DE level during pregnancy in relation to adjusted odds of cryptorchidism, hypospadias, and polythelia [extra nipples] among their male offspring. We evaluated prenatal PCB exposure in relation to cognitive test scores (IQ) on the Wechsler Intelligence Scale for Children (WISC) at age

DE level during pregnancy in relation to adjusted odds of cryptorchidism, hypospadias, and polythelia [ excess nipple ] among their male offspring. We evaluated prenatal PCB vulnerability in relative to cognitive test scores (IQ) on the Wechsler Intelligence Scale for Children (WISC) at historic period

DE pevel during pregnancy ik relation to adlysted mdds or cryptofchidism, hypospadias, and polbtheoia [eztra nipples] among thekr male ovfspring. We tvaluated prenatal PCB exijsurs in xeoation to cognltive test vcores (IQ) on tve Wzchsler Intelligence Scale for Childwen (WISV) wt age

DE level during pregnancy in relation to of hypospadias, and [extra nipples] among prenatal exposure in relation cognitive test scores on the Wechsler Intelligence Scale for (WISC) at age

DE level during pregnancy in rElation to aDjustEd oDds Of CrypTorcHidism, hypospadIAs, anD polythelia [extra nippleS] amonG tHEir mALe OffspRing. We eVAlUATed PrEnAtaL Pcb eXposuRe iN relatiOn to cognitIve TeSt scores (IQ) on THe wechsler InTelLigence Scale For childrEn (wISc) At age

DE level during pregnancyin relatio n toadj ust ed  odd s of  cryptorchidis m , hy pospadias, and polythe lia [ ex t ra n i pp les]among t h ei r mal eof fsp ri n g.  We e val uated p renatal PC B e xp osure in rel a ti on to cogn iti ve test scor es(IQ) o nthe Wechs ler  Inte lligen c e Scal e for Chi ld r en (WI S C) at a g e

DE level_during pregnancy_in relation to adjusted_odds of_cryptorchidism,_hypospadias, and_polythelia_[extra nipples] among_their male offspring._We evaluated prenatal PCB_exposure in relation_to_cognitive test scores (IQ) on the Wechsler Intelligence Scale for Children (WISC) at age


electroporation resulted in enhanced cellular viability compared to post-electroporation transduction. Flow cytometry revealed efficient rAAV transduction at 4 days post-transduction (range 18-46% copGFP+ cells). The percentage of cells expressing copGFP slowly decreased over the extended culture period, stabilizing at approximately 5-10

electroporation resulted in enhanced cellular viability compared to post - electroporation transduction. Flow cytometry reveal effective rAAV transduction at 4 days post - transduction (compass 18 - 46% copGFP+ cell). The percentage of cells express copGFP lento decreased over the extended culture period, stabilizing at approximately 5 - 10

elfctroporation resulted ik enhanced cellular viauility dompared to post-electroporation tranddyctiob. Flow cytometry reveaued efficpent rAAV traisduction at 4 daba post-tvcnsdudbion (xaige 18-46% copGFP+ celks). The perwentage of celns erpressing copGFP slowly decreased ovqr the rxhended culture perpoq, stzbilizing at approximately 5-10

electroporation resulted in enhanced cellular viability compared transduction. cytometry revealed rAAV transduction at copGFP+ The percentage of expressing copGFP slowly over the extended culture period, stabilizing approximately 5-10

electroporation resulted in Enhanced ceLlulaR viAbiLiTy coMparEd to post-electrOPoraTion transduction. Flow cyTometRy REveaLEd EfficIent rAAv TrANSduCtIoN at 4 DaYS pOst-trAnsDuction (Range 18-46% copGFp+ ceLlS). The percentaGE oF cells exprEssIng copGFP sloWly DecreaSeD ovER the eXteNded cUlture PEriod, sTabilizinG aT ApproxIMately 5-10

electroporation resultedin enhance d cel lul arvi abil itycompared to po s t-el ectroporation transduc tion.  F l ow c y to metry  reveal e de f fic ie nt  rA AV tr ansdu cti on at 4  days post -tr an sduction (ra n ge  18-46% co pGF P+ cells). T hepercen ta geo f cel lsexpre ssingc opGFPslowly de cr e ased o v er thee x te nded  culture period,s ta b ilizing at app roxima te l y5 - 10

electroporation_resulted in_enhanced cellular viability compared_to post-electroporation_transduction._Flow cytometry_revealed_efficient rAAV transduction_at 4 days_post-transduction (range 18-46% copGFP+_cells). The percentage_of_cells expressing copGFP slowly decreased over the extended culture period, stabilizing at approximately 5-10


mice were viable, fertile and indistinguishable from wild type littermates. Examination of beta-galactosidase expression as a surrogate for EpCAM revealed that EpCAM was expressed in a variety of developing epitehelial structures in skin and other organs. Mating of EpCAM +/- male and female mice gave rise to only wild type

mice were viable, fertile and indistinguishable from raving mad character littermates. Examination of beta - galactosidase expression as a deputy for EpCAM revealed that EpCAM was express in a variety of develop epitehelial structures in skin and early organ. Mating of EpCAM + /- male and female mouse gave rise to entirely crazy type

mife were viable, fertile akd indistinguishcvle frmm wils type lkttermates. Examination of beva-gaoactowidase expression as a surrogatv for EpCQM rtvealed that EpCAM was exixesses in c tariety of devekoping epidehelial strucdufed in skin and other organs. Mating os EpCAM +/- lale and femalg mict gwve dpst to only wild type

mice were viable, fertile and indistinguishable from littermates. of beta-galactosidase as a surrogate was in a variety developing epitehelial structures skin and other organs. Mating of +/- male and female mice gave rise to only wild type

mice were viable, fertile and iNdistinguiShablE frOm wIlD typE litTermates. ExaminATion Of beta-galactosidase expRessiOn AS a suRRoGate fOr EpCAM REvEALed ThAt epCaM WAs ExpreSseD in a varIety of deveLopInG epitehelial STrUctures in sKin And other orgaNs. MAting oF EPCAm +/- Male aNd fEmale Mice gaVE rise tO only wild TyPE

mice were viable, fertile  and indis tingu ish abl efrom  wil d type litterm a tes.  Examination of beta-g alact os i dase ex press ion asa  s u r rog at efor  E p CA M rev eal ed that  EpCAM was  ex pr essed in a v a ri ety of dev elo ping epitehe lia l stru ct ure s  in s kin  andothero rgans.  Mating o fE pCAM + / - malea n dfema le mice gave rise to only wild type

mice_were viable,_fertile and indistinguishable from_wild type_littermates._Examination of_beta-galactosidase_expression as a_surrogate for EpCAM_revealed that EpCAM was_expressed in a_variety_of developing epitehelial structures in skin and other organs. Mating of EpCAM +/- male_and_female mice_gave_rise_to only wild type


its suppression by anesthetics, we previously screened for changes in sensitivity to halothane in lines that were missing one copy of a large block of DNA. Are the hits we found genetically complex or simple? We had previously shown that the effect of the 75 kb ED1 deletion could be reversed by adding back a 15 kb

its suppression by anesthetics, we previously screened for changes in sensitivity to halothane in occupation that were miss one copy of a big engine block of DNA. Are the hits we found genetically complex or dim-witted? We had previously show that the effect of the 75 kb ED1 omission could be overrule by adding back a 15 kilobyte

itd suppression by anestheuics, we previousli wcreenxd for dhanges kn sensitivity to halothane mn lunes ukat were missing one copy of w large vlocj of DNA. Arx the hibf we nound jenetically comklex or simpne? We had prevhojspy shown that the effect of the 75 kb ED1 delrtlon could be rgverstd fy asding back a 15 kb

its suppression by anesthetics, we previously screened in to halothane lines that were large of DNA. Are hits we found complex or simple? We had previously that the effect of the 75 kb ED1 deletion could be reversed by back a 15 kb

its suppression by anesthetiCs, we previoUsly sCreEneD fOr chAngeS in sensitivity TO halOthane in lines that were mIssinG oNE copY Of A largE block oF dNa. aRe tHe HiTs wE fOUnD geneTicAlly comPlex or simpLe? WE hAd previously SHoWn that the eFfeCt of the 75 kb ED1 dEleTion coUlD be REversEd bY addiNg back A 15 Kb

its suppression by anesth etics, weprevi ous lysc reen ed f or changes ins ensi tivity to halothane in  line st hatw er e mis sing on e  c o p y o falar ge bl ock o f D NA. Are  the hitswefo und genetica l ly  complex o r s imple? We ha d p reviou sl y s h own t hat  theeffect of the  75 kb ED 1d eletio n  couldb e  r ever sed by adding bac k  a 15 kb

its_suppression by_anesthetics, we previously screened_for changes_in_sensitivity to_halothane_in lines that_were missing one_copy of a large_block of DNA._Are_the hits we found genetically complex or simple? We had previously shown that the_effect_of the_75_kb_ED1 deletion could be reversed_by adding back a 15_kb


-flanked reporter cassette and the endogenous ITGB2 target gene are concomitantly cleaved by Cas9, thus promoting NHEJ-mediated transgene insertion at the site of the Cas9-induced chromosomal double-strand break. To determine the optimal time of rAAV transduction, HSPCs were transduced with rAA

-flanked reporter cassette and the endogenous ITGB2 target gene are concomitantly cleaved by Cas9, thus promoting NHEJ - intercede transgene interpolation at the site of the Cas9 - induced chromosomal bivalent - strand open frame. To determine the optimal clock time of rAAV transduction, HSPCs were transduced with rAA

-flajked reporter cassette akd the endogenous ITGB2 varget fene are concomitantly cleaved by Cad9, rhus kgomoting NHEJ-mediated transgenv insertiin au the site of the Cas9-indugzd chdlmosmnal double-strakd break. To determine the ootnmal time of rAAV transduction, HSPCs were ttajsduced with rWA

-flanked reporter cassette and the endogenous ITGB2 are cleaved by thus promoting NHEJ-mediated of Cas9-induced chromosomal double-strand To determine the time of rAAV transduction, HSPCs were with rAA

-flanked reporter cassette anD the endogeNous ItGB2 TarGeT genE are Concomitantly cLEaveD by Cas9, thus promoting NHEj-mediAtED traNSgEne inSertion AT tHE SitE oF tHe CAs9-INdUced cHroMosomal Double-straNd bReAk. To determinE ThE optimal tiMe oF rAAV transduCtiOn, HSPCS wEre TRansdUceD with RAA

-flanked reporter cassette  and the e ndoge nou s I TG B2 t arge t gene are con c omit antly cleaved by Cas9,  thus  p r omot i ng  NHEJ -mediat e dt r ans ge ne  in se r ti on at  th e siteof the Cas 9-i nd uced chromos o ma l double-s tra nd break. To  de termin ethe optim altimeof rAA V  trans duction,HS P Cs wer e  transd u c ed  wit h rAA

-flanked reporter_cassette and_the endogenous ITGB2 target_gene are_concomitantly_cleaved by_Cas9,_thus promoting NHEJ-mediated_transgene insertion at_the site of the_Cas9-induced chromosomal double-strand_break._To determine the optimal time of rAAV transduction, HSPCs were transduced with rAA


and human HCC (n=139). The Jun-signature successfully discriminated human HCC into clusters displaying either WT or Jun-KO signatures. Notably, integration of the Jun signature with the human data revealed a clear and significant association of Jun-KO and Jun-WT signatures, respectively, with either Hepatocyte (HC)

and human HCC (n=139). The Jun - signature successfully discriminated human HCC into clusters displaying either WT or Jun - KO signature. Notably, consolidation of the Jun signature with the human data reveal a well-defined and significant association of Jun - KO and Jun - WT key signature, respectively, with either Hepatocyte (HC )

anf human HCC (n=139). The Jun-sigkature successfully disrriminafed humav HCC into clusters displayiig euther WT or Jun-KO signaturer. Notably, integrarion if the Jun signatuvz witg the iuman data revesled a cledr and signifiwavt association of Jun-KO and Jun-WT siggatures, rfspectively, wijh eiuhew Helatocyte (HC)

and human HCC (n=139). The Jun-signature successfully HCC clusters displaying WT or Jun-KO Jun with the human revealed a clear significant association of Jun-KO and Jun-WT respectively, with either Hepatocyte (HC)

and human HCC (n=139). The Jun-signatuRe successfUlly dIscRimInAted HumaN HCC into clusteRS disPlaying either WT or Jun-KO SignaTuREs. NoTAbLy, intEgratioN Of THE JuN sIgNatUrE WiTh the HumAn data rEvealed a clEar AnD significant ASsOciation of jun-kO and Jun-WT siGnaTures, rEsPecTIvely, WitH eithEr HepaTOcyte (Hc)

and human HCC (n=139). Th e Jun-sign ature  su cce ss full y di scriminated hu m an H CC into clusters displ aying  e i ther WT  or J un-KO s i gn a t ure s.  N ota bl y ,integ rat ion ofthe Jun si gna tu re with theh um an data re vea led a clearand  signi fi can t  asso cia tionof Jun - KO and  Jun-WT s ig n atures ,  respec t i ve ly,with either Hepat o cy t e (HC)

and_human HCC_(n=139). The Jun-signature successfully_discriminated human_HCC_into clusters_displaying_either WT or_Jun-KO signatures. Notably,_integration of the Jun_signature with the_human_data revealed a clear and significant association of Jun-KO and Jun-WT signatures, respectively, with_either_Hepatocyte (HC)


For ED4065, our mutant analysis implicates the orc4 gene as the locus of haploinsufficiency. This gene is well known as a key component of the Origin Recognition Complex, a multi-protein ensemble first identified for its role in loading replication origins with key proteins. However, in both flies

For ED4065, our mutant analysis implicates the orc4 gene as the locus of haploinsufficiency. This gene is well known as a cardinal part of the Origin Recognition Complex, a multi - protein corps de ballet first identified for its role in load replication origins with cardinal proteins. However, in both flies

Fog ED4065, our mutant analysis implicates the orc4 geie as tge locus of haploinsufficiency. This jene is wtjl known as a key zomponent of the Irigmn Recognition Complex, a multi-lvoteiu xnsemble first ldentified xor its role it uocding replication origins with key pwoteins. Hlwever, in both flits

For ED4065, our mutant analysis implicates the as locus of This gene is component the Origin Recognition a multi-protein ensemble identified for its role in loading origins with key proteins. However, in both flies

For ED4065, our mutant analysis impLicates the Orc4 geNe aS thE lOcus Of haPloinsufficienCY. ThiS gene is well known as a key CompoNeNT of tHE ORigin recogniTIoN cOmpLeX, a MulTi-PRoTein eNseMble firSt identifiEd fOr Its role in loaDInG replicatiOn oRigins with keY prOteins. hoWevER, in boTh fLies

For ED4065, our mutant an alysis imp licat esthe  o rc4gene  as the locuso f ha ploinsufficiency. This  gene  i s  wel l  k nownas a ke y  c o m pon en tofth e  O rigin  Re cogniti on Complex , a  m ulti-protein en semble fir stidentified f orits ro le  in loadi ngrepli cation origin s with ke yp rotein s . Howev e r ,in b oth flies

For_ED4065, our_mutant analysis implicates the_orc4 gene_as_the locus_of_haploinsufficiency. This gene_is well known_as a key component_of the Origin_Recognition_Complex, a multi-protein ensemble first identified for its role in loading replication origins with_key_proteins. However,_in_both_flies


for natural killer cells (Raet1a-e) and simultaneous repression of MHC-I. We confirmed these results using FACS analysis of hepatocytes isolated from 3-m-old dysplastic livers. However, the most dramatic changes of gene expression were found in tumors. The functional categories of differentially expressed genes involved translation

for natural killer cells (Raet1a - e) and coincident repression of MHC - I. We confirm these results using FACS psychoanalysis of hepatocytes isolated from 3 - thousand - old dysplastic livers. However, the about dramatic changes of gene expression were found in tumor. The running categories of differentially expressed gene involved translation

fog natural killer cells (Rxet1a-e) and simuljabeous cepressjon of MFC-I. We confirmed these resulvs uwing DACS analysis of hepatucytes isllated feom 3-n-ild dysplastic livcxs. Hoscver, chx most dramatic changes ox gene expresshov cere found in tumors. The functional sategoroed of differentyallj qxprsssed genes involved translation

for natural killer cells (Raet1a-e) and simultaneous MHC-I. confirmed these using FACS analysis dysplastic However, the most changes of gene were found in tumors. The functional of differentially expressed genes involved translation

for natural killer cells (Raet1A-e) and simulTaneoUs rEprEsSion Of MHc-I. We confirmed tHEse rEsults using FACS analysiS of hePaTOcytES iSolatEd from 3-m-OLd DYSplAsTiC liVeRS. HOweveR, thE most drAmatic chanGes Of Gene expressiON wEre found in TumOrs. The functiOnaL categOrIes OF diffEreNtialLy exprESsed geNes involvEd TRanslaTIon

for natural killer cells(Raet1a-e)  andsim ult an eous  rep ression of MHC - I. W e confirmed these resu lts u si n g FA C Sanaly sis ofh ep a t ocy te siso la t ed  from  3- m-old d ysplasticliv er s. However,t he  most dram ati c changes of  ge ne exp re ssi o n wer e f oundin tum o rs. Th e functio na l  categ o ries of d if fere ntially expressed ge n es involved tr anslat io n

for_natural killer_cells (Raet1a-e) and simultaneous_repression of_MHC-I._We confirmed_these_results using FACS_analysis of hepatocytes_isolated from 3-m-old dysplastic_livers. However, the_most_dramatic changes of gene expression were found in tumors. The functional categories of differentially_expressed_genes involved_translation


avita Singh (RTB) on a major surface antigen of infected red cells, viz., VAR2CSA. This protein is a member of the large PfEMP1 family and has been implicated in pregnancy associated malaria through binding to chondroitin sulfate A (CSA) in the placenta. Dr. Singh

avita Singh (RTB) on a major surface antigen of infected red cells, viz. , VAR2CSA. This protein is a extremity of the big PfEMP1 family and has been implicated in pregnancy associated malaria through bind to chondroitin sulfate A (CSA) in the placenta. Dr. Singh

aviha Singh (RTB) on a major rurface antigen of infxcted rsd cells, viz., VAR2CSA. This protein is e menber if the large PfEMP1 famkly and hws been umplmcated in pregnaidy assognated lalaxie through bindikg to chondsoitin sulfate A (CDA) in the placenta. Dr. Singh

avita Singh (RTB) on a major surface infected cells, viz., This protein is PfEMP1 and has been in pregnancy associated through binding to chondroitin sulfate A in the placenta. Dr. Singh

avita Singh (RTB) on a major surfAce antigen Of infEctEd rEd CellS, viz., vAR2CSA. This protEIn is A member of the large PfEMP1 FamilY aND has BEeN implIcated iN PrEGNanCy AsSocIaTEd MalarIa tHrough bInding to chOndRoItin sulfate A (csA) In the placeNta. dr. Singh

avita Singh (RTB) on a maj or surface  anti gen  of  i nfec tedred cells, viz . , VA R2CSA. This protein is  a me mb e r of th e lar ge PfEM P 1f a mil yan d h as be en im pli cated i n pregnanc y a ss ociated mala r ia  through b ind ing to chond roi tin su lf ate A (CS A)in th e plac e nta. D r. Singh

avita Singh_(RTB) on_a major surface antigen_of infected_red_cells, viz.,_VAR2CSA._This protein is_a member of_the large PfEMP1 family_and has been_implicated_in pregnancy associated malaria through binding to chondroitin sulfate A (CSA) in the placenta._Dr._Singh


the interaction of naive T cells with foreign antigen ligands in the form of oligomers of foreign peptide-MHC class II molecule complexes (pMHC tetramers), we have made the remarkable finding that the affinity of TCRs for self-ligand as determined in the thymus during positive selection directly correlates with the

the interaction of naive T cells with foreign antigen ligand in the human body of oligomers of foreign peptide - MHC class II atom complexes (pMHC tetramers), we have make the remarkable finding that the affinity of TCRs for self - ligand equally specify in the thymus during convinced selection directly correlate with the

thf interaction of naive T cells with forgitn antmgen lifands in the form of oligomers of foceigb pepupde-MHC class II molecjle complvxes (pMHC tetcamers), we have mese the vzmarkznle fnnving that the anfinity of DCRs for self-lhgxnb as determined in the thymus during positife selection dirgctly sorrslates with the

the interaction of naive T cells with ligands the form oligomers of foreign (pMHC we have made remarkable finding that affinity of TCRs for self-ligand as in the thymus during positive selection directly correlates with the

the interaction of naive T celLs with foreIgn anTigEn lIgAnds In thE form of oligomeRS of fOreign peptide-MHC class Ii moleCuLE comPLeXes (pMhC tetraMErS), WE haVe MaDe tHe REmArkabLe fInding tHat the affiNitY oF TCRs for self-LIgAnd as deterMinEd in the thymuS duRing poSiTivE SelecTioN direCtly coRRelateS with the

the interaction of naiveT cells wi th fo rei gnan tige n li gands in the f o rm o f oligomers of foreign  pept id e -MHC cl ass I I molec u le c omp le xe s ( pM H Ctetra mer s), wehave madethe  r emarkable fi n di ng that th e a ffinity of T CRs  for s el f-l i gandasdeter minedi n thethymus du ri n g posi t ive sel e c ti on d irectly correlate s  w i th the

the_interaction of_naive T cells with_foreign antigen_ligands_in the_form_of oligomers of_foreign peptide-MHC class_II molecule complexes (pMHC_tetramers), we have_made_the remarkable finding that the affinity of TCRs for self-ligand as determined in the_thymus_during positive_selection_directly_correlates with the


2 may play an important role in social behavior; recent work in other laboratories support this view. To gain further insight into the molecular profile of CA2 neurons, we used RNAseq to measure mRNA from specific cellular compartments of tissue isolated by LCM. These studies have revealed that CA2 neurons express an unusually large number of

2 may play an important role in social behavior; late workplace in other laboratories confirm this opinion. To gain further insight into the molecular visibility of CA2 neurons, we used RNAseq to measure mRNA from specific cellular compartment of tissue isolated by LCM. These studies have reveal that CA2 neurons express an unusually big number of

2 maj play an important role in social beharuor; rerent wodk in otfer laboratories support thid ciew. Uj gain further inskght into the molwculer profile of CA2 neurons, we ussf RNCsxq to measure mTNA from spewific cellular cum'artments of tissue isolated by LCM. Ehese syufies have revewled ehat BA2 neurons express an unusually large iumber of

2 may play an important role in recent in other support this view. the profile of CA2 we used RNAseq measure mRNA from specific cellular compartments tissue isolated by LCM. These studies have revealed that CA2 neurons express an large number of

2 may play an important role in sOcial behavIor; reCenT woRk In otHer lAboratories supPOrt tHis view. To gain further inSight InTO the MOlEculaR profilE Of ca2 NeuRoNs, We uSeD rNaseq tO meAsure mRnA from specIfiC cEllular compaRTmEnts of tissUe iSolated by LCM. theSe studIeS haVE reveAleD that cA2 neurONs exprEss an unusUaLLy largE Number oF

2 may play an important ro le in soci al be hav ior ;rece nt w ork in other l a bora tories support this vi ew. T og ainf ur therinsight in t o  th emo lec ul a rprofi leof CA2neurons, w e u se d RNAseq tom ea sure mRNAfro m specific c ell ular c om par t ments  of  tiss ue iso l ated b y LCM. Th es e  studi e s haver e ve aled  that CA2 neurons ex p ress an unusua lly la rg e  n u m ber  of

2 may_play an_important role in social_behavior; recent_work_in other_laboratories_support this view._To gain further_insight into the molecular_profile of CA2_neurons,_we used RNAseq to measure mRNA from specific cellular compartments of tissue isolated by_LCM._These studies_have_revealed_that CA2 neurons express an_unusually large number of


or marine mammals. To facilitate interpretation of experimental data on polychlorinated biphenyl (PCB) toxicity, we determined whether the PCB doses used in animal experiments result in tissue levels that were comparable to those observed in background-exposed humans. We identified 8 animal studies in which PCB tissue levels had been measured after oral

or marine mammals. To facilitate interpretation of experimental datum on polychlorinated biphenyl (PCB) perniciousness, we determine whether the PCB doses use in animal experiment result in tissue levels that were comparable to those respect in background - exposed world. We identified 8 animal studies in which PCB tissue level had been measured after oral

or marine mammals. To facilltate interpretajiin of xxperimsntal daga on polychlorinated biphenbl (PXB) tozicity, we determined wfether thv PCB dosws uwwd in animem experlienta resblv in tissue levgls that wera comparable tm ghlse observed in background-exposed htmans. Wr ldentified 8 anymal ftudjvs in which PCB tissue levels hzd been measured aftrr oral

or marine mammals. To facilitate interpretation of on biphenyl (PCB) we determined whether animal result in tissue that were comparable those observed in background-exposed humans. We 8 animal studies in which PCB tissue levels had been measured after oral

or marine mammals. To facilitaTe interpreTatioN of ExpErImenTal dAta on polychlorINateD biphenyl (PCB) toxicity, we DeterMiNEd whEThEr the pCB doseS UsED In aNiMaL exPeRImEnts rEsuLt in tisSue levels tHat WeRe comparable TO tHose observEd iN background-eXpoSed humAnS. We IDentiFieD 8 animAl studIEs in whIch PCB tisSuE Levels HAd been mEASuRed aFter oral

or marine mammals. To fac ilitate in terpr eta tio nof e xper imental data o n  pol ychlorinated biphenyl(PCB)  t o xici t y,  we d etermin e dw h eth er  t hePC B  d osesuse d in an imal exper ime nt s result int is sue levels  th at were comp ara ble to  t hos e  obse rve d inbackgr o und-ex posed hum an s . We i d entifie d 8anim al studies in whi c hP CB tissue leve ls had  b e en m eas ure d after or al

or_marine mammals._To facilitate interpretation of_experimental data_on_polychlorinated biphenyl_(PCB)_toxicity, we determined_whether the PCB_doses used in animal_experiments result in_tissue_levels that were comparable to those observed in background-exposed humans. We identified 8 animal_studies_in which_PCB_tissue_levels had been measured after_oral


is to understand how cellular process work at the molecular scale. To accomplish this, current tools were inadequate. Thus, we focused on the development and application of new imaging methods to uncover the structure of molecules and organelles inside cells. In my group we continue to pioneer four novel imaging technologies. These include, 1) high

is to understand how cellular process work at the molecular scale. To carry through this, current creature were inadequate. Thus, we focused on the development and lotion of new imaging methods to uncover the social organization of atom and organelles inside cell. In my group we continue to pioneer four fresh imaging technologies. These include, 1) high

is to understand how celluuar process work at thx molechlar scaue. To accomplish this, currenv toils wtge inadequate. Thus, we focused ln the dwvelipment and elplicatljn or new mmaging methods to uncoves the structura uf molecules and organelles inside cejls. In ky group we contynue eo pjoneer four novel imaging technolofies. Thtse include, 1) high

is to understand how cellular process work molecular To accomplish current tools were the and application of imaging methods to the structure of molecules and organelles cells. In my group we continue to pioneer four novel imaging technologies. These 1) high

is to understand how cellular Process worK at thE moLecUlAr scAle. TO accomplish thiS, CurrEnt tools were inadequate. thus, wE fOCuseD On The deVelopmeNT aND AppLiCaTioN oF NeW imagIng Methods To uncover tHe sTrUcture of moleCUlEs and organEllEs inside cellS. In My grouP wE coNTinue To pIoneeR four nOVel imaGing technOlOGies. ThESe incluDE, 1) HiGh

is to understand how cell ular proce ss wo rkatth e mo lecu lar scale. Toa ccom plish this, current to ols w er e  ina d eq uate.  Thus,w ef o cus ed  o n t he de velop men t and a pplication  of  n ew imaging m e th ods to unc ove r the struct ure  of mo le cul e s and  or ganel les in s ide ce lls. In m yg roup w e  contin u e  t o pi oneer four noveli ma g ing technologi es. Th es e  i n c lud e,1) high

is_to understand_how cellular process work_at the_molecular_scale. To_accomplish_this, current tools_were inadequate. Thus,_we focused on the_development and application_of_new imaging methods to uncover the structure of molecules and organelles inside cells. In_my_group we_continue_to_pioneer four novel imaging technologies._These include, 1) high


associated with the steepest declines in BMIz (p <.001) and fat mass (p <=.03). Thus, in obesity-prone adolescent girls, IPT was associated with improvements in BMIz over 3 years among youth with high social-adjustment problems or trait anxiety. Future studies are planned to

associated with the steepest declines in BMIz (p < .001) and fat mass (phosphorus < = .03). therefore, in fleshiness - prone adolescent girls, IPT was associated with improvements in BMIz over 3 long time among youth with high social - alteration problems or trait anxiety. Future studies are plan to

asdociated with the steepert declines in YNIz (p <.001) and fzt mass (o <=.03). Thus, in obesity-prone adolxscebt giels, IPT was associated with impgovements in UMIz over 3 years among youth wjbh hiyh social-adjustmgnt problems or trait anxiath. Yuture studies are planned to

associated with the steepest declines in BMIz and mass (p Thus, in obesity-prone with in BMIz over years among youth high social-adjustment problems or trait anxiety. studies are planned to

associated with the steepest Declines in bMIz (p <.001) And Fat MaSs (p <=.03). THus, iN obesity-prone aDOlesCent girls, IPT was associaTed wiTh IMproVEmEnts iN BMIz ovER 3 yEARs aMoNg YouTh WItH high SocIal-adjuStment probLemS oR trait anxietY. fuTure studieS arE planned to

associated with the steep est declin es in  BM Iz(p  <.0 01)and fat mass ( p  <=. 03). Thus, in obesity- prone  a d oles c en t gir ls, IPT wa s ass oc ia ted  w i th  impr ove ments i n BMIz ove r 3  y ears among y o ut h with hig h s ocial-adjust men t prob le mso r tra itanxie ty. Fu t ure st udies are  p l annedt o

associated_with the_steepest declines in BMIz_(p <.001)_and_fat mass_(p_<=.03). Thus, in_obesity-prone adolescent girls,_IPT was associated with_improvements in BMIz_over_3 years among youth with high social-adjustment problems or trait anxiety. Future studies are_planned_to


? end of ORFs. Experiments based on the production of new integration events revealed that the association of Tf1 with LTRs was the result of integration preference. To define the determinants of the target sites we developed an in vivo assay for integration using a plasmid that contained ade6 as the target and a plasmid

? end of ORFs. Experiments based on the production of newfangled consolidation events revealed that the affiliation of Tf1 with LTRs was the result of consolidation preference. To define the determinant of the target sites we develop an in vivo assay for integration using a plasmid that contain ade6 as the target and a plasmid

? enf of ORFs. Experiments bared on the prodocrion oh new ihtegratiun events revealed that the essoxiatiin of Tf1 with LTRs was the resupt of inregretion preference. To defikz the fetexmmnants of the tsrget sitev we developed av nn vivo assay for integration using w plasmod that containeq adt6 af ths target and a plasmid

? end of ORFs. Experiments based on of integration events that the association the of integration preference. define the determinants the target sites we developed an vivo assay for integration using a plasmid that contained ade6 as the target a plasmid

? end of ORFs. Experiments based On the produCtion Of nEw iNtEgraTion Events revealed THat tHe association of Tf1 with LtRs waS tHE resULt Of intEgratioN PrEFEreNcE. TO deFiNE tHe detErmInants oF the target SitEs We developed aN In Vivo assay fOr iNtegration usIng A plasmId ThaT ContaIneD ade6 aS the taRGet and A plasmid

? end of ORFs. Experiments  based onthe p rod uct io n of  new  integration e v ents  revealed that the ass ociat io n  ofT f1  with  LTRs w a st h e r es ul t o fi nt egrat ion  prefer ence. To d efi ne  the determi n an ts of thetar get sites we  de velope dani n viv o a ssayfor in t egrati on usingap lasmid that co n t ai nedade6 as the targe t  a n d a plasmid

? end_of ORFs._Experiments based on the_production of_new_integration events_revealed_that the association_of Tf1 with_LTRs was the result_of integration preference._To_define the determinants of the target sites we developed an in vivo assay for_integration_using a_plasmid_that_contained ade6 as the target_and a plasmid


focused on the role of the Rac guanine nucleotide exchange factor, -PIX, documenting its depletion from FA during myosin-mediated FA maturation and its role in negative regulation of FA maturation to promote rapid FA turnover, lamellipodial protrusion and fast cell migration. A mthods paper describing our method was

focused on the role of the Rac guanine nucleotide exchange factor, -PIX, documenting its depletion from FA during myosin - intercede FA growth and its role in negative regulation of FA festering to promote rapid FA turnover, lamellipodial bulge and fast cell migration. A mthods paper describe our method was

fofused on the role of the Rac guanine nueoeotidx exchahge factur, -PIX, documenting its deplevion from FA during myosin-mediaged FA manuration qnd mts role in negavjve regmjatikk of YA maturation to promote rdpid FA turnovar, lcmellipodial protrusion and fast celj migrayiln. A mthods paker dtscwibihg our method was

focused on the role of the Rac exchange -PIX, documenting depletion from FA its in negative regulation FA maturation to rapid FA turnover, lamellipodial protrusion and cell migration. A mthods paper describing our method was

focused on the role of the Rac gUanine nuclEotidE exChaNgE facTor, -PiX, documenting iTS depLetion from FA during myosIn-medIaTEd FA MAtUratiOn and itS RoLE In nEgAtIve ReGUlAtion Of Fa maturaTion to promOte RaPid FA turnoveR, LaMellipodiaL prOtrusion and fAst Cell miGrAtiON. A mthOds Paper DescriBIng our Method was

focused on the role of th e Rac guan ine n ucl eot id e ex chan ge factor, -PI X , do cumenting its depletio n fro mF A du r in g myo sin-med i at e d  FA  m at ura ti o nand i tsrole in  negativereg ul ation of FAm at uration to  pr omote rapidFAturnov er , l a melli pod ial p rotrus i on and  fast cel lm igrati o n. A mt h o ds  pap er describing our me t hod was

focused_on the_role of the Rac_guanine nucleotide_exchange_factor, -PIX,_documenting_its depletion from_FA during myosin-mediated_FA maturation and its_role in negative_regulation_of FA maturation to promote rapid FA turnover, lamellipodial protrusion and fast cell migration._A_mthods paper_describing_our_method was


-inflammatory function as suggested by others. The results also suggest that EpCAM may be anti-adhesive, rather than pro-adhesive as previously suggested. In studies that are ongoing, we are additionally characterizing the role of EpCAM in Langerhans cell-keratinocyte interactions and in additional immune

-inflammatory function as suggested by others. The results also indicate that EpCAM may be anti - adhesive, preferably than pro - adhesive as previously suggested. In studies that are ongoing, we are additionally characterizing the character of EpCAM in Langerhans cell - keratinocyte interactions and in extra immune

-infpammatory function as sungested by others. The rxsults zlso sugeest that EpCAM may be anti-avhesuve, rqther than pro-adhesive as previlusly sutgesued. In studies thef are okyoing, ae axe additionally gharacterizhng the role ox DpEAM in Langerhans cell-keratinocyte igteractoojs and in addijionak immhne

-inflammatory function as suggested by others. The suggest EpCAM may anti-adhesive, rather than studies are ongoing, we additionally characterizing the of EpCAM in Langerhans cell-keratinocyte interactions in additional immune

-inflammatory function as sugGested by otHers. THe rEsuLtS alsO sugGest that EpCAM mAY be aNti-adhesive, rather than pRo-adhEsIVe as PReViousLy suggeSTeD. iN stUdIeS thAt ARe OngoiNg, wE are addItionally cHarAcTerizing the rOLe Of EpCAM in LAngErhans cell-keRatInocytE iNteRActioNs aNd in aDditioNAl immuNe

-inflammatory function assuggestedby ot her s.Th e re sult s also suggest that  EpCAM may be anti-adh esive ,r athe r  t han p ro-adhe s iv e aspr ev iou sl y  s ugges ted . In st udies that  ar eongoing, wea re  additiona lly  characteriz ing  the r ol e o f  EpCA M i n Lan gerhan s  cell- keratinoc yt e  inter a ctionsa n din a dditional immune

-inflammatory function_as suggested_by others. The results_also suggest_that_EpCAM may_be_anti-adhesive, rather than_pro-adhesive as previously_suggested. In studies that_are ongoing, we_are_additionally characterizing the role of EpCAM in Langerhans cell-keratinocyte interactions and in additional immune


Vpu protein indicating that CBF regulates Vif expression post-transcriptionally. Kinetic studies revealed effects of CBF both on metabolic stability and on the rate of Vif biosynthesis. These effects were dependent on the ability of CBF to interact with Vif pointing to a chaperone function of CBF. Importantly

Vpu protein indicating that CBF regulates Vif expression post - transcriptionally. energizing cogitation revealed effect of CBF both on metabolic constancy and on the rate of Vif biosynthesis. These effects were dependent on the ability of CBF to interact with Vif bespeak to a chaperone function of CBF. Importantly

Vpk protein indicating thau CBF regulates Vnd exprxssion lost-tranrcriptionally. Kinetic studied eeveaoed effects of CBF botf on metaholic stqbilmty and on the refe of Vly bioannthevms. These effectx were depandent on the dbklnty of CBF to interact with Vif poineing to a chaperone funstiom of DBF. Importantly

Vpu protein indicating that CBF regulates Vif Kinetic revealed effects CBF both on rate Vif biosynthesis. These were dependent on ability of CBF to interact with pointing to a chaperone function of CBF. Importantly

Vpu protein indicating that CbF regulateS Vif eXprEssIoN posT-traNscriptionally. kInetIc studies revealed effecTs of CbF BOth oN MeTabolIc stabiLItY ANd oN tHe RatE oF viF biosYntHesis. ThEse effects WerE dEpendent on thE AbIlity of CBF To iNteract with VIf pOintinG tO a cHAperoNe fUnctiOn of CBf. importAntly

Vpu protein indicating th at CBF reg ulate s V ifex pres sion  post-transcri p tion ally. Kinetic studiesrevea le d  eff e ct s ofCBF bot h  o n met ab ol icst a bi lityand  on the  rate of V ifbi osynthesis.T he se effects  we re dependent  on  the a bi lit y  of C BFto in teract with V if pointi ng to a c h aperone f un ctio n of CBF. Importa n tl y

Vpu_protein indicating_that CBF regulates Vif_expression post-transcriptionally._Kinetic_studies revealed_effects_of CBF both_on metabolic stability_and on the rate_of Vif biosynthesis._These_effects were dependent on the ability of CBF to interact with Vif pointing to_a_chaperone function_of_CBF._Importantly


shown to be related to immunologic and pro-inflammatory factors. Circulating microbial products such as LPS and markers associated with microbial translocation have been shown to play an important role in disease pathogenesis of certain infections like HIV. Similarly, proteins associated with the acute phase response and related cytokines also play an important role in pathogenesis. We

shown to be related to immunologic and pro - inflammatory divisor. circulate microbial products such as LPS and markers associated with microbial translocation have been prove to play an important function in disease pathogenesis of certain infections like HIV. Similarly, protein consociate with the acute phase reply and related cytokines also toy an important role in pathogenesis. We

shlwn to be related to immmnologic and pro-nbflammetory fzctors. Ckrculating microbial productd wuch qs LPS and markers assuciated wpth microvial rranslocatmkn have been amown co play an imporjant role in disease pathocevedis of certain infections like HIV. Fimilarky, proteins assosiattd rith nht acute phase response and relates cytokpnes also play an important role in pathogejesid. We

shown to be related to immunologic and Circulating products such LPS and markers been to play an role in disease of certain infections like HIV. Similarly, associated with the acute phase response and related cytokines also play an important in pathogenesis. We

shown to be related to immunolOgic and pro-InflaMmaTorY fActoRs. CiRculating microBIal pRoducts such as LPS and marKers aSsOCiatED wIth miCrobial TRaNSLocAtIoN haVe BEeN showN to Play an iMportant roLe iN dIsease pathogENeSis of certaIn iNfections likE HIv. SimilArLy, pROteinS asSociaTed witH The acuTe phase reSpONse and RElated cYTOkInes Also play an importaNT rOLe in pathogenesIs. We

shown to be related to im munologicand p ro- inf la mmat oryfactors. Circu l atin g microbial products s uch a sL PS a n dmarke rs asso c ia t e d w it hmic ro b ia l tra nsl ocation  have been  sh ow n to play an im portant ro lein disease p ath ogenes is  of certa ininfec tionsl ike HI V. Simila rl y , prot e ins ass o c ia tedwith the acute ph a se response and r elated  c y to k i nes  al so play an  i mport a nt role in p a tho g enesis. We

shown_to be_related to immunologic and_pro-inflammatory factors._Circulating_microbial products_such_as LPS and_markers associated with_microbial translocation have been_shown to play_an_important role in disease pathogenesis of certain infections like HIV. Similarly, proteins associated with_the_acute phase_response_and_related cytokines also play an_important role in pathogenesis. We


used transgenic rescue constructs containing genes from the region that were wildtype or individually mutated. This showed that, for ED1, the critical gene is glutathione-S-transferase S1 (GstS1). In Drosophila this enzyme functions as an antioxidant, implicating redox regulation as an important contributor to anesthetic sensitivity.

used transgenic rescue constructs containing genes from the area that were wildtype or individually mutate. This show that, for ED1, the critical gene is glutathione - S - transferase S1 (GstS1). In Drosophila this enzyme function as an antioxidant, entail redox regulation as an important subscriber to anesthetic sensitivity.

usfd transgenic rescue conrtructs containnbg genxs from the regkon that were wildtype or invivieuallt mutated. This showed ghat, for VD1, the cruticel gene is glutavgione-S-tvcnsfedwse V1 (GstS1). In Drosokhila this etzyme functionv xs an antioxidant, implicating redox rqgulatipn as an importagt cpgtrigltir to anesthetic sensitivity.

used transgenic rescue constructs containing genes from that wildtype or mutated. This showed gene glutathione-S-transferase S1 (GstS1). Drosophila this enzyme as an antioxidant, implicating redox regulation an important contributor to anesthetic sensitivity.

used transgenic rescue constRucts contaIning GenEs fRoM the RegiOn that were wildTYpe oR individually mutated. ThIs shoWeD That, FOr eD1, the CriticaL GeNE Is gLuTaThiOnE-s-tRansfEraSe S1 (GstS1). in DrosophiLa tHiS enzyme functIOnS as an antioXidAnt, implicatiNg rEdox reGuLatIOn as aN imPortaNt contRIbutor To anestheTiC SensitIVity.

used transgenic rescue co nstructs c ontai nin g g en es f romthe region tha t  wer e wildtype or individu allymu t ated .  T his s howed t h at , for  E D1 , t he cr itica l g ene isglutathion e-S -t ransferase S 1  ( GstS1). In  Dr osophila thi s e nzymefu nct i ons a s a n ant ioxida n t, imp licatingre d ox reg u lationa s  a n im portant contribut o rt o anesthetic s ensiti vi t y.

used_transgenic rescue_constructs containing genes from_the region_that_were wildtype_or_individually mutated. This_showed that, for_ED1, the critical gene_is glutathione-S-transferase S1_(GstS1)._In Drosophila this enzyme functions as an antioxidant, implicating redox regulation as an important_contributor_to anesthetic_sensitivity.


self-renewing stem cell population and a quiescent stem cell population. The self-renewing stem cells highly express Lgr5 and reside between Paneth cells at the crypt base where Wnt signaling is active whereas quiescent stem cells express Bmi1 and reside at the position 4. Thus the lineage-specific precursor

self - renewing stem cell population and a quiescent stem cellular telephone population. The self - regenerate stem cells highly carry Lgr5 and rest between Paneth cells at the crypt base where Wnt bespeak is active whereas quiescent bow cells carry Bmi1 and reside at the position 4. therefore the lineage - specific precursor

sepf-renewing stem cell popmlation and a qunwscent stem dell popjlation. The self-renewing stel xells highly express Lgr5 ana reside hetween Paneuh cells at the ccgpt basc whedc Wnt wignaling is agtive whereds quiescent sdeo eells express Bmi1 and reside at the [ositiom 4. Thus the linewge-skecyfic irtcursor

self-renewing stem cell population and a quiescent population. self-renewing stem highly express Lgr5 at crypt base where signaling is active quiescent stem cells express Bmi1 and at the position 4. Thus the lineage-specific precursor

self-renewing stem cell populAtion and a qUiescEnt SteM cEll pOpulAtion. The self-reNEwinG stem cells highly expresS Lgr5 aNd REsidE BeTween paneth cELlS AT thE cRyPt bAsE WhEre WnT siGnaling Is active whEreAs Quiescent steM CeLls express bmi1 And reside at tHe pOsitioN 4. THus THe linEagE-specIfic prECursor

self-renewing stem cell p opulationand a  qu ies ce nt s temcell populatio n . Th e self-renewing stem c ellshi g hlye xp ressLgr5 an d  r e s ide  b et wee nP an eth c ell s at th e crypt ba sewh ere Wnt sign a li ng is acti vewhereas quie sce nt ste mcel l s exp res s Bmi 1 andr esideat the po si t ion 4. Thus th e li neag e-specific precur s or

self-renewing_stem cell_population and a quiescent_stem cell_population._The self-renewing_stem_cells highly express_Lgr5 and reside_between Paneth cells at_the crypt base_where_Wnt signaling is active whereas quiescent stem cells express Bmi1 and reside at the_position_4. Thus_the_lineage-specific_precursor


M as well as in eggs and chickens. In AGM, two doses of NDV-HA induced a substantial titer of HPAIV-neutralizing serum antibodies;in addition, a substantial respiratory mucosal IgA response was induced following one and two doses, which would be particularly important in controlling a respiratory pathogen. We

M as well as in eggs and chickens. In AGM, two venereal disease of NDV - HA induce a substantial titer of HPAIV - neutralizing serum antibodies;in addition, a hearty respiratory mucosal IgA response was induced surveil one and two doses, which would be particularly significant in controlling a respiratory pathogen. We

M ad well as in eggs and chlckens. In AGM, two doses of NDB-HA induzed a substantial titer of H'AIV-beutrqlizing serum antibodids;in addinion, a suvstaitial respiratorb mucosal IgA dcsponvx was induced fpllowing ote and two dosas, wkich would be particularly important in conyrllling a respitatorj [athkgen. We

M as well as in eggs and AGM, doses of induced a substantial addition, substantial respiratory mucosal response was induced one and two doses, which would particularly important in controlling a respiratory pathogen. We

M as well as in eggs and chickenS. In AGM, two dOses oF NDv-HA InDuceD a suBstantial titer OF HPAiV-neutralizing serum antIbodiEs;IN addITiOn, a suBstantiAL rESPirAtOrY muCoSAl igA reSpoNse was iNduced follOwiNg One and two dosES, wHich would bE paRticularly imPorTant in CoNtrOLling A reSpiraTory paTHogen. WE

M as well as in eggs and c hickens. I n AGM , t wodo sesof N DV-HA induceda  sub stantial titer of HPAI V-neu tr a lizi n gserum  antibo d ie s ; inad di tio n, asubst ant ial res piratory m uco sa l IgA respon s ewas induce d f ollowing one  an d twodo ses ,  whic h w ouldbe par t icular ly import an t  in co n trollin g aresp iratory pathogen. We

M as_well as_in eggs and chickens._In AGM,_two_doses of_NDV-HA_induced a substantial_titer of HPAIV-neutralizing_serum antibodies;in addition, a_substantial respiratory mucosal_IgA_response was induced following one and two doses, which would be particularly important in_controlling_a respiratory_pathogen._We


ords a unique opportunity to prospectively study lagged effects of three types of cognitive interventions on functional decline in this well-characterized cohort that, given its advancing age, is now at imminent risk for both IADL and ADL decline. We will be able to test the basic question in this study: For older adults

ords a unique opportunity to prospectively study lagged effects of three type of cognitive interposition on functional decline in this well - characterized age group that, given its advancing age, is nowadays at imminent risk for both IADL and ADL decay. We will be able to test the basic question in this sketch: For older adults

ordd a unique opportunity tu prospectively study nagged effects of three types of cognitive ibtervtutions on functional decline pn this wwll-ciaracterized cohort that, given lts abvencing age, is npw at immitent risk for togh IADL and ADL decline. We will be abje to trsh the basic qugstiom in fhis study: For older adults

ords a unique opportunity to prospectively study of types of interventions on functional that, its advancing age, now at imminent for both IADL and ADL decline. will be able to test the basic question in this study: For older

ords a unique opportunity to pRospectiveLy stuDy lAggEd EffeCts oF three types of cOGnitIve interventions on funcTionaL dEClinE In This wEll-charACtERIzeD cOhOrt ThAT, gIven iTs aDvancinG age, is now aT imMiNent risk for bOTh iADL and ADL DecLine. We will be AblE to tesT tHe bASic quEstIon in This stUDy: For oLder adultS

ords a unique opportunityto prospec tivel y s tud ylagg ed e ffects of thre e  typ es of cognitive interv entio ns on f u nc tiona l decli n ei n  th is  w ell -c h ar acter ize d cohor t that, gi ven  i ts advancing ag e, is nowatimminent ris k f or bot hIAD L  andADL  decl ine. W e  willbe able t ot est th e  basicq u es tion  in this study: F o ro lder adults

ords a_unique opportunity_to prospectively study lagged_effects of_three_types of_cognitive_interventions on functional_decline in this_well-characterized cohort that, given_its advancing age,_is_now at imminent risk for both IADL and ADL decline. We will be able_to_test the_basic_question_in this study: For older_adults


with GluR1, as well as their multi-meric structure. 5. Compensatory endocytosis is a distinct form of endocytosis that compensates for exocytotic activity. It plays an essential role in the maintenance of cell surface homeostasis. In our fifth project we have developed a new imaging based assay for testing

with GluR1, as well as their multi - meric structure. 5. Compensatory endocytosis is a distinct form of endocytosis that cover for exocytotic natural process. It plays an essential role in the alimony of cell surface homeostasis. In our fifth undertaking we have developed a new imaging establish assay for testing

wihh GluR1, as well as their multi-meric strocrure. 5. Rompensztory enaocytosis is a distinct form od endicytosis that compensages for eqocytotic actmvity. It plays ai essentlcl romc in chx maintenance on cell surfdce homeostasiv. Kn our fifth project we have developeq a new ilaging based afsay sor fvsuing

with GluR1, as well as their multi-meric Compensatory is a form of endocytosis It an essential role the maintenance of surface homeostasis. In our fifth project have developed a new imaging based assay for testing

with GluR1, as well as their multI-meric struCture. 5. comPenSaTory EndoCytosis is a distINct fOrm of endocytosis that coMpensAtES for EXoCytotIc activITy. iT PlaYs An EssEnTIaL role In tHe maintEnance of ceLl sUrFace homeostaSIs. in our fifth ProJect we have deVelOped a nEw ImaGIng baSed Assay For tesTIng

with GluR1, as well as th eir multi- meric  st ruc tu re.5. C ompensatory en d ocyt osis is a distinct for m ofen d ocyt o si s tha t compe n sa t e s f or  e xoc yt o ti c act ivi ty. Itplays an e sse nt ial role int he  maintenan ceof cell surf ace  homeo st asi s . Inour  fift h proj e ct wehave deve lo p ed a n e w imagi n g  b ased  assay for testin g

with_GluR1, as_well as their multi-meric_structure. 5._Compensatory_endocytosis is_a_distinct form of_endocytosis that compensates_for exocytotic activity. It_plays an essential_role_in the maintenance of cell surface homeostasis. In our fifth project we have developed_a_new imaging_based_assay_for testing


with age, there are global and regional changes in cortical volume, thickness and surface area. Age-related atrophy, in most cortical regions was indicated by a reduction in thickness however, most striking was that the prefrontal cortex showed a reduced thickness, surface area, in addition to volume which confirmed previously published reports. Interestingly, the

with age, there are global and regional changes in cortical bulk, thickness and open area. Age - related atrophy, in most cortical area was indicated by a reduction in thickness however, about striking was that the prefrontal cortex showed a boil down thickness, surface area, in summation to volume which confirmed previously published reputation. Interestingly, the

wihh age, there are global xnd regional chcbges ii cortidal voluoe, thickness and surface aree. Agw-relauvd atrophy, in most coftical rehions waw invicated by a redndtion ik thidnnesv however, most xtriking wds that the praffoutal cortex showed a reduced thicknefs, surfscf area, in addijion uo dolujv chich confirmed previously publjshed rtports. Interestingky, the

with age, there are global and regional cortical thickness and area. Age-related atrophy, indicated a reduction in however, most striking that the prefrontal cortex showed a thickness, surface area, in addition to volume which confirmed previously published reports. Interestingly,

with age, there are global and rEgional chaNges iN coRtiCaL volUme, tHickness and surFAce aRea. Age-related atrophy, in Most cOrTIcal REgIons wAs indicATeD BY a rEdUcTioN iN ThIckneSs hOwever, mOst strikinG waS tHat the prefroNTaL cortex shoWed A reduced thicKneSs, surfAcE arEA, in adDitIon to Volume WHich coNfirmed prEvIOusly pUBlished REPoRts. INterestingly, the

with age, there are globa l and regi onalcha nge sin c orti cal volume, th i ckne ss and surface area. A ge-re la t ed a t ro phy,in most co r t ica lre gio ns wa s ind ica ted bya reductio n i nthickness ho w ev er, most s tri king was tha t t he pre fr ont a l cor tex  show ed a r e ducedthickness ,s urface area, i n ad diti on to volume whic h  c o nfirmed previo usly p ub l is h e d r epo rts. Inter es tingl y , the

with_age, there_are global and regional_changes in_cortical_volume, thickness_and_surface area. Age-related_atrophy, in most_cortical regions was indicated_by a reduction_in_thickness however, most striking was that the prefrontal cortex showed a reduced thickness, surface_area,_in addition_to_volume_which confirmed previously published reports._Interestingly, the


are gammaretroviruses linked to induction of neoplasms and to neurological and immunodeficiency diseases. Inbred strains of laboratory mice and wild mouse species differ in their susceptibility to mouse gammaretrovirus infection and to virus-induced diseases, and they also differ in the types of MLVs that they carry. Susceptibility

are gammaretroviruses linked to induction of neoplasms and to neurological and immunodeficiency diseases. Inbred tune of lab mice and wild mouse coinage differ in their susceptibility to mouse gammaretrovirus infection and to virus - induce diseases, and they also disagree in the type of MLVs that they carry. Susceptibility

arf gammaretroviruses linktd to induction oy neoplesms ans to neufological and immunodeficienry duseastf. Inbred strains ow laboratlry mice and qild mouse species diffed in chxir susceptibillty to mousa gammaretrovisur nnfection and to virus-induced diseasqs, and yhfy also differ in uhe typss of MLVs that they carry. Susceptjbility

are gammaretroviruses linked to induction of neoplasms neurological immunodeficiency diseases. strains of laboratory differ their susceptibility to gammaretrovirus infection and virus-induced diseases, and they also differ the types of MLVs that they carry. Susceptibility

are gammaretroviruses linkeD to inductiOn of nEopLasMs And tO neuRological and imMUnodEficiency diseases. InbreD straInS Of laBOrAtory Mice and WIlD MOusE sPeCieS dIFfEr in tHeiR suscepTibility to MouSe GammaretroviRUs Infection aNd tO virus-induceD diSeases, AnD thEY also DifFer in The typES of MLVS that they CaRRy. SuscEPtibiliTY

are gammaretroviruses lin ked to ind uctio n o f n eo plas ms a nd to neurolog i caland immunodeficiency d iseas es .  Inb r ed  stra ins ofl ab o r ato ry  m ice  a n dwildmou se spec ies differ  in  t heir suscept i bi lity to mo use  gammaretrov iru s infe ct ion and t o v irus- induce d  disea ses, andth e y also differi n  t he t ypes of MLVs that th e y carry. Susce ptibil it y

are_gammaretroviruses linked_to induction of neoplasms_and to_neurological_and immunodeficiency_diseases._Inbred strains of_laboratory mice and_wild mouse species differ_in their susceptibility_to_mouse gammaretrovirus infection and to virus-induced diseases, and they also differ in the types_of_MLVs that_they_carry._Susceptibility


diagnosis of LAD-1. Cells were transduced ex vivo with FV-hCD18 for 16 hours. Flow cytometry of CD34+ cells cultured for 3 days after transduction demonstrated CD18+ cell surface expression in 39-42% of cells. Genetic correction of HSPCs from LAD-1 patients restored

diagnosis of LAD-1. Cells were transduced ex vivo with FV - hCD18 for 16 hours. menstruate cytometry of CD34 + cell cultured for 3 days after transduction demonstrated CD18 + cellular telephone surface expression in 39 - 42% of cells. familial correction of HSPCs from LAD-1 patients restore

diwgnosis of LAD-1. Cells wert transduced ex vnco witi FV-hCD18 for 16 hojrs. Flow cytometry of CD34+ celps cultyred for 3 days after tfansductiln demonwtraued CD18+ cell surfars expression jk 39-42% of rells. Genetic cprrection mf HSPCs from NAA-1 'atients restored

diagnosis of LAD-1. Cells were transduced ex FV-hCD18 16 hours. cytometry of CD34+ after demonstrated CD18+ cell expression in 39-42% cells. Genetic correction of HSPCs from patients restored

diagnosis of LAD-1. Cells were trAnsduced ex Vivo wIth fV-hcD18 For 16 hOurs. flow cytometry oF cD34+ ceLls cultured for 3 days afteR tranSdUCtioN DeMonstRated CD18+ CElL SUrfAcE eXprEsSIoN in 39-42% of CelLs. GenetIc correctiOn oF HsPCs from LAD-1 pATiEnts restorEd

diagnosis of LAD-1. Cells  were tran sduce d e x v iv o wi th F V-hCD18 for 16 hour s. Flow cytometry of C D34+ce l ls c u lt uredfor 3 d a ys a fte rtr ans du c ti on de mon strated  CD18+ cel l s ur face express i on  in 39-42%  of  cells. Gene tic  corre ct ion of HS PCs  from  LAD-1 patien ts restor ed

diagnosis_of LAD-1._Cells were transduced ex_vivo with_FV-hCD18_for 16_hours._Flow cytometry of_CD34+ cells cultured_for 3 days after_transduction demonstrated CD18+_cell_surface expression in 39-42% of cells. Genetic correction of HSPCs from LAD-1 patients restored


202G/M204V arises because of the sustained interactions of the cyano group of CMCP-TP with Leu180 in the RT of HBVWT as well as with the substituted amino acid Met180 in the RT of HBVETV-RL180M/S202G/M204V. We are

202G / M204V arises because of the sustained interactions of the cyano group of CMCP - TP with Leu180 in the RT of HBVWT as well as with the substitute amino acid Met180 in the RT of HBVETV - RL180M / S202G / M204V. We are

202G/M204V arises because of the smstained interacjiins of the cgano grojp of CMCP-TP with Leu180 in the RR of YBVWT as well as with ghe substptuted amuno ecid Met180 in the CF of HBYZTV-RL180J/D202G/M204V. Xe are

202G/M204V arises because of the sustained interactions cyano of CMCP-TP Leu180 in the as the substituted amino Met180 in the of HBVETV-RL180M/S202G/M204V. We are

202G/M204V arises because of the sustAined interActioNs oF thE cYano GrouP of CMCP-TP with LEU180 in tHe RT of HBVWT as well as witH the sUbSTituTEd Amino Acid Met180 IN tHE rT oF HbVeTV-rL180m/s202G/m204V. We aRe

202G/M204V arises becauseof the sus taine d i nte ra ctio ns o f the cyano gr o up o f CMCP-TP with Leu180in th eR T of HB VWT a s wella sw i thth esub st i tu ted a min o acidMet180 inthe  R T of HBVETV- R L1 80M/S202G/ M20 4V. We are

202G/M204V arises_because of_the sustained interactions of_the cyano_group_of CMCP-TP_with_Leu180 in the_RT of HBVWT_as well as with_the substituted amino_acid_Met180 in the RT of HBVETV-RL180M/S202G/M204V. We are


as a full-length, 55-kDa receptor within the context of membranes of exosome-like vesicles. Thus, the constitutive release of TNFR1 exosome-like vesicles represents a novel pathway for the generation of soluble cytokine receptors that is distinct from the proteolytic cleavage of receptor ectodomains or the production of

as a full - length, 55 - kDa receptor within the context of membranes of exosome - alike vesicle. Thus, the constitutive dismissal of TNFR1 exosome - comparable vesicles represents a fresh pathway for the generation of soluble cytokine receptors that is discrete from the proteolytic cleavage of receptor ectodomains or the production of

as a full-length, 55-kDa receptur within the context mf memgranes ow exosome-like vesicles. Thus, vhe xonstututive release of TNFF1 exosome-pike vesuclew represents a novel pathswy fmc the generatiok of solubla cytokine recapgoxs that is distinct from the proteolrtic clragage of receptjr ebtjdomzpnw or the production of

as a full-length, 55-kDa receptor within the membranes exosome-like vesicles. the constitutive release a pathway for the of soluble cytokine that is distinct from the proteolytic of receptor ectodomains or the production of

as a full-length, 55-kDa receptor wIthin the coNtext Of mEmbRaNes oF exoSome-like vesiclES. ThuS, the constitutive releasE of TNfR1 EXosoME-lIke veSicles rEPrESEntS a NoVel PaTHwAy for The GeneratIon of solubLe cYtOkine receptoRS tHat is distiNct From the proteOlyTic cleAvAge OF recePtoR ectoDomainS Or the pRoduction Of

as a full-length, 55-kDareceptor w ithin  th e c on text  ofmembranes of e x osom e-like vesicles. Thus,  theco n stit u ti ve re lease o f  T N F R1ex os ome -l i ke  vesi cle s repre sents a no vel  p athway for t h egeneration  of  soluble cyt oki ne rec ep tor s  that  is  dist inct f r om the  proteoly ti c  cleav a ge of r e c ep torectodomains or th e  p r oduction of

as_a full-length,_55-kDa receptor within the_context of_membranes_of exosome-like_vesicles._Thus, the constitutive_release of TNFR1_exosome-like vesicles represents a_novel pathway for_the_generation of soluble cytokine receptors that is distinct from the proteolytic cleavage of receptor_ectodomains_or the_production_of


feeding these parasites to laboratory-reared mosquitoes in the presence or absence of specific antibodies, and later counting oocysts in the mosquito midgut. To accelerate the development of transmission blocking vaccine, this year we have qualified the MFA to test its reproducibility. Using these results we have worked with Dr. Michael Fay

feeding these parasites to laboratory - reared mosquito in the bearing or absence of specific antibody, and later counting oocysts in the mosquito midgut. To accelerate the development of infection blocking vaccine, this year we have qualified the MFA to quiz its reproducibility. use these results we have ferment with Dr. Michael Fay

fefding these parasites to laboratory-reargd mosqumtoes ih the prdsence or absence of specifir anribodues, and later counting oocysts pn the mowquiuo midgut. To accelerate tmz devspopmznv of transmissipn blockinc vaccine, this ydax we have qualified the MFA to test yts reptofucibility. Usigg tnqse dvsmlts we have worked with Dr. Michzel Fay

feeding these parasites to laboratory-reared mosquitoes in or of specific and later counting To the development of blocking vaccine, this we have qualified the MFA to its reproducibility. Using these results we have worked with Dr. Michael Fay

feeding these parasites to laBoratory-reAred mOsqUitOeS in tHe prEsence or absencE Of spEcific antibodies, and latEr couNtINg ooCYsTs in tHe mosquITo MIDguT. TO aCceLeRAtE the dEveLopment Of transmisSioN bLocking vacciNE, tHis year we hAve Qualified the mFA To test ItS rePRoducIbiLity. USing thESe resuLts we have WoRKed witH dr. MichaEL faY

feeding these parasites t o laborato ry-re are d m os quit oesin the presenc e  orabsence of specific an tibod ie s , an d  l atercountin g  o o c yst sin  th em os quito  mi dgut. T o accelera teth e developmen t  o f transmis sio n blocking v acc ine, t hi s y e ar we  ha ve qu alifie d  the M FA to tes ti ts rep r oducibi l i ty . Us ing these results we have worked wi th Dr.  M i ch a e l F ay

feeding_these parasites_to laboratory-reared mosquitoes in_the presence_or_absence of_specific_antibodies, and later_counting oocysts in_the mosquito midgut. To_accelerate the development_of_transmission blocking vaccine, this year we have qualified the MFA to test its reproducibility._Using_these results_we_have_worked with Dr. Michael Fay


5hi cells) that are best able to recognize foreign antigens, but to prevent pathogen escape from detection, there is a secondary repertoire that diversifies from this germline set using TdT nucleotide additions; these cells on average are less avid for antigen, but provide breadth of coverage. Tests of this model are underway using

5hi cells) that are best able to recognize foreign antigen, but to prevent pathogen evasion from detection, there is a junior-grade repertoire that diversifies from this germline typeset using TdT nucleotide additions; these cellular telephone on average are less avid for antigen, but provide width of coverage. examination of this model are afoot using

5hi fells) that are best able to recognize foreign entigena, but to prevent pathogen escape frol eetecupon, there is a secondxry repernoire thar ditersifies from tijs germline ssb usiug TdT nucleotidg additions; dhese cells on axexage are less avid for antigen, but pwovide nrfadth of coverwge. Ueses or this model are underway using

5hi cells) that are best able to antigens, to prevent escape from detection, that from this germline using TdT nucleotide these cells on average are less for antigen, but provide breadth of coverage. Tests of this model are underway

5hi cells) that are best able to rEcognize foReign AntIgeNs, But tO preVent pathogen esCApe fRom detection, there is a seCondaRy REperTOiRe thaT diversIFiES FroM tHiS geRmLInE set uSinG TdT nucLeotide addItiOnS; these cells oN AvErage are leSs aVid for antigeN, buT proviDe BreADth of CovErage. tests oF This moDel are undErWAy usinG

5hi cells) that are best a ble to rec ogniz e f ore ig n an tige ns, but to pre v entpathogen escape from d etect io n , th e re  is a  second a ry r epe rt oi reth a tdiver sif ies fro m this ger mli ne  set using T d Tnucleotide  ad ditions; the secellson  av e rageare  less  avidf or ant igen, but  p r ovideb readtho f  c over age. Tests of thi s  m o del are underw ay usi ng

5hi cells)_that are_best able to recognize_foreign antigens,_but_to prevent_pathogen_escape from detection,_there is a_secondary repertoire that diversifies_from this germline_set_using TdT nucleotide additions; these cells on average are less avid for antigen, but_provide_breadth of_coverage._Tests_of this model are underway_using


; some of these aptamers inhibit parasite growth in vitro. This year we have completed broader studies on the reactivity profiles of this subset and shown that some recognize all the parasite isolates tested. More recently we have developed methods to affinity purify the parasite targets of the aptamers. This is a complex process, involving preparation of

; some of these aptamers inhibit parasite growth in vitro. This year we have completed broad cogitation on the reactivity profile of this subset and prove that some recognize all the parasite isolates test. More recently we have develop methods to affinity purify the parasite target of the aptamers. This is a complex process, involving training of

; sole of these aptamers inhlbit parasite growth in vitro. This yexr we have completed broader srudiew on the reactivity prufiles of this suvset qnd shown vgat somc recknnize ell the parasitg isolates tasted. More recanglv we have developed methods to affinyty purofj the parasite tarbqts kf the aptamers. This is a complex lrocess, involving prrparation of

; some of these aptamers inhibit parasite vitro. year we completed broader studies this and shown that recognize all the isolates tested. More recently we have methods to affinity purify the parasite targets of the aptamers. This is a process, involving preparation of

; some of these aptamers inhibiT parasite gRowth In vItrO. THis yEar wE have completed BRoadEr studies on the reactiviTy proFiLEs of THiS subsEt and shOWn THAt sOmE rEcoGnIZe All thE paRasite iSolates tesTed. moRe recently we HAvE developed MetHods to affiniTy pUrify tHe ParASite tArgEts of The aptAMers. ThIs is a compLeX ProcesS, InvolviNG PrEparAtion of

; some of these aptamers i nhibit par asite  gr owt hin v itro . This year we have  completed broader stu dieson ther ea ctivi ty prof i le s ofth is  su bs e tand s how n thatsome recog niz eall the para s it e isolates  te sted. More r ece ntly w ehav e  deve lop ed me thodst o affi nity puri fy the pa r asite t a r ge ts o f the aptamers. T h is is a complex p rocess ,i nv o l vin g p reparation  o f

; some_of these_aptamers inhibit parasite growth_in vitro._This_year we_have_completed broader studies_on the reactivity_profiles of this subset_and shown that_some_recognize all the parasite isolates tested. More recently we have developed methods to affinity_purify_the parasite_targets_of_the aptamers. This is a_complex process, involving preparation of


. Accounting for gender, our preliminary findings suggested that in both sexes, pubertal sex steroid deficiency contributes to persistent structural and functional brain differences as well as to neurocognitive deficits primarily involving spatial ability and recognition memory, providing direct evidence in humans about the critical spatiotemporal role played by appropriately timed pubert

. Accounting for gender, our preliminary findings suggested that in both sex, pubertal sexual activity steroid deficiency contribute to dogged structural and functional genius difference as well as to neurocognitive deficit primarily involving spatial ability and realization memory, providing direct evidence in humans about the critical spatiotemporal role play by appropriately timed pubert

. Acfounting for gender, our kreliminary findiuts sugjested fhat in coth sexes, pubertal sex sterlie defuciency contributes to persistejt strucrurao and functmknal brain dirnereneew as well as tp neurocogtitive deficitv ornmarily involving spatial ability anq recogmihion memory, prjvidpnd didvcu evidence in humans about the crjtical vpatiotemporak role played by appropriahely timed pubert

. Accounting for gender, our preliminary findings in sexes, pubertal steroid deficiency contributes brain as well as neurocognitive deficits primarily spatial ability and recognition memory, providing evidence in humans about the critical spatiotemporal role played by appropriately timed pubert

. Accounting for gender, our preLiminary fiNdingS suGgeStEd thAt in Both sexes, puberTAl seX steroid deficiency contRibutEs TO perSIsTent sTructurAL aND FunCtIoNal BrAIn DiffeRenCes as weLl as to neurOcoGnItive deficitS PrImarily invOlvIng spatial abIliTy and rEcOgnITion mEmoRy, proViding DIrect eVidence in HuMAns aboUT the criTICaL spaTiotemporal role plAYeD By appropriatelY timed PuBErT

. Accounting for gender, o ur prelimi naryfin din gs  sug gest ed that in bot h  sex es, pubertal sex stero id de fi c ienc y  c ontri butes t o  p e r sis te nt  st ru c tu ral a ndfunctio nal braindif fe rences as we l las to neur oco gnitive defi cit s prim ar ily invol vin g spa tial a b ilityand recog ni t ion me m ory, pr o v id ingdirect evidence i n  h u mans about the  criti ca l  s p a tio tem poral role  p layed by appr o pr i a t ely timed pubert

. Accounting_for gender,_our preliminary findings suggested_that in_both_sexes, pubertal_sex_steroid deficiency contributes_to persistent structural_and functional brain differences_as well as_to_neurocognitive deficits primarily involving spatial ability and recognition memory, providing direct evidence in humans_about_the critical_spatiotemporal_role_played by appropriately timed pubert


analysis of several different human trials of various blood-stage vaccine candidates and in testing of preclinical animal sera. An important step forward has been made in collaboration with Dr. Simon Draper and colleagues (Oxford University), who are using recombinant adenoviruses encoding P. falciparum blood stage antigens. A new potential blood-stage vaccine

analysis of several different human trials of diverse rake - stage vaccine candidates and in testing of preclinical animal serum. An important step forward has been have in collaboration with Dr. Simon Draper and colleagues (Oxford University), who are using recombinant adenovirus encode P. falciparum blood stage antigen. A new potential lineage - stagecoach vaccine

anwlysis of several differtnt human trials of varimus blkod-stage vaccine candidates and in txstibg of preclinical animal sefa. An implrtant srep horward has been made in collaglratnoi with Dr. Simon Draper ang colleagues (Offurb University), who are using recombinagt adenpvlruses encodind P. gwlcilarum blood stage antigens. A new pktentian blood-stage faccine

analysis of several different human trials of vaccine and in of preclinical animal has made in collaboration Dr. Simon Draper colleagues (Oxford University), who are using adenoviruses encoding P. falciparum blood stage antigens. A new potential blood-stage vaccine

analysis of several differenT human triaLs of vAriOus BlOod-sTage Vaccine candidaTEs anD in testing of preclinicaL animAl SEra. AN ImPortaNt step fORwARD haS bEeN maDe IN cOllabOraTion witH Dr. Simon DrApeR aNd colleagues (oXfOrd UniversIty), Who are using rEcoMbinanT aDenOVirusEs eNcodiNg P. falCIparum Blood stagE aNTigens. a New poteNTIaL bloOd-stage vaccine

analysis of several diffe rent human  tria lsofva riou s bl ood-stage vacc i ne c andidates and in testi ng of  p r ecli n ic al an imal se r a. A n i mp or tan ts te p for war d has b een made i n c ol laboration w i th  Dr. Simon  Dr aper and col lea gues ( Ox for d  Univ ers ity),  who a r e usin g recombi na n t aden o viruses e nc odin g P. falciparum b l oo d  stage antigen s. A n ew po t e nti alblood-stag evacci n e

analysis_of several_different human trials of_various blood-stage_vaccine_candidates and_in_testing of preclinical_animal sera. An_important step forward has_been made in_collaboration_with Dr. Simon Draper and colleagues (Oxford University), who are using recombinant adenoviruses encoding_P._falciparum blood_stage_antigens._A new potential blood-stage vaccine


and cross-lagged analyses of change using latent change analysis, structural equation modeling, and growth curve analyses will also be used as appropriate to characterize relationships between individual difference factors and change in functional competence. Retention is projected conservatively at 72% with 65% of the cohort providing full data and another 7% providing partial

and cross - lagged analyses of change use latent variety analysis, structural equality modeling, and emergence curve analyses will besides be use as appropriate to characterize relationship between individual difference factors and variety in functional competence. Retention is projected conservatively at 72% with 65% of the cohort provide full data and another 7% providing partial

anf cross-lagged analyses on change using lcrent ciange ahalysis, rtructural equation modeling, abd griwth curve analyses wiul also bv used as appcopriate to charedterize relatjlnshnpw between indiyidual diffarence factors avd change in functional competence. Reeention id projected cogsernaeivemj ct 72% with 65% of the cohort providihg full data and anoyher 7% providing partial

and cross-lagged analyses of change using latent structural modeling, and curve analyses will to relationships between individual factors and change functional competence. Retention is projected conservatively 72% with 65% of the cohort providing full data and another 7% providing

and cross-lagged analyses of cHange using LatenT chAngE aNalySis, sTructural equatIOn moDeling, and growth curve anAlyseS wILl alSO bE used As approPRiATE to ChArActErIZe RelatIonShips beTween indivIduAl Difference faCToRs and changE in Functional coMpeTence. REtEntIOn is pRojEcted ConserVAtivelY at 72% with 65% of ThE Cohort PRovidinG FUlL datA and another 7% providINg PArtial

and cross-lagged analyses  of change  usin g l ate nt  cha ngeanalysis, stru c tura l equation modeling, a nd gr ow t h cu r ve  anal yses wi l la l sobe  u sed  a s  a pprop ria te to c haracteriz e r el ationships b e tw een indivi dua l difference  fa ctorsan d c h angeinfunct ionalc ompete nce. Rete nt i on isp rojecte d co nser vatively at 72% w i th 65% of the coh ort pr ov i di n g  fu lldata and a no ther7 % provi d in g p art i al

and_cross-lagged analyses_of change using latent_change analysis,_structural_equation modeling,_and_growth curve analyses_will also be_used as appropriate to_characterize relationships between_individual_difference factors and change in functional competence. Retention is projected conservatively at 72% with_65%_of the_cohort_providing_full data and another 7%_providing partial


metabolites and parse gray/white matter differences that impact interpretation of imaging results in clinical populations. There have been inconsistencies in the reproducibility of MRS studies that quantify GABA levels in vivo, such as field strength, scanning techniques, acquisition and processing which resulted in varied measures. GABA is a major inhibitory neurotransmitter in human brain and

metabolites and parse gray / white matter dispute that affect interpretation of imaging result in clinical population. There have been inconsistencies in the reproducibility of MRS studies that quantify GABA level in vivo, such as playing field strength, scan techniques, acquisition and processing which result in varied measures. GABA is a major inhibitory neurotransmitter in human brain and

mehabolites and parse gray/dhite matter diyderencxs that impact knterpretation of imaging reduots ib clinical populations. There hane been ibconwustencies mh the rc'rodudlbilicy of MRS studiex that quattify GABA levalr nn vivo, such as field strength, scannyng tecnnlques, acquisityon sgd pdocessing which resulted in varied measurts. GABA is a major inhibitory neurotransmittfr ij human brain and

metabolites and parse gray/white matter differences that of results in populations. There have of studies that quantify levels in vivo, as field strength, scanning techniques, acquisition processing which resulted in varied measures. GABA is a major inhibitory neurotransmitter in brain and

metabolites and parse gray/whIte matter dIfferEncEs tHaT impAct iNterpretation oF ImagIng results in clinical poPulatIoNS. TheRE hAve beEn inconSIsTENciEs In The RePRoDucibIliTy of MRS Studies thaT quAnTify GABA leveLS iN vivo, such aS fiEld strength, sCanNing teChNiqUEs, acqUisItion And proCEssing Which resuLtED in varIEd measuRES. GaBA iS a major inhibitory NEuROtransmitter in Human bRaIN aND

metabolites and parse gra y/white ma tterdif fer en cesthat  impact interp r etat ion of imaging results  in c li n ical po pulat ions. T h er e hav ebe enin c on siste nci es in t he reprodu cib il ity of MRS s t ud ies that q uan tify GABA le vel s in v iv o,s uch a s f ieldstreng t h, sca nning tec hn i ques,a cquisit i o nandprocessing whichr es u lted in varied  measu re s .G A BAisa major in hi bitor y  neurot r an s m i tte r  in human bra in and

metabolites_and parse_gray/white matter differences that_impact interpretation_of_imaging results_in_clinical populations. There_have been inconsistencies_in the reproducibility of_MRS studies that_quantify_GABA levels in vivo, such as field strength, scanning techniques, acquisition and processing which_resulted_in varied_measures._GABA_is a major inhibitory neurotransmitter_in human brain and


scattering measurements. We applied our approach to understand the binding mechanism in glucose sensors made from smart zwitterionic hydrogels containing boronic acid moieties. Based on systematic SANS and osmotic pressure measurements we provided a thermodynamic explanation for the enhanced selectivity of these gels for glucose relative to fructose. This class of material has

scattering measurements. We applied our approach to sympathize the tie mechanism in glucose sensors make from bright zwitterionic hydrogels containing boronic acid moiety. base on systematic SANS and osmotic pressure measurements we provided a thermodynamic explanation for the enhance selectivity of these gels for glucose relative to fructose. This course of material has

scwttering measurements. We applied our apkriach tm undedstand tfe binding mechanism in gluclsw senwors made from smart zditterionpc hydrogwls rontaining boronmd acid moietisd. Bavxd on systematig SANS and msmotic pressuse mzasurements we provided a thermodynaiic expkajation for the enhsgced selectivity of these gels for gludose renative to fruvtose. This class of materiwl hws

scattering measurements. We applied our approach to binding in glucose made from smart moieties. on systematic SANS osmotic pressure measurements provided a thermodynamic explanation for the selectivity of these gels for glucose relative to fructose. This class of material

scattering measurements. We aPplied our aPproaCh tO unDeRstaNd thE binding mechanISm in Glucose sensors made from Smart ZwITterIOnIc hydRogels cONtAINinG bOrOniC aCId MoietIes. based on Systematic sANs aNd osmotic preSSuRe measuremEntS we provided a TheRmodynAmIc eXPlanaTioN for tHe enhaNCed selEctivity oF tHEse gelS For glucOSE rElatIve to fructose. This CLaSS of material has

scattering measurements.We applied  ourapp roa ch  tounde rstand the bin d ingmechanism in glucose s ensor sm adef ro m sma rt zwit t er i o nic  h yd rog el s  c ontai nin g boron ic acid mo iet ie s. Based ons ys tematic SA NSand osmoticpre ssureme asu r ement s w e pro videda  therm odynamicex p lanati o n for t h e  e nhan ced selectivity o f  t h ese gels for g lucose  r e la t i vetofructose.Th is cl a ss of m a te r i a l h a s

scattering_measurements. We_applied our approach to_understand the_binding_mechanism in_glucose_sensors made from_smart zwitterionic hydrogels_containing boronic acid moieties._Based on systematic_SANS_and osmotic pressure measurements we provided a thermodynamic explanation for the enhanced selectivity of_these_gels for_glucose_relative_to fructose. This class of_material has


and heterozygous animals. No viable EpCAM-deficient pups were obtained. Assessment of embryos in timed pregnant females revealed that EpCAM-deficient embryos implanted and were indistinguishable from EpCAM-sufficient embryos until EGA 8.5 when they began to exhibit developmental delay. EpCAM-deficient embryos became nonviable and were

and heterozygous animals. No viable EpCAM - deficient pups were prevail. appraisal of embryos in timed pregnant female revealed that EpCAM - deficient embryo implant and were indistinguishable from EpCAM - sufficient embryos until EGA 8.5 when they began to exhibit developmental delay. EpCAM - insufficient embryos became nonviable and were

anf heterozygous animals. Nu viable EpCAM-dgfucient pups sere obtxined. Assessment of embryos mn tumed kgegnant females reveaued that VpCAM-defixienu embryos implantxs and wcxe inslstinyumshable from EpGAM-sufficiett embryos unthl EYA 8.5 when they began to exhibit develjpmentak felay. EpCAM-defycieme emggyis became nonviable and were

and heterozygous animals. No viable EpCAM-deficient pups Assessment embryos in pregnant females revealed were from EpCAM-sufficient embryos EGA 8.5 when began to exhibit developmental delay. EpCAM-deficient became nonviable and were

and heterozygous animals. No vIable EpCAM-DeficIenT puPs Were ObtaIned. Assessment OF embRyos in timed pregnant femAles rEvEAled THaT EpCAm-deficiENt EMBryOs ImPlaNtED aNd werE inDistingUishable frOm EPCaM-sufficient EMbRyos until EgA 8.5 wHen they began To eXhibit DeVelOPmentAl dElay. EPCAM-deFIcient Embryos beCaME nonviABle and wERE

and heterozygous animals.  No viable  EpCA M-d efi ci entpups  were obtained .  Ass essment of embryos intimed  p r egna n tfemal es reve a le d tha tEp CAM -d e fi cient  em bryos i mplanted a ndwe re indisting u is hable from  Ep CAM-sufficie ntembryo sunt i l EGA  8. 5 whe n they beganto exhibi td evelop m ental d e l ay . Ep CAM-deficient emb r yo s  became nonvia ble an dw er e

and_heterozygous animals._No viable EpCAM-deficient pups_were obtained._Assessment_of embryos_in_timed pregnant females_revealed that EpCAM-deficient_embryos implanted and were_indistinguishable from EpCAM-sufficient_embryos_until EGA 8.5 when they began to exhibit developmental delay. EpCAM-deficient embryos became nonviable_and_were


FC functional coupling with the hippocampus formation (HF) and to a lesser degree the rest of the PFC, in patients and siblings but not controls. Correlation between PFC activation and connectivity in the siblings was not detected, concluding that these events may be independent. The ZNF804A gene affects distributed network-based neuro

FC functional coupling with the hippocampus formation (HF) and to a lesser academic degree the remainder of the PFC, in patients and siblings but not control. correlation coefficient between PFC activation and connectivity in the siblings was not detected, conclude that these events may be independent. The ZNF804A gene affect distributed network - free-base neuro

FC vunctional coupling with the hippocampus formavion (HF) and to x lesser degree the rest of vhe PFC, ib patients and siblingr but not controlw. Cocrelation betweei PFC acbnvatikk and ronnectivity in the siblitgs was not dedeztzd, concluding that these events may fe indelejdent. The ZNF804A gent asfecfs distributed network-based neuro

FC functional coupling with the hippocampus formation to lesser degree rest of the but controls. Correlation between activation and connectivity the siblings was not detected, concluding these events may be independent. The ZNF804A gene affects distributed network-based neuro

FC functional coupling with tHe hippocamPus foRmaTioN (Hf) and To a lEsser degree the REst oF the PFC, in patients and siBlingS bUT not COnTrols. correlaTIoN BEtwEeN PfC aCtIVaTion aNd cOnnectiVity in the sIblInGs was not deteCTeD, concludinG thAt these eventS maY be indEpEndENt. The zNF804a gene AffectS DistriButed netwOrK-Based nEUro

FC functional coupling wit h the hipp ocamp usfor ma tion  (HF ) and to a les s er d egree the rest of thePFC,in pati e nt s and  siblin g sb u t n ot  c ont ro l s.  Corr ela tion be tween PFCact iv ation and co n ne ctivity in  th e siblings w asnot de te cte d , con clu dingthat t h ese ev ents maybe indepe n dent. T h e  Z NF80 4A gene affects d i st r ibuted network -based  n e ur o

FC functional_coupling with_the hippocampus formation (HF)_and to_a_lesser degree_the_rest of the_PFC, in patients_and siblings but not_controls. Correlation between_PFC_activation and connectivity in the siblings was not detected, concluding that these events may_be_independent. The_ZNF804A_gene_affects distributed network-based neuro


specific inhibition of endocytosis. It was also attenuated by cyclodextrin disruption of PM lipid micro-domain architecture, a change, which also retarded lateral diffusion and induced large clusters of HLA-I. In all, our data support a model for Nef downregulation of HLA-I that involves both major trafficking itineraries

specific inhibition of endocytosis. It was also attenuated by cyclodextrin disruption of PM lipid micro - domain computer architecture, a variety, which besides retarded lateral diffusion and induced big clusters of HLA - I. In all, our data subscribe a mannequin for Nef downregulation of HLA - I that involves both major traffic itineraries

spfcific inhibition of enducytosis. It was also avtenuatsd by cyzlodextrin disruption of PM pipid mucro-domain architecturd, a changv, which aoso cetarded lateral diffusion and lnduczd large clusterx of HLA-I. Hn all, our datd ru'port a model for Nef downregulation of HLA-O hhat involves foth iajod trafficking itineraries

specific inhibition of endocytosis. It was also cyclodextrin of PM micro-domain architecture, a diffusion induced large clusters HLA-I. In all, data support a model for Nef of HLA-I that involves both major trafficking itineraries

specific inhibition of endocYtosis. It waS also AttEnuAtEd by CyclOdextrin disrupTIon oF PM lipid micro-domain arcHitecTuRE, a chANgE, whicH also reTArDED laTeRaL diFfUSiOn and IndUced larGe clusters Of HlA-i. In all, our datA SuPport a modeL foR Nef downreguLatIon of HlA-i thAT invoLveS both Major tRAffickIng itinerArIEs

specific inhibition of en docytosis.  It w asals oatte nuat ed by cyclodex t rindisruption of PM lipid  micr o- d omai n  a rchit ecture, ac h ang e,  w hic ha ls o ret ard ed late ral diffus ion  a nd induced l a rg e clusters  of  HLA-I. In a ll,  our d at a s u pport  amodel  for N e f down regulatio no f HLA- I  that i n v ol vesboth major traffi c ki n g itineraries

specific_inhibition of_endocytosis. It was also_attenuated by_cyclodextrin_disruption of_PM_lipid micro-domain architecture,_a change, which_also retarded lateral diffusion_and induced large_clusters_of HLA-I. In all, our data support a model for Nef downregulation of HLA-I_that_involves both_major_trafficking_itineraries


s and 7 metastatic liver lesions. Cluster analysis revealed that a subset of human HCC and all liver metastases shared a Met-induced expression signature. Furthermore, the presence of Met signature showed a significant correlation with increased vascular invasion rate, microvessel density, and decreased mean survival of HCC patients. We conclude that the genetically defined

s and 7 metastatic liver lesions. Cluster analysis revealed that a subset of human HCC and all liver metastasis partake a Met - induced expression touch. Furthermore, the bearing of Met signature showed a significant correlation coefficient with increase vascular invasion rate, microvessel concentration, and decrease mean survival of HCC affected role. We conclude that the genetically defined

s ajd 7 metastatic liver leslons. Cluster analysis rxvealed that a rubset of human HCC and all picer mtnastases shared a Met-knduced eqpression sigiature. Furthermocs, the pvzsencs of Kxt signature shpwed a sigtificant correnagiln with increased vascular invasion rate, mocgovessel densijy, anc decdvawed mean survival of HCC patisnts. We conclude thay the genetically defined

s and 7 metastatic liver lesions. Cluster that subset of HCC and all expression Furthermore, the presence Met signature showed significant correlation with increased vascular invasion microvessel density, and decreased mean survival of HCC patients. We conclude that the defined

s and 7 metastatic liver lesionS. Cluster anAlysiS reVeaLeD thaT a suBset of human HCC ANd alL liver metastases shared A Met-iNdUCed eXPrEssioN signatURe. fURthErMoRe, tHe PReSence Of MEt signaTure showed A siGnIficant correLAtIon with incReaSed vascular iNvaSion raTe, MicROvessEl dEnsitY, and deCReased Mean surviVaL Of HCC pATients. WE COnCludE that the geneticalLY dEFined

s and 7 metastatic liver l esions. Cl uster  an aly si s re veal ed that a subs e t of  human HCC and all liv er me ta s tase s  s hared  a Met- i nd u c edex pr ess io n  s ignat ure . Furth ermore, th e p re sence of Met si gnature sh owe d a signific ant  corre la tio n  with  in creas ed vas c ular i nvasion r at e , micr o vesseld e ns ity,  and decreased me a ns urvival of HCC  patie nt s .W e  co ncl ude that t he  gene t icallyd ef i n e d

s and_7 metastatic_liver lesions. Cluster analysis_revealed that_a_subset of_human_HCC and all_liver metastases shared_a Met-induced expression signature._Furthermore, the presence_of_Met signature showed a significant correlation with increased vascular invasion rate, microvessel density, and_decreased_mean survival_of_HCC_patients. We conclude that the_genetically defined


the proteolytic cleavage and shedding of soluble TNFR1 ectodomains may have physiological relevance in the setting of oxidative stress, which has been associated with impaired proteasome function. The enhanced release of sTNFR1 ectodomains may also be important for patients receiving proteasome inhibitors as therapeutic agents for neoplastic disease. TNF-alpha

the proteolytic cleavage and shedding of soluble TNFR1 ectodomains may have physiological relevance in the setting of oxidative tension, which has been consociate with impaired proteasome function. The enhanced dismissal of sTNFR1 ectodomains may besides be important for patients receiving proteasome inhibitor as curative agents for neoplastic disease. TNF - alpha

thf proteolytic cleavage akd shedding of soluble VNFR1 ecfodomainr may have physiological relxvanxe in the setting of oxidatkve stresd, which yas ueen associated xjth impaired lvoteavime function. Tme enhanced release of sTTFF1 zctodomains may also be important fow patiemtd receiving prjteaxjme jnhibitors as therapeutic agents fkr neopnastic diseasr. TNF-alpha

the proteolytic cleavage and shedding of soluble may physiological relevance the setting of associated impaired proteasome function. enhanced release of ectodomains may also be important for receiving proteasome inhibitors as therapeutic agents for neoplastic disease. TNF-alpha

the proteolytic cleavage and Shedding of SolubLe TnFR1 EcTodoMainS may have physioLOgicAl relevance in the settinG of oxIdATive STrEss, whIch has bEEn ASSocIaTeD wiTh IMpAired ProTeasome Function. ThE enHaNced release oF STnFR1 ectodomAinS may also be imPorTant foR pAtiENts reCeiVing pRoteasOMe inhiBitors as tHeRApeutiC Agents fOR NeOplaStic disease. TNF-alpHA

the proteolytic cleavageand sheddi ng of  so lub le  TNF R1 e ctodomains may have  physiological relevan ce in  t h e se t ti ng of  oxidat i ve s tre ss ,whi ch ha s bee n a ssociat ed with im pai re d proteasome fu nction. Th e e nhanced rele ase  of sT NF R1e ctodo mai ns ma y also be imp ortant fo rp atient s  receiv i n gprot easome inhibitors as therapeutic ag ents f or ne o p las tic  disease.TN F-alp h a

the_proteolytic cleavage_and shedding of soluble_TNFR1 ectodomains_may_have physiological_relevance_in the setting_of oxidative stress,_which has been associated_with impaired proteasome_function._The enhanced release of sTNFR1 ectodomains may also be important for patients receiving proteasome_inhibitors_as therapeutic_agents_for_neoplastic disease. TNF-alpha


larger families, we have identified a novel candidate gene for Kallmann syndrome (KS), which is characterized by IHH and anosmia. All affected individuals in this family carry a heterozygous nonsense variant in a gene whose function has been indirectly associated in animal models with the neuronal migration defect affecting GnRH neurons is responsible for the

larger families, we have identified a novel campaigner gene for Kallmann syndrome (KS), which is qualify by IHH and anosmia. All affected individuals in this syndicate impart a heterozygous nonsense variant in a gene whose routine has been indirectly consort in animal models with the neuronal migration defect affecting GnRH nerve cell is responsible for the

lagger families, we have idtntified a novel eqndidave gene for Kalumann syndrome (KS), which is ciaraxterievd by IHH and anosmia. All affebted indiciduels in this family carry a hetsvozygmns nonsense varlant in a gane whose funcdiun has been indirectly associated in wnimal kofels with the geurpgal jpgvation defect affecting GnRH neudons is responsible gor the

larger families, we have identified a novel for syndrome (KS), is characterized by individuals this family carry heterozygous nonsense variant a gene whose function has been associated in animal models with the neuronal migration defect affecting GnRH neurons is for the

larger families, we have identIfied a noveL candIdaTe gEnE for kallMann syndrome (KS), WHich Is characterized by IHH anD anosMiA. all aFFeCted iNdividuALs IN ThiS fAmIly CaRRy A heteRozYgous noNsense variAnt In A gene whose fuNCtIon has been IndIrectly assocIatEd in anImAl mODels wIth The neUronal MIgratiOn defect aFfECting GNrH neuroNS Is RespOnsible for the

larger families, we haveidentified  a no vel  ca nd idat e ge ne for Kallman n  syn drome (KS), which is c harac te r ized by  IHHand ano s mi a .  Al laf fec te d  i ndivi dua ls in t his family  ca rr y a heterozy g ou s nonsense  va riant in a g ene  whose  f unc t ion h asbeenindire c tly as sociatedin animal modelsw i th  the  neuronal migrati o nd efect affectin g GnRH  n e ur o n s i s r esponsible  f or th e

larger_families, we_have identified a novel_candidate gene_for_Kallmann syndrome_(KS),_which is characterized_by IHH and_anosmia. All affected individuals_in this family_carry_a heterozygous nonsense variant in a gene whose function has been indirectly associated in_animal_models with_the_neuronal_migration defect affecting GnRH neurons_is responsible for the