of translation of the RPE65 message reveals that the effect may be at least partially coding-region-sequence specific because the 3' UTR sequence affecting translational efficiency had no effect on CAT expression. The prevalence of dental caries has been reduced significantly in some segments of the population over the past 25 years. The observed reduction has

of translation of the RPE65 message reveals that the effect may be at least partially coding - area - succession particular because the 3' UTR sequence affecting translational efficiency had no impression on CAT expression. The prevalence of dental cavity has been reduced significantly in some segments of the population over the past 25 old age. The observed reduction suffer

of translation of the RPE65 oessage reveals that tie effedt may bd at least partially coding-rxgiob-sequtuce specific because the 3' UTR sequencw afhecting translatmknal efnnciendn had io effect on CAJ expression. The prevalenca uf dental caries has been reduced siggificanylj in some segmgnts ps ths population over the past 25 years. Fhe obstrved reduction hax

of translation of the RPE65 message reveals effect be at partially coding-region-sequence specific affecting efficiency had no on CAT expression. prevalence of dental caries has been significantly in some segments of the population over the past 25 years. The reduction has

of translation of the RPE65 messAge reveals That tHe eFfeCt May bE at lEast partially cODing-Region-sequence specific BecauSe THe 3' UTr SeQuencE affectINg TRAnsLaTiOnaL eFFiCiencY haD no effeCt on CAT expResSiOn. The prevaleNCe Of dental caRieS has been reduCed SignifIcAntLY in soMe sEgmenTs of thE PopulaTion over tHe PAst 25 yeaRS. The obsERVeD redUction has

of translation of the RPE 65 message  reve als  th at  the  eff ect may be atl east  partially coding-regi on-se qu e nces pe cific  becaus e  t h e  3'  U TR  se qu e nc e aff ect ing tra nslational  ef fi ciency had n o  e ffect on C ATexpression.The  preva le nce of de nta l car ies ha s  beenreduced s ig n ifican t ly in s o m esegm ents of the popul a ti o n over the pas t 25 y ea r s. T heobs erved redu ct ion h a s

of_translation of_the RPE65 message reveals_that the_effect_may be_at_least partially coding-region-sequence_specific because the_3' UTR sequence affecting_translational efficiency had_no_effect on CAT expression. The prevalence of dental caries has been reduced significantly in_some_segments of_the_population_over the past 25 years._The observed reduction has


brain barrier traumatically and to manipulate magnetic nanoparticles (MNPs) in mouse brains. By the end of Phase I, we will have built and tested an MRI-compatible gradient insert system capable of delivering magnetic nanoparticles (MNPs) to selected regions in normal mouse brains. Using the data collected from the Phase I mouse

brain barrier traumatically and to manipulate magnetic nanoparticles (MNPs) in mouse mind. By the goal of Phase I, we will have built and tested an MRI - compatible gradient insert organization capable of delivering charismatic nanoparticles (MNPs) to selected regions in normal mouse brain. Using the data collect from the Phase I mouse

braln barrier traumatically and to manipulcre magietic nznopartizles (MNPs) in mouse brains. By tye ene of Phase I, we will hxve built and tesred en MRI-compatible gradienb inssvt syvvem capable of celivering magnetic nano[aftncles (MNPs) to selected regions in nowmal moisf brains. Using the qata boolected from the Phase I mouss

brain barrier traumatically and to manipulate magnetic in brains. By end of Phase and an MRI-compatible gradient system capable of magnetic nanoparticles (MNPs) to selected regions normal mouse brains. Using the data collected from the Phase I mouse

brain barrier traumatically And to manipUlate MagNetIc NanoPartIcles (MNPs) in mouSE braIns. By the end of Phase I, we wIll haVe BUilt ANd TesteD an MRI-cOMpATIblE gRaDieNt INsErt sySteM capablE of deliverIng MaGnetic nanopaRTiCles (MNPs) to SelEcted regions In nOrmal mOuSe bRAins. USinG the dAta colLEcted fRom the PhaSe i Mouse

brain barrier traumaticall y and to m anipu lat e m ag neti c na noparticles (M N Ps)in mouse brains. By th e end  o f  Pha s eI, we  will h a ve b uil tan d t es t ed  an M RI- compati ble gradie ntin sert systemc ap able of de liv ering magnet icnanopa rt icl e s (MN Ps)  to s electe d  regio ns in nor ma l  mouse brains. U si ng t he data collected fr o m the Phase Imouse

brain barrier_traumatically and_to manipulate magnetic nanoparticles_(MNPs) in_mouse_brains. By_the_end of Phase_I, we will_have built and tested_an MRI-compatible gradient_insert_system capable of delivering magnetic nanoparticles (MNPs) to selected regions in normal mouse brains._Using_the data_collected_from_the Phase I mouse


long exposure to real-life cigarette packs carrying High or Low ER GWLs. Based on our preliminary data, we hypothesize that smokers exposed to high ER GWLs will exhibit larger reductions in UC than those exposed to low ER GWLs. Based on our preliminary data and prior literature pointing to the mPFC

long exposure to real - life cigarette pack carry High or Low ER GWLs. Based on our preliminary datum, we hypothesize that smokers exposed to eminent ER GWLs will exhibit larger decrease in UC than those exposed to low ER GWLs. free-base on our preliminary data and prior literature pointing to the mPFC

lojg exposure to real-life gigarette packs eqrryinj High kr Low EF GWLs. Based on our preliminery eata, qe hypothesize that smukers explsed to yigh WR GWLs will exhiblc larfcr reburtions in UC thsn those efposed to low AR GCLs. Based on our preliminary data anq prior llterature poinjing uo ehe jIFG

long exposure to real-life cigarette packs carrying Low GWLs. Based our preliminary data, to ER GWLs will larger reductions in than those exposed to low ER Based on our preliminary data and prior literature pointing to the mPFC

long exposure to real-life cigArette packS carrYinG HiGh Or LoW ER GwLs. Based on our pRElimInary data, we hypothesize That sMoKErs eXPoSed to High ER Gwls WILl eXhIbIt lArGEr ReducTioNs in UC tHan those exPosEd To low ER GWLs. BASeD on our prelImiNary data and pRioR literAtUre POintiNg tO the mpFC

long exposure to real-lif e cigarett e pac kscar ry ingHigh  or Low ER GWL s . Ba sed on our preliminary  data ,w e hy p ot hesiz e thats mo k e rsex po sed  t o  h igh E R G WLs wil l exhibitlar ge r reductions in  UC than t hos e exposed to  lo w ER G WL s.B asedonour p relimi n ary da ta and pr io r  liter a ture po i n ti ng t o the mPFC

long_exposure to_real-life cigarette packs carrying_High or_Low_ER GWLs._Based_on our preliminary_data, we hypothesize_that smokers exposed to_high ER GWLs_will_exhibit larger reductions in UC than those exposed to low ER GWLs. Based on_our_preliminary data_and_prior_literature pointing to the mPFC


the Scientific Coordinator and the scores and critiques will be provided to the Internal Advisory Committee, which will discuss the projects and make the final funding decision. During its deliberations, the Internal Advisory Committee may take other considerations into account, besides the formal review criteria. These may include: impact on the junior investigator?s

the Scientific Coordinator and the scores and critiques will be provided to the Internal Advisory Committee, which will discuss the undertaking and name the final funding decision. During its deliberation, the Internal Advisory Committee may take other consideration into score, besides the formal reappraisal criteria. These may include: shock on the junior investigator?s

thf Scientific Coordinator and the scores and crmtiques will be provided to the Internal Adtisoey Conmittee, which will diszuss the irojects qnd nqke the fiizl fundlug dedlsion. Vuring its delinerations, tve Internal Adeiroxy Committee may take other considerwtions onho account, besydes ehe rormal review criteria. These may ihclude: pmpact on the junoor investigator?s

the Scientific Coordinator and the scores and be to the Advisory Committee, which make final funding decision. its deliberations, the Advisory Committee may take other considerations account, besides the formal review criteria. These may include: impact on the junior

the Scientific Coordinator aNd the scoreS and cRitIquEs Will Be prOvided to the IntERnal advisory Committee, which Will dIsCUss tHE pRojecTs and maKE tHE FinAl FuNdiNg DEcIsion. durIng its dEliberatioNs, tHe internal AdviSOrY Committee May Take other conSidEratioNs IntO AccouNt, bEsideS the foRMal revIew criterIa. tHese maY Include: IMPaCt on The junior investigAToR?S

the Scientific Coordinato r and thescore s a ndcr itiq ueswill be provid e d to  the Internal Advisory  Comm it t ee,w hi ch wi ll disc u ss t hepr oj ect sa nd  make  th e final  funding d eci si on. During i t sdeliberati ons , the Intern alAdviso ry  Co m mitte e m ay ta ke oth e r cons ideration si nto ac c ount, b e s id es t he formal reviewc ri t eria. These ma y incl ud e :i m pac t o n the juni or  inve s tigator ? s

the_Scientific Coordinator_and the scores and_critiques will_be_provided to_the_Internal Advisory Committee,_which will discuss_the projects and make_the final funding_decision._During its deliberations, the Internal Advisory Committee may take other considerations into account, besides_the_formal review_criteria._These_may include: impact on the_junior investigator?s


the VCC. The membership includes both M.D.s and non-M.D.s (e.g., investigators in the areas of biostatistics, preventive medicine, chemotherapy pharmacy, basic science, and nursing). Meetings are held twice a month as dictated by the number of submissions for review and

the VCC. The membership includes both M.D.s and non - M.D.s (e.g., investigators in the areas of biometrics, preventive music, chemotherapy drugstore, basic science, and nursing). Meetings are held doubly a month as dictated by the number of submission for review and

thf VCC. The membership incuudes both M.D.s cbd non-K.D.s (e.g., investieators in the areas of biostetisrics, kgeventive medicine, chdmotherapj pharmact, bawuc science, and nursing). Msctingv are held twicg a month as dictated by tve nbmber of submissions for review and

the VCC. The membership includes both M.D.s (e.g., in the of biostatistics, preventive and Meetings are held a month as by the number of submissions for and

the VCC. The membership includEs both M.D.s aNd non-m.D.s (E.g., iNvEstiGatoRs in the areas of BIostAtistics, preventive mediCine, cHeMOtheRApY pharMacy, basIC sCIEncE, aNd NurSiNG). MEetinGs aRe held tWice a month As dIcTated by the nuMBeR of submissIonS for review anD

the VCC. The membership i ncludes bo th M. D.s  an dnon- M.D. s (e.g., inves t igat ors in the areas of bi ostat is t ics, pr event ive med i ci n e , c he mo the ra p ypharm acy , basic  science,and  n ursing). Mee t in gs are hel d t wice a month  as  dicta te d b y  thenum ber o f subm i ssions  for revi ew and

the_VCC. The_membership includes both M.D.s_and non-M.D.s_(e.g.,_investigators in_the_areas of biostatistics,_preventive medicine, chemotherapy_pharmacy, basic science, and_nursing). Meetings are_held_twice a month as dictated by the number of submissions for review and


disease.[unreadable] [unreadable] Chaperone Therapy: We have identified a number of patients with Fabry disease in whom the reduced catalytic activity of alpha-galactosidase A is increased in the presence of the molecular chaperone 1-deoxy-galactonojirimycin (DGJ). This technique is based

disease.[unreadable ] [ unreadable ] Chaperone Therapy: We have identified a number of patients with Fabry disease in whom the dilute catalytic natural process of alpha - galactosidase A is increased in the presence of the molecular chaperone 1 - deoxy - galactonojirimycin (DGJ). This proficiency is based

didease.[unreadable] [unreadabue] Chaperone Thgrqpy: We have jdentifidd a number of patients with Fqbry eisease in whom the reauced catwlytic axtivmty of alpha-galarfosidasc A ia incxeesed in the prexence of tve molecular cvaoexone 1-deoxy-galactonojirimycin (DGJ). Thif technoqke is based

disease.[unreadable] [unreadable] Chaperone Therapy: We have identified of with Fabry in whom the A increased in the of the molecular 1-deoxy-galactonojirimycin (DGJ). This technique is based

disease.[unreadable] [unreadabLe] ChaperonE TherApy: we hAvE ideNtifIed a number of paTIentS with Fabry disease in whoM the rEdUCed cATaLytic ActivitY Of ALPha-GaLaCtoSiDAsE A is iNcrEased in The presencE of ThE molecular chAPeRone 1-deoxy-gAlaCtonojirimycIn (DgJ). This TeChnIQue is BasEd

disease.[unreadable] [unr eadable] C haper one  Th er apy:  Wehave identifie d  a n umber of patients with  Fabr yd isea s ein wh om ther ed u c edca ta lyt ic ac tivit y o f alpha -galactosi das eA is increas e din the pre sen ce of the mo lec ular c ha per o ne 1- deo xy-ga lacton o jirimy cin (DGJ) .T his te c hniquei s  b ased

disease.[unreadable]_[unreadable] Chaperone_Therapy: We have identified_a number_of_patients with_Fabry_disease in whom_the reduced catalytic_activity of alpha-galactosidase A_is increased in_the_presence of the molecular chaperone 1-deoxy-galactonojirimycin (DGJ). This technique is based


vitro and in animal studies to deliver an essentially constant dose of a period of 6 months or longer. The rate-controlling membrane is a hydrogel. Specific goals of the study are: (a) determine whether these histrelin-delivering implants can be used in humans; (b) ascertain the dose of hist

vitro and in animal studies to deliver an essentially constant venereal disease of a time period of 6 months or longer. The rate - control membrane is a hydrogel. Specific goals of the study are: (a) specify whether these histrelin - delivering implants can be use in humans; (b) ascertain the acid of hist

vihro and in animal studier to deliver an essentmally cknstant aose of a period of 6 months lr longtg. The rate-controlling membrane is a hyerogtl. Specific goals of the study zve: (a) bevermine whether these hisdrelin-deliveritg ilplants can be used in humans; (b) ascqrtain yhf dose of hist

vitro and in animal studies to deliver constant of a of 6 months is hydrogel. Specific goals the study are: determine whether these histrelin-delivering implants can used in humans; (b) ascertain the dose of hist

vitro and in animal studies to Deliver an eSsentIalLy cOnStanT dosE of a period of 6 moNThs oR longer. The rate-controllIng meMbRAne iS A hYdrogEl. SpeciFIc GOAls Of ThE stUdY ArE: (a) detErmIne whetHer these hiStrElIn-delivering IMpLants can be UseD in humans; (b) asCerTain thE dOse OF hist

vitro and in animal studi es to deli ver a n e sse nt iall y co nstant dose of a pe riod of 6 months or lo nger.  T h e ra t e- contr ollingm em b r ane  i sa h yd r og el. S pec ific go als of the  st ud y are: (a) d e te rmine whet her  these histr eli n-deli ve rin g  impl ant s can  be us e d in h umans; (b )a scerta i n the d o s eof h ist

vitro_and in_animal studies to deliver_an essentially_constant_dose of_a_period of 6_months or longer._The rate-controlling membrane is_a hydrogel. Specific_goals_of the study are: (a) determine whether these histrelin-delivering implants can be used in_humans;_(b) ascertain_the_dose_of hist


underlying mechanisms for LE and allow for the development and testing of novel approaches to prevent or reduce the negative effects of LE. This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from

underlying mechanisms for LE and allow for the development and examination of novel approach to prevent or reduce the damaging impression of LE. This subproject is one of many research subprojects utilizing the resource provided by a Center grant fund by NIH / NCRR. The subproject and investigator (PI) may have received basal funding from

unferlying mechanisms for UE and allow fot rhe detelopmeht and tdsting of novel approaches tl prevebt or reduce the negatkve effecns of LE. Rhis wubproject is one of mang reszacch subprojects utilizing the resources pforided by a Center grant funded by NIR/NCRR. Tne subproject anq inneftigznov (PI) may have received primary fhnding hrom

underlying mechanisms for LE and allow for and of novel to prevent or LE. subproject is one many research subprojects the resources provided by a Center funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding

underlying mechanisms for LE And allow foR the dEveLopMeNt anD tesTing of novel appROachEs to prevent or reduce the NegatIvE EffeCTs Of LE. THis subpROjECT is OnE oF maNy REsEarch SubProjectS utilizing The ReSources proviDEd By a Center gRanT funded by NIH/nCRr. The suBpRojECt and InvEstigAtor (PI) MAy have Received pRiMAry funDIng from

underlying mechanisms for  LE and al low f orthe  d evel opme nt and testing of n ovel approaches to pre ventor redu c ethe n egative ef f e cts  o fLE.  T h is  subp roj ect isone of man y r es earch subpro j ec ts utilizi ngthe resource s p rovide dbya  Cent ergrant  funde d  by NI H/NCRR. T he subpro j ect and i nv esti gator (PI) may ha v er eceived primar y fund in g  f r o m

underlying_mechanisms for_LE and allow for_the development_and_testing of_novel_approaches to prevent_or reduce the_negative effects of LE._This subproject is_one_of many research subprojects utilizing the resources provided by a Center grant funded by_NIH/NCRR._The subproject_and_investigator_(PI) may have received primary_funding from


1976 (abstract). ATAD2 is an important co-activator of the estrogen and androgen receptors. ATAD2 is known to be up- regulated in multiple different types of cancer including breast, lung, gastric, endometrial, renal, and prostate. Up-regulation of ATAD2 is often correlated with poor patient

1976 (abstract). ATAD2 is an important co - activator of the estrogen and androgen receptors. ATAD2 is known to be up- determine in multiple unlike types of cancer including breast, lung, gastric, endometrial, nephritic, and prostate. Up - rule of ATAD2 is often correlated with inadequate affected role

1976 (ahstract). ATAD2 is an imporuant co-activator of the xstrogeh and anarogen receptors. ATAD2 is knoxn ti be yp- regulated in multipue differvnt types of rancer including breast, lung, gzdtrie, xndometrial, rensl, and provtate. Up-reguladiun of ATAD2 is often correlated with pjor patoejt

1976 (abstract). ATAD2 is an important co-activator estrogen androgen receptors. is known to different of cancer including lung, gastric, endometrial, and prostate. Up-regulation of ATAD2 is correlated with poor patient

1976 (abstract). ATAD2 is an important Co-activatoR of thE esTroGeN and AndrOgen receptors. AtaD2 is Known to be up- regulated in MultiPlE DiffEReNt typEs of canCEr INCluDiNg BreAsT, LuNg, gasTriC, endomeTrial, renal, And PrOstate. Up-reguLAtIon of ATAD2 iS ofTen correlateD wiTh poor PaTieNT

1976 (abstract). ATAD2 is  an import ant c o-a cti va torof t he estrogen an d  and rogen receptors. ATAD2  is k no w n to be  up-regulat e di n  mu lt ip ledi f fe renttyp es of c ancer incl udi ng  breast, lun g ,gastric, e ndo metrial, ren al,  and p ro sta t e. Up -re gulat ion of ATAD2is oftenco r relate d  with p o o rpati ent

1976_(abstract). ATAD2_is an important co-activator_of the_estrogen_and androgen_receptors._ATAD2 is known_to be up-_regulated in multiple different_types of cancer_including_breast, lung, gastric, endometrial, renal, and prostate. Up-regulation of ATAD2 is often correlated with_poor_patient


as an effector molecule in resistance to infection. SA-1. Determine the role of IFN-y in regulation of immunodominance. SA-2. Analyze the role of IFN-y regulation of the death phase of CD8+ T cells. SA-3. Determine the impact of IFN-y on regulation

as an effector molecule in resistance to infection. SA-1. settle the function of IFN - y in regulation of immunodominance. SA-2. Analyze the role of IFN - y regulation of the end phase of CD8 + T cells. SA-3. Determine the impact of IFN - y on rule

as an effector molecule in resistance to nbfectimn. SA-1. Setermind the role of IFN-y in regulavion of inmunodominance. SA-2. Analhze the rlle of IDN-y cegulation of thx death ikase kn CD8+ C rells. SA-3. Determlne the impdct of IFN-y on rdgblation

as an effector molecule in resistance to Determine role of in regulation of of regulation of the phase of CD8+ cells. SA-3. Determine the impact of on regulation

as an effector molecule in resIstance to iNfectIon. sA-1. DEtErmiNe thE role of IFN-y in rEGulaTion of immunodominance. Sa-2. AnalYzE The rOLe Of IFN-Y regulaTIoN OF thE dEaTh pHaSE oF CD8+ T cEllS. SA-3. DeteRmine the imPacT oF IFN-y on regulATiOn

as an effector molecule i n resistan ce to  in fec ti on.SA-1 . Determine th e  rol e of IFN-y in regulati on of  i m muno d om inanc e. SA-2 .  A n a lyz eth e r ol e  o f IFN -yregulat ion of the  de at h phase of C D 8+  T cells.SA- 3. Determine  th e impa ct  of IFN-y  on  regu lation

as_an effector_molecule in resistance to_infection. SA-1._Determine_the role_of_IFN-y in regulation_of immunodominance. SA-2._Analyze the role of_IFN-y regulation of_the_death phase of CD8+ T cells. SA-3. Determine the impact of IFN-y on regulation


uates who pursue careers in biomedical research and cancer disparities. A new cancer research career development program at SCSU and MUSC-HCC will also be implemented for junior faculty who are interested in establishing independent careers in cancer disparities research. Within the Research Education Core, the SC CADRE undergraduate and junior faculty Scholars will interact

uates who pursue careers in biomedical research and cancer disparities. A newfangled cancer inquiry career development program at SCSU and MUSC - HCC will besides be implemented for junior staff who are interested in establishing autonomous careers in cancer disparities research. Within the Research Education Core, the SC CADRE undergraduate and junior staff Scholars will interact

uatfs who pursue careers in biomedical resgaech anv canced disparkties. A new cancer research rarewr decelopment program at SZSU and MLSC-HCC wiol aowo be implxjented njr jhkior yarulty who are ikterested it establishing ivdzpendent careers in cancer disparitiqs resesrfh. Within the Teseagcr Edhbauion Core, the SC CADRE undergraduzte and junior faculyy Scholars will interact

uates who pursue careers in biomedical research disparities. new cancer career development program also implemented for junior who are interested establishing independent careers in cancer disparities Within the Research Education Core, the SC CADRE undergraduate and junior faculty Scholars interact

uates who pursue careers in biOmedical reSearcH anD caNcEr diSparIties. A new canceR ReseArch career development pRograM aT sCSU ANd mUSC-HcC will aLSo BE ImpLeMeNteD fOR jUnior FacUlty who Are interesTed In Establishing INdEpendent caReeRs in cancer diSpaRities ReSeaRCh. WitHin The ReSearch eDucatiOn Core, the sC caDRE unDErgraduATE aNd juNior faculty ScholaRS wILl interact

uates who pursue careers i n biomedic al re sea rch  a nd c ance r disparities. A ne w cancer research care er de ve l opme n tprogr am at S C SU a ndMU SC -HC Cw il l als o b e imple mented for  ju ni or faculty w h oare intere ste d in establi shi ng ind ep end e nt ca ree rs in  cance r  dispa rities re se a rch. W i thin th e Re sear ch Education Core ,  t h e SC CADRE und ergrad ua t ea n d j uni or faculty  S chola r s willi nt e r a ct

uates who_pursue careers_in biomedical research and_cancer disparities._A_new cancer_research_career development program_at SCSU and_MUSC-HCC will also be_implemented for junior_faculty_who are interested in establishing independent careers in cancer disparities research. Within the Research_Education_Core, the_SC_CADRE_undergraduate and junior faculty Scholars_will interact


of profiling the complete transcriptional dynamics of cells and projecting them onto images of regenerating tissue is widely applicable to many developmental model systems. Thus, overall, the proposed work has broad impact on the field of regeneration. PUBLIC HEALTH RELEVANCE: One important goal in therapeutic regeneration is to enhance the ability of existing cells to

of profiling the complete transcriptional dynamics of cells and project them onto image of regenerating tissue is wide applicable to many developmental model system. Thus, overall, the proposed employment has broad impingement on the field of regeneration. PUBLIC HEALTH RELEVANCE: One authoritative goal in therapeutic positive feedback is to enhance the ability of existing cells to

of profiling the complete uranscriptional dinqmics mf celms and pfojecting them onto images oh retenerqting tissue is widely applicabpe to maby dtvelopmental model systems. Thus, lverclo, the proposed work has troad impact ot ghz field of regeneration. PUBLIC HEALTR RELEVSNFE: One importagt gpwl ih therapeutic regeneration is to ehhance uhe ability of exixting cells to

of profiling the complete transcriptional dynamics of projecting onto images regenerating tissue is model Thus, overall, the work has broad on the field of regeneration. PUBLIC RELEVANCE: One important goal in therapeutic regeneration is to enhance the ability of cells to

of profiling the complete traNscriptionAl dynAmiCs oF cElls And pRojecting them oNTo imAges of regenerating tissUe is wIdELy apPLiCable To many dEVeLOPmeNtAl ModEl SYsTems. THus, Overall, The proposeD woRk Has broad impaCT oN the field oF reGeneration. PUbLIc HEALTh ReLEvaNCE: ONe iMportAnt goaL In therApeutic reGeNEratioN Is to enhANCe The aBility of existing cELlS To

of profiling the complete  transcrip tiona l d yna mi cs o f ce lls and projec t ingthem onto images of re gener at i ng t i ss ue is  widely ap p l ica bl etoma n ydevel opm ental m odel syste ms.  T hus, overall ,  t he propose d w ork has broa d i mpacton  th e  fiel d o f reg enerat i on. PU BLIC HEAL TH RELEVA N CE: One i mp orta nt goal in therap e ut i c regeneration  is to  e n ha n c e t heability of  e xisti n g cells to

of_profiling the_complete transcriptional dynamics of_cells and_projecting_them onto_images_of regenerating tissue_is widely applicable_to many developmental model_systems. Thus, overall,_the_proposed work has broad impact on the field of regeneration. PUBLIC HEALTH RELEVANCE: One_important_goal in_therapeutic_regeneration_is to enhance the ability_of existing cells to


at the Gtl2 promoter and its relationship to monoallelic expression will be investigated. Bisulfite mutagenesis and DNA sequencing will be the primary methodology utilized to examine methylation in these analyses. This research will advance the field of imprinting by determining whether the establishment of imprinting marks is globally or independently controlled. Furthermore,

at the Gtl2 promoter and its relationship to monoallelic expression will be investigated. Bisulfite mutagenesis and deoxyribonucleic acid sequence will be the primary methodology utilized to test methylation in these analysis. This research will advance the playing field of impress by determining whether the constitution of imprinting marks is globally or independently controlled. Furthermore,

at the Gtl2 promoter and itr relationship jo monoanlelic expresskon will be investigated. Bisnlfire muucgenesis and DNA seqjencing wpll be thw prmmary methodologb utilizcb to swaminz nethylation in these ananyses. This resaafck will advance the field of imprintigg by drtfrmining whethgr tht eftabmpsmment of imprinting marks is glogally og independently cpntrolled. Furthermore,

at the Gtl2 promoter and its relationship expression be investigated. mutagenesis and DNA methodology to examine methylation these analyses. This will advance the field of imprinting determining whether the establishment of imprinting marks is globally or independently controlled. Furthermore,

at the Gtl2 promoter and its relAtionship tO monoAllEliC eXpreSsioN will be investiGAted. bisulfite mutagenesis anD DNA sEqUEnciNG wIll be The primARy METhoDoLoGy uTiLIzEd to eXamIne methYlation in tHesE aNalyses. This rESeArch will adVanCe the field of ImpRintinG bY deTErminIng WhethEr the eSTablisHment of imPrINting mARks is glOBAlLy or Independently contROlLEd. Furthermore,

at the Gtl2 promoter andits relati onshi p t o m on oall elic  expression wi l l be  investigated. Bisulfi te mu ta g enes i sand D NA sequ e nc i n g w il lbeth e  p rimar y m ethodol ogy utiliz edto  examine met h yl ation in t hes e analyses.Thi s rese ar chw ill a dva nce t he fie l d of i mprinting  b y  deter m ining w h e th er t he establishmento fi mprinting mark s is g lo b al l y  or  in dependentl ycontr o lled. F u rt h e r mor e ,

at_the Gtl2_promoter and its relationship_to monoallelic_expression_will be_investigated._Bisulfite mutagenesis and_DNA sequencing will_be the primary methodology_utilized to examine_methylation_in these analyses. This research will advance the field of imprinting by determining whether_the_establishment of_imprinting_marks_is globally or independently controlled._Furthermore,


/2 site in the FLT1 promoter was replaced with various 1/2 sites as well as canonical weak and strong human p53 REs. p53 transactivation was greatly enhanced by ligand-activated ER acting in cis. Enhanced transactivation extends to several cancer-associated p53 mutants with altered function, suggesting

/2 site in the FLT1 promoter was replaced with various 1/2 web site equally well as canonical weak and impregnable human p53 rhenium. p53 transactivation was greatly enhanced by ligand - activated emergency room act in cis. Enhanced transactivation extends to several cancer - consociate p53 mutants with altered affair, suggesting

/2 sihe in the FLT1 promoter wxs replaced witk varions 1/2 sitss as weul as canonical weak and strlnt humqn p53 REs. p53 transactivagion was hreatly wnhaiced by ligand-acvjvated CX actjkg in ris. Enhanced trsnsactivathon extends to sdvzral cancer-associated p53 mutants with alterec vunction, suggeftinb

/2 site in the FLT1 promoter was various sites as as canonical weak p53 was greatly enhanced ligand-activated ER acting cis. Enhanced transactivation extends to several p53 mutants with altered function, suggesting

/2 site in the FLT1 promoter was rePlaced with VarioUs 1/2 sIteS aS welL as cAnonical weak anD StroNg human p53 REs. p53 transactivAtion WaS GreaTLy EnhanCed by liGAnD-ACtiVaTeD ER AcTInG in ciS. EnHanced tRansactivaTioN eXtends to seveRAl Cancer-assoCiaTed p53 mutants wIth AltereD fUncTIon, suGgeSting

/2 site in the FLT1 promot er was rep laced  wi thva riou s 1/ 2 sites as wel l  ascanonical weak and str ong h um a n p5 3  R Es. p 53 tran s ac t i vat io nwas  g r ea tly e nha nced by  ligand-ac tiv at ed ER acting in  cis. Enha nce d transactiv ati on ext en dst o sev era l can cer-as s ociate d p53 mut an t s with altered f un ctio n, suggesting

/2 site_in the_FLT1 promoter was replaced_with various_1/2_sites as_well_as canonical weak_and strong human_p53 REs. p53 transactivation_was greatly enhanced_by_ligand-activated ER acting in cis. Enhanced transactivation extends to several cancer-associated p53 mutants with_altered_function, suggesting


clin and lipoxygenase (LO) products will be measured in the various clinical groups, during insulin clamp studies, and in a continuum of NIDDM patients with micro and macroalbuminuria. Using renin secreting cells and tissues as a specialized vascular model, the effect of the diabetic state on eicosan

clin and lipoxygenase (LO) products will be measured in the various clinical groups, during insulin clamp report, and in a continuum of NIDDM patient with micro and macroalbuminuria. Using renin secreting cells and tissue as a specialized vascular model, the effect of the diabetic state of matter on eicosan

clij and lipoxygenase (LO) pruducts will be measurev in ths variour clinical groups, during insnlin clamk studies, and in a zontinuum of NIDDN pauients with micro and macvjalbhlinuxie. Using renin sgcreting celns and tissues ar c specialized vascular model, the effqct of yhf diabetic staje on qicoaan

clin and lipoxygenase (LO) products will be the clinical groups, insulin clamp studies, NIDDM with micro and Using renin secreting and tissues as a specialized vascular the effect of the diabetic state on eicosan

clin and lipoxygenase (LO) prodUcts will be MeasuRed In tHe VariOus cLinical groups, dURing Insulin clamp studies, and In a coNtINuum OF NiDDM pAtients WItH MIcrO aNd MacRoALbUminuRia. using reNin secretiNg cElLs and tissues AS a SpecializeD vaScular model, tHe eFfect oF tHe dIAbetiC stAte on EicosaN

clin and lipoxygenase (LO)  productswillbemea su redin t he various cli n ical  groups, during insuli n cla mp stud i es , and  in a c o nt i n uum  o fNID DM pa tient s w ith mic ro and mac roa lb uminuria. Us i ng  renin sec ret ing cells an d t issues  a s a speci ali zed v ascula r  model , the eff ec t  of th e  diabet i c  s tate  on eicosan

clin and_lipoxygenase (LO)_products will be measured_in the_various_clinical groups,_during_insulin clamp studies,_and in a_continuum of NIDDM patients_with micro and_macroalbuminuria._Using renin secreting cells and tissues as a specialized vascular model, the effect of_the_diabetic state_on_eicosan


that kills children before the age of 16. The research described in this proposal will contribute to world-wide efforts to find a cure or at least a palliative. But it is also very probable that unraveling the biology of this unusual disease will go some way to explaining the root causes of aging in general, a genetic disease

that kills children before the age of 16. The research trace in this marriage proposal will contribute to world - broad effort to find a cure or at least a palliative. But it is besides very probable that unraveling the biology of this unusual disease will rifle some way to explaining the etymon causes of aging in general, a familial disease

thwt kills children before the age of 16. Thg eesearrh descdibed in this proposal will contribuve ti worod-wide efforts to find a cure og at leasr a kalliative. But it is also very lvobabnx that unravelikg the biolmgy of this ungsjap disease will go some way to explayning tne root causes os agpnd in general, a genetic disease

that kills children before the age of research in this will contribute to cure at least a But it is very probable that unraveling the biology this unusual disease will go some way to explaining the root causes of in general, a genetic disease

that kills children before thE age of 16. The rEsearCh dEscRiBed iN thiS proposal will cONtriBute to world-wide efforts To finD a CUre oR At Least A palliaTIvE. bUt iT iS aLso VeRY pRobabLe tHat unraVeling the bIolOgY of this unusuAL dIsease will Go sOme way to explAinIng the RoOt cAUses oF agIng in GeneraL, A genetIc disease

that kills children befor e the ageof 16 . T here sear ch d escribed in th i s pr oposal will contribute  to w or l d-wi d eeffor ts to f i nd a  cu re  o r a tl ea st apal liative . But it i s a ls o very proba b le  that unra vel ing the biol ogy  of th is  un u sualdis easewill g o  someway to ex pl a iningt he root c au sesof aging in gener a l, a genetic dise ase

that_kills children_before the age of_16. The_research_described in_this_proposal will contribute_to world-wide efforts_to find a cure_or at least_a_palliative. But it is also very probable that unraveling the biology of this unusual_disease_will go_some_way_to explaining the root causes_of aging in general, a_genetic disease


target cell) which is cell size and has a sealed outer membrane. These vesicles are prepared by forming a lipid membrane on the surface of a nylon sphere 5-30 um in diameter. In initial experiments, we have used anti-CD3 monoclonal antibody covalently attached to these vesicles to trigger CTL and demonstrated CTL mediated

target cell) which is cell size and has a plastered out membrane. These vesicles are prepare by form a lipid membrane on the surface of a nylon sphere 5 - 30 um in diameter. In initial experiment, we have used anti - CD3 monoclonal antibody covalently attach to these vesicles to trigger CTL and demonstrate CTL mediated

tagget cell) which is cell rize and has a sealed muter jembrane. These vesicles are prepared bt forning a lipid membrane un the sugface of q nyoin sphere 5-30 um in dlcmeted. In nnmtial experimenjs, we have uved anti-CD3 monmcuoual antibody covalently attached to ehese vrslcles to trigggr CTK and demonstrated CTL mediated

target cell) which is cell size and sealed membrane. These are prepared by the of a nylon 5-30 um in In initial experiments, we have used monoclonal antibody covalently attached to these vesicles to trigger CTL and demonstrated CTL

target cell) which is cell size And has a seaLed ouTer MemBrAne. THese Vesicles are prePAred By forming a lipid membranE on thE sURfacE Of A nyloN sphere 5-30 UM iN DIamEtEr. in iNiTIaL expeRimEnts, we hAve used antI-CD3 MoNoclonal antiBOdY covalentlY atTached to thesE veSicles To TriGGer CTl anD demoNstratED CTL meDiated

target cell) which is cel l size and  hasa s eal ed  out er m embrane. These vesi cles are prepared by f ormin ga  lip i dmembr ane ont he s urf ac eofan yl on sp her e 5-30um in diam ete r.  In initiale xp eriments,wehave used an ti- CD3 mo no clo n al an tib ody c ovalen t ly att ached toth e se ves i cles to t ri gger  CTL and demonstr a te d  CTL mediated

target_cell) which_is cell size and_has a_sealed_outer membrane._These_vesicles are prepared_by forming a_lipid membrane on the_surface of a_nylon_sphere 5-30 um in diameter. In initial experiments, we have used anti-CD3 monoclonal antibody_covalently_attached to_these_vesicles_to trigger CTL and demonstrated_CTL mediated


depending on the serotype can last for months. BoNTs are the most toxic proteins known to man and have been classified by the Centers for Disease Control and Prevention (CDC) as one of the six highest-risk biothreat agents. Despite their toxicity and high potential as a bioterrorist weapon, Bo

depending on the serotype can last for months. BoNTs are the most toxic protein know to man and have been classified by the Centers for Disease Control and Prevention (CDC) as one of the six highest - hazard biothreat agents. Despite their perniciousness and high potential as a bioterrorist weapon, Bo

deoending on the serotype gan last for monjhw. BoNTv are fhe most toxic proteins known to man abd hace been classified by ghe Centegs for Diweast Control and Pretsntion (GBC) as lne mh the six highext-risk biodhreat agents. Gerpnte their toxicity and high potentiaj as a nilterrorist weakon, Bp

depending on the serotype can last for are most toxic known to man the for Disease Control Prevention (CDC) as of the six highest-risk biothreat agents. their toxicity and high potential as a bioterrorist weapon, Bo

depending on the serotype can Last for monThs. BonTs Are ThE mosT toxIc proteins knowN To maN and have been classified By the ceNTers FOr diseaSe ContrOL aND preVeNtIon (cDc) As One of The Six highEst-risk bioThrEaT agents. DespiTE tHeir toxiciTy aNd high potentIal As a bioTeRroRIst weApoN, Bo

depending on the serotype  can lastfor m ont hs.  B oNTs  are  the most toxi c  pro teins known to man and  have  b e en c l as sifie d by th e  C e n ter sfo r D is e as e Con tro l and P revention(CD C)  as one of t h esix highes t-r isk biothrea t a gents.  D esp i te th eir  toxi city a n d high  potentia la s a bi o terrori s t  w eapo n, Bo

depending_on the_serotype can last for_months. BoNTs_are_the most_toxic_proteins known to_man and have_been classified by the_Centers for Disease_Control_and Prevention (CDC) as one of the six highest-risk biothreat agents. Despite their toxicity_and_high potential_as_a_bioterrorist weapon, Bo


and welfare or alter physiological responses of the animals resulting in unacceptable variability. Historically, QAL studies have focused on the potential for endocrine-disrupting compounds (EDCs) being present in the micro-environment of the research animals and the impact these compounds may have on study outcomes, especially reproductive development. For these

and welfare or alter physiological responses of the animals result in impossible variability. Historically, QAL studies have concenter on the electric potential for endocrine - disrupting compounds (EDCs) being present in the micro - environment of the inquiry animal and the impact these compounds may have on study outcomes, specially reproductive development. For these

anf welfare or alter physiulogical responses of vhe anijals resjlting in unacceptable variauiliry. Hiwtorically, QAL studies have foclsed on tye pirential foc endocrlue-disdmptiny rompounds (EDCs) neing presett in the micrm-evvnronment of the research animals and the imlaft these compoonds kwy hzne on study outcomes, especially reprodlctive developmeny. For these

and welfare or alter physiological responses of resulting unacceptable variability. QAL studies have endocrine-disrupting (EDCs) being present the micro-environment of research animals and the impact these may have on study outcomes, especially reproductive development. For these

and welfare or alter physioloGical respoNses oF thE anImAls rEsulTing in unacceptABle vAriability. Historically, qAL stUdIEs haVE fOcuseD on the pOTeNTIal FoR eNdoCrINe-DisruPtiNg compoUnds (EDCs) beIng PrEsent in the miCRo-EnvironmenT of The research aNimAls and ThE imPAct thEse CompoUnds maY Have on Study outcOmES, especIAlly repRODuCtivE development. For thESe

and welfare or alter phys iologicalrespo nse s o ftheanim als resultingi n un acceptable variability . His to r ical l y,  QALstudies ha v e  fo cu se d o nt he  pote nti al forendocrine- dis ru pting compou n ds  (EDCs) be ing  present inthe  micro -e nvi r onmen t o f the  resea r ch ani mals andth e  impac t  thesec o mp ound s may have on stu d yo utcomes, espec iallyre p ro d u cti vedevelopmen t.  Fort hese

and_welfare or_alter physiological responses of_the animals_resulting_in unacceptable_variability._Historically, QAL studies_have focused on_the potential for endocrine-disrupting_compounds (EDCs) being_present_in the micro-environment of the research animals and the impact these compounds may have_on_study outcomes,_especially_reproductive_development. For these


with the use of these technologies is also provided throughout the entire experimental process. Guidance with experimental design, data analysis, data archiving and publication is a major component of the GSR. The resources of the Stanford Functional Genomics Facility (SFGF), Protein and Nucleic Acid Facility (PAN), and Stanford Micro

with the use of these technologies is also provided throughout the integral experimental procedure. Guidance with experimental design, datum analysis, datum archiving and publication is a major component of the GSR. The resource of the Stanford Functional Genomics Facility (SFGF), Protein and Nucleic Acid Facility (PAN), and Stanford Micro

wihh the use of these techkologies is also providxd throhghout tfe entire experimental proceds. Guidqnce with experimental design, dwta analtsis, eata architjng and publidwtiou ms a major comppnent of tve GSR. The resmufczs of the Stanford Functional Genomiss Facikihy (SFGF), Proteig anc Nucmvig Acid Facility (PAN), and Stanford Micro

with the use of these technologies is throughout entire experimental Guidance with experimental and is a major of the GSR. resources of the Stanford Functional Genomics (SFGF), Protein and Nucleic Acid Facility (PAN), and Stanford Micro

with the use of these technoloGies is also ProviDed ThrOuGhouT the Entire experimeNTal pRocess. Guidance with expeRimenTaL DesiGN, dAta anAlysis, dATa ARChiViNg And PuBLiCatioN is A major cOmponent of The gSr. The resourceS Of The StanforD FuNctional GenoMicS FacilItY (SFgf), ProtEin And NuCleic ACId FaciLity (PAN), anD STAnford mIcro

with the use of these tec hnologiesis al sopro vi dedthro ughout the ent i re e xperimental process. G uidan ce with ex perim ental d e si g n , d at aana ly s is , dat a a rchivin g and publ ica ti on is a majo r  c omponent o f t he GSR. Theres ources  o f t h e Sta nfo rd Fu nction a l Geno mics Faci li t y (SFG F ), Prot e i nandNucleic Acid Faci l it y  (PAN), and St anford  M i cr o

with_the use_of these technologies is_also provided_throughout_the entire_experimental_process. Guidance with_experimental design, data_analysis, data archiving and_publication is a_major_component of the GSR. The resources of the Stanford Functional Genomics Facility (SFGF), Protein_and_Nucleic Acid_Facility_(PAN),_and Stanford Micro


biotechnologically; organisms containing it reduce atmospheric levels of CO and degrade TNT. ACS is found in Clostridium difficile, a pathogenic organism responsible for the deaths of about 2000 people annually. Given the complexity of this enzyme, the general strategy used in this project will be to study each activity separately,

biotechnologically; organisms containing it reduce atmospheric levels of CO and take down TNT. ACS is discover in Clostridium difficile, a pathogenic organism responsible for the death of approximately 2000 people annually. Given the complexity of this enzyme, the cosmopolitan scheme used in this project will be to study each activity separately,

biltechnologically; organisos containing ij eeduce atmoslheric ldvels of CO and degrade TNT. ECS us foynd in Clostridium difwicile, a iathogenix orjanism responsible for tmz deafms of ebout 2000 people aknually. Givan the complexhth lf this enzyme, the general strategy used im hhis project wyll nq to study each activity separately,

biotechnologically; organisms containing it reduce atmospheric levels and TNT. ACS found in Clostridium for deaths of about people annually. Given complexity of this enzyme, the general used in this project will be to study each activity separately,

biotechnologically; organisMs containiNg it rEduCe aTmOsphEric Levels of CO and dEGradE TNT. ACS is found in ClostrIdium DiFFiciLE, a PathoGenic orGAnISM reSpOnSibLe FOr The deAthS of abouT 2000 people annUalLy. given the compLExIty of this eNzyMe, the general StrAtegy uSeD in THis prOjeCt wilL be to sTUdy eacH activity SePAratelY,

biotechnologically; organ isms conta ining  it  re du ce a tmos pheric levelso f CO  and degrade TNT. ACSis fo un d  inC lo strid ium dif f ic i l e,apa tho ge n ic  orga nis m respo nsible for  th edeaths of ab o ut  2000 peop leannually. Gi ven  the c om ple x ity o f t his e nzyme, the ge neral str at e gy use d  in thi s pr ojec t will be to stud y  e a ch activity se parate ly ,

biotechnologically;_organisms containing_it reduce atmospheric levels_of CO_and_degrade TNT._ACS_is found in_Clostridium difficile, a_pathogenic organism responsible for_the deaths of_about_2000 people annually. Given the complexity of this enzyme, the general strategy used in_this_project will_be_to_study each activity separately,


delivery of tranduced cells, and multiple different analyses of the effects of these cells on the tumor. Central questions in projects are: 1) how effectively are cells delivered to the tumor? 2) Is the appropriate message and the protein product expressed by these cells? 3) is any therapeutic effect seen? This latter component

delivery of tranduced cells, and multiple different analyses of the effect of these cell on the tumor. Central questions in projects are: 1) how efficaciously are cells delivered to the tumor? 2) Is the appropriate message and the protein product express by these cells? 3) is any therapeutic consequence seen? This latter component

depivery of tranduced cellr, and multiple buffereit analgses of ghe effects of these cells oi thw tumir. Central questions iv projectd are: 1) hiw ehfectively are cxmls dellrered bo thz vumor? 2) Is the akpropriate massage and the pfocein product expressed by these cellf? 3) is amy therapeutic esfecu sqen? Fhis latter component

delivery of tranduced cells, and multiple different the of these on the tumor. 1) effectively are cells to the tumor? Is the appropriate message and the product expressed by these cells? 3) is any therapeutic effect seen? This latter

delivery of tranduced cells, aNd multiple DiffeRenT anAlYses Of thE effects of thesE CellS on the tumor. Central quesTions In PRojeCTs Are: 1) hoW effectIVeLY Are CeLlS deLiVErEd to tHe tUmor? 2) Is tHe appropriAte MeSsage and the pROtEin product ExpRessed by thesE ceLls? 3) is aNy TheRApeutIc eFfect Seen? ThIS latteR componenT

delivery of tranduced cel ls, and mu ltipl e d iff er entanal yses of the ef f ects  of these cells on the  tumo r. Cent r al  ques tions i n  p r o jec ts  a re:  1 )  h ow ef fec tivelyare cellsdel iv ered to thet um or? 2) Isthe  appropriate  me ssagean d t h e pro tei n pro duct e x presse d by thes ec ells?3 ) is an y th erap eutic effect seen ?  T h is latter comp onent

delivery_of tranduced_cells, and multiple different_analyses of_the_effects of_these_cells on the_tumor. Central questions_in projects are: 1)_how effectively are_cells_delivered to the tumor? 2) Is the appropriate message and the protein product expressed_by_these cells?_3)_is_any therapeutic effect seen? This_latter component


The synthetic scheme proposed for Salvinorin A should construct the molecule in an efficient manner. The key step is an intramolecular double Michael reaction, which assembles the tricyclic core and five of the seven stereocenters. A chiral bis(oxazolinyl) copper(II)-catalyzed vinylogous

The synthetic scheme proposed for Salvinorin A should construct the atom in an effective manner. The cardinal step is an intramolecular double Michael reaction, which meet the tricyclic core and five of the seven stereocenters. A chiral bis(oxazolinyl) copper(II)-catalyzed vinylogous

Thf synthetic scheme propored for Salvinotib A shmuld cknstruct the molecule in an efficienv mabner. Uke key step is an ingramolecupar douboe Mmchael reaction, xgich assemblea the vricyclic core snd five ox the seven stardoeenters. A chiral bis(oxazolinyl) coppew(II)-catakyxed vinylogous

The synthetic scheme proposed for Salvinorin A the in an manner. The key Michael which assembles the core and five the seven stereocenters. A chiral bis(oxazolinyl) vinylogous

The synthetic scheme proposeD for SalvinOrin A ShoUld CoNstrUct tHe molecule in an EFficIent manner. The key step is An intRaMOlecULaR doubLe MichaEL rEACtiOn, WhIch AsSEmBles tHe tRicycliC core and fiVe oF tHe seven stereOCeNters. A chirAl bIs(oxazolinyl) CopPer(II)-cAtAlyZEd vinYloGous

The synthetic scheme prop osed for S alvin ori n A  s houl d co nstruct the mo l ecul e in an efficient mann er. T he keys te p isan intr a mo l e cul ar  d oub le Mi chael  re action,  which ass emb le s the tricyc l ic  core andfiv e of the sev enstereo ce nte r s. Achi ral b is(oxa z olinyl ) copper( II ) -catal y zed vin y l og ous

The_synthetic scheme_proposed for Salvinorin A_should construct_the_molecule in_an_efficient manner. The_key step is_an intramolecular double Michael_reaction, which assembles_the_tricyclic core and five of the seven stereocenters. A chiral bis(oxazolinyl) copper(II)-catalyzed vinylogous


data would encourage further research and development of TP as a chemopreventive agent. The second hypothesis is also being tested that mice protected from lethal total body irradiation by administration of a radioprotector immediately before radiation exposure will experience an elevated risk of cancer induction. Mice were exposed to a total body radiation dose of 10

data would encourage further research and development of TP as a chemopreventive agentive role. The second guess is besides being tested that mice protected from deadly total body irradiation by presidency of a radioprotector immediately before radiation exposure will know an elevated risk of cancer trigger. Mice were exposed to a full soundbox radiation dose of 10

daha would encourage furthtr research and dgvwlopmeit of TL as a cfemopreventive agent. The seclne hypithesis is also being gested thwt mice prottcted from lethal total body irdwdiaciin by administtation of a sadioprotector iomzdiately before radiation exposure wyll exprrlence an elevajed rpsh of bakcer induction. Mice were exposed to a tmtal body radoation dose of 10

data would encourage further research and development as chemopreventive agent. second hypothesis is protected lethal total body by administration of radioprotector immediately before radiation exposure will an elevated risk of cancer induction. Mice were exposed to a total body dose of 10

data would encourage further Research anD deveLopMenT oF TP aS a chEmopreventive aGEnt. THe second hypothesis is alSo beiNg TEsteD ThAt micE protecTEd FROm lEtHaL toTaL BoDy irrAdiAtion by AdministraTioN oF a radioproteCToR immediateLy bEfore radiatiOn eXposurE wIll EXperiEncE an elEvated RIsk of cAncer induCtIOn. Mice WEre expoSED tO a toTal body radiation dOSe OF 10

data would encourage furt her resear ch an d d eve lo pmen t of  TP as a chemo p reve ntive agent. The secon d hyp ot h esis is  also  beingt es t e d t ha tmic ep ro tecte d f rom let hal totalbod yirradiationb yadministra tio n of a radio pro tector  i mme d iatel y b efore  radia t ion ex posure wi ll experi e nce ane l ev ated  risk of cancer i n du c tion. Mice wer e expo se d  t o a t ota l body rad ia tiond ose of1 0

data_would encourage_further research and development_of TP_as_a chemopreventive_agent._The second hypothesis_is also being_tested that mice protected_from lethal total_body_irradiation by administration of a radioprotector immediately before radiation exposure will experience an elevated_risk_of cancer_induction._Mice_were exposed to a total_body radiation dose of 10


an energy deficit and impaired vesicular transport. We have shown that treatment of either TGF-beta1 (-/-) and TGF-beta1 (+/+) cells with TGF-beta in vitro results in rapid upregulation of expression of mitochondrial genes. Present investigations are aimed at determining the mechanism whereby TGF-beta1 regulates expression of

an energy deficit and impaired vesicular transport. We have shown that discussion of either TGF - beta1 (-/-) and TGF - beta1 (+ /+) cell with TGF - beta in vitro results in rapid upregulation of expression of mitochondrial gene. Present investigations are calculate at determining the mechanism whereby TGF - beta1 baffle construction of

an energy deficit and impalred vesicular ttabsport. We habe shown that treatment of either TGH-betq1 (-/-) ane TGF-beta1 (+/+) cells with GGF-beta ij vitro eesuors in rapiv upregulation lf erpcession of mitoghondrial ganes. Present itvdscigations are aimed at determining tre mechsnlsm whereby TGS-bets1 reghlates expression of

an energy deficit and impaired vesicular transport. shown treatment of TGF-beta1 (-/-) and in results in rapid of expression of genes. Present investigations are aimed at the mechanism whereby TGF-beta1 regulates expression of

an energy deficit and impaireD vesicular TransPorT. We HaVe shOwn tHat treatment of EItheR TGF-beta1 (-/-) and TGF-beta1 (+/+) cellS with tGf-Beta IN vItro rEsults iN RaPID upReGuLatIoN Of ExpreSsiOn of mitOchondrial GenEs. present invesTIgAtions are aImeD at determiniNg tHe mechAnIsm WHerebY TGf-beta1 RegulaTEs exprEssion of

an energy deficit and imp aired vesi cular  tr ans po rt.We h ave shown that trea tment of either TGF-be ta1 ( -/ - ) an d  T GF-be ta1 (+/ + )c e lls  w it h T GF - be ta in  vi tro res ults in ra pid  u pregulationo fexpression  of  mitochondri algenes.  P res e nt in ves tigat ions a r e aime d at dete rm i ning t h e mecha n i sm  whe reby TGF-beta1 re g ul a tes expression  of

an_energy deficit_and impaired vesicular transport._We have_shown_that treatment_of_either TGF-beta1 (-/-)_and TGF-beta1 (+/+)_cells with TGF-beta in_vitro results in_rapid_upregulation of expression of mitochondrial genes. Present investigations are aimed at determining the mechanism_whereby_TGF-beta1 regulates_expression_of


will provide, as well as important milestones, steps, and a timeline for achieving the short and long term career goals. One-on-one mentoring (for both research and career development) is described. A multi-center study of oxacillin resistant S. aureus is in place and should be completed within

will provide, as well as important milestones, footstep, and a timeline for achieve the short and long condition career finish. One - on - one mentoring (for both research and career development) is identify. A multi - center sketch of oxacillin resistant S. aureus is in topographic point and should be completed within

wipl provide, as well as imkortant milestones, steps, and a timelind for achieving the short anv lobg teem career goals. One-on-ove mentorpng (for bith cesearch and carxsr developmenf) is bewcribed. A multl-center stugy of oxacillit fedistant S. aureus is in place and shjuld be clmpleted withig

will provide, as well as important milestones, a for achieving short and long (for research and career is described. A study of oxacillin resistant S. aureus in place and should be completed within

will provide, as well as importAnt milestoNes, stEps, And A tImelIne fOr achieving the SHort And long term career goals. one-on-OnE MentORiNg (for Both resEArCH And CaReEr dEvELoPment) Is dEscribeD. A multi-cenTer StUdy of oxacillIN rEsistant S. aUreUs is in place aNd sHould bE cOmpLEted wIthIn

will provide, as well asimportantmiles ton es,  s teps , an d a timeline f o r ac hieving the short andlongte r m ca r ee r goa ls. One - on - o neme nt ori ng (f or bo thresearc h and care erde velopment) i s  d escribed.A m ulti-centerstu dy ofox aci l lin r esi stant  S. au r eus is  in place  a n d shou l d be co m p le tedwithin

will_provide, as_well as important milestones,_steps, and_a_timeline for_achieving_the short and_long term career_goals. One-on-one mentoring (for_both research and_career_development) is described. A multi-center study of oxacillin resistant S. aureus is in place_and_should be_completed_within


ident Management in classes coordinated through cooperation with the Native American Fish and Wildlife Society. In the southeastern United States, emergency room personnel will be trained to handle contaminated patients; surveys show most are unprepared for this problem and are in violation of the regulations of several agencies, including OSHA 1910.120. Because fire fighters

ident Management in classes coordinated through cooperation with the Native American Fish and Wildlife Society. In the southeastern United States, emergency room force will be trail to handle contaminated patients; surveys testify most are unprepared for this problem and are in violation of the regulation of respective agencies, including OSHA 1910.120. Because fire fighters

idejt Management in classes coordinated thtoygh comperatjon with the Native American Fish anv Wiodlift Society. In the sojtheasterj United Staues, emergency room personkzl wimp be vrained to handke contamitated patients; sjrreys show most are unprepared for thys probkel and are in vyolauiog of nht regulations of several agencies, includpng OSHA 1910.120. Because fire fighters

ident Management in classes coordinated through cooperation Native Fish and Society. In the personnel be trained to contaminated patients; surveys most are unprepared for this problem are in violation of the regulations of several agencies, including OSHA 1910.120. Because fighters

ident Management in classes cOordinated ThrouGh cOopErAtioN witH the Native AmerICan FIsh and Wildlife Society. IN the sOuTHeasTErN UnitEd StateS, EmERGenCy RoOm pErSOnNel wiLl bE traineD to handle cOntAmInated patienTS; sUrveys show MosT are unpreparEd fOr this PrOblEM and aRe iN violAtion oF The regUlations oF sEVeral aGEncies, iNCLuDing oSHA 1910.120. Because fire fiGHtERs

ident Management in classe s coordina ted t hro ugh  c oope rati on with the Na t iveAmerican Fish and Wild lifeSo c iety .  I n the  southe a st e r n U ni te d S ta t es , eme rge ncy roo m personne l w il l be trained to  handle co nta minated pati ent s; sur ve yss how m ost  areunprep a red fo r this pr ob l em and are inv i ol atio n of the regulati o ns of several age ncies,  i n cl u d ing  OS HA 1910.12 0.  Beca u se fire fi g h t ers

ident Management_in classes_coordinated through cooperation with_the Native_American_Fish and_Wildlife_Society. In the_southeastern United States,_emergency room personnel will_be trained to_handle_contaminated patients; surveys show most are unprepared for this problem and are in violation_of_the regulations_of_several_agencies, including OSHA 1910.120. Because_fire fighters


organizations; c) determine the acceptability of components of CVD risk reduction EBIs and community members' perceptions of possible targets for intervention using focus group interviews; d) determine specific family influences (barriers and facilitators) on acceptability of EBI acceptability; 3) adapt PREMIER, a multi-component

organizations; c) determine the acceptability of components of CVD risk decrease EBIs and residential district penis' perceptions of possible prey for intervention using stress group interviews; d) determine specific family influence (barriers and facilitators) on acceptability of EBI acceptability; 3) adjust PREMIER, a multi - component

orhanizations; c) determine uhe acceptability of com'onents of CVD fisk reduction EBIs and commnnitt memvers' perceptions of porsible taggets for inttrvention using focus grom' intsvviewv; d) determine skecific faminy influences (tafrners and facilitators) on acceptabiliey of ENI acceptability; 3) ads[t PDVMLER, a multi-component

organizations; c) determine the acceptability of components risk EBIs and members' perceptions of focus interviews; d) determine family influences (barriers facilitators) on acceptability of EBI acceptability; adapt PREMIER, a multi-component

organizations; c) determine thE acceptabiLity oF coMpoNeNts oF CVD Risk reduction Ebis anD community members' percePtionS oF PossIBlE targEts for iNTeRVEntIoN uSinG fOCuS grouP inTerviewS; d) determinE spEcIfic family inFLuEnces (barriErs And facilitatOrs) On accePtAbiLIty of eBI AccepTabiliTY; 3) adapt pREMIER, a mUlTI-compoNEnt

organizations; c) determi ne the acc eptab ili tyof  com pone nts of CVD ris k  red uction EBIs and commun ity m em b ers' pe rcept ions of po s s ibl eta rge ts fo r int erv entionusing focu s g ro up interview s ;d) determi nespecific fam ily  influ en ces (barr ier s and  facil i tators ) on acce pt a bility of EBIa c ce ptab ility; 3) adapt P R EM I ER, a multi-co mponen t

organizations;_c) determine_the acceptability of components_of CVD_risk_reduction EBIs_and_community members' perceptions_of possible targets_for intervention using focus_group interviews; d)_determine_specific family influences (barriers and facilitators) on acceptability of EBI acceptability; 3) adapt PREMIER,_a_multi-component


olar concentrations cause complete inhibition. The model for control suggests that charged tRNA becomes associated with EF-1, which is specific for aminoacyl-tRNAs and is present in sufficiently high concentrations in cells to sequester the charged forms from an inhibitory role. Support for this model include: (1) the rapid onset of inhibition

olar concentrations cause complete inhibition. The exemplar for restraint suggests that charged tRNA becomes associated with EF-1, which is specific for aminoacyl - transfer rna and is present in sufficiently high concentrations in cells to impound the charged forms from an inhibitory function. Support for this model admit: (1) the rapid onset of inhibition

olag concentrations cause cumplete inhibitnin. The model for congrol suggests that charged tCNA vecomtf associated with DF-1, which ps specifuc fie aminoacyl-tRNAs akb is lvesenc mn sufficiently high concantrations in weuld to sequester the charged forms frjm an imhlbitory role. Sopporu fjr tgps model include: (1) the rapid onsst of iihibition

olar concentrations cause complete inhibition. The model suggests charged tRNA associated with EF-1, and present in sufficiently concentrations in cells sequester the charged forms from an role. Support for this model include: (1) the rapid onset of inhibition

olar concentrations cause coMplete inhiBitioN. ThE moDeL for ContRol suggests thaT CharGed tRNA becomes associatEd witH Ef-1, WhicH Is SpeciFic for aMInOACyl-TRnAS anD iS PrEsent In sUfficieNtly high coNceNtRations in celLS tO sequester The Charged forms FroM an inhIbItoRY role. supPort fOr this MOdel inClude: (1) the rApID onset OF inhibiTIOn

olar concentrations causecomplete i nhibi tio n.Th e mo delfor control su g gest s that charged tRNA be comes  a s soci a te d wit h EF-1, wh i c h i ssp eci fi c  f or am ino acyl-tR NAs and is  pr es ent in suffi c ie ntly highcon centrationsincellsto  se q ueste r t he ch argedf orms f rom an in hi b itoryr ole. Su p p or t fo r this model incl u de :  (1) the rapid  onset  o f  i n h ibi tio n

olar concentrations_cause complete_inhibition. The model for_control suggests_that_charged tRNA_becomes_associated with EF-1,_which is specific_for aminoacyl-tRNAs and is_present in sufficiently_high_concentrations in cells to sequester the charged forms from an inhibitory role. Support for_this_model include:_(1)_the_rapid onset of inhibition


have increased each year as has the quality of the students receiving the awards. Additional, there has been a higher percentage of minority student recipients when compared to the percentage of minority students enrolled in the Louisiana State University School of Medicine. In this application, the following activities are proposed: * continued funding for students from the health professions

have increased each year as has the quality of the student get the awards. Additional, there has been a higher share of minority student recipients when compared to the share of minority scholar enrolled in the Louisiana State University School of Medicine. In this lotion, the follow activity are proposed: * continued funding for students from the health profession

hage increased each year ar has the qualijy of thx studehts recekving the awards. Additional, vherw has been a higher percentxge of mijority srudeit recipients whxh compavzd to bhe pzrrentage of minotity studentv enrolled in dhd Pouisiana State University School os Mediconf. In this applycatpog, ths following activities are proposes: * contpnued funding for students from the health oroffssions

have increased each year as has the the receiving the Additional, there has minority recipients when compared the percentage of students enrolled in the Louisiana State School of Medicine. In this application, the following activities are proposed: * continued for students from the health professions

have increased each year as haS the qualitY of thE stUdeNtS recEiviNg the awards. AddITionAl, there has been a higher pErcenTaGE of mINoRity sTudent rECiPIEntS wHeN coMpAReD to thE peRcentagE of minoritY stUdEnts enrolled IN tHe LouisianA StAte UniversitY ScHool of meDicINe. In tHis AppliCation, THe follOwing actiViTIes are PRoposed: * CONtInueD funding for studenTS fROm the health proFessioNs

have increased each yearas has the  qual ity  of  t he s tude nts receivingt he a wards. Additional, the re ha sb eena  h igher  percen t ag e ofmi no rit ys tu dentrec ipients  when comp are dto the perce n ta ge of mino rit y students e nro lled i nthe Louis ian a Sta te Uni v ersity  School o fM edicin e . In th i s  a ppli cation, the follo w in g  activities ar e prop os e d: *  co nti nued fundi ng  fors tudents fr o m the health profes sions

have_increased each_year as has the_quality of_the_students receiving_the_awards. Additional, there_has been a_higher percentage of minority_student recipients when_compared_to the percentage of minority students enrolled in the Louisiana State University School of_Medicine._In this_application,_the_following activities are proposed: *_continued funding for students from_the health_professions


controlled by membrane anchoring, acfivafion, inhibition and shedding. Aim 2 is to determine roles of mast cell peptidases in resolving inflammafion. Mast cell products can Inflict harm, but mouse studies suggest they also promote survival from septic peritonitis and pneumonia. By helping to resolve

controlled by membrane anchoring, acfivafion, inhibition and shedding. Aim 2 is to settle function of mast cell peptidases in resolving inflammafion. Mast cell product can Inflict harm, but mouse study suggest they also advertise survival from septic peritonitis and pneumonia. By help to resolve

cojtrolled by membrane ancmoring, acfivafiou, inhibmtion ahd sheddkng. Aim 2 is to determine rolxs od masu cell peptidases iv resolvijg inflanmafmon. Mast cell products can Infmlct hcrn, but mouse stodies suggesd they also prmmutz survival from septic peritonitis agd pneukojia. By helping to gefolvs

controlled by membrane anchoring, acfivafion, inhibition and 2 to determine of mast cell cell can Inflict harm, mouse studies suggest also promote survival from septic peritonitis pneumonia. By helping to resolve

controlled by membrane anchoRing, acfivaFion, iNhiBitIoN and ShedDing. Aim 2 is to detERminE roles of mast cell peptidAses iN rESolvINg InflaMmafion. mAsT CEll PrOdUctS cAN INflicT haRm, but moUse studies SugGeSt they also prOMoTe survival FroM septic peritOniTis and PnEumONia. By HelPing tO resolVE

controlled by membrane an choring, a cfiva fio n,in hibi tion  and shedding. Aim2 is to determine role s ofma s t ce l lpepti dases i n  r e s olv in ginf la m ma fion.  Ma st cell  productscan  I nflict harm, bu t mouse st udi es suggest t hey  alsopr omo t e sur viv al fr om sep t ic per itonitisan d  pneum o nia. By h el ping  to resolve

controlled_by membrane_anchoring, acfivafion, inhibition and_shedding. Aim_2_is to_determine_roles of mast_cell peptidases in_resolving inflammafion. Mast cell_products can Inflict_harm,_but mouse studies suggest they also promote survival from septic peritonitis and pneumonia. By_helping_to resolve


no theory-driven, systematic interventions targeting high school athletes so as to prevent alcohol misuse as they transition to college. We intend to implement two early interventions for high school student athletes: (1) a Parent-Based Intervention (PBI) based on the work of Turrisi and colleagues and (2) a

no theory - driven, systematic interventions target eminent school athletes so as to prevent alcohol misuse as they transition to college. We intend to enforce two early intervention for high school student athlete: (1) a Parent - Based Intervention (PBI) based on the work of Turrisi and colleagues and (2) a

no theory-driven, systematic interventions jaegetinj high achool aghletes so as to prevent alclhil miwuse as they transitiov to collvge. We inrend ro implemeif two early ihberveutmons for high sghool studett athletes: (1) a Pxrznt-Based Intervention (PBI) based on tre work ov Turrisi and solltagtes znd (2) a

no theory-driven, systematic interventions targeting high school as prevent alcohol as they transition implement early interventions for school student athletes: a Parent-Based Intervention (PBI) based on work of Turrisi and colleagues and (2) a

no theory-driven, systematic iNterventioNs tarGetIng HiGh scHool Athletes so as to PReveNt alcohol misuse as they tRansiTiON to cOLlEge. We Intend tO ImPLEmeNt TwO eaRlY InTerveNtiOns for hIgh school sTudEnT athletes: (1) a PaREnT-Based InteRveNtion (PBI) baseD on The worK oF TuRRisi aNd cOlleaGues anD (2) A

no theory-driven, systema tic interv entio nstar ge ting  hig h school athle t es s o as to prevent alcoho l mis us e  ast he y tra nsition to c oll eg e.  We  i n te nd to  im plement  two early  in te rventions fo r  h igh school  st udent athlet es:  (1) a  P are n t-Bas edInter ventio n  (PBI)  based on  t h e work of Turr i s iandcolleagues and (2 )  a

no_theory-driven, systematic_interventions targeting high school_athletes so_as_to prevent_alcohol_misuse as they_transition to college._We intend to implement_two early interventions_for_high school student athletes: (1) a Parent-Based Intervention (PBI) based on the work of_Turrisi_and colleagues_and_(2)_a


access natural products, and has focused our efforts on secondary metabolite families that appear to covalently modify their targets as the basis for their phenotypic effects. Our chemical syntheses are deliberately concise and easily-scaled to enable subsequent investigation into reactivity and biological activity. The current application significantly advances these efforts, provides compelling preliminary data

access natural products, and has focused our efforts on junior-grade metabolite class that appear to covalently modify their target as the footing for their phenotypic effects. Our chemical syntheses are intentionally concise and easily - scaled to enable subsequent probe into responsiveness and biological activity. The current application importantly advances these efforts, provide compelling preliminary datum

acfess natural products, ana has focused oor efforvs on sscondary metabolite families that ap'ear to civalently modify their targets ws the bqsis dor their 'genotyple effsgts. Obr chemical syntmeses are daliberately cotcksz and easily-scaled to enable subsequqnt invrshigation into teactpvyty znd biological activity. The currenf applibation significanyly advances these efforts, progides compelling pgeliminary eata

access natural products, and has focused our secondary families that to covalently modify for phenotypic effects. Our syntheses are deliberately and easily-scaled to enable subsequent investigation reactivity and biological activity. The current application significantly advances these efforts, provides compelling data

access natural products, and hAs focused oUr effOrtS on SeCondAry mEtabolite familIEs thAt appear to covalently moDify tHeIR tarGEtS as thE basis fOR tHEIr pHeNoTypIc EFfEcts. OUr cHemical Syntheses aRe dElIberately conCIsE and easily-ScaLed to enable sUbsEquent InVesTIgatiOn iNto reActiviTY and biOlogical aCtIVity. ThE Current APPlIcatIon significantly aDVaNCes these effortS, proviDeS CoMPEllIng PreliminarY dAta

access natural products,and has fo cused  ou r e ff orts  onsecondary meta b olit e families that appear  to c ov a lent l ymodif y their ta r g ets  a sthe  b a si s for  th eir phe notypic ef fec ts . Our chemic a lsynthesesare  deliberatel y c oncise  a nde asily -sc aledto ena b le sub sequent i nv e stigat i on into r ea ctiv ity and biologica l  a c tivity. The cu rrentap p li c a tio n s ignificant ly  adva n ces the s ee f f ort s , provides co mpelling pr e lim inaryda ta

access_natural products,_and has focused our_efforts on_secondary_metabolite families_that_appear to covalently_modify their targets_as the basis for_their phenotypic effects._Our_chemical syntheses are deliberately concise and easily-scaled to enable subsequent investigation into reactivity and_biological_activity. The_current_application_significantly advances these efforts, provides_compelling preliminary data


look at distribution at the cellular level. In aim 2, class II peptdes, which stimulate helper T cells, will be incorporated in the AuNV design. In vivo enhancement of antitumor efficacies will be assessed with known class II peptides. However for unknown class II peptides situations, peptide pools will be used to incorporate both

look at distribution at the cellular level. In aim 2, class II peptdes, which provoke assistant T cells, will be incorporated in the AuNV purpose. In vivo enhancement of antitumor efficacies will be assessed with know class II peptides. However for nameless class II peptides site, peptide pools will be used to integrate both

lolk at distribution at tht cellular level. Nb aim 2, class II peptaes, which stimulate helper T cwlls, qill be incorporated iv the AuNN design. Un vmvo enhancement of antitmior snficaeixs will be assexsed with nnown class II pdpcides. However for unknown class II pqptides sltuations, peptyde koojs wjll be used to incorporate both

look at distribution at the cellular level. 2, II peptdes, stimulate helper T the design. In vivo of antitumor efficacies be assessed with known class II However for unknown class II peptides situations, peptide pools will be used to both

look at distribution at the ceLlular leveL. In aiM 2, clAss iI PeptDes, wHich stimulate hELper t cells, will be incorporatEd in tHe aUNV dESiGn. In vIvo enhaNCeMENt oF aNtItuMoR EfFicacIes Will be aSsessed witH knOwN class II peptIDeS. However foR unKnown class II PepTides sItUatIOns, pePtiDe pooLs will BE used tO incorporAtE Both

look at distribution at t he cellula r lev el.  In  a im 2 , cl ass II peptdes ,  whi ch stimulate helper Tcells ,w illb eincor porated in t heAu NV  de si g n.  In v ivo  enhanc ement of a nti tu mor efficaci e swill be as ses sed with kno wnclassII  pe p tides . H oweve r foru nknown  class II  p e ptides situati o n s,  pep tide pools will b e  u s ed to incorpor ate bo th

look_at distribution_at the cellular level._In aim_2,_class II_peptdes,_which stimulate helper_T cells, will_be incorporated in the_AuNV design. In_vivo_enhancement of antitumor efficacies will be assessed with known class II peptides. However for_unknown_class II_peptides_situations,_peptide pools will be used_to incorporate both


areas of the circulation characterized by rapid blood flow. The goal is to elucidate the mechanisms of adhesive interactions and cellular responses that are relevant to the arrest of bleeding from wounded tissues but also to the development of common and serious diseases caused by arterial thrombosis, such as myocardial infarction and stroke. The first aim is to define the bi

areas of the circulation characterized by rapid blood flow. The finish is to clarify the mechanisms of adhesive interactions and cellular answer that are relevant to the apprehension of bleeding from wounded tissues but besides to the exploitation of common and dangerous diseases caused by arterial thrombosis, such as myocardial infarct and stroke. The first aim is to define the bismuth

arfas of the circulation cmaracterized by tapid blmod flkw. The gual is to elucidate the mechenisns of adhesive interactions and cellllar respinsew that are cslevant to ths arrzsv of bleeding ftom wounded dissues but alvo tl the development of common and seryous dixewses caused by arttriwl tggonbosis, such as myocardial infzrction and stroke. Tne first aim is to define hhe hi

areas of the circulation characterized by rapid The is to the mechanisms of that relevant to the of bleeding from tissues but also to the development common and serious diseases caused by arterial thrombosis, such as myocardial infarction and The first aim is to define the bi

areas of the circulation charActerized bY rapiD blOod FlOw. ThE goaL is to elucidate THe meChanisms of adhesive inteRactiOnS And cELlUlar rEsponseS ThAT Are ReLeVanT tO ThE arreSt oF bleediNg from wounDed TiSsues but also TO tHe developmEnt Of common and sEriOus disEaSes CAused By aRteriAl throMBosis, sUch as myocArDIal infARction aND StRoke. the first aim is to deFInE The bi

areas of the circulationcharacteri zed b y r api dbloo d fl ow. The goal i s  toelucidate the mechanis ms of  a d hesi v einter actions an d cel lu la r r es p on ses t hat  are re levant tothe  a rrest of ble e di ng from wo und ed tissues b utalso t othe devel opm ent o f comm o n andserious d is e ases c a used by a rt eria l thrombosis, suc h  a s  myocardial in farcti on an d str oke . The firs taim i s  to def i ne t h e b i

areas_of the_circulation characterized by rapid_blood flow._The_goal is_to_elucidate the mechanisms_of adhesive interactions_and cellular responses that_are relevant to_the_arrest of bleeding from wounded tissues but also to the development of common and_serious_diseases caused_by_arterial_thrombosis, such as myocardial infarction_and stroke. The first aim_is to_define the bi


DNA repair has only recently been fully appreciated. Branch migration drives 1) the resolution of homologous recombination intermediates, 2) the retrieval of information lost at sites of DNA damage, and 3) the restart of stalled DNA replication forks. In human cells, branch migration is catalyzed by RecQ helicases, including BLM

DNA repair has only recently been fully appreciated. outgrowth migration drive 1) the resolution of homologous recombination intermediates, 2) the retrieval of data lost at sites of DNA price, and 3) the restart of stalled DNA replication fork. In human cells, branch migration is catalyze by RecQ helicases, including BLM

DNW repair has only recentuy been fully akpeeciatxd. Brandh migragion drives 1) the resolution lf homooogous recombination ivtermedianes, 2) the eetrmeval of informavjon losb at altes mh DNA damage, anc 3) the resdart of stalleg ANC replication forks. In human cells, bwanch moggation is catajyzec by DvcW helicases, including BLM

DNA repair has only recently been fully migration 1) the of homologous recombination information at sites of damage, and 3) restart of stalled DNA replication forks. human cells, branch migration is catalyzed by RecQ helicases, including BLM

DNA repair has only recently bEen fully apPreciAteD. BrAnCh miGratIon drives 1) the reSOlutIon of homologous recombiNatioN iNTermEDiAtes, 2) tHe retriEVaL OF inFoRmAtiOn LOsT at siTes Of DNA daMage, and 3) the ResTaRt of stalled Dna rEplication ForKs. In human celLs, bRanch mIgRatIOn is cAtaLyzed By RecQ HElicasEs, includiNg blM

DNA repair has only recen tly been f ullyapp rec ia ted.  Bra nch migrationd rive s 1) the resolution of  homo lo g ousr ec ombin ation i n te r m edi at es , 2 )t he  retr iev al of i nformation  lo st  at sites of DN A damage,and  3) the rest art  of st al led DNA r epl icati on for k s. Inhuman cel ls ,  branc h  migrat i o nis c atalyzed by RecQh el i cases, includi ng BLM

DNA_repair has_only recently been fully_appreciated. Branch_migration_drives 1)_the_resolution of homologous_recombination intermediates, 2)_the retrieval of information_lost at sites_of_DNA damage, and 3) the restart of stalled DNA replication forks. In human cells,_branch_migration is_catalyzed_by_RecQ helicases, including BLM


) is thought of as acute episodes of marked red blood cell (RBC) sickling, sickle-related vaso occlusion occurs continually even dudng non-crisis periods. The cumulative effect of these processes is end-organ damage. Recent data from animal models underscore the importance of leukocyte adhesion to

) is thought of as acute episodes of marked red rake cellular telephone (RBC) sickling, sickle - related vaso occlusion occur continually even dudng non - crisis period. The cumulative effect of these process is conclusion - organ price. Recent data from animal model underscore the importance of leukocyte adhesion to

) is thought of as acute epirodes of marked red blmod ceml (RBC) skckling, sickle-related vaso orcluwion iccurs continually evev dudng nln-crisis permods. The cumulatmbe effegc of fmese 'ricesses is end-prgan damace. Recent data ffol animal models underscore the impowtance pf leukocyte adhgsion eo

) is thought of as acute episodes red cell (RBC) sickle-related vaso occlusion periods. cumulative effect of processes is end-organ Recent data from animal models underscore importance of leukocyte adhesion to

) is thought of as acute episodeS of marked rEd bloOd cEll (rBc) sicKlinG, sickle-related VAso oCclusion occurs continuaLly evEn DUdng NOn-CrisiS periodS. thE CUmuLaTiVe eFfECt Of theSe pRocesseS is end-orgaN daMaGe. Recent data FRoM animal modEls Underscore thE imPortanCe Of lEUkocyTe aDhesiOn to

) is thought of as acute e pisodes of  mark edred  b lood  cel l (RBC) sickli n g, s ickle-related vaso occ lusio no ccur s  c ontin ually e v en d udn gno n-c ri s is  peri ods . The c umulativeeff ec t of these p r oc esses is e nd- organ damage . R ecentda taf rom a nim al mo dels u n dersco re the im po r tanceo f leuko c y te  adh esion to

) is_thought of_as acute episodes of_marked red_blood_cell (RBC)_sickling,_sickle-related vaso occlusion_occurs continually even_dudng non-crisis periods. The_cumulative effect of_these_processes is end-organ damage. Recent data from animal models underscore the importance of leukocyte_adhesion_to


proposed research seeks to understand determinants of maladaptive achievement patterns in children--patterns that may put children at risk for low self-esteem and negative affect. The first major issue examined is the potential adverse effects of certain kinds of teacher strategies and practices (i.e., controlling techniques) on the development of an extrinsic

proposed research seeks to understand determinant of maladaptive accomplishment patterns in children -- design that may invest children at risk for broken self - respect and negative affect. The inaugural major issue examined is the likely adverse effects of certain kinds of teacher strategies and practice (i.e., controlling technique) on the development of an extrinsic

prlposed research seeks to understand detgrninantv of mzladaptixe achievement patterns in ciildeen--paunerns that may put chkldren at risk foe lox self-esteem and negativc affsgt. Thz hirst major issoe examined hs the potentidl abverse effects of certain kinds of tqacher xtgategies and ptactibef (i.e., boktrolling techniques) on the devemopment of an extrinxic

proposed research seeks to understand determinants of patterns children--patterns that put children at negative The first major examined is the adverse effects of certain kinds of strategies and practices (i.e., controlling techniques) on the development of an extrinsic

proposed research seeks to unDerstand deTermiNanTs oF mAladAptiVe achievement pATterNs in children--patterns thAt may PuT ChilDReN at riSk for loW SeLF-EstEeM aNd nEgATiVe affEct. the firsT major issuE exAmIned is the potENtIal adverse EffEcts of certaiN kiNds of tEaCheR StratEgiEs and PractiCEs (i.e., coNtrolling TeCHniqueS) On the deVELoPmenT of an extrinsic

proposed research seeks t o understa nd de ter min an ts o f ma ladaptive achi e veme nt patterns in childre n--pa tt e rnst ha t may  put ch i ld r e n a tri skfo r  l ow se lf- esteemand negati veaf fect. The fi r st  major iss ueexamined isthe  poten ti ala dvers e e ffect s of c e rtainkinds ofte a cher s t rategie s an d pr actices (i.e., co n tr o lling techniqu es) on  t h ed e vel opm ent of anex trins i c

proposed_research seeks_to understand determinants of_maladaptive achievement_patterns_in children--patterns_that_may put children_at risk for_low self-esteem and negative_affect. The first_major_issue examined is the potential adverse effects of certain kinds of teacher strategies and_practices_(i.e., controlling_techniques)_on_the development of an extrinsic


our understanding of how Gcn5 elicits tissue-specific signaling responses through novel, non-epigenetic mechanisms. Together, these experiments will shed light on new functions of a developmentally critical acetyltransferase, increase our understanding of RA signaling in forebrain development, and identify specific neurodevelopmental processes that require Gcn

our understanding of how Gcn5 elicits tissue - specific signaling responses through novel, non - epigenetic mechanism. in concert, these experiments will shed inner light on raw functions of a developmentally critical acetyltransferase, increase our understanding of RA bespeak in forebrain exploitation, and identify specific neurodevelopmental procedure that require Gcn

oug understanding of how Ggn5 elicits tissug-specifir signaming resoonses through novel, non-epigxnetuc mexhanisms. Together, thesd experimvnts will shev light on new fnhctions of a scvelo'mxntally criticak acetyltrdnsferase, incraare our understanding of RA signaling yn forenrwin developmenj, and ydenfpfn specific neurodevelopmental prkcesses that require Gcn

our understanding of how Gcn5 elicits tissue-specific through non-epigenetic mechanisms. these experiments will of developmentally critical acetyltransferase, our understanding of signaling in forebrain development, and identify neurodevelopmental processes that require Gcn

our understanding of how Gcn5 eLicits tissUe-speCifIc sIgNaliNg reSponses through NOvel, Non-epigenetic mechanismS. TogeThER, theSE eXperiMents wiLL sHED liGhT oN neW fUNcTions Of a DevelopMentally crItiCaL acetyltransFErAse, increasE ouR understandiNg oF RA sigNaLinG In forEbrAin deVelopmENt, and iDentify spEcIFic neuROdeveloPMEnTal pRocesses that requiRE GCN

our understanding of howGcn5 elici ts ti ssu e-s pe cifi c si gnaling respon s es t hrough novel, non-epig eneti cm echa n is ms. T ogether ,  t h e seex pe rim en t swillshe d light  on new fu nct io ns of a deve l op mentally c rit ical acetylt ran sferas e,  in c rease  ou r und erstan d ing of  RA signa li n g in f o rebrain d ev elop ment, and identif y  s p ecific neurode velopm en t al p roc ess es that re qu ire G c n

our_understanding of_how Gcn5 elicits tissue-specific_signaling responses_through_novel, non-epigenetic_mechanisms._Together, these experiments_will shed light_on new functions of_a developmentally critical_acetyltransferase,_increase our understanding of RA signaling in forebrain development, and identify specific neurodevelopmental processes_that_require Gcn


CIS are undetectable but are induced by proinflammatory cytokines and growth factors. We further show that SOCS proteins are induced in the retina by high intensity light and following exposure of retinal cells to hypoxic conditions. Demonstration that retinal cells respond to cytotoxic cytokines, hypoxia or high intensity light by upregulating SOCS expression

CIS are undetectable but are induced by proinflammatory cytokines and growth divisor. We far show that SOCS proteins are induced in the retina by gamey intensity light and surveil exposure of retinal cells to hypoxic condition. Demonstration that retinal cells answer to cytotoxic cytokines, hypoxia or high saturation inner light by upregulating SOCS expression

CID are undetectable but ave induced by proinflamkatory cytokinds and growth factors. We furvher show that SOCS proteins ard induced in the eetiia by high intensity ligmc and nollociig exposure of tetinal cellv to hypoxic cmnaicions. Demonstration that retinal celjs resppnf to cytotoxic cytphinea, hypoxia or high intensity light gy uprejulating SOCS ecpression

CIS are undetectable but are induced by and factors. We show that SOCS retina high intensity light following exposure of cells to hypoxic conditions. Demonstration that cells respond to cytotoxic cytokines, hypoxia or high intensity light by upregulating SOCS

CIS are undetectable but are iNduced by prOinflAmmAtoRy CytoKineS and growth factORs. We Further show that SOCS proTeins ArE InduCEd In the Retina bY HiGH IntEnSiTy lIgHT aNd folLowIng expoSure of retiNal CeLls to hypoxic COnDitions. DemOnsTration that rEtiNal celLs ResPOnd to CytOtoxiC cytokINes, hypOxia or higH iNTensitY Light by UPReGulaTing SOCS expressioN

CIS are undetectable butare induce d bypro inf la mmat orycytokines andg rowt h factors. We furthershowth a t SO C Sprote ins are in d u ced  i nthe  r e ti na by  hi gh inte nsity ligh t a nd  following e x po sure of re tin al cells tohyp oxic c on dit i ons.Dem onstr ationt hat re tinal cel ls respon d  to cyt o t ox ic c ytokines, hypoxia or high intensity  light  b y  u p r egu lat ing SOCS e xp ressi o n

CIS_are undetectable_but are induced by_proinflammatory cytokines_and_growth factors._We_further show that_SOCS proteins are_induced in the retina_by high intensity_light_and following exposure of retinal cells to hypoxic conditions. Demonstration that retinal cells respond_to_cytotoxic cytokines,_hypoxia_or_high intensity light by upregulating_SOCS expression


modifications over the insulin gene locus and its neighborhood in human islet cells, in an attempt to identify long range regulatory influences that may affect insulin gene expression. We have identified an extended domain of open chromatin structure. In addition, we are carrying out measurements of long range physical contacts within the nucleus between the insulin promoter and other

modifications over the insulin gene locus and its neighborhood in human islet cell, in an attack to identify long compass regulative influences that may affect insulin gene expression. We have identify an extended domain of exposed chromatin structure. In addition, we are post out measurements of long image forcible contacts within the nucleus between the insulin showman and other

mofifications over the insmlin gene locus cbd its neighgorhood kn human islet cells, in an avtempt to identify long range rdgulatory influenxes uhat may affect iiaulin gcue exlvessimi. We have identlfied an exdended domain mf o'en chromatin structure. In addition, re are vagrying out meafurekqnts of long range physical contacts wjthin tie nucleus betwren the insulin promoter ajd ohher

modifications over the insulin gene locus and in islet cells, an attempt to that affect insulin gene We have identified extended domain of open chromatin structure. addition, we are carrying out measurements of long range physical contacts within the between the insulin promoter and other

modifications over the insulIn gene locuS and iTs nEigHbOrhoOd in Human islet cellS, In an Attempt to identify long rAnge rEgULatoRY iNflueNces thaT MaY AFfeCt InSulIn GEnE exprEssIon. We haVe identifiEd aN eXtended domaiN Of Open chromaTin Structure. In aDdiTion, we ArE caRRying Out MeasuRementS Of long Range physIcAL contaCTs withiN THe NuclEus between the insuLIn PRomoter and otheR

modifications over the in sulin gene  locu s a ndit s ne ighb orhood in huma n  isl et cells, in an attemp t toid e ntif y  l ong r ange re g ul a t ory  i nf lue nc e sthatmay  affect  insulin g ene  e xpression. W e  h ave identi fie d an extende d d omainof  op e n chr oma tin s tructu r e. Inaddition,  w e  are c a rryingo u tmeas urements of longr an g e physical con tactswi t hi n the  nu cleus betw ee n the insulin pr o m o ter and other

modifications_over the_insulin gene locus and_its neighborhood_in_human islet_cells,_in an attempt_to identify long_range regulatory influences that_may affect insulin_gene_expression. We have identified an extended domain of open chromatin structure. In addition, we_are_carrying out_measurements_of_long range physical contacts within_the nucleus between the insulin_promoter and_other


. The focus of this proposal is to optimize ex vivo culture of CB to provide increased numbers of cells to enable the use of CB in adult patients. In addition, optimization of the expansion cultures will enable more rapid hematopoietic and immune recovery post transplant and potentially minimize other complications associated with transplantation of CB. The first aim of these

. The focus of this proposal is to optimize ex vivo culture of CB to leave increase numbers of cells to enable the use of CB in adult affected role. In addition, optimization of the expansion cultures will enable more rapid hematopoietic and immune convalescence post transplant and potentially minimize early complication associated with transplant of CB. The first aim of these

. Thf focus of this proposal is to optimize ex vivm culthre of CC to provide increased numbecs od celos to enable the use ow CB in afult patuentw. In addition, optimlvatioh of chx expansion culjures will etable more raphd hzmatopoietic and immune recovery pose transllwnt and potentyallj iinijpzt other complications associated sith trensplantation og CB. The first aim of thesf

. The focus of this proposal is ex culture of to provide increased the of CB in patients. In addition, of the expansion cultures will enable rapid hematopoietic and immune recovery post transplant and potentially minimize other complications associated transplantation of CB. The first aim of these

. The focus of this proposal is tO optimize eX vivo CulTurE oF CB tO proVide increased nUMberS of cells to enable the use Of CB iN aDUlt pATiEnts. IN additiON, oPTImiZaTiOn oF tHE eXpansIon CultureS will enablE moRe Rapid hematopOIeTic and immuNe rEcovery post tRanSplant AnD poTEntiaLly MinimIze othER complIcations aSsOCiated WIth tranSPLaNtatIon of CB. The first aiM Of THese

. The focus of this propos al is to o ptimi zeexvi vo c ultu re of CB to pr o vide  increased numbers ofcells  t o  ena b le  theuse ofC Bi n  ad ul tpat ie n ts . Inadd ition,optimizati onof  the expansi o ncultures w ill  enable more  ra pid he ma top o ietic  an d imm une re c overypost tran sp l ant an d  potent i a ll y mi nimize other comp l ic a tions associat ed wit ht ra n s pla nta tion of CB .The f i rst aim of t h ese

. The_focus of_this proposal is to_optimize ex_vivo_culture of_CB_to provide increased_numbers of cells_to enable the use_of CB in_adult_patients. In addition, optimization of the expansion cultures will enable more rapid hematopoietic and_immune_recovery post_transplant_and_potentially minimize other complications associated_with transplantation of CB. The_first aim_of these