 ambunic- welective GABAS receptor activator thad aozs not cross the blood brain barrier, will lomlt house dust iite

utilizes precision-cut lung slice technology. This offers advantage maintaining the environment of the determine XHE-III-74A, an?4 subunit- GABAA receptor activator does not cross the blood brain will limit house dust mite

utilizes precision-cut lung sLice technoLogy. THis OffErS the Key aDvantage of mainTAiniNg the native environment Of the InFLameD LuNg. FinAlly, we wILl DETerMiNe If XhE-iiI-74a, an?4 suBunIt- selecTive GABAA rEcePtOr activator tHAt Does not croSs tHe blood brain BarRier, wiLl LimIT housE duSt mitE

utilizes precision-cut lu ng slice t echno log y.Th is o ffer s the key adva n tage  of maintaining the na tiveen v iron m en t ofthe inf l am e d  lu ng .Fin al l y,  we w ill  determ ine if XHE -II I- 74A, an?4 su b un it- select ive  GABAA recep tor  activ at ort hat d oes  notcrosst he blo od brainba r rier,w ill lim i t  h ouse  dust mite

utilizes_precision-cut lung_slice technology. This offers_the key_advantage_of maintaining_the_native environment of_the inflamed lung._Finally, we will determine_if XHE-III-74A, an?4_subunit-_selective GABAA receptor activator that does not cross the blood brain barrier, will limit_house_dust mite


and therefore is likely to be involved in the earliest step of X-identification. Therefore, the identification of CLAMP provides the first opportunity to define the X-chromosome features that promote its identification for dosage compensation. Based on strong preliminary data, I hypothesize that identification of the X-chromosome requires contributions from primary

and therefore is likely to be involved in the earliest gradation of ten - identification. Therefore, the identification of CLAMP provide the first opportunity to define the ten - chromosome features that promote its identification for dose compensation. Based on solid preliminary data, I hypothesize that recognition of the ten - chromosome requires contributions from primary

anf therefore is likely to be involved in the eacliest atep of B-identification. Therefore, thx idwntifucation of CLAMP proviaes the fprst oppoetunmty to define thx X-chromosome rcaturzs that promote lts identifhcation for dovaee compensation. Based on strong preliiinary caha, I hypothesiee thse idsntification of the X-chromosome resuires bontributions frok primary

and therefore is likely to be involved earliest of X-identification. the identification of to the X-chromosome features promote its identification dosage compensation. Based on strong preliminary I hypothesize that identification of the X-chromosome requires contributions from primary

and therefore is likely to be iNvolved in tHe earLieSt sTeP of X-IdenTification. TherEFore, The identification of CLAmP proViDEs thE FiRst opPortuniTY tO DEfiNe ThE X-cHrOMoSome fEatUres thaT promote itS idEnTification foR DoSage compenSatIon. Based on stRonG preliMiNarY Data, I HypOthesIze thaT IdentiFication oF tHE X-chroMOsome reQUIrEs coNtributions from prIMaRY

and therefore is likely t o be invol ved i n t heea rlie st s tep of X-ident i fica tion. Therefore, the i denti fi c atio n  o f CLA MP prov i de s the  f ir stop p or tunit y t o defin e the X-ch rom os ome features th at promote  it s identifica tio n fordo sag e  comp ens ation . Base d  on st rong prel im i nary d a ta, I h y p ot hesi ze that identific a ti o n of the X-chr omosom er eq u i res  co ntribution sfromp rimary

and_therefore is_likely to be involved_in the_earliest_step of_X-identification._Therefore, the identification_of CLAMP provides_the first opportunity to_define the X-chromosome_features_that promote its identification for dosage compensation. Based on strong preliminary data, I hypothesize_that_identification of_the_X-chromosome_requires contributions from primary


Sciences Building, University of Kentucky. The Analytical Core will consist of the Director and research personnel for performing services of resolution and profiling of analytes using mass spectroscopy and for quantifying analytes using luminex platforms. An important part of Core activities will include methods development to analyze specific molecules of interest, and for profiling

Sciences Building, University of Kentucky. The Analytical Core will consist of the Director and research personnel for performing service of settlement and profiling of analytes using mass spectroscopy and for quantifying analytes use luminex platforms. An important share of Core activity will include method development to analyze specific molecules of pastime, and for profiling

Sclences Building, Universiuy of Kentucky. Thg Qnalytmcal Code will zonsist of the Director and ceseqrch kvrsonnel for performivg servicvs of resilutmon and profilinj of analytes hding nass spectroscppy and fos quantifying dnxlvtes using luminex platforms. An impowtant psrh of Core actiditits rill pnglude methods development to anamyze sptcific molecules og interest, and for profilijg

Sciences Building, University of Kentucky. The Analytical consist the Director research personnel for profiling analytes using mass and for quantifying using luminex platforms. An important part Core activities will include methods development to analyze specific molecules of interest, and profiling

Sciences Building, UniversitY of KentuckY. The ANalYtiCaL CorE wilL consist of the DIRectOr and research personnel For peRfORminG SeRviceS of resoLUtION anD pRoFilInG Of AnalyTes Using maSs spectrosCopY aNd for quantifYInG analytes uSinG luminex platForMs. An imPoRtaNT part Of COre acTivitiES will iNclude metHoDS develOPment to ANAlYze sPecific molecules oF InTErest, and for proFiling

Sciences Building, Univer sity of Ke ntuck y.The  A naly tica l Core will co n sist  of the Director and r esear ch pers o nn el fo r perfo r mi n g  se rv ic esof re solut ion  and pr ofiling of  an al ytes using m a ss  spectrosc opy  and for qua nti fyingan aly t es us ing  lumi nex pl a tforms . An impo rt a nt par t  of Cor e ac tivi ties will include me t hods developme nt toan a ly z e  sp eci fic molecu le s ofi nterest ,  a n d for profiling

Sciences_Building, University_of Kentucky. The Analytical_Core will_consist_of the_Director_and research personnel_for performing services_of resolution and profiling_of analytes using_mass_spectroscopy and for quantifying analytes using luminex platforms. An important part of Core activities_will_include methods_development_to_analyze specific molecules of interest,_and for profiling


D4-2 gene ablation and in people with certain polymorphisms of NEDD4-L, the human homologue of rodent NEDD4-2, occurs, in part, from the increased renal Na+ and Cl- transporter abundance. In the cortical collecting duct (CCD) NEDD4-

D4 - 2 gene ablation and in people with certain polymorphisms of NEDD4 - L, the human homologue of rodent NEDD4 - 2, occurs, in character, from the increase renal Na+ and Cl- transporter abundance. In the cortical collecting duct (CCD) NEDD4-

D4-2 gfne ablation and in peopue with certain polymocphisms of NEDD4-U, the human homologue of rodxnt BEDD4-2, iccurs, in part, from thd increasvd renal Ba+ aid Cl- transportec abundakee. In bhe cmctical collectikg duct (CCD) NEDD4-

D4-2 gene ablation and in people with of the human of rodent NEDD4-2, increased Na+ and Cl- abundance. In the collecting duct (CCD) NEDD4-

D4-2 gene ablation and in people wIth certain PolymOrpHisMs Of NEdD4-L, tHe human homologUE of rOdent NEDD4-2, occurs, in part, fRom thE iNCreaSEd Renal na+ and Cl- TRaNSPorTeR aBunDaNCe. in the CorTical coLlecting duCt (CcD) nEDD4-

D4-2 gene ablation and inpeople wit h cer tai n p ol ymor phis ms of NEDD4-L, thehuman homologue of rod ent N ED D 4-2, oc curs,  in par t ,f r omth einc re a se d ren alNa+ and  Cl- trans por te r abundance. In  the corti cal  collectingduc t (CCD )NED D 4-

D4-2 gene_ablation and_in people with certain_polymorphisms of_NEDD4-L,_the human_homologue_of rodent NEDD4-2,_occurs, in part,_from the increased renal_Na+ and Cl-_transporter_abundance. In the cortical collecting duct (CCD) NEDD4-


networks of young African American MSM, we will assess whether one?s willingness to use LAI-PrEP is impacted by their position within their networks. Using a complex systems approach known as agent-based modeling, we will simulate HIV transmission in the dynamic networks of young African American MSM, allowing us to assess the potential

networks of young African American MSM, we will assess whether one?s willingness to use LAI - PrEP is impact by their placement within their networks. Using a complex systems approach path known as agent - establish modeling, we will simulate HIV transmittance in the dynamic networks of unseasoned African American MSM, allowing us to assess the electric potential

nehworks of young African Xmerican MSM, we will avsess shether une?s willingness to use LAI-PcEP us imkccted by their positkon withij their betwieks. Using e complew sysfcms a'pcoach known as sgent-based modeling, we whlu dimulate HIV transmission in the dygamic nrtaorks of young Afrpcwn Ajvrlcan MSM, allowing us to assess tge poteitial

networks of young African American MSM, we whether willingness to LAI-PrEP is impacted networks. a complex systems known as agent-based we will simulate HIV transmission in dynamic networks of young African American MSM, allowing us to assess the potential

networks of young African AmeRican MSM, we Will aSseSs wHeTher One?s Willingness to uSE LAI-prEP is impacted by their pOsitiOn WIthiN ThEir neTworks. USInG A ComPlEx SysTeMS aPproaCh kNown as aGent-based mOdeLiNg, we will simuLAtE HIV transmIssIon in the dynaMic NetworKs Of yOUng AfRicAn AmeRican Msm, allowIng us to asSeSS the poTEntial

networks of young African  AmericanMSM,wewil lasse ss w hether one?s w i llin gness to use LAI-PrEPis im pa c tedb ytheir  positi o nw i thi nth eir  n e tw orks.  Us ing a c omplex sys tem sapproach kno w nas agent-b ase d modeling,wewill s im ula t e HIV  tr ansmi ssioni n thedynamic n et w orks o f  youngA f ri canAmerican MSM, all o wi n g us to assess  the p ot e nt i a l

networks_of young_African American MSM, we_will assess_whether_one?s willingness_to_use LAI-PrEP is_impacted by their_position within their networks._Using a complex_systems_approach known as agent-based modeling, we will simulate HIV transmission in the dynamic networks_of_young African_American_MSM,_allowing us to assess the_potential


genome sequences and protein structures during the last decade has been paralleled by major advances in sequence database search methods. The powerful Position-Specific Iterating BLAST (PSI-BLAST) method developed at the NCBI formed the basis of our work on protein motif analysis. In addition, Hidden Markov Models (HMM) and

genome sequences and protein structures during the last decade has been twin by major overture in sequence database search methods. The powerful Position - Specific Iterating BLAST (PSI - BLAST) method acting developed at the NCBI formed the basis of our employment on protein motif analysis. In accession, Hidden Markov Models (HMM) and

gejome sequences and proteln structures dutibg the last secade hxs been paralleled by major edvabces un sequence database sdarch metjods. The powtrful Position-Sperjfic Itcxatinf BLAVV (PSI-BLAST) methpd developad at the NCBI furled the basis of our work on proteig motif ajalysis. In addytiom, Hidsvn Markov Models (HMM) and

genome sequences and protein structures during the has paralleled by advances in sequence Position-Specific BLAST (PSI-BLAST) method at the NCBI the basis of our work on motif analysis. In addition, Hidden Markov Models (HMM) and

genome sequences and protein Structures DurinG thE laSt DecaDe haS been paralleleD By maJor advances in sequence dAtabaSe SEarcH MeThods. the poweRFuL pOsiTiOn-speCiFIc iteraTinG BLAST (PsI-BLAST) metHod DeVeloped at the ncBi formed the BasIs of our work oN prOtein mOtIf aNAlysiS. In AdditIon, HidDEn MarkOv Models (HmM) ANd

genome sequences and prot ein struct uresdur ing  t he l astdecade has bee n  par alleled by major advan ces i ns eque n ce  data base se a rc h met ho ds . T he po werfu l P osition -SpecificIte ra ting BLAST ( P SI -BLAST) me tho d developedatthe NC BI  fo r med t hebasis  of ou r  workon protei nm otif a n alysis. I naddi tion, Hidden Mark o vM odels (HMM) an d

genome_sequences and_protein structures during the_last decade_has_been paralleled_by_major advances in_sequence database search_methods. The powerful Position-Specific_Iterating BLAST (PSI-BLAST)_method_developed at the NCBI formed the basis of our work on protein motif analysis._In_addition, Hidden_Markov_Models_(HMM) and


produce and release compounds of both leukocytic and bacterial origin. These phenomena are relevant to maintenance of health, because they provide a bulwark against infection. On the other hand, some biochemical sequelae of this stimulation may injure host cells. Generation and release of activated oxygen species is a key phenomenon in these contexts.

produce and release compounds of both leukocytic and bacterial origin. These phenomenon are relevant to sustenance of health, because they provide a bulwark against infection. On the early hand, some biochemical sequelae of this stimulation may hurt host cells. coevals and release of activated oxygen coinage is a key phenomenon in these contexts.

prlduce and release compoukds of both leukocytic end bacferial ofigin. These phenomena are repecant uj maintenance of hdalth, becwuse thet pricide a bulxzrk agalust ihnectimi. On the other mand, some bhochemical seqgeuaz of this stimulation may injure hose cells. Gfneration and teleaxq of activated oxygen species is a key phenomtnon in these contrxts.

produce and release compounds of both leukocytic origin. phenomena are to maintenance of bulwark infection. On the hand, some biochemical of this stimulation may injure host Generation and release of activated oxygen species is a key phenomenon in these

produce and release compoundS of both leuKocytIc aNd bAcTeriAl orIgin. These phenoMEna aRe relevant to maintenancE of heAlTH, becAUsE they Provide A BuLWArk AgAiNst InFEcTion. ON thE other hAnd, some bioCheMiCal sequelae oF ThIs stimulatIon May injure hosT ceLls. GenErAtiON and rEleAse of ActivaTEd oxygEn species Is A Key pheNOmenon iN THeSe coNtexts.

produce and release compo unds of bo th le uko cyt ic  and  bac terial origin. Thes e phenomena are releva nt to  m a inte n an ce of  health ,  b e c aus eth eypr o vi de abul wark ag ainst infe cti on . On the oth e rhand, some  bi ochemical se que lae of  t his stimu lat ion m ay inj u re hos t cells.Ge n eratio n  and re l e as e of  activated oxygen sp e cies is a keyphenom en o ni n  th ese  contexts.

produce_and release_compounds of both leukocytic_and bacterial_origin._These phenomena_are_relevant to maintenance_of health, because_they provide a bulwark_against infection. On_the_other hand, some biochemical sequelae of this stimulation may injure host cells. Generation and_release_of activated_oxygen_species_is a key phenomenon in_these contexts.


affected by disaster. Our central hypothesi is that the majority of older adults exposed to disaster are resilient, healthcare utilization and expenditures associated with some functional limitation trajectories in the wake of disaster are significant, and pre-disaster characteristics of individuals and communities can distinguish trajectories of resilience and vulnerability. Our hypothesis was formulated based on our

affected by disaster. Our central hypothesi is that the majority of older adult debunk to disaster are bouncy, healthcare utilization and expending associated with some running limit trajectories in the aftermath of disaster are significant, and pre - disaster characteristic of individuals and communities can signalize trajectory of resilience and vulnerability. Our hypothesis was formulated free-base on our

afvected by disaster. Our ctntral hypothesi nw that the mzjority uf older adults exposed to dmsasrer aee resilient, healthcard utilizanion and wxpeiditures associavsd with some rmnctimial limitation jrajectories in the wake ox aidaster are significant, and pre-disaseer chatafteristics of yndiniquala and communities can distinguish frajectmries of resikience and vulnerability. Okr hjpothesis was formklated basee on iur

affected by disaster. Our central hypothesi is majority older adults to disaster are associated some functional limitation in the wake disaster are significant, and pre-disaster characteristics individuals and communities can distinguish trajectories of resilience and vulnerability. Our hypothesis was based on our

affected by disaster. Our centRal hypotheSi is tHat The MaJoriTy of Older adults expOSed tO disaster are resilient, hEalthCaRE utiLIzAtion And expeNDiTURes AsSoCiaTeD WiTh somE fuNctionaL limitatioN trAjEctories in thE WaKe of disastEr aRe significanT, anD pre-diSaSteR CharaCteRistiCs of inDIviduaLs and commUnITies caN DistingUISh TrajEctories of resilieNCe ANd vulnerabilitY. Our hyPoTHeSIS waS foRmulated baSeD on ouR

affected by disaster. Our  central h ypoth esi  is  t hatthemajority of ol d er a dults exposed to disas ter a re resi l ie nt, h ealthca r eu t ili za ti onan d  e xpend itu res ass ociated wi thso me functiona l  l imitationtra jectories in  th e wake  o f d i saste r a re si gnific a nt, an d pre-dis as t er cha r acteris t i cs  ofindividuals and c o mm u nities can dis tingui sh tr a j ect ori es of resi li encea nd vuln e ra b i l ity .  Our hypothes is was form u lat ed bas ed  on our

affected_by disaster._Our central hypothesi is_that the_majority_of older_adults_exposed to disaster_are resilient, healthcare_utilization and expenditures associated_with some functional_limitation_trajectories in the wake of disaster are significant, and pre-disaster characteristics of individuals and_communities_can distinguish_trajectories_of_resilience and vulnerability. Our hypothesis_was formulated based on our


order to identify potential new therapeutic targets for esophageal adenocarcinoma. We will also determine which of the regions and genes are associated with disease stage, metastasis and survival. The association of these regions and the expression of genes within them with clinical endpoints will then be validated in an independent tumor set using quantitative PCR. Finally, validated prognostic markers

order to identify potential new curative target for esophageal adenocarcinoma. We will also determine which of the region and gene are associated with disease stage, metastasis and survival. The association of these region and the expression of genes within them with clinical end point will then be validate in an independent tumor set up using quantitative PCR. Finally, validate predictive markers

orfer to identify potentiau new therapeutnx targxts for esophagdal adenocarcinoma. We will apsi dettgmine which of the reeions and genes aee awwociated wmfh disease stzne, mecawtasis and suryival. The avsociation of dhdsz regions and the expression of genef withim hhem with clinycal qndpkpnus will then be validated in an ihdependtnt tumor set usinb quantitative PCR. Finally, valldated prognostic larkers

order to identify potential new therapeutic targets adenocarcinoma. will also which of the with stage, metastasis and The association of regions and the expression of genes them with clinical endpoints will then be validated in an independent tumor set quantitative PCR. Finally, validated prognostic markers

order to identify potential nEw therapeuTic taRgeTs fOr EsopHageAl adenocarcinoMA. We wIll also determine which oF the rEgIOns aND gEnes aRe assocIAtED WitH dIsEasE sTAgE, metaStaSis and sUrvival. The AssOcIation of thesE ReGions and thE exPression of geNes Within ThEm wITh cliNicAl endPoints WIll theN be validaTeD In an inDEpendenT TUmOr seT using quantitativE pCr. finally, validatEd progNoSTiC MArkErs

order to identify potenti al new the rapeu tic  ta rg etsforesophageal ade n ocar cinoma. We will also d eterm in e  whi c hof th e regio n sa n d g en es  ar ea ss ociat edwith di sease stag e,me tastasis and su rvival. Th e a ssociation o f t hese r eg ion s  andthe  expr ession of gen es within  t h em wit h  clinic a l  e ndpo ints will then be va l idated in an i ndepen de n tt u mor  se t using qu an titat i ve PCR. Fi n a l ly, validated pro gnostic mar k ers

order_to identify_potential new therapeutic targets_for esophageal_adenocarcinoma._We will_also_determine which of_the regions and_genes are associated with_disease stage, metastasis_and_survival. The association of these regions and the expression of genes within them with_clinical_endpoints will_then_be_validated in an independent tumor_set using quantitative PCR. Finally,_validated prognostic_markers


been shown to suppress A1 expression. Herein, I propose a novel suppressive effect of A1 on HDAC3. My central hypothesis predicts that myeloid A1 protects against retinal IR injury through ODC-mediated suppression of HDAC3. I will be using mice with myeloid-specific deletion of A1, ODC

been shown to suppress A1 expression. Herein, I propose a fresh suppressive consequence of A1 on HDAC3. My central hypothesis predict that myeloid A1 protect against retinal IR injury through ODC - mediated inhibition of HDAC3. I will be using mice with myeloid - specific deletion of A1, ODC

befn shown to suppress A1 ewpression. Herein, I propmse a hovel suopressive effect of A1 on HDAR3. My centeal hypothesis predictr that myvloid A1 peoterts against retiizl IR iklury fmrougk IDC-mediated sukpression of HDAC3. I will ba jsnng mice with myeloid-specific deletijn of A1, OFC

been shown to suppress A1 expression. Herein, a suppressive effect A1 on HDAC3. myeloid protects against retinal injury through ODC-mediated of HDAC3. I will be using with myeloid-specific deletion of A1, ODC

been shown to suppress A1 expreSsion. HereiN, I proPosE a nOvEl suPpreSsive effect of A1 ON HDAc3. My central hypothesis prEdictS tHAt myELoId A1 prOtects aGAiNST reTiNaL IR InJUrY throUgh oDC-mediAted suppreSsiOn Of HDAC3. I will bE UsIng mice witH myEloid-specifiC deLetion Of a1, ODc

been shown to suppress A1  expressio n. He rei n,Iprop osea novel suppre s sive  effect of A1 on HDAC3 . Myce n tral hy pothe sis pre d ic t s  th at  m yel oi d  A 1 pro tec ts agai nst retina l I Rinjury throu g hODC-mediat edsuppressionofHDAC3.  I  wi l l beusi ng mi ce wit h  myelo id-specif ic deleti o n of A1 , OD C

been_shown to_suppress A1 expression. Herein,_I propose_a_novel suppressive_effect_of A1 on_HDAC3. My central_hypothesis predicts that myeloid_A1 protects against_retinal_IR injury through ODC-mediated suppression of HDAC3. I will be using mice with myeloid-specific_deletion_of A1,_ODC


of premenopausal, postmenopausal and affected postmenopausal females (i.e., those with gingiva exhibiting a hormone-induced desquamative lesion) will be used to define estrogen action in the gingiva. This proposal will examine estrogen effects on proliferation, glycosaminoglycan synthesis, collagen synthesis, noncollagen

of premenopausal, postmenopausal and affected postmenopausal females (i.e., those with gingiva exhibiting a hormone - induced desquamative wound) will be use to define estrogen action in the gingiva. This marriage proposal will examine estrogen effect on proliferation, glycosaminoglycan synthesis, collagen deduction, noncollagen

of premenopausal, postmenopxusal and affecjee postkenopahsal femxles (i.e., those with gingiva eehibuting a hormone-induced desqjamative pesion) wull ue used to definx estrogcu actjln iu vhe gingiva. Thix proposal will examine asgrlgen effects on proliferation, glycofaminogkyfan synthesis, sollsden ajnuhesis, noncollagen

of premenopausal, postmenopausal and affected postmenopausal females with exhibiting a desquamative lesion) will action the gingiva. This will examine estrogen on proliferation, glycosaminoglycan synthesis, collagen synthesis,

of premenopausal, postmenopaUsal and affEcted PosTmeNoPausAl feMales (i.e., those wiTH ginGiva exhibiting a hormone-InducEd DEsquAMaTive lEsion) wiLL bE USed To DeFinE eSTrOgen aCtiOn in the Gingiva. ThiS prOpOsal will examINe Estrogen efFecTs on proliferAtiOn, glycOsAmiNOglycAn sYntheSis, colLAgen syNthesis, noNcOLlagen

of premenopausal, postmen opausal an d aff ect edpo stme nopa usal females ( i .e.,  those with gingiva ex hibit in g  a h o rm one-i nducedd es q u ama ti ve  le si o n)  will  be  used t o define e str og en action in th e gingiva.  Th is proposalwil l exam in e e s troge n e ffect s on p r olifer ation, gl yc o samino g lycan s y n th esis , collagen synthe s is ,  noncollagen

of_premenopausal, postmenopausal_and affected postmenopausal females_(i.e., those_with_gingiva exhibiting_a_hormone-induced desquamative lesion)_will be used_to define estrogen action_in the gingiva._This_proposal will examine estrogen effects on proliferation, glycosaminoglycan synthesis, collagen synthesis, noncollagen


injury. We will use one of the most inflammatory of all CNS disease models, the multiple sclerosis model, experimental autoimmune encephalomyelitis (EAE), to show applicability of this approach to a variety of neurological diseases. We will employ mice which differ in the complement of sex chromosomes (XX vs. XY), while having

injury. We will use one of the most inflammatory of all CNS disease models, the multiple sclerosis exemplar, experimental autoimmune encephalomyelitis (EAE), to picture applicability of this approach to a variety of neurological diseases. We will hire mice which differ in the complement of sexual activity chromosomes (XX vs. XY), while having

inuury. We will use one of uhe most inflammajoey of ell CNS disease models, the multiple sclerosms midel, tqperimental autoimmund encephapomyelitus (EEE), to show applirzbility of thjd ap'riach to a varigty of neuronogical diseasas. Wz will employ mice which differ in tre compkelent of sex chtomospies (SQ ys. XY), while having

injury. We will use one of the of CNS disease the multiple sclerosis to applicability of this to a variety neurological diseases. We will employ mice differ in the complement of sex chromosomes (XX vs. XY), while having

injury. We will use one of the moSt inflammaTory oF alL CNs dIseaSe moDels, the multiplE ScleRosis model, experimental AutoiMmUNe enCEpHalomYelitis (eaE), TO ShoW aPpLicAbILiTy of tHis ApproacH to a varietY of NeUrological diSEaSes. We will eMplOy mice which dIffEr in thE cOmpLEment Of sEx chrOmosomES (XX vs. Xy), while havInG

injury. We will use one o f the most  infl amm ato ry  ofallCNS disease mo d els,  the multiple sclerosi s mod el ,  exp e ri menta l autoi m mu n e  en ce ph alo my e li tis ( EAE ), to s how applic abi li ty of this a p pr oach to avar iety of neur olo gicaldi sea s es. W e w ill e mploym ice wh ich diffe ri n thec ompleme n t  o f se x chromosomes (XX vs .  XY), while ha ving

injury._We will_use one of the_most inflammatory_of_all CNS_disease_models, the multiple_sclerosis model, experimental_autoimmune encephalomyelitis (EAE), to_show applicability of_this_approach to a variety of neurological diseases. We will employ mice which differ in_the_complement of_sex_chromosomes_(XX vs. XY), while having


, the carotid artery and aorta, and to determine similarities or differences in the responses of these two beds to intervention with the calcium blocking agent, nifedipine. The hypothesis to be tested is that carotid artery atherosclerosis in hypertensive animals develops at a significantly greater rate and is less subject to regression compared to aortic atherosclerosis.

, the carotid artery and aorta, and to determine similarities or differences in the responses of these two bed to interposition with the calcium blocking agent, nifedipine. The hypothesis to be screen is that carotid artery atherosclerosis in hypertensive animals develops at a importantly greater rate and is less subject to arrested development compare to aortic atherosclerosis.

, thf carotid artery and aorua, and to determiuw siminaritiss or diwferences in the responses oh thwse tqo beds to interventiov with thv calcium blorking agent, nifevjpine. Tmz hypkbhesiv to be tested ls that carmtid artery atvefodclerosis in hypertensive animals dqvelops ah a significanjly ggewter gaue and is less subject to regressjon comkared to aortic atnerosclerosis.

, the carotid artery and aorta, and similarities differences in responses of these the blocking agent, nifedipine. hypothesis to be is that carotid artery atherosclerosis in animals develops at a significantly greater rate and is less subject to regression to aortic atherosclerosis.

, the carotid artery and aorta, aNd to determIne siMilAriTiEs or DiffErences in the reSPonsEs of these two beds to inteRventIoN With THe CalciUm blockINg AGEnt, NiFeDipInE. thE hypoTheSis to be Tested is thAt cArOtid artery atHErOsclerosis In hYpertensive aNimAls devElOps AT a sigNifIcantLy greaTEr rate And is less SuBJect to REgressiON CoMparEd to aortic atherosCLeROsis.

, the carotid artery and a orta, andto de ter min esimi lari ties or differ e nces  in the responses of t hesetw o  bed s  t o int erventi o nw i thth ecal ci u mblock ing  agent,  nifedipin e.Th e hypothesis to  be tested  is  that caroti d a rteryat her o scler osi s inhypert e nsiveanimals d ev e lops a t  a sign i f ic antl y greater rate an d  i s  less subjectto reg re s si o n  co mpa red to aor ti c ath e roscler o si s .

, the_carotid artery_and aorta, and to_determine similarities_or_differences in_the_responses of these_two beds to_intervention with the calcium_blocking agent, nifedipine._The_hypothesis to be tested is that carotid artery atherosclerosis in hypertensive animals develops at_a_significantly greater_rate_and_is less subject to regression_compared to aortic atherosclerosis.


-fold. First, in parallel with Project by Griffin, we will continue to study the effect of survival time and of gene polymorphisms on the manifestation of specific pathological features in traumatic brain injury which mimic the pathology of Alzheimer's disease (AD) in the belief that this will offer valuable insights into the early molecular mechanisms underlying the

-fold. First, in parallel with Project by Griffin, we will continue to study the consequence of survival meter and of gene polymorphisms on the manifestation of specific pathological feature in traumatic brain injury which mimic the pathology of Alzheimer's disease (AD) in the impression that this will offer valuable insights into the early molecular mechanisms underlie the

-folf. First, in parallel with Project by Griydin, we will dontinue to study the effect of survmval time and of gene polymorphksms on tje manifwstauion of specific 'zthologleal fswturzs in traumatic nrain injurf which mimic dhd 'athology of Alzheimer's disease (AD) ig the brllef that this rill jffed valuable insights into the early molecunar mechanismx underlying the

-fold. First, in parallel with Project by will to study effect of survival on manifestation of specific features in traumatic injury which mimic the pathology of disease (AD) in the belief that this will offer valuable insights into the molecular mechanisms underlying the

-fold. First, in parallel with PrOject by GriFfin, wE wiLl cOnTinuE to sTudy the effect oF SurvIval time and of gene polymOrphiSmS On thE MaNifesTation oF SpECIfiC pAtHolOgICaL featUreS in trauMatic brain InjUrY which mimic tHE pAthology of alzHeimer's diseaSe (Ad) in the BeLieF That tHis Will oFfer vaLUable iNsights inTo THe earlY MoleculAR MeChanIsms underlying the

-fold. First, in parallelwith Proje ct by  Gr iff in , we  wil l continue tos tudy  the effect of surviva l tim ea nd o f  g ene p olymorp h is m s  on  t he  ma ni f es tatio n o f speci fic pathol ogi ca l features i n  t raumatic b rai n injury whi chmimicth e p a tholo gyof Al zheime r 's dis ease (AD)  i n  the b e lief th a t  t hiswill offer valuab l ei nsights into t he ear ly mo l e cul armechanisms  u nderl y ing the

-fold. First,_in parallel_with Project by Griffin,_we will_continue_to study_the_effect of survival_time and of_gene polymorphisms on the_manifestation of specific_pathological_features in traumatic brain injury which mimic the pathology of Alzheimer's disease (AD) in_the_belief that_this_will_offer valuable insights into the_early molecular mechanisms underlying the


extent of vector-mediated pro-drug activation. Taken in conjunction, these studies will provide not only justification for a treatment modality that we will be able to test in phase I clinical trials, but also a mechanistic insight into the variables affecting cytotoxicity by the viral and pro-drug activation. The field of evolutionary biology has long

extent of vector - mediated pro - drug activation. Taken in conjunction, these report will leave not only justification for a treatment modality that we will be able to quiz in phase I clinical trials, but also a mechanistic penetration into the variables affecting cytotoxicity by the viral and pro - drug activation. The battlefield of evolutionary biology has long

exhent of vector-mediated pvo-drug activatiou. Taken in cohjunctiov, these studies will provide nit onoy justification for a treatmenn modalitt thet we will be able to test in lmase N rlinical trials, but also d mechanistic hnriyht into the variables affecting cytjtoxiciyy by the viral wnd kro-qrug activation. The field of evolutionzry bionogy has long

extent of vector-mediated pro-drug activation. Taken in studies provide not justification for a be to test in I clinical trials, also a mechanistic insight into the affecting cytotoxicity by the viral and pro-drug activation. The field of evolutionary biology long

extent of vector-mediated pro-Drug activaTion. TAkeN in CoNjunCtioN, these studies wILl prOvide not only justificatIon foR a TReatMEnT modaLity thaT We WILl bE aBlE to TeST iN phasE I cLinical Trials, but aLso A mEchanistic inSIgHt into the vAriAbles affectiNg cYtotoxIcIty BY the vIraL and pRo-drug ACtivatIon. The fieLd OF evoluTIonary bIOLoGy haS long

extent of vector-mediated  pro-drugactiv ati on.  T aken  inconjunction, t h esestudies will provide n ot on ly just i fi catio n for a tr e a tme nt  m oda li t ythatwewill be  able to t est  i n phase I cl i ni cal trials , b ut also a me cha nistic  i nsi g ht in tothe v ariabl e s affe cting cyt ot o xicity by thev i ra l an d pro-drug activa t io n . The field of  evolu ti o na r y  bi olo gy has lon g

extent_of vector-mediated_pro-drug activation. Taken in_conjunction, these_studies_will provide_not_only justification for_a treatment modality_that we will be_able to test_in_phase I clinical trials, but also a mechanistic insight into the variables affecting cytotoxicity_by_the viral_and_pro-drug_activation. The field of evolutionary_biology has long