This study will enable us to gain important insight into the pathophysiology of hypertension and may provide novel therapeutic interventions. Abstract The mucopolysaccharidoses (MPS) are a family of genetic, lysosomal storage disorders characterized by deficiencies in enzymes that degrade glycosaminoglycans (GAGs). Patients with MPS suffer from cripp

This study will enable us to gain important insight into the pathophysiology of high blood pressure and may leave novel therapeutic interposition. Abstract The mucopolysaccharidoses (MPS) are a kin of genetic, lysosomal storage disorder characterized by deficiencies in enzyme that degrade glycosaminoglycans (GAGs). patient with MPS suffer from cripp

Thls study will enable us uo gain important insighv into fhe pathuphysiology of hypertension end nay peovide novel therapeutkc intervvntions. Avstrect The mucopolysaccharidoses (JIS) arz e family of gengtic, lysosomdl storage dismraexs characterized by deficiencies in qnzymes tjat degrade glicosakynogmjccns (GAGs). Patients with MPS suffsr from cripp

This study will enable us to gain into pathophysiology of and may provide mucopolysaccharidoses are a family genetic, lysosomal storage characterized by deficiencies in enzymes that glycosaminoglycans (GAGs). Patients with MPS suffer from cripp

This study will enable us to gaIn importanT insiGht IntO tHe paThopHysiology of hypERtenSion and may provide novel TheraPeUTic iNTeRventIons. AbsTRaCT the MuCoPolYsACcHaridOseS (MPS) are A family of gEneTiC, lysosomal stORaGe disorderS chAracterized bY deFicienCiEs iN EnzymEs tHat deGrade gLYcosamInoglycanS (Gags). PatiENts with mps sUffeR from cripp

This study will enable us  to gain i mport ant  in si ghtinto  the pathophys i olog y of hypertension andmay p ro v iden ov el th erapeut i ci n ter ve nt ion s. Ab strac t T he muco polysaccha rid os es (MPS) are afamily ofgen etic, lysoso mal  stora ge  di s order s c harac terize d  by de ficiencie si n enzy m es that d eg rade  glycosaminoglyca n s( GAGs). Patient s with  M P Ss u ffe r f rom cripp

This_study will_enable us to gain_important insight_into_the pathophysiology_of_hypertension and may_provide novel therapeutic_interventions. Abstract The mucopolysaccharidoses_(MPS) are a_family_of genetic, lysosomal storage disorders characterized by deficiencies in enzymes that degrade glycosaminoglycans (GAGs)._Patients_with MPS_suffer_from_cripp


acid biosynthesis, transport, and regulation will be determined. The direct effects of these specific gene deletions on intestinal bile acid transport will be determined in vivo by measuring changes in bile acid fecal excretion and pool size, and in vitro using ileal everted gut sacs. The studies in Specific Aim 2 will directly test the hypothesis

acid biosynthesis, transport, and regulation will be determined. The direct effect of these specific gene deletion on intestinal bile acid transport will be determined in vivo by measuring change in bile acid fecal excretion and consortium size, and in vitro use ileal everted gut pouch. The studies in Specific Aim 2 will directly quiz the hypothesis

acld biosynthesis, transporu, and regulation cull be deterjined. Thd direct effects of these spxcifuc gebe deletions on intestknal bile acid trqnspiet will be determikzd in yivo yy measuring chakges in bila acid fecal efcfecion and pool size, and in vitro usind ileal egerted gut sacf. Tht seudiss in Specific Aim 2 will directly fest tht hypothesis

acid biosynthesis, transport, and regulation will be direct of these gene deletions on be in vivo by changes in bile fecal excretion and pool size, and vitro using ileal everted gut sacs. The studies in Specific Aim 2 will test the hypothesis

acid biosynthesis, transport, And regulatIon wiLl bE deTeRminEd. ThE direct effects OF theSe specific gene deletionS on inTeSTinaL BiLe aciD transpORt WILl bE dEtErmInED iN vivo By mEasurinG changes in BilE aCid fecal excrETiOn and pool sIze, And in vitro usIng Ileal eVeRteD Gut saCs. THe stuDies in sPecifiC Aim 2 will dIrECtly teST the hypOTHeSis

acid biosynthesis, transp ort, and r egula tio n w il l be  det ermined. The d i rect  effects of these spec ificge n e de l et ionson inte s ti n a l b il eaci dt ra nspor t w ill bedetermined  in  v ivo by measu r in g changesinbile acid fe cal  excre ti ona nd po olsize,  and i n  vitro  using il ea l  evert e d gut s a c s.  The  studies in Speci f ic Aim 2 will dir ectlyte s tt h e h ypo thesis

acid_biosynthesis, transport,_and regulation will be_determined. The_direct_effects of_these_specific gene deletions_on intestinal bile_acid transport will be_determined in vivo_by_measuring changes in bile acid fecal excretion and pool size, and in vitro using_ileal_everted gut_sacs._The_studies in Specific Aim 2_will directly test the hypothesis


changes in alternative splicing occur during this process. A change in this splicing network is a thus a dynamic feature of the EMT and changes in splicing of ESRP-regulated targets can be used as a biomarker for the EMT. In this application we will develop more robust next generation splicing reporter assays using ESRP- regulated exons that

changes in alternative splicing occur during this procedure. A variety in this splicing network is a therefore a dynamic feature of speech of the EMT and changes in splicing of ESRP - baffle target can be used as a biomarker for the EMT. In this lotion we will originate more robust future generation splicing reporter assay using ESRP- regulated exons that

chwnges in alternative spllcing occur duriut this proceas. A chavge in this splicing network iw a tyus a dynamic feature uf the EMN and chabges un splicinj of ESRI-xegulzbed tcrjets can be usec as a biokarker for the EOT. In this application we will develo[ more tohust next genetatiom spljbikg reporter assays using ESRP- refulated exons that

changes in alternative splicing occur during this change this splicing is a thus EMT changes in splicing ESRP-regulated targets can used as a biomarker for the In this application we will develop more robust next generation splicing reporter assays ESRP- regulated exons that

changes in alternative splicIng occur duRing tHis ProCeSs. A cHangE in this splicinG NetwOrk is a thus a dynamic featUre of ThE eMT aND cHangeS in spliCInG OF ESrP-ReGulAtED tArgetS caN be used As a biomarkEr fOr The EMT. In this APpLication we WilL develop more RobUst nexT gEneRAtion SplIcing ReportER assayS using ESRp- rEGulateD Exons thAT

changes in alternative sp licing occ ur du rin g t hi s pr oces s. A change in this  splicing network is a  thus  a dyna m ic  feat ure oft he E MTan dcha ng e sin sp lic ing ofESRP-regul ate dtargets canb eused as abio marker for t heEMT. I nthi s  appl ica tionwe wil l  devel op more r ob u st nex t  genera t i on  spl icing reporter as s ay s  using ESRP- r egulat ed ex o n s t hat

changes_in alternative_splicing occur during this_process. A_change_in this_splicing_network is a_thus a dynamic_feature of the EMT_and changes in_splicing_of ESRP-regulated targets can be used as a biomarker for the EMT. In this_application_we will_develop_more_robust next generation splicing reporter_assays using ESRP- regulated exons_that


developed a rigorous theory that describes how statistics of photons is influenced by protein conformational dynamics, the diffusion of the protein through the laser spot, shot noise, etc. It was shown that the exact FRET efficiency and photon counting histograms can be obtained by solving an appropriate reaction-diffusion equation. We have obtained a simple analytical

developed a rigorous theory that describes how statistics of photon is charm by protein conformational dynamics, the diffusion of the protein through the laser smudge, stroke noise, etc. It was shown that the accurate FRET efficiency and photon counting histograms can be obtained by solve an appropriate reaction - diffusion equality. We have obtained a simple analytical

degeloped a rigorous theorn that describes how stetistica of phogons is influenced by proteii cobformqtional dynamics, the dkffusion lf the peotemn through the leaer spob, shof noivx, etc. It was shpwn that tve exact FRET afwieiency and photon counting histogramf can br lbtained by sojvinb an zipvopriate reaction-diffusion equatjon. We iave obtained a simple analytical

developed a rigorous theory that describes how photons influenced by conformational dynamics, the the spot, shot noise, It was shown the exact FRET efficiency and photon histograms can be obtained by solving an appropriate reaction-diffusion equation. We have obtained simple analytical

developed a rigorous theory tHat describEs how StaTisTiCs of PhotOns is influenceD By prOtein conformational dynAmics, ThE DiffUSiOn of tHe proteIN tHROugH tHe LasEr SPoT, shot NoiSe, etc. It Was shown thAt tHe Exact FRET effICiEncy and phoTon Counting histOgrAms can Be ObtAIned bY soLving An apprOPriate Reaction-dIfFUsion eQUation. WE HAvE obtAined a simple analyTIcAL

developed a rigorous theo ry that de scrib eshow  s tati stic s of photons i s  inf luenced by protein con forma ti o nald yn amics , the d i ff u s ion  o fthe  p r ot ein t hro ugh the  laser spo t,sh ot noise, et c .It was sho wnthat the exa ctFRET e ff ici e ncy a ndphoto n coun t ing hi stogramsca n  be ob t ained b y so lvin g an appropriater ea c tion-diffusion  equat io n .W e  ha veobtained a  s imple analyti c al

developed_a rigorous_theory that describes how_statistics of_photons_is influenced_by_protein conformational dynamics,_the diffusion of_the protein through the_laser spot, shot_noise,_etc. It was shown that the exact FRET efficiency and photon counting histograms can_be_obtained by_solving_an_appropriate reaction-diffusion equation. We have_obtained a simple analytical


will seek to integrate the microtransfer with molecular profiling of specific cells within tissues, including routine proteomic and lipidomic analyses, particularly for the large number of less abundant molecular species. If microdissection and molecular analysis can be made clinically practical, the expression levels of sets of approximately 20 to 100 critical, stage-specific

will seek to integrate the microtransfer with molecular profiling of specific cells within tissues, include everyday proteomic and lipidomic analyses, particularly for the big phone number of less abundant molecular species. If microdissection and molecular analysis can be have clinically practical, the expression degree of sets of approximately 20 to 100 critical, stage - specific

wipl seek to integrate the microtransfer cuth moneculad profilkng of specific cells within tussuew, including routine pruteomic ajd lipidimic qnalyses, pedticulavjy fkv the oarge number on less abungant molecular soeeies. If microdissection and moleculaw analyxid can be made slinpcwlly ircctical, the expression levels or sets mf approximatrly 20 to 100 critical, stage-spefifif

will seek to integrate the microtransfer with of cells within including routine proteomic the number of less molecular species. If and molecular analysis can be made practical, the expression levels of sets of approximately 20 to 100 critical, stage-specific

will seek to integrate the micRotransfer With mOleCulAr ProfIlinG of specific celLS witHin tissues, including rouTine pRoTEomiC AnD lipiDomic anALySES, paRtIcUlaRlY FoR the lArgE number Of less abunDanT mOlecular specIEs. if microdisSecTion and molecUlaR analySiS caN Be madE clInicaLly praCTical, tHe expressIoN Levels OF sets of APPrOximAtely 20 to 100 critical, stAGe-SPecific

will seek to integrate th e microtra nsfer  wi thmo lecu larprofiling of s p ecif ic cells within tissue s, in cl u ding ro utine  proteo m ic a ndli pi dom ic an alyse s,particu larly forthe  l arge numbero fless abund ant  molecular s pec ies. I fmic r odiss ect ion a nd mol e cularanalysisca n  be ma d e clini c a ll y pr actical, the expr e ss i on levels of s ets of  a p pr o x ima tel y 20 to 10 0criti c al, sta g e- s p e cif i c

will_seek to_integrate the microtransfer with_molecular profiling_of_specific cells_within_tissues, including routine_proteomic and lipidomic_analyses, particularly for the_large number of_less_abundant molecular species. If microdissection and molecular analysis can be made clinically practical, the_expression_levels of_sets_of_approximately 20 to 100 critical,_stage-specific


dramatically affect the cost-effectiveness ratios for treatments. Further research to assess the contribution of anxiety to utility assessments for these men is on-going. This study serves as a specific core example of the overall career goal of understanding the role of emotions in medical decision-making in older adults. Older adults care occurs in a

dramatically affect the cost - effectiveness ratios for treatment. Further inquiry to assess the contribution of anxiety to utility assessment for these man is on - going. This study suffice as a specific core exercise of the overall career goal of understand the role of emotions in aesculapian decision - making in older adults. old adults care occurs in a

drwmatically affect the cort-effectiveness ratios for tdeatmentr. Further research to assess tye cobtribution of anxiety go utilitj assessmwnts dor these men is ok-yoing. Bhis vvudy serves as s specific core example mf tke overall career goal of understandyng the rlle of emotionf in iedidal decision-making in older adults. Older edults care occirs in a

dramatically affect the cost-effectiveness ratios for treatments. to the contribution anxiety to utility on-going. study serves as specific core example the overall career goal of understanding role of emotions in medical decision-making in older adults. Older adults care occurs a

dramatically affect the cost-EffectivenEss raTioS foR tReatMentS. Further researCH to aSsess the contribution of AnxieTy TO utiLItY asseSsments FOr THEse MeN iS on-GoINg. this sTudY serves As a specifiC coRe Example of the OVeRall career GoaL of understanDinG the roLe Of eMOtionS in MedicAl deciSIon-makIng in oldeR aDUlts. OlDEr adultS CArE occUrs in a

dramatically affect the c ost-effect ivene ssrat io s fo r tr eatments. Furt h er r esearch to assess thecontr ib u tion of  anxi ety tou ti l i tyas se ssm en t sfor t hes e men i s on-going . T hi s study serv e sas a speci fic  core exampl e o f theov era l l car eer  goal  of un d erstan ding thero l e of e m otionsi n  m edic al decision-makin g  i n  older adults.  Older  a d ul t s  ca reoccurs ina

dramatically_affect the_cost-effectiveness ratios for treatments._Further research_to_assess the_contribution_of anxiety to_utility assessments for_these men is on-going._This study serves_as_a specific core example of the overall career goal of understanding the role of_emotions_in medical_decision-making_in_older adults. Older adults care_occurs in a


. The primary objective of this project is to secure tissue from CaP patients (during the course of their diagnosis and treatment) for the purpose of biological studies designed to characterize cancers with respect to their biological potentials. Frozen samples as well as paraffin-embedded samples of prostate tissue will be provided for study at the University of

. The primary objective of this project is to secure tissue from CaP patient (during the path of their diagnosis and treatment) for the purpose of biological studies design to characterize cancers with regard to their biological electric potential. Frozen sample as well as paraffin - embed samples of prostate tissue will be provide for sketch at the University of

. Thf primary objective of tmis project is to securx tissus from CxP patients (during the coursx of theie diagnosis and treatmdnt) for tje purpowe oh biological stuvjes deslyned fl chcrecterize cancerx with res[ect to their tiullgical potentials. Frozen samples as well ax oaraffin-embeddgd sak[les of prostate tissue will be providsd for vtudy at the Iniversity of

. The primary objective of this project secure from CaP (during the course for purpose of biological designed to characterize with respect to their biological potentials. samples as well as paraffin-embedded samples of prostate tissue will be provided for at the University of

. The primary objective of this Project is tO secuRe tIssUe From caP pAtients (during tHE couRse of their diagnosis and TreatMeNT) for THe PurpoSe of bioLOgICAl sTuDiEs dEsIGnEd to cHarActerizE cancers wiTh rEsPect to their bIOlOgical poteNtiAls. Frozen samPleS as welL aS paRAffin-EmbEdded SampleS Of prosTate tissuE wILl be prOVided foR STuDy at The University of

. The primary objective of  this proj ect i s t o s ec uretiss ue from CaP pa t ient s (during the course o f the ir diag n os is an d treat m en t )  fo rth e p ur p os e ofbio logical  studies d esi gn ed to charac t er ize cancer s w ith respecttotheirbi olo g icalpot entia ls. Fr o zen sa mples aswe l l as p a raffin- e m be dded  samples of prost a te tissue will be  provi de d  f o r  st udy  at the Un iv ersit y  of

. The_primary objective_of this project is_to secure_tissue_from CaP_patients_(during the course_of their diagnosis_and treatment) for the_purpose of biological_studies_designed to characterize cancers with respect to their biological potentials. Frozen samples as well_as_paraffin-embedded samples_of_prostate_tissue will be provided for_study at the University of


1993 to conduct the research described here. The Ukraine Placental Study had the following goals: 1. To document the levels of common pollutants experienced by pregnant women in two urban areas, using environmental measurements and biological markers 2. To describe the reproductive outcomes of these women 3. To determine what relationship, if any, exists

1993 to conduct the research described here. The Ukraine Placental Study had the follow goal: 1. To document the levels of common pollutants know by pregnant women in two urban sphere, use environmental measurements and biological marker 2. To describe the reproductive consequence of these women 3. To determine what kinship, if any, exists

1993 tl conduct the research dtscribed here. The Ukrainx Placehtal Stuay had the following goals: 1. Vo dicumebt the levels of commov pollutajts expeeienred by pregnant xkmen in two udnan axees, using envirokmental meavurements and tiullgical markers 2. To describe the repwoductife outcomes of trese romeh 3. To determine what relationship, jf any, txists

1993 to conduct the research described here. Placental had the goals: 1. To pollutants by pregnant women two urban areas, environmental measurements and biological markers 2. describe the reproductive outcomes of these women 3. To determine what relationship, if exists

1993 to conduct the research descrIbed here. ThE UkraIne plaCeNtal studY had the followiNG goaLs: 1. To document the levels oF commOn POlluTAnTs expErienceD By PREgnAnT wOmeN iN TwO urbaN arEas, usinG environmeNtaL mEasurements aND bIological mArkErs 2. To describE thE reproDuCtiVE outcOmeS of thEse womEN 3. To detErmine whaT rELationSHip, if anY, EXiSts

1993 to conduct the resea rch descri bed h ere . T he  Ukr aine  Placental Stu d y ha d the following goals:  1. T od ocum e nt  thelevelso fc o mmo npo llu ta n ts  expe rie nced by  pregnantwom en  in two urba n  a reas, usin g e nvironmental  me asurem en tsa nd bi olo gical  marke r s 2. T o describ et he rep r oductiv e ou tcom es of these women 3. To determine w hat re la t io n s hip , i f any, exi st s

1993_to conduct_the research described here._The Ukraine_Placental_Study had_the_following goals: 1._To document the_levels of common pollutants_experienced by pregnant_women_in two urban areas, using environmental measurements and biological markers 2. To describe the_reproductive_outcomes of_these_women_3. To determine what relationship,_if any, exists


of the DF/HCC sponsored symposia and event. This proposal requests 5 years of funding to support 10 pre-doctoral students and 1 post-doctoral fellow annually. The development of drugs that inhibit the K-Ras oncogene represents one of the greatest unmet needs in the treatment of human cancer. The

of the DF / HCC sponsored symposia and event. This proposal requests 5 days of support to support 10 pre - doctoral students and 1 post - doctoral fellow per annum. The development of drugs that inhibit the K - Ras oncogene represent one of the greatest unmet needs in the discussion of human cancer. The

of the DF/HCC sponsored symkosia and event. Tkus pro'osal rsquests 5 years of funding to support 10 pre-doxtoral students and 1 pust-doctorwl felloq aniually. The development on drufd thct inhibit the K-Tas oncogene represents ona uf the greatest unmet needs in the trqatment ov human cancer. The

of the DF/HCC sponsored symposia and event. requests years of to support 10 fellow The development of that inhibit the oncogene represents one of the greatest needs in the treatment of human cancer. The

of the DF/HCC sponsored symposIa and event. this pRopOsaL rEqueSts 5 yEars of funding tO SuppOrt 10 pre-doctoral students And 1 poSt-DOctoRAl FelloW annualLY. THE DevElOpMenT oF DrUgs thAt iNhibit tHe K-Ras oncoGenE rEpresents one OF tHe greatest UnmEt needs in the TreAtment Of HumAN cancEr. THe

of the DF/HCC sponsored s ymposia an d eve nt.  Th is  pro posa l requests 5 y e arsof funding to support10 pr e- d octo r al  stud ents an d  1 p ost -d oc tor al fe llowann ually.The develo pme nt  of drugs th a tinhibit th e K -Ras oncogen e r eprese nt s o n e ofthe  grea test u n met ne eds in th et reatme n t of hu m a ncanc er. The

of_the DF/HCC_sponsored symposia and event._This proposal_requests_5 years_of_funding to support_10 pre-doctoral students_and 1 post-doctoral fellow_annually. The development_of_drugs that inhibit the K-Ras oncogene represents one of the greatest unmet needs in_the_treatment of_human_cancer._The


to PARP inhibition remains an unmet clinical need. Notably, our preliminary data suggest a synergy between EZH2 inhibitor and PARP inhibitor in a CARM1-dependent manner. Further, EZH2 inhibition enhances CD8+ effector T cell trafficking into tumors by upregulating Th1-type chemokines

to PARP inhibition remains an unmet clinical need. Notably, our preliminary data indicate a synergy between EZH2 inhibitor and PARP inhibitor in a CARM1 - pendent manner. Further, EZH2 inhibition enhances CD8 + effecter T cell trafficking into tumors by upregulating Th1 - character chemokines

to PARP inhibition remains an unmet clinieql neev. Notabmy, our pfeliminary data suggest a syiergt betqeen EZH2 inhibitor and PARP inhpbitor in a CERM1-dependent manisr. Furtmzr, EZG2 inhnbmtion enhances GD8+ effector T cell traffiwkkny into tumors by upregulating Th1-type chemokonfs

to PARP inhibition remains an unmet clinical our data suggest synergy between EZH2 a manner. Further, EZH2 enhances CD8+ effector cell trafficking into tumors by upregulating chemokines

to PARP inhibition remains an Unmet cliniCal neEd. NOtaBlY, our PrelIminary data sugGEst a Synergy between EZH2 inhibItor aNd paRP iNHiBitor In a CARM1-DEpENDenT mAnNer. fuRThEr, EZH2 InhIbition Enhances CD8+ EffEcTor T cell trafFIcKing into tuMorS by upregulatIng th1-type ChEmoKInes

to PARP inhibition remain s an unmet  clin ica l n ee d. N otab ly, our prelim i nary  data suggest a synerg y bet we e n EZ H 2inhib itor an d  P A R P i nh ib ito ri na CAR M1- depende nt manner.  Fu rt her, EZH2 in h ib ition enha nce s CD8+ effec tor  T cel ltra f ficki ngintotumors by upr egulating  T h 1-type chemoki n e s

to_PARP inhibition_remains an unmet clinical_need. Notably,_our_preliminary data_suggest_a synergy between_EZH2 inhibitor and_PARP inhibitor in a_CARM1-dependent manner. Further,_EZH2_inhibition enhances CD8+ effector T cell trafficking into tumors by upregulating Th1-type chemokines


nuclear NMR, Raman and IR, to identify the local structure around the central metal ion in these complexes. We will use the method that we have developed for EXAFS data analysis of mixtures for similar Cd(II), Hg(II) and Pb(II) complexes with cysteine and penicillamine (3,

nuclear NMR, Raman and IR, to identify the local structure around the central metal ion in these complex. We will practice the method that we have developed for EXAFS datum analysis of mix for similar Cd(II), Hg(II) and Pb(II) building complex with cysteine and penicillamine (3,

nucpear NMR, Raman and IR, to identify the local stcucture around ghe central metal ion in thede compoexes. We will use the oethod thwt we hace dtveloped for EXAFS data akclysia of kmxtures for simllar Cd(II), Hc(II) and Pb(II) cmmolzxes with cysteine and penicillamine (3,

nuclear NMR, Raman and IR, to identify structure the central ion in these method we have developed EXAFS data analysis mixtures for similar Cd(II), Hg(II) and complexes with cysteine and penicillamine (3,

nuclear NMR, Raman and IR, to ideNtify the loCal stRucTurE aRounD the Central metal ioN In thEse complexes. We will use tHe metHoD That WE hAve deVeloped FOr exaFS DaTa AnaLySIs Of mixTurEs for siMilar Cd(II), HG(II) AnD Pb(II) complexES wIth cysteinE anD penicillamiNe (3,

nuclear NMR, Raman and IR,  to identi fy th e l oca lstru ctur e around the c e ntra l metal ion in these c omple xe s . We wi ll us e the m e th o d  th at  w e h av e  d evelo ped  for EX AFS data a nal ys is of mixtur e sfor simila r C d(II), Hg(II ) a nd Pb( II ) c o mplex eswithcystei n e andpenicilla mi n e (3,

nuclear NMR,_Raman and_IR, to identify the_local structure_around_the central_metal_ion in these_complexes. We will_use the method that_we have developed_for_EXAFS data analysis of mixtures for similar Cd(II), Hg(II) and Pb(II) complexes with cysteine_and_penicillamine (3,


collaborative team is working to validate and characterize previously identified hits from primary SENP screening. As a center, the NCGC has fostered and maintained over 130 active collaborations with both NIH and extramural investigators, facilitating drug discovery efforts across the entire spectrum of human disease. These efforts have led to dozens of high

collaborative team is working to validate and characterize previously identified hits from basal SENP cover. As a center, the NCGC has fostered and sustain over 130 active collaboration with both NIH and extramural investigators, facilitating drug discovery campaign across the integral spectrum of human disease. These efforts have led to dozens of high

coplaborative team is worklng to validate cbd chacacteriae previuusly identified hits from pcimaey SEBP screening. As a centdr, the NCHC has fisteced and maintainxs over 130 activs colneborations with both NIH dnd extramural ivvzstigators, facilitating drug discovewy effottd across the egtirt s[ectdlm of human disease. These efforfs have led to dozenx of high

collaborative team is working to validate and identified from primary screening. As a and over 130 active with both NIH extramural investigators, facilitating drug discovery efforts the entire spectrum of human disease. These efforts have led to dozens of

collaborative team is workinG to validatE and cHarActErIze pReviOusly identifieD Hits From primary SENP screeniNg. As a CeNTer, tHE NcGC haS fosterED aND MaiNtAiNed OvER 130 aCtive ColLaboratIons with boTh NiH And extramuraL InVestigatorS, faCilitating drUg dIscoveRy EffORts acRosS the eNtire sPEctrum Of human diSeASe. ThesE Efforts HAVe Led tO dozens of high

collaborative team is wor king to va lidat e a ndch arac teri ze previouslyi dent ified hits from primar y SEN Ps cree n in g. As  a cent e r, t heNC GC  ha sf os tered  an d maint ained over  13 0active colla b or ations wit h b oth NIH andext ramura linv e stiga tor s, fa cilita t ing dr ug discov er y  effor t s acros s th e en tire spectrum ofh um a n disease. The se eff or t sh a veled  to dozens  o f hig h

collaborative_team is_working to validate and_characterize previously_identified_hits from_primary_SENP screening. As_a center, the_NCGC has fostered and_maintained over 130_active_collaborations with both NIH and extramural investigators, facilitating drug discovery efforts across the entire_spectrum_of human_disease._These_efforts have led to dozens_of high


cellular environments. We propose solutions to the challenging stereochemical problems posed by the monohydroxy dimers and show how chemistry developed in our lab can generate a combinatorial library of sulfur electrophiles. In a third area, we investigate the challenging architecture and reactivity of the isocyanoterpenes, which we recently demonstrated

cellular environments. We propose solutions to the challenging stereochemical trouble pose by the monohydroxy dimers and show how chemistry developed in our lab can beget a combinatorial library of sulfur electrophiles. In a third area, we investigate the ambitious architecture and reactivity of the isocyanoterpenes, which we recently demonstrated

ceplular environments. We pvopose solutions to the challsnging sgereochemical problems posed bt the monohydroxy dimers ana show hoa chemisrry veveloped in our lab can generzbe a eonbinatorial linrary of sunfur electrophhlds. In a third area, we investigate the challemglng architectute anc readniyity of the isocyanoterpenes, whidh we rtcently demonstratrd

cellular environments. We propose solutions to the problems by the dimers and show lab generate a combinatorial of sulfur electrophiles. a third area, we investigate the architecture and reactivity of the isocyanoterpenes, which we recently demonstrated

cellular environments. We proPose solutiOns to The ChaLlEngiNg stEreochemical prOBlemS posed by the monohydroxy DimerS aND shoW HoW chemIstry deVElOPEd iN oUr Lab CaN GeNeratE a cOmbinatOrial libraRy oF sUlfur electroPHiLes. In a thirD arEa, we investigAte The chaLlEngINg arcHitEcturE and reACtivitY of the isoCyANoterpENes, whicH WE rEcenTly demonstrated

cellular environments. We  propose s oluti ons  to  t he c hall enging stereoc h emic al problems posed by t he mo no h ydro x ydimer s and s h ow h owch em ist ry de velop edin ourlab can ge ner at e a combinat o ri al library  of  sulfur elec tro philes .Ina  thir d a rea,we inv e stigat e the cha ll e nginga rchitec t u re  and  reactivity of th e  i s ocyanoterpenes , whic hw er e cen tly  demonstra te d

cellular_environments. We_propose solutions to the_challenging stereochemical_problems_posed by_the_monohydroxy dimers and_show how chemistry_developed in our lab_can generate a_combinatorial_library of sulfur electrophiles. In a third area, we investigate the challenging architecture and_reactivity_of the_isocyanoterpenes,_which_we recently demonstrated


vivo. In collaborative studies, we showed that the Mitf-Tfe proteins can bind the E-box sequence as homodimers or as heterodimers with other family members. To investigate the function of the Tfe genes in mammalian development, we used embryonic stem (ES) cell knockout technology to make

vivo. In collaborative studies, we showed that the Mitf - Tfe proteins can bind the east - corner sequence as homodimers or as heterodimers with other syndicate member. To investigate the function of the Tfe genes in mammalian exploitation, we use embryonic stem (ES) cellular telephone smasher technology to make

vigo. In collaborative studles, we showed thcr the Kitf-Tfs proteivs can bind the E-box sequencx as homoeimers or as heterodimdrs with lther fanily nembers. To investincte tgc funetmon of the Tfe nenes in makmalian develo[mdnc, we used embryonic stem (ES) cell knoskout trcjnology to makg

vivo. In collaborative studies, we showed that proteins bind the sequence as homodimers family To investigate the of the Tfe in mammalian development, we used embryonic (ES) cell knockout technology to make

vivo. In collaborative studieS, we showed tHat thE MiTf-TFe ProtEins Can bind the E-box SEqueNce as homodimers or as hetErodiMeRS witH OtHer faMily memBErS. tO inVeStIgaTe THe FunctIon Of the TfE genes in maMmaLiAn developmenT, We Used embryoNic Stem (ES) cell knOckOut tecHnOloGY to maKe

vivo. In collaborative st udies, weshowe d t hat  t he M itf- Tfe proteins c a n bi nd the E-box sequenceas ho mo d imer s  o r asheterod i me r s  wi th  o the rf am ily m emb ers. To  investiga teth e function o f  t he Tfe gen esin mammalian  de velopm en t,w e use d e mbryo nic st e m (ES)  cell kno ck o ut tec h nologyt o  m ake

vivo._In collaborative_studies, we showed that_the Mitf-Tfe_proteins_can bind_the_E-box sequence as_homodimers or as_heterodimers with other family_members. To investigate_the_function of the Tfe genes in mammalian development, we used embryonic stem (ES) cell_knockout_technology to_make


than ESM for large panel studies. The broad goals of this project are to critically evaluate the psychometric properties of these three approaches and to incorporate both experiential approaches into an on-going, nationally representative panel study that already includes evaluative measures. The first specific aim is to thoroughly evaluate the properties of the DRM

than ESM for large panel studies. The broad goal of this undertaking are to critically evaluate the psychometric properties of these three access and to integrate both experiential approaches into an on - going, nationally representative panel cogitation that already includes evaluative measure. The first specific aim is to thoroughly measure the properties of the DRM

thwn ESM for large panel suudies. The broad yials oh this lroject xre to critically evaluate tie pwychonetric properties of tfese threv approacyes end to incorporavs both crperisktial epproaches into an on-goinc, nationally rapfedentative panel study that already yncludex fvaluative meafurex. The first specific aim is to thoroughmy evallate the propertirs of the DRM

than ESM for large panel studies. The of project are critically evaluate the approaches to incorporate both approaches into an nationally representative panel study that already evaluative measures. The first specific aim is to thoroughly evaluate the properties of DRM

than ESM for large panel studiEs. The broad Goals Of tHis PrOjecT are To critically evALuatE the psychometric properTies oF tHEse tHReE apprOaches aND tO INcoRpOrAte BoTH eXperiEntIal apprOaches into An oN-gOing, nationalLY rEpresentatIve Panel study thAt aLready InCluDEs evaLuaTive mEasureS. the firSt specifiC aIM is to tHOroughlY EVaLuatE the properties of tHE Drm

than ESM for large panelstudies. T he br oad  go al s of  thi s project aret o cr itically evaluate thepsych om e tric pr opert ies oft he s e  th re eapp ro a ch es an d t o incor porate bot h e xp eriential ap p ro aches into  an  on-going, n ati onally  r epr e senta tiv e pan el stu d y that  alreadyin c ludese valuati v e  m easu res. The first sp e ci f ic aim is to t horoug hl y  e v a lua tethe proper ti es of the DRM

than_ESM for_large panel studies. The_broad goals_of_this project_are_to critically evaluate_the psychometric properties_of these three approaches_and to incorporate_both_experiential approaches into an on-going, nationally representative panel study that already includes evaluative measures._The_first specific_aim_is_to thoroughly evaluate the properties_of the DRM


a novel mechanism that UCH-L1 serves as a key molecule in assembling inflammatory signaling complex thereby fine tuning vascular inflammatory responses and lesion formation. It is our view that the outcome will provide novel insight into the understanding of the complex sequelae of inflammation in vascular lesion formation. Our hypothesis will be tested by uitilzing

a novel mechanism that UCH - L1 serves as a key molecule in assemble incendiary signaling complex thereby fine tune vascular incendiary responses and lesion formation. It is our horizon that the outcome will provide fresh penetration into the understanding of the complex sequelae of ignition in vascular lesion formation. Our hypothesis will be test by uitilzing

a jovel mechanism that UCH-U1 serves as a kgy molecnle in zssemblivg inflammatory signaling colpoex tyereby fine tuning vaszular infpammatort rewponses and lesion njrmaflon. Ic ms our view thaj the outcoma will provide nuvzl insight into the understanding of the cokppex sequelae os ingjammzniin in vascular lesion formatikn. Our iypothesis will be tested by uitilzing

a novel mechanism that UCH-L1 serves as molecule assembling inflammatory complex thereby fine lesion It is our that the outcome provide novel insight into the understanding the complex sequelae of inflammation in vascular lesion formation. Our hypothesis will be by uitilzing

a novel mechanism that UCH-L1 seRves as a key MolecUle In aSsEmblIng iNflammatory sigNAlinG complex thereby fine tunIng vaScULar iNFlAmmatOry respONsES And LeSiOn fOrMAtIon. It Is oUr view tHat the outcOme WiLl provide novEL iNsight into The UnderstandinG of The comPlEx sEQuelaE of InflaMmatioN In vascUlar lesioN fORmatioN. our hypoTHEsIs wiLl be tested by uitilZInG

a novel mechanism that UC H-L1 serve s asa k eymo lecu le i n assembling i n flam matory signaling compl ex th er e by f i ne  tuni ng vasc u la r inf la mm ato ry re spons esand les ion format ion .It is our vi e wthat the o utc ome will pro vid e nove lins i ght i nto  theunders t anding  of the c om p lex se q uelae o f in flam mation in vascula r  l e sion formation . Ourhy p ot h e sis  wi ll be test ed  by u i tilzing

a_novel mechanism_that UCH-L1 serves as_a key_molecule_in assembling_inflammatory_signaling complex thereby_fine tuning vascular_inflammatory responses and lesion_formation. It is_our_view that the outcome will provide novel insight into the understanding of the complex_sequelae_of inflammation_in_vascular_lesion formation. Our hypothesis will_be tested by uitilzing


in airway remodeling. We will: 1) Evaluate the hypothesis that the reduced expression of cav1 is associated with the expression of inflammatory markers, more specifically IL-4 and TGF-beta, and the development of airway remodeling in allergen challenged mice. 2) Investigate the hypothesis that among the Th2 cytokines expressed

in airway remodeling. We will: 1) Evaluate the hypothesis that the dilute formula of cav1 is associated with the expression of inflammatory marker, more specifically IL-4 and TGF - beta, and the development of airway recast in allergen challenge mice. 2) Investigate the guess that among the Th2 cytokine expressed

in airway remodeling. We wiul: 1) Evaluate thg yypothxsis thzt the rdduced expression of cav1 is essoxiatee with the expression uf inflamlatory mqrkecs, more specificemly IL-4 and TGR-neta, cnv the developmekt of airwaf remodeling it xlpergen challenged mice. 2) Investigate the hylohhesis that amjng uhe Th2 djtikines expressed

in airway remodeling. We will: 1) Evaluate that reduced expression cav1 is associated markers, specifically IL-4 and and the development airway remodeling in allergen challenged mice. Investigate the hypothesis that among the Th2 cytokines expressed

in airway remodeling. We will: 1) EValuate the HypotHesIs tHaT the ReduCed expression oF Cav1 iS associated with the exprEssioN oF InflAMmAtory Markers, MOrE SPecIfIcAllY Il-4 AnD TGF-bEta, And the dEvelopment Of aIrWay remodelinG In Allergen chAllEnged mice. 2) InvEstIgate tHe HypOThesiS thAt amoNg the TH2 CytokiNes expresSeD

in airway remodeling. Wewill: 1) E valua tethe  h ypot hesi s that the red u cedexpression of cav1 isassoc ia t ed w i th  theexpress i on o f i nf la mma to r ymarke rs,  more s pecificall y I L- 4 and TGF-be t a,  and the d eve lopment of a irw ay rem od eli n g inall ergen  chall e nged m ice. 2) I nv e stigat e  the hy p o th esis  that among the T h 2c ytokines expre ssed

in_airway remodeling._We will: 1) Evaluate_the hypothesis_that_the reduced_expression_of cav1 is_associated with the_expression of inflammatory markers,_more specifically IL-4_and_TGF-beta, and the development of airway remodeling in allergen challenged mice. 2) Investigate the_hypothesis_that among_the_Th2_cytokines expressed


The Administrative Core will also organize CIRA's AIDS Science Day. Project Summary/Abstract Cardiovascular disease (CVD) is the leading cause of death in the US, however African American residents of rural areas in the south and southeast regions have the highest prevalence of CVD of any group. African Americans carry a significant burden of

The Administrative Core will also organize CIRA's AIDS Science Day. Project Summary / Abstract Cardiovascular disease (CVD) is the leading cause of end in the US, however African American resident of rural areas in the south and southeast region own the highest prevalence of CVD of any group. African Americans behave a significant burden of

Thf Administrative Core wiul also organizg XIRA's EIDS Scjence Dah. Project Summary/Abstract Cacdiocascuoar disease (CVD) is the leading bause of eeati in the US, howetsr Afrigcn Amsvican cesidents of rutal areas in the south and suucheast regions have the highest prevwlence pf CVD of any grjup. Ssriczn Americans carry a significant bhrden oh

The Administrative Core will also organize CIRA's Day. Summary/Abstract Cardiovascular (CVD) is the the however African American of rural areas the south and southeast regions have highest prevalence of CVD of any group. African Americans carry a significant burden

The Administrative Core will Also organiZe CIRa's AiDS scIencE Day. project Summary/aBstrAct Cardiovascular diseaSe (CVD) Is THe leADiNg cauSe of deaTH iN THe Us, hOwEveR AFRiCan AmEriCan resiDents of rurAl aReAs in the south ANd Southeast rEgiOns have the hiGheSt prevAlEncE Of CVD Of aNy groUp. AfriCAn AmerIcans carrY a SIgnifiCAnt burdEN Of

The Administrative Core w ill also o rgani zeCIR A' s AI DS S cience Day. Pr o ject  Summary/Abstract Card iovas cu l ar d i se ase ( CVD) is th e lea di ng  ca us e  o f dea thin theUS, howeve r A fr ican America n  r esidents o f r ural areas i n t he sou th  an d  sout hea st re gionsh ave th e highest  p r evalen c e of CV D of  any  group. African A m er i cans carry a s ignifi ca n tb u rde n o f

The_Administrative Core_will also organize CIRA's_AIDS Science_Day._Project Summary/Abstract_Cardiovascular_disease (CVD) is_the leading cause_of death in the_US, however African_American_residents of rural areas in the south and southeast regions have the highest prevalence_of_CVD of_any_group._African Americans carry a significant_burden of


on a genome-wide scale in the context of proper chromatin structure. With this assay aspects of gene expression regulation will be investigated in regards to transcription factor binding and the transcriptional requirements of histone modifications. These studies are intended to shed light on two fundamental questions in gene regulation: Can transcription factors intrinsically access their binding sites in native

on a genome - wide scale in the context of proper chromatin structure. With this assay aspects of gene formula rule will be investigated in regards to arrangement divisor binding and the transcriptional requirements of histone change. These study are intended to shed light on two fundamental doubt in gene regulation: Can transcription factors intrinsically access their bind sites in native

on a genome-wide scale in tme context of proper chcomatin structufe. With this assay aspects oh gebe exkgession regulation wiul be invvstigated in cegards to transrdiption factod binbiig and the tranxcriptionan requirements ow kistone modifications. These studies wre intrnfed to shed lidht pg twk fundamental questions in gene refulatioi: Can transcripyion factors intrinsically accfss their binding dites in najjve

on a genome-wide scale in the context chromatin With this aspects of gene in to transcription factor and the transcriptional of histone modifications. These studies are to shed light on two fundamental questions in gene regulation: Can transcription factors access their binding sites in native

on a genome-wide scale in the coNtext of proPer chRomAtiN sTrucTure. with this assay aSPectS of gene expression regulAtion WiLL be iNVeStigaTed in reGArDS To tRaNsCriPtIOn FactoR biNding anD the transcRipTiOnal requiremENtS of histone ModIfications. ThEse StudieS aRe iNTendeD to Shed lIght on TWo fundAmental quEsTIons in GEne reguLATiOn: CaN transcription facTOrS Intrinsically aCcess tHeIR bINDinG siTes in nativE

on a genome-wide scale in  the conte xt of  pr ope rchro mati n structure. W i th t his assay aspects of g ene e xp r essi o nregul ation w i ll b e i nv es tig at e din re gar ds to t ranscripti onfa ctor binding an d the tran scr iptional req uir ements  o f h i stone  mo dific ations .  These  studiesar e  inten d ed to s h e dligh t on two fundamen t al questions in g ene re gu l at i o n:Can  transcrip ti on fa c tors in t ri n s i cal l y access thei r binding s i tes  in na ti ve

on_a genome-wide_scale in the context_of proper_chromatin_structure. With_this_assay aspects of_gene expression regulation_will be investigated in_regards to transcription_factor_binding and the transcriptional requirements of histone modifications. These studies are intended to shed_light_on two_fundamental_questions_in gene regulation: Can transcription_factors intrinsically access their binding_sites in_native


or role of the sodium pump isoforms in epileptic hippocampal neuronal death. Our preliminary studies indicate a heterogeneous distribution of each isoform in rat hippocampal neurons. In TLE, we have discovered an inverse relationship between the level of one Na, K-ATPase isoform, and the susceptibility to neuronal death. This proposal outlines studies to

or role of the sodium pump isoforms in epileptic hippocampal neuronal death. Our preliminary report bespeak a heterogeneous distribution of each isoform in rat hippocampal neurons. In TLE, we have discovered an inverse kinship between the level of one Na, K - ATPase isoform, and the susceptibility to neuronal death. This marriage proposal draft studies to

or role of the sodium pump isoforms in epnoeptic hippodampal nduronal death. Our preliminarb stydies indicate a heterogeneuus distrpbution od earh isoform in rav hippocampal hcuronv. In TLE, we havg discovered an inverse renagilnship between the level of one Na, H-ATPase idoform, and the susbe[tibjlity to neuronal death. This propoaal outnines studies to

or role of the sodium pump isoforms hippocampal death. Our studies indicate a in hippocampal neurons. In we have discovered inverse relationship between the level of Na, K-ATPase isoform, and the susceptibility to neuronal death. This proposal outlines studies

or role of the sodium pump isofOrms in epilEptic HipPocAmPal nEuroNal death. Our preLIminAry studies indicate a hetErogeNeOUs diSTrIbutiOn of eacH IsOFOrm In RaT hiPpOCaMpal nEurOns. In TLe, we have disCovErEd an inverse rELaTionship beTweEn the level of One na, K-ATPAsE isOForm, aNd tHe susCeptibILity to Neuronal dEaTH. This pROposal oUTLiNes sTudies to

or role of the sodium pum p isoforms  in e pil ept ic  hip poca mpal neuronald eath . Our preliminary stud ies i nd i cate aheter ogeneou s  d i s tri bu ti onof ea ch is ofo rm in r at hippoca mpa lneurons. InT LE , we havedis covered an i nve rse re la tio n shipbet weenthe le v el ofone Na, K -A T Pase i s oform,a n dthesusceptibility to ne u ronal death. T his pr op o sa l out lin es studies  t o

or_role of_the sodium pump isoforms_in epileptic_hippocampal_neuronal death._Our_preliminary studies indicate_a heterogeneous distribution_of each isoform in_rat hippocampal neurons._In_TLE, we have discovered an inverse relationship between the level of one Na, K-ATPase_isoform,_and the_susceptibility_to_neuronal death. This proposal outlines_studies to


the acquisition of HIV infection or another immunosuppressive condition. 1. The role of foxa2 in the survival of dopamine neurons. [unreadable] [unreadable] Animals that have only one copy of the foxa2 gene show spontaneous loss of dopamine neurons with age. This mouse will likely be very widely used because although many mutations

the acquisition of HIV infection or another immunosuppressive condition. 1. The role of foxa2 in the survival of dopamine nerve cell. [ indecipherable ] [ indecipherable ] Animals that have only one transcript of the foxa2 gene show spontaneous loss of dopamine nerve cell with long time. This mouse will likely be very widely used because although many mutation

thf acquisition of HIV inftction or another immunovuppreasive covdition. 1. The role of foxa2 in tye suevival of dopamine neufons. [unrewdable] [ubreavable] Animals thef have only ohc copv if the foxa2 geke show spottaneous loss mf dlpamine neurons with age. This mouse will lokfly be very wiqely tsed because although many mutations

the acquisition of HIV infection or another 1. role of in the survival Animals have only one of the foxa2 show spontaneous loss of dopamine neurons age. This mouse will likely be very widely used because although many mutations

the acquisition of HIV infectIon or anothEr immUnoSupPrEssiVe coNdition. 1. The role OF foxA2 in the survival of dopamiNe neuRoNS. [unrEAdAble] [uNreadabLE] ANIMalS tHaT haVe ONlY one cOpy Of the foXa2 gene show SpoNtAneous loss of DOpAmine neuroNs wIth age. This moUse Will liKeLy bE Very wIdeLy useD becauSE althoUgh many muTaTIons

the acquisition of HIV in fection or  anot her  im mu nosu ppre ssive conditio n . 1.  The role of foxa2 inthe s ur v ival of  dopa mine ne u ro n s . [ un re ada bl e ][unre ada ble] An imals that  ha ve  only one co p yof the fox a2gene show sp ont aneous  l oss of do pam ine n eurons with a ge. Thismo u se wil l  likely b every  widely used beca u se although manymutati on s

the_acquisition of_HIV infection or another_immunosuppressive condition._1._The role_of_foxa2 in the_survival of dopamine_neurons. [unreadable] [unreadable] Animals_that have only_one_copy of the foxa2 gene show spontaneous loss of dopamine neurons with age. This_mouse_will likely_be_very_widely used because although many_mutations


efficiency of parent training groups as a treatment strategy is then being evaluated. Therapeutic effect is being assessed at the conclusion of eight weeks of structured group intervention and in a six-month post-treatment follow-up to evaluate short-term gains and maintenance of change in both child behavior and parenting skills. The objectives of this

efficiency of parent training groups as a treatment strategy is then being measure. curative effect is being assessed at the ending of eight workweek of structured group intervention and in a six - calendar month post - treatment follow - up to evaluate short - term addition and maintenance of change in both child demeanor and parenting skills. The objectives of this

efviciency of parent trainlng groups as a jrwatmenv stratsgy is tfen being evaluated. Therapeuvic wffecu is being assessed at the clnclusiob of wight weeks of strmetures grobp intervention snd in a shx-month post-traagmznt follow-up to evaluate short-term gwins anc laintenance of chamde ih both child behavior and parentinf skillv. The objectifes of this

efficiency of parent training groups as a is being evaluated. effect is being eight of structured group and in a post-treatment follow-up to evaluate short-term gains maintenance of change in both child behavior and parenting skills. The objectives of

efficiency of parent traininG groups as a TreatMenT stRaTegy Is thEn being evaluatED. TheRapeutic effect is being aSsessEd AT the COnClusiOn of eigHT wEEKs oF sTrUctUrED gRoup iNteRventioN and in a six-MonTh Post-treatmenT FoLlow-up to evAluAte short-term GaiNs and mAiNteNAnce oF chAnge iN both cHIld behAvior and pArENting sKIlls. The OBJeCtivEs of this

efficiency of parent trai ning group s asa t rea tm entstra tegy is then b e ingevaluated. Therapeutic  effe ct is b e in g ass essed a t  t h e  co nc lu sio no feight  we eks ofstructured  gr ou p interventi o nand in a s ix- month post-t rea tmentfo llo w -up t o e valua te sho r t-term  gains an dm ainten a nce ofc h an ge i n both child beha v io r  and parenting  skill s. Th e obj ect ives of th is

efficiency_of parent_training groups as a_treatment strategy_is_then being_evaluated._Therapeutic effect is_being assessed at_the conclusion of eight_weeks of structured_group_intervention and in a six-month post-treatment follow-up to evaluate short-term gains and maintenance of_change_in both_child_behavior_and parenting skills. The objectives_of this


injecting drug users. This study will provide new knowledge on young drug users in Hungary and will also contribute to advancing research methods and capability in other Eastern European countries. Examine differences between pre-term and full-term human milk. This study is also designed to identify material factorswhich may influence the concentrations and determine changes

injecting drug users. This study will provide newfangled cognition on young drug users in Hungary and will besides contribute to advance research methods and capability in early easterly European countries. analyze differences between pre - term and wide - term human milk. This study is besides designed to identify corporeal factorswhich may influence the concentrations and specify changes

injfcting drug users. This suudy will provide new knmwledgs on youvg drug users in Hungary and wull aoso contribute to advavcing resvarch metyods qnd capability in other Swstexn European counjries. Examina differences tegwzen pre-term and full-term human milk. Ehis stidj is also desidned eo isvnuify material factorswhich may inrluence the concentrstions and determine changfs

injecting drug users. This study will provide on drug users Hungary and will methods capability in other European countries. Examine between pre-term and full-term human milk. study is also designed to identify material factorswhich may influence the concentrations and changes

injecting drug users. This stuDy will provIde neW knOwlEdGe on YounG drug users in HuNGary And will also contribute tO advaNcINg reSEaRch meThods anD CaPABilItY iN otHeR eaStern eurOpean coUntries. ExaMinE dIfferences beTWeEn pre-term aNd fUll-term human MilK. This sTuDy iS Also dEsiGned tO identIFy mateRial factoRsWHich maY InfluenCE ThE conCentrations and detERmINe changes

injecting drug users. This  study wil l pro vid e n ew  kno wled ge on young dr u g us ers in Hungary and wil l als oc ontr i bu te to  advanc i ng r ese ar ch  me th o ds  andcap ability  in otherEas te rn Europeanc ou ntries. Ex ami ne differenc esbetwee npre - termand  full -termh uman m ilk. This  s t udy is also de s i gn ed t o identify materi a lf actorswhich ma y infl ue n ce t hecon centration sand d e termine ch a n g es

injecting drug_users. This_study will provide new_knowledge on_young_drug users_in_Hungary and will_also contribute to_advancing research methods and_capability in other_Eastern_European countries. Examine differences between pre-term and full-term human milk. This study is also_designed_to identify_material_factorswhich_may influence the concentrations and_determine changes


Mammalian Gametogenesis and Embryogenesis Conference will enhance the quality of this meeting, which has consistently been rated extremely high by the attendees. Inhibitors of the enzyme sarco/endoplasmic reticulum Ca2+ATPase (SERCA) are valuable research tools for the study of the enzyme's role in

Mammalian Gametogenesis and Embryogenesis Conference will enhance the quality of this meeting, which has consistently been rated highly eminent by the attendees. Inhibitors of the enzyme sarco / endoplasmic reticulum Ca2+ATPase (SERCA) are valuable inquiry tools for the sketch of the enzyme's role in

Malmalian Gametogenesis ana Embryogenesis Conferxnce wiml enhanze the quality of this meetiig, wyich yas consistently been fated extgemely hith bb the attendees. Mhhibitovf of bhe euzbme sarco/endoplssmic retiwulum Ca2+ATPase (SDREA) are valuable research tools for tre studu lf the enzyme's rolt ig

Mammalian Gametogenesis and Embryogenesis Conference will enhance of meeting, which consistently been rated Inhibitors the enzyme sarco/endoplasmic Ca2+ATPase (SERCA) are research tools for the study of enzyme's role in

Mammalian Gametogenesis and embryogeneSis CoNfeRenCe Will EnhaNce the quality oF This Meeting, which has consistEntly BeEN ratED eXtremEly high BY tHE AttEnDeEs. INhIBiTors oF thE enzyme Sarco/endopLasMiC reticulum Ca2+atPAse (SERCA) arE vaLuable researCh tOols foR tHe sTUdy of The EnzymE's role IN

Mammalian Gametogenesis a nd Embryog enesi s C onf er ence  wil l enhance theq uali ty of this meeting, wh ich h as cons i st ently  been r a te d ext re me lyhi g hby th e a ttendee s. Inhibit ors  o f the enzyme sa rco/endopl asm ic reticulum  Ca 2+ATPa se  (S E RCA)are  valu able r e search  tools fo rt he stu d y of th e en zyme 's role in

Mammalian_Gametogenesis and_Embryogenesis Conference will enhance_the quality_of_this meeting,_which_has consistently been_rated extremely high_by the attendees. Inhibitors_of the enzyme_sarco/endoplasmic_reticulum Ca2+ATPase (SERCA) are valuable research tools for the study of the enzyme's role_in


53 transcription factor family. Additionally, it was proposed that imatinib mesylate rescued oocytes from apoptosis by blocking activation of p63 by c-Abl. Our preliminary studies of p63-null oocytes confirmed the essential role of p63 in cisplatin induced death of oocytes. In addition, our studies suggested that the gene dosage

53 transcription factor family. Additionally, it was proposed that imatinib mesylate rescue oocyte from apoptosis by blocking activation of p63 by c - Abl. Our preliminary report of p63 - null oocyte confirmed the essential role of p63 in cisplatin induce death of oocytes. In accession, our studies suggested that the gene dose

53 trwnscription factor familn. Additionally, ij qas prmposed that imxtinib mesylate rescued oocyves drom qpoptosis by blocking xctivatioj of p63 bt c-Aul. Our preliminacg studicf of i63-null iocytes confirked the esvential role ox o63 nn cisplatin induced death of oocytef. In adcihion, our studigs subdestsd that the gene dosage

53 transcription factor family. Additionally, it was imatinib rescued oocytes apoptosis by blocking Our studies of p63-null confirmed the essential of p63 in cisplatin induced death oocytes. In addition, our studies suggested that the gene dosage

53 transcription factor family. additionalLy, it wAs pRopOsEd thAt imAtinib mesylate REscuEd oocytes from apoptosis By bloCkINg acTIvAtion Of p63 by c-ABL. OUR PreLiMiNarY sTUdIes of P63-nuLl oocytEs confirmeD thE eSsential role OF p63 In cisplatiN inDuced death of OocYtes. In AdDitIOn, our StuDies sUggestED that tHe gene dosAgE

53 transcription factor fa mily. Addi tiona lly , i twasprop osed that imat i nibmesylate rescued oocyt es fr om apop t os is by  blocki n ga c tiv at io n o fp 63  by c -Ab l. Ourpreliminar y s tu dies of p63- n ul l oocytescon firmed the e sse ntialro leo f p63  in  cisp latini nduced  death of  o o cytes. In addi t i on , ou r studies suggest e dt hat the gene d osage

53 transcription_factor family._Additionally, it was proposed_that imatinib_mesylate_rescued oocytes_from_apoptosis by blocking_activation of p63_by c-Abl. Our preliminary_studies of p63-null_oocytes_confirmed the essential role of p63 in cisplatin induced death of oocytes. In addition,_our_studies suggested_that_the_gene dosage


ensure accurate execution. These treatments are delivered using our twin Clinac-21EX accelerators. A Hi-ART system (Tomotherapy Inc.) for delivering treatments via helical tomotherapy has been installed, accepted and is currently treating patients. This system provides ROB with cutting edge treatment technology to support future clinical trials. We have

ensure accurate execution. These treatments are delivered use our duplicate Clinac-21EX accelerators. A Hi - ART system (Tomotherapy Inc.) for hand over treatment via helical tomotherapy has been installed, accept and is currently treating patient. This system provides ROB with cut edge treatment engineering to support future clinical trials. We have

endure accurate execution. Uhese treatments cee delmvered hsing ouf twin Clinac-21EX accelerators. A Hi-ARU system (Tomotheraph Inc.) for deliverung ureatments via helical tomotherziy hav been installec, accepted and is currendlh creating patients. This system providqs ROB eihh cutting edgg tresemenf technology to support future clihical tgials. We have

ensure accurate execution. These treatments are delivered twin accelerators. A system (Tomotherapy Inc.) tomotherapy been installed, accepted is currently treating This system provides ROB with cutting treatment technology to support future clinical trials. We have

ensure accurate execution. ThEse treatmeNts arE deLivErEd usIng oUr twin Clinac-21EX ACcelErators. A Hi-ART system (TomOtherApY inc.) fOR dEliveRing treATmENTs vIa HeLicAl TOmOtherApy Has been Installed, aCcePtEd and is curreNTlY treating pAtiEnts. This systEm pRovideS RoB wITh cutTinG edge TreatmENt techNology to sUpPOrt futURe cliniCAL tRialS. We have

ensure accurate execution . These tr eatme nts  ar edeli vere d using our tw i n Cl inac-21EX accelerators . A H i- A RT s y st em (T omother a py I nc. )fo r d el i ve ringtre atments  via helic alto motherapy ha s  b een instal led , accepted a ndis cur re ntl y  trea tin g pat ients. This s ystem pro vi d es ROB with cu t t in g ed ge treatment tech n ol o gy to supportfuture  c l in i c altri als. We ha ve

ensure_accurate execution._These treatments are delivered_using our_twin_Clinac-21EX accelerators._A_Hi-ART system (Tomotherapy_Inc.) for delivering_treatments via helical tomotherapy_has been installed,_accepted_and is currently treating patients. This system provides ROB with cutting edge treatment technology_to_support future_clinical_trials._We have


that match electrodes across ears result in improved bilateral performance; and (7) bilateral fittings are superior to unilateral fittings in patients who are experienced unilateral listeners. We use several new tests, including ones of distance perception, movement direction, speech recognition with localization cues, and speech recognition while performing a visual thinking task. We

that match electrodes across ears result in better bilateral operation; and (7) bilateral fittings are superior to unilateral appointment in affected role who are experienced unilateral listeners. We practice several new tests, include ones of distance perception, apparent motion direction, speech realization with localization cues, and speech recognition while performing a visual thinking task. We

thwt match electrodes acrors ears result nb imprmved bjlateral performance; and (7) bilateral hittungs qre superior to unilatdral fittpngs in pqtieits who are expecjenced muilatsval lnsveners. We use sgveral new tasts, including oved of distance perception, movement dyrectiom, dpeech recognijion eyth mocalization cues, and speech recoghition xhile performinb a visual thinking task. Wf

that match electrodes across ears result in performance; (7) bilateral are superior to are unilateral listeners. We several new tests, ones of distance perception, movement direction, recognition with localization cues, and speech recognition while performing a visual thinking task.

that match electrodes across Ears result In impRovEd bIlAterAl peRformance; and (7) biLAterAl fittings are superior tO unilAtERal fITtIngs iN patienTS wHO Are ExPeRieNcED uNilatEraL listenErs. We use seVerAl New tests, inclUDiNg ones of diStaNce perceptioN, moVement DiRecTIon, spEecH recoGnitioN With loCalizatioN cUEs, and sPEech recOGNiTion While performing a vISuAL thinking task. WE

that match electrodes acr oss ears r esult  in  im pr oved  bil ateral perform a nce;  and (7) bilateral fit tings  a r e su p er ior t o unila t er a l  fi tt in gsin pa tient s w ho areexperience d u ni lateral list e ne rs. We use  se veral new te sts , incl ud ing onesofdista nce pe r ceptio n, moveme nt direct i on, spe e c hreco gnition with loca l iz a tion cues, and  speec hr ec o g nit ion  while per fo rming a visua l  t h i n kin g  task. We

that_match electrodes_across ears result in_improved bilateral_performance;_and (7)_bilateral_fittings are superior_to unilateral fittings_in patients who are_experienced unilateral listeners._We_use several new tests, including ones of distance perception, movement direction, speech recognition with_localization_cues, and_speech_recognition_while performing a visual thinking_task. We


the spinning disk confocal system in the Laboratory of Cellular and Molecular Biology Microscopy Core. 27 researchers used the resources of the Laboratory of Cellular and Molecular Biology Microscopy Core. While most of the researchers come from the Laboratory of Cellular and Molecular Biology, the Core has been used by scientists from the Laboratory of Immune

the spinning disk confocal system in the Laboratory of Cellular and Molecular Biology Microscopy Core. 27 researchers used the resource of the Laboratory of Cellular and Molecular Biology Microscopy Core. While most of the research worker come from the Laboratory of Cellular and Molecular Biology, the Core has been used by scientist from the Laboratory of Immune

thf spinning disk confocal system in the Laboratmry of Cellulaf and Molecular Biology Micrlsxopy Xore. 27 researchers used the resolrces of rhe Oqboratory of Cellular ans Molzcnlar Biology Migroscopy Cose. While most mf tke researchers come from the Laboratjry of Veplular and Molgculag Fiolkgy, the Core has been used by sciehtists hrom the Laborayory of Immune

the spinning disk confocal system in the Cellular Molecular Biology Core. 27 researchers Laboratory Cellular and Molecular Microscopy Core. While of the researchers come from the of Cellular and Molecular Biology, the Core has been used by scientists from Laboratory of Immune

the spinning disk confocal syStem in the LAboraTorY of ceLlulAr anD Molecular BiolOGy MiCroscopy Core. 27 researcherS used ThE ResoURcEs of tHe LaborAToRY Of CElLuLar AnD moLeculAr BIology MIcroscopy COre. whIle most of the REsEarchers coMe fRom the LaboraTorY of CelLuLar ANd MolEcuLar BiOlogy, tHE Core hAs been useD bY ScientISts from THE LAborAtory of Immune

the spinning disk confoca l system i n the  La bor at oryof C ellular and Mo l ecul ar Biology MicroscopyCore.  2 7  res e ar chers  used t h er e sou rc es  of  t h eLabor ato ry of C ellular an d M ol ecular Biolo g yMicroscopy  Co re. While mo stof the  r ese a rcher s c ome f rom th e  Labor atory ofCe l lulara nd Mole c u la r Bi ology, the Core h a sb een used by sc ientis ts fr o m  th e L aboratoryof  Immu n e

the_spinning disk_confocal system in the_Laboratory of_Cellular_and Molecular_Biology_Microscopy Core. 27_researchers used the_resources of the Laboratory_of Cellular and_Molecular_Biology Microscopy Core. While most of the researchers come from the Laboratory of Cellular_and_Molecular Biology,_the_Core_has been used by scientists_from the Laboratory of Immune


arrest in granulocytopoiesis. Although sympathetic stimulation is known to accompany both clinical and experimental thermal injury and adrenergic stimulation modulates immune cell function, cytokine release and myelopoiesis under non-stressed conditions there is a lack of information on bone marrow noepinephrine (NE) release during trauma and its

arrest in granulocytopoiesis. Although sympathetic stimulation is known to company both clinical and experimental thermal wound and adrenergic stimulation modulates immune cell affair, cytokine handout and myelopoiesis under non - stressed conditions there is a lack of data on bone marrow noepinephrine (NE) release during trauma and its

argest in granulocytopoiesls. Although sympcrhetic stimumation ir known to accompany both clmnicql ane experimental thermal injury ajd adrenwrgir stimulation movhlates limuns celn function, cytoline releave and myelopoherid under non-stressed conditions therq is a kafk of informatyon pg bohv narrow noepinephrine (NE) releaae duriig trauma and iys

arrest in granulocytopoiesis. Although sympathetic stimulation is accompany clinical and thermal injury and function, release and myelopoiesis non-stressed conditions there a lack of information on bone noepinephrine (NE) release during trauma and its

arrest in granulocytopoiesiS. Although sYmpatHetIc sTiMulaTion Is known to accomPAny bOth clinical and experimeNtal tHeRMal iNJuRy and AdrenerGIc STImuLaTiOn mOdULaTes imMunE cell fuNction, cytoKinE rElease and myeLOpOiesis undeR noN-stressed conDitIons thErE is A Lack oF inFormaTion on BOne marRow noepinEpHRine (NE) RElease dURInG traUma and its

arrest in granulocytopoie sis. Altho ugh s ymp ath et ic s timu lation is know n  toaccompany both clinica l and  e x peri m en tal t hermali nj u r y a nd  a dre ne r gi c sti mul ation m odulates i mmu ne  cell functi o n,  cytokinerel ease and mye lop oiesis  u nde r  non- str essed  condi t ions t here is a  l a ck ofi nformat i o non b one marrow noepin e ph r ine (NE) relea se dur in g  t r a uma  an d its

arrest_in granulocytopoiesis._Although sympathetic stimulation is_known to_accompany_both clinical_and_experimental thermal injury_and adrenergic stimulation_modulates immune cell function,_cytokine release and_myelopoiesis_under non-stressed conditions there is a lack of information on bone marrow noepinephrine (NE)_release_during trauma_and_its


will use our expertise of mapping protein-DNA interactions in these genomic assays to sort with high precision the interactions of the INO80 subunits along with nucleosome movement, composition and structural features at ~bp resolution to provide a detailed analysis of each of these nucleosomes in a time resolved manner when remodeled. This approach will

will use our expertise of mapping protein - DNA interaction in these genomic assay to sort with high precision the interaction of the INO80 subunits along with nucleosome movement, composition and morphologic feature at ~bp resolution to supply a detailed analysis of each of these nucleosomes in a time answer manner when remodeled. This approach will

wipl use our expertise of oapping protein-BBA intxractiohs in thdse genomic assays to sort wmth yigh kgecision the interactkons of tje INO80 sybunmts along with nndleosomc movslent, romposition and structuran features at ~tp rzsolution to provide a detailed analrsis of ewch of these nocleoxjmes pn a time resolved manner when demodeltd. This approach woll

will use our expertise of mapping protein-DNA these assays to with high precision subunits with nucleosome movement, and structural features ~bp resolution to provide a detailed of each of these nucleosomes in a time resolved manner when remodeled. This will

will use our expertise of mappIng protein-dNA inTerActIoNs in ThesE genomic assays TO sorT with high precision the iNteraCtIOns oF ThE INO80 sUbunits ALoNG WitH nUcLeoSoME mOvemeNt, cOmpositIon and struCtuRaL features at ~bP ReSolution to ProVide a detaileD anAlysis Of EacH Of theSe nUcleoSomes iN A time rEsolved maNnER when rEModeled. tHIs ApprOach will

will use our expertise of  mapping p rotei n-D NAin tera ctio ns in these ge n omic  assays to sort with h igh p re c isio n  t he in teracti o ns o f t he  I NO8 0s ub units  al ong wit h nucleoso memo vement, comp o si tion and s tru ctural featu res  at ~b pres o lutio n t o pro vide a detail ed analys is of eac h  of the s e  n ucle osomes in a timer es o lved manner wh en rem od e le d .  Th isapproach w il l

will_use our_expertise of mapping protein-DNA_interactions in_these_genomic assays_to_sort with high_precision the interactions_of the INO80 subunits_along with nucleosome_movement,_composition and structural features at ~bp resolution to provide a detailed analysis of each_of_these nucleosomes_in_a_time resolved manner when remodeled._This approach will


a possible therapy for both primary and secondary pulmonary hypertension and recent phase I/II studies from the intramural NIH suggest it is well tolerated and efficacious in this population. Furthermore, a number of recent studies have suggested that NO based therapies may have a favorable impact on sickle red cells at the molecular level and could improve

a possible therapy for both primary and secondary pulmonary high blood pressure and late phase I / II cogitation from the intramural NIH suggest it is well tolerate and effective in this population. Furthermore, a number of recent studies have suggest that NO based therapies may suffer a favorable impact on sickle crimson cells at the molecular level and could better

a oossible therapy for botm primary and seeindary pulmohary hypdrtension and recent phase I/MI srudiew from the intramural VIH suggedt it is welo tolerated and effleaciohd in vhis population. Furthermose, a number of rdcznt studies have suggested that NO bwsed thrrwpies may have a fsdoragle impact on sickle red cells at fhe moltcular level and cpuld improve

a possible therapy for both primary and hypertension recent phase studies from the well and efficacious in population. Furthermore, a of recent studies have suggested that based therapies may have a favorable impact on sickle red cells at the level and could improve

a possible therapy for both prImary and seCondaRy pUlmOnAry hYperTension and receNT phaSe I/II studies from the intRamurAl niH suGGeSt it iS well toLErATEd aNd EfFicAcIOuS in thIs pOpulatiOn. FurthermOre, A nUmber of recenT StUdies have sUggEsted that NO bAseD theraPiEs mAY have A faVorabLe impaCT on sicKle red celLs AT the moLEcular lEVEl And cOuld improve

a possible therapy for bo th primary  andsec ond ar y pu lmon ary hypertensi o n an d recent phase I/II st udies  f r om t h eintra mural N I Hs u gge st  i t i sw el l tol era ted and  efficacio usin  this popula t io n. Further mor e, a numberofrecent  s tud i es ha vesugge sted t h at NObased the ra p ies ma y  have a f av orab le impact on sick l er ed cells at th e mole cu l ar l eve l a nd could i mp rove

a_possible therapy_for both primary and_secondary pulmonary_hypertension_and recent_phase_I/II studies from_the intramural NIH_suggest it is well_tolerated and efficacious_in_this population. Furthermore, a number of recent studies have suggested that NO based therapies_may_have a_favorable_impact_on sickle red cells at_the molecular level and could_improve


areas of hyperemia occur following the application of chemical carcinogens or ultraviolet (UV) light to mouse skin. Hyperemia preceded tumor formation, tumors were found to invariably occur in these areas of hyperemia, and these areas were seen to persist and expand following the cessation of an initial carcinogenic UV exposure. Only areas

areas of hyperemia occur following the application of chemical carcinogen or ultraviolet (ultraviolet) lighter to mouse hide. Hyperemia precede tumor formation, tumors were establish to invariably occur in these areas of hyperemia, and these areas were seen to persevere and expand following the cessation of an initial carcinogenic ultraviolet exposure. Only areas

arfas of hyperemia occur fullowing the apklucatioi of chsmical cxrcinogens or ultraviolet (UV) lught uj mouse skin. Hyperdmia precvded tumoe focmation, tumors wxde found to ihyariaylb occur in thesg areas of hfperemia, and tvere areas were seen to persist and expwnd folkoaing the cessajion ps an pnltial carcinogenic UV exposure. Ohly arees

areas of hyperemia occur following the application carcinogens ultraviolet (UV) to mouse skin. were to invariably occur these areas of and these areas were seen to and expand following the cessation of an initial carcinogenic UV exposure. Only areas

areas of hyperemia occur follOwing the apPlicaTioN of ChEmicAl caRcinogens or ultRAvioLet (UV) light to mouse skin. HYpereMiA PrecEDeD tumoR formatIOn, TUMorS wErE foUnD To InvarIabLy occur In these areAs oF hYperemia, and tHEsE areas were SeeN to persist anD exPand foLlOwiNG the cEssAtion Of an inITial caRcinogeniC Uv ExposuRE. Only arEAS

areas of hyperemia occurfollowingthe a ppl ica ti on o f ch emical carcino g ensor ultraviolet (UV) li ght t om ouse sk in. H yperemi a  p r e ced ed  t umo rf or matio n,tumorswere found  to  i nvariably oc c ur  in theseare as of hypere mia , andth ese areas  we re se en top ersist  and expa nd follow i ng thec e ss atio n of an initial c a rc i nogenic UV exp osure.  O n ly a rea s

areas_of hyperemia_occur following the application_of chemical_carcinogens_or ultraviolet_(UV)_light to mouse_skin. Hyperemia preceded_tumor formation, tumors were_found to invariably_occur_in these areas of hyperemia, and these areas were seen to persist and expand_following_the cessation_of_an_initial carcinogenic UV exposure. Only_areas


waveform, 2) suppression of image smear by the extraretinal signals for CN, and 3) neural sharpening of the moving retinal image by "deblurring", as has been reported to occur in normal vision. The third aim of this research is to document the effects of the retinal image motion in CN on two

waveform, 2) suppression of image smear by the extraretinal signals for CN, and 3) nervous sharpening of the move retinal image by " deblurring ", as has been reported to happen in normal vision. The third bearing of this research is to document the effects of the retinal double motion in CN on two

wageform, 2) suppression of ioage smear by tkw extreretinam signalr for CN, and 3) neural sharpenmng if tht moving retinal imxge by "dehlurring", as ias been reportev to occmx in hlrman vision. The thlrd aim of dhis research hs tl document the effects of the retinwl imagr lotion in CN og twp

waveform, 2) suppression of image smear by signals CN, and neural sharpening of "deblurring", has been reported occur in normal The third aim of this research to document the effects of the retinal image motion in CN on two

waveform, 2) suppression of imagE smear by thE extrAreTinAl SignAls fOr CN, and 3) neural sHArpeNing of the moving retinal Image By "DEbluRRiNg", as hAs been rEPoRTEd tO oCcUr iN nORmAl visIon. the thirD aim of this ResEaRch is to documENt The effects Of tHe retinal imaGe mOtion iN Cn on TWo

waveform, 2) suppressionof image s mearbythe  e xtra reti nal signals fo r  CN,  and 3) neural sharpen ing o ft he m o vi ng re tinal i m ag e by"d eb lur ri n g" , ashas  been r eported to  oc cu r in normalv is ion. The t hir d aim of thi s r esearc hist o doc ume nt th e effe c ts ofthe retin al imagem otion i n CN  ontwo

waveform,_2) suppression_of image smear by_the extraretinal_signals_for CN,_and_3) neural sharpening_of the moving_retinal image by "deblurring",_as has been_reported_to occur in normal vision. The third aim of this research is to document_the_effects of_the_retinal_image motion in CN on_two


1 of TYRP1. The structure of SLC45A2 is predicted as a multi-pass trans-membrane protein. The missense mutation L60R is predicted to be deleterious. To test our predictions on tyrosinase activity we engineered a construct of human C-terminal truncated tyrosinase

1 of TYRP1. The structure of SLC45A2 is predicted as a multi - pass trans - membrane protein. The missense mutation L60R is predict to be deleterious. To screen our predictions on tyrosinase activity we engineered a concept of human C - terminal truncated tyrosinase

1 ov TYRP1. The structure of RLC45A2 is predictgd as a kulti-pzss tranr-membrane protein. The missende mutaupon L60R is predicted tu be delenerious. Ti tewr our predmdtions on tyrkdinavx activity we ekgineered a construct of vuoau C-terminal truncated tyrosinase

1 of TYRP1. The structure of SLC45A2 as multi-pass trans-membrane The missense mutation deleterious. test our predictions tyrosinase activity we a construct of human C-terminal truncated

1 of TYRP1. The structure of SLC45A2 iS predicted As a muLti-PasS tRans-MembRane protein. The MIsseNse mutation L60R is predictEd to bE dELeteRIoUs. To tEst our pREdICTioNs On TyrOsINaSe actIviTy we engIneered a coNstRuCt of human C-teRMiNal truncatEd tYrosinase

1 of TYRP1. The structure  of SLC45A 2 ispre dic te d as  a m ulti-pass tran s -mem brane protein. The mis sense  m u tati o nL60Ris pred i ct e d  to  b edel et e ri ous.Totest ou r predicti ons  o n tyrosinase ac tivity weeng ineered a co nst ruct o fhum a n C-t erm inaltrunca t ed tyr osinase

1_of TYRP1._The structure of SLC45A2_is predicted_as_a multi-pass_trans-membrane_protein. The missense_mutation L60R is_predicted to be deleterious._To test our_predictions_on tyrosinase activity we engineered a construct of human C-terminal truncated tyrosinase


epithelial conversion of renal progenitor cells during renal development. We plan to clone Midkine receptor gene using either an expression cloning approach or ligand affinity chromatography to purify the MK receptor protein. Additionally, we also plan to examine Midkine signal transduction pathway, then define the basic developmental pattern in the kidney of expression of all

epithelial conversion of renal progenitor cells during renal development. We design to clone Midkine sense organ gene practice either an expression cloning approach or ligand affinity chromatography to purify the MK sense organ protein. Additionally, we also plan to examine Midkine signal transduction nerve pathway, then specify the basic developmental pattern in the kidney of saying of all

eplthelial conversion of rtnal progenitor cglos durmng renzl develupment. We plan to clone Midkmne eecepujr gene using eithdr an expgession cooniig approach or lmfand afnnnity ghromctigraphy to purlfy the MK seceptor protehn. Abditionally, we also plan to examine Iidkine slgnal transducjion katrway, nhtn define the basic developmental patteri in the kidney of expression of all

epithelial conversion of renal progenitor cells during We to clone receptor gene using or affinity chromatography to the MK receptor Additionally, we also plan to examine signal transduction pathway, then define the basic developmental pattern in the kidney of of all

epithelial conversion of renAl progenitOr celLs dUriNg RenaL devElopment. We plan TO cloNe Midkine receptor gene uSing eItHEr an EXpRessiOn cloniNG aPPRoaCh Or LigAnD AfFinitY chRomatogRaphy to purIfy ThE MK receptor pROtEin. AdditioNalLy, we also plan To eXamine miDkiNE signAl tRansdUction PAthway, Then definE tHE basic DEvelopmENTaL patTern in the kidney of EXpREssion of all

epithelial conversion ofrenal prog enito r c ell sduri ng r enal developme n t. W e plan to clone Midkin e rec ep t or g e ne  usin g eithe r  a n exp re ss ion  c l on ing a ppr oach or  ligand af fin it y chromatogr a ph y to purif y t he MK recept orprotei n.  Ad d ition all y, we  alsop lan to  examineMi d kine s i gnal tr a n sd ucti on pathway, thend ef i ne the basic d evelop me n ta l pat ter n in the k id ney o f  expres s io n o f a l l

epithelial_conversion of_renal progenitor cells during_renal development._We_plan to_clone_Midkine receptor gene_using either an_expression cloning approach or_ligand affinity chromatography_to_purify the MK receptor protein. Additionally, we also plan to examine Midkine signal transduction_pathway,_then define_the_basic_developmental pattern in the kidney_of expression of all


(NF-?B) family are evolutionarily conserved master regulators of immune and inflammatory responses. They are activated in response to ligation of many receptors including T-cell receptors, B-cell receptors, members of the tumor necrosis factor (TNF) receptor superfamily and the Toll-like receptor/interleukin-

(NF-?B) family are evolutionarily conserved master regulators of immune and incendiary answer. They are activated in response to ligation of many receptor include T - cell sense organ, bel - cell receptor, members of the tumor necrosis factor (TNF) sense organ superfamily and the Toll - like receptor / interleukin-

(NF-?H) family are evolutionarlly conserved master rejulatora of immjne and inflammatory responsxs. Tyey aee activated in responre to ligwtion of manb receptors inclnsing T-ccjl rsgeptoxs, B-cell receptots, members ox the tumor newrusns factor (TNF) receptor superfamily agd the Yopl-like receptot/integlqukih-

(NF-?B) family are evolutionarily conserved master regulators and responses. They activated in response including receptors, B-cell receptors, of the tumor factor (TNF) receptor superfamily and the receptor/interleukin-

(NF-?B) family are evolutionarilY conserved MasteR reGulAtOrs oF immUne and inflammaTOry rEsponses. They are activatEd in rEsPOnse TO lIgatiOn of manY ReCEPtoRs InCluDiNG T-Cell rEcePtors, B-cEll receptoRs, mEmBers of the tumOR nEcrosis facTor (tNF) receptor sUpeRfamilY aNd tHE Toll-LikE recePtor/inTErleukIn-

(NF-?B) family are evolut ionarily c onser ved  ma st er r egul ators of immun e  and  inflammatory response s. Th ey area ct ivate d in re s po n s e t oli gat io n  o f man y r eceptor s includin g T -c ell receptor s ,B-cell rec ept ors, members  of  the t um orn ecros isfacto r (TNF )  recep tor super fa m ily an d  the To l l -l ikereceptor/interleu k in -

(NF-?B)_family are_evolutionarily conserved master regulators_of immune_and_inflammatory responses._They_are activated in_response to ligation_of many receptors including_T-cell receptors, B-cell_receptors,_members of the tumor necrosis factor (TNF) receptor superfamily and the Toll-like receptor/interleukin-


preparations (of Ciprofloxacin and Tetracycline); (2) investigate, in a rodent model, the degree of drug accumulation inside and in the near vicinity of target cells, and (3) evaluate efficacy in infected cells. If successful, this project will result in the development of a new class of preparations and

preparations (of Ciprofloxacin and Tetracycline); (2) investigate, in a rodent model, the degree of drug accumulation inwardly and in the approximate vicinity of target cells, and (3) evaluate efficacy in septic cells. If successful, this project will result in the growth of a new class of preparation and

prfparations (of Ciprofloxagin and Tetracycline); (2) iivestigzte, in a rodent model, the degree of vrug accunulation inside and in the near vicinitt of rarget cells, and (3) craluafc effncecy in infected cells. If vuccessful, thiv orlject will result in the developmene of a mea class of prekaratpogs ahd

preparations (of Ciprofloxacin and Tetracycline); (2) investigate, rodent the degree drug accumulation inside of cells, and (3) efficacy in infected If successful, this project will result the development of a new class of preparations and

preparations (of CiprofloxacIn and TetraCycliNe); (2) iNveStIgatE, in a Rodent model, the DEgreE of drug accumulation insIde anD iN The nEAr VicinIty of taRGeT CEllS, aNd (3) EvaLuATe EfficAcy In infecTed cells. If SucCeSsful, this proJEcT will resulT in The developmeNt oF a new cLaSs oF PrepaRatIons aNd

preparations (of Ciproflo xacin andTetra cyc lin e) ; (2 ) in vestigate, ina  rod ent model, the degreeof dr ug accu m ul ation  inside an d inth enea rv ic inity  of  target  cells, an d ( 3)  evaluate ef f ic acy in inf ect ed cells. If  su ccessf ul , t h is pr oje ct wi ll res u lt inthe devel op m ent of a new c l a ss  ofpreparations and

preparations_(of Ciprofloxacin_and Tetracycline); (2) investigate,_in a_rodent_model, the_degree_of drug accumulation_inside and in_the near vicinity of_target cells, and_(3)_evaluate efficacy in infected cells. If successful, this project will result in the development_of_a new_class_of_preparations and


containing buffers, (vi) is difficul to use in serum, (vii) is inherently unstable due to the sloughing of Annexin V, (viii) is likely t have high endotoxin levels, (ix) is expensive to manufacture and maintain, therefore adding significant cost to the end- user.

containing buffers, (vi) is difficul to use in serum, (vii) is inherently unstable due to the shedding of Annexin V, (eight) is probable t have high endotoxin grade, (ix) is expensive to manufacture and maintain, consequently adding significant cost to the end- exploiter.

conhaining buffers, (vi) is dinficul to use in serum, (tii) is jnherentuy unstable due to the slougiing of Abnexin V, (viii) is likelh t have jigh enditoxmn levels, (ix) is xspensivc to jwnufccvure and maintaln, therefora adding signixizaut cost to the end- user.

containing buffers, (vi) is difficul to use (vii) inherently unstable to the sloughing likely have high endotoxin (ix) is expensive manufacture and maintain, therefore adding significant to the end- user.

containing buffers, (vi) is diffIcul to use iN seruM, (viI) is InHereNtly Unstable due to tHE sloUghing of Annexin V, (viii) is LikelY t HAve hIGh EndotOxin levELs, (IX) Is eXpEnSivE tO MaNufacTurE and maiNtain, thereForE aDding signifiCAnT cost to the End- User.

containing buffers, (vi) i s difficul  to u seinse rum,  (vi i) is inherent l y un stable due to the slou ghing  o f  Ann e xi n V,(viii)i sl i kel ythav eh ig h end oto xin lev els, (ix)isex pensive to m a nu facture an d m aintain, the ref ore ad di ngs ignif ica nt co st tot he end - user.

containing buffers,_(vi) is_difficul to use in_serum, (vii)_is_inherently unstable_due_to the sloughing_of Annexin V,_(viii) is likely t_have high endotoxin_levels,_(ix) is expensive to manufacture and maintain, therefore adding significant cost to the end-_user.


Screening Program will be prepared and submitted for testing. This application requests funding to identify risk factors for chronic back pain disability. The proposed study will draw on our existing data base of physical, psychological, and work-related premorbid data. This data base is unequalled in population size and scope of independent variables

Screening Program will be prepared and submitted for testing. This application request support to identify risk factors for chronic spinal column pain disability. The proposed sketch will guide on our existing datum basis of physical, psychological, and oeuvre - related premorbid data. This datum base is unequalled in population size and scope of independent variables

Scgeening Program will be krepared and submnrted fmr tesfing. Thir application requests fundiig ti idebtify risk factors for chronic hack paib diwqbility. Thx proposcb stusn wiln draw on our ewisting datd base of physhcxl, psychological, and work-related premjrbid dstw. This data bafe ix uneslaoled in population size and sdope of independent fariables

Screening Program will be prepared and submitted This requests funding identify risk factors The study will draw our existing data of physical, psychological, and work-related premorbid This data base is unequalled in population size and scope of independent variables

Screening Program will be prePared and suBmittEd fOr tEsTing. this Application reqUEsts Funding to identify risk fActorS fOR chrONiC back Pain disABiLITy. THe PrOpoSeD StUdy wiLl dRaw on ouR existing dAta BaSe of physical, PSyChological, And Work-related pRemOrbid dAtA. ThIS data BasE is unEquallED in popUlation siZe ANd scopE Of indepENDeNt vaRiables

Screening Program will be  preparedand s ubm itt ed  for  tes ting. This app l icat ion requests funding t o ide nt i fy r i sk  fact ors for ch r o nic  b ac k p ai n  d isabi lit y. Theproposed s tud ywill draw on ou r existing  da ta base of p hys ical,ps ych o logic al,  andwork-r e latedpremorbid  d a ta. Th i s datab a se  isunequalled in pop u la t ion size and s cope o fi nd e p end ent  variables

Screening_Program will_be prepared and submitted_for testing._This_application requests_funding_to identify risk_factors for chronic_back pain disability. The_proposed study will_draw_on our existing data base of physical, psychological, and work-related premorbid data. This data_base_is unequalled_in_population_size and scope of independent_variables


of a modified therapeutic community (TC) program for drug-abusing prison inmates. The Amity prison TC Program, established in 1990 at the R.J. Donovan Correctional Facility near San Diego, has been evaluated previously in a process and outcome study as one project of the NDRI Center on Therapeutic Community Research

of a modified therapeutic community (TC) program for drug - abuse prison convict. The Amity prison TC Program, established in 1990 at the R.J. Donovan Correctional Facility near San Diego, has been evaluated previously in a process and consequence study as one project of the NDRI Center on Therapeutic Community Research

of a modified therapeutic gommunity (TC) proyeam foc drug-agusing pfison inmates. The Amity prisln TC Peogram, established in 1990 at the R.U. Donovab Cocrectional Facilmfy near San Djcgo, hcs been evaluatec previousny in a procesv xnb outcome study as one project of thq NDRI Vejter on Therapgutic Sommhnity Research

of a modified therapeutic community (TC) program prison The Amity TC Program, established Donovan Facility near San has been evaluated in a process and outcome study one project of the NDRI Center on Therapeutic Community Research

of a modified therapeutic comMunity (TC) prOgram For DruG-aBusiNg prIson inmates. The aMity Prison TC Program, establiShed iN 1990 aT The R.j. doNovan correctIOnAL facIlItY neAr sAn diego, Has Been evaLuated prevIouSlY in a process aND oUtcome studY as One project of The nDRI CeNtEr oN theraPeuTic CoMmunitY researCh

of a modified therapeutic  community  (TC)  pr ogr am  for  dru g-abusing pris o n in mates. The Amity priso n TCPr o gram ,  e stabl ished i n  1 9 9 0 a tth e R .J .  D onova n C orrecti onal Facil ity  n ear San Dieg o ,has been e val uated previo usl y in a  p roc e ss an d o utcom e stud y  as on e project  o f  the N D RI Cent e r  o n Th erapeutic Communi t yR esearch

of_a modified_therapeutic community (TC) program_for drug-abusing_prison_inmates. The_Amity_prison TC Program,_established in 1990_at the R.J. Donovan_Correctional Facility near_San_Diego, has been evaluated previously in a process and outcome study as one project_of_the NDRI_Center_on_Therapeutic Community Research


critical cellular processes. Notably, abnormal lysine acetylation is observed in multiple human disorders, including cancer; thus HDACs are a validated drug target. Despite their critical biological functions and clinical roles as drug targets, little is known about the molecular basis for HDAC substrate specificity and inhibition. This is particularly the case for HDACs 10

critical cellular processes. Notably, abnormal lysine acetylation is observed in multiple human disorders, including cancer; therefore HDACs are a validated drug prey. Despite their critical biological functions and clinical roles as drug target, fiddling is known about the molecular basis for HDAC substrate specificity and prohibition. This is particularly the case for HDACs 10

crltical cellular processer. Notably, abnormal lysmne acefylation is observed in multiple humen dusordtgs, including cancer; tfus HDACs are a vqlideted drug target. Despite their gritieao biological fonctions and clinical rolev xs drug targets, little is known about the mokefular basis fot HDAB fubsfgaue specificity and inhibition. Thia is pagticularly the caxe for HDACs 10

critical cellular processes. Notably, abnormal lysine acetylation in human disorders, cancer; thus HDACs Despite critical biological functions clinical roles as targets, little is known about the basis for HDAC substrate specificity and inhibition. This is particularly the case for 10

critical cellular processes. notably, abnOrmal LysIne AcEtylAtioN is observed in mULtipLe human disorders, includIng caNcER; thuS hDaCs arE a validATeD DRug TaRgEt. DEsPItE theiR crItical bIological fUncTiOns and clinicAL rOles as drug TarGets, little is KnoWn abouT tHe mOLeculAr bAsis fOr HDAC SUbstraTe specifiCiTY and inHIbition. tHIs Is paRticularly the case FOr hdACs 10

critical cellular process es. Notabl y, ab nor mal  l ysin e ac etylation is o b serv ed in multiple human d isord er s , in c lu dingcancer; th u s  HD AC sare  a va lidat eddrug ta rget. Desp ite  t heir critica l  b iologicalfun ctions and c lin ical r ol esa s dru g t arget s, lit t le isknown abo ut the mo l ecularb a si s fo r HDAC substrates pe c ificity and in hibiti on .  T h i s i s p articularl ythe c a se forH DA C s 10

critical_cellular processes._Notably, abnormal lysine acetylation_is observed_in_multiple human_disorders,_including cancer; thus_HDACs are a_validated drug target. Despite_their critical biological_functions_and clinical roles as drug targets, little is known about the molecular basis for_HDAC_substrate specificity_and_inhibition._This is particularly the case_for HDACs 10


nicotine (CS) is reliably paired with the appetitive effects of sucrose (US). An association is evidenced when nicotine differentially evokes anticipatory food-seeking behavior. Specific Aim 1 will test whether changing the nature of the nicotine CS alters development or expression of conditioned responding; alterations include changes in nicotine dose and time between nicotine

nicotine (CS) is reliably paired with the appetitive effects of sucrose (US). An association is tell when nicotine differentially educe anticipatory food - seeking behavior. Specific Aim 1 will test whether change the nature of the nicotine CS alters development or expression of condition answer; alterations include changes in nicotine dose and prison term between nicotine

nifotine (CS) is reliably palred with the apkeritive effecfs of suzrose (US). An association is etidebced qhen nicotine differengially evlkes antucipetory food-seekinj behavior. Spedlfic Cin 1 will test wmether chancing the natura uf the nicotine CS alters development or exptedsion of condijionec reslonding; alterations include changea in nibotine dose and tome between nicotine

nicotine (CS) is reliably paired with the of (US). An is evidenced when behavior. Aim 1 will whether changing the of the nicotine CS alters development expression of conditioned responding; alterations include changes in nicotine dose and time between

nicotine (CS) is reliably paireD with the apPetitIve EffEcTs of SucrOse (US). An associaTIon iS evidenced when nicotine DiffeReNTialLY eVokes AnticipAToRY FooD-sEeKinG bEHaVior. SPecIfic Aim 1 Will test whEthEr Changing the nATuRe of the nicOtiNe CS alters deVelOpment Or ExpREssioN of CondiTioned REspondIng; alteraTiONs inclUDe changES In NicoTine dose and time beTWeEN nicotine

nicotine (CS) is reliably  paired wi th th e a ppe ti tive  eff ects of sucros e  (US ). An association is e viden ce d  whe n  n icoti ne diff e re n t ial ly  e vok es an ticip ato ry food -seeking b eha vi or. Specific Ai m 1 will t est  whether cha ngi ng the  n atu r e ofthe  nico tine C S  alter s develop me n t or e x pressio n of  con ditioned respondi n g; alterations in cludech a ng e s  in  ni cotine dos eand t i me betw e en n i cot i ne

nicotine_(CS) is_reliably paired with the_appetitive effects_of_sucrose (US)._An_association is evidenced_when nicotine differentially_evokes anticipatory food-seeking behavior._Specific Aim 1_will_test whether changing the nature of the nicotine CS alters development or expression of_conditioned_responding; alterations_include_changes_in nicotine dose and time_between nicotine