. Next, rhesus monkeys were infected twice with HPIV3 and, 11 months following the second infection, were immunized with two doses of HPIV3/EboGP given 4 weeks apart. ELISA assay of EBOV-specific serum IgG and IgA showed that the level of EBOV-specific serum antibodies following

. Next, rhesus monkeys were infected twice with HPIV3 and, 11 months follow the second contagion, were immunized with two doses of HPIV3 / EboGP give 4 workweek apart. ELISA assay of EBOV - specific serum IgG and IgA showed that the horizontal surface of EBOV - specific serum antibodies trace

. Nedt, rhesus monkeys were ikfected twice wijh HPIV3 end, 11 mohths foluowing the second infection, xere immubized with two doses ow HPIV3/EboHP given 4 wetks apart. ELISA assay of CYOV-spsgific werum IgG and LgA showed dhat the level ow ZBOV-specific serum antibodies followyng

. Next, rhesus monkeys were infected twice and, months following second infection, were HPIV3/EboGP 4 weeks apart. assay of EBOV-specific IgG and IgA showed that the of EBOV-specific serum antibodies following

. Next, rhesus monkeys were infeCted twice wIth HPiV3 aNd, 11 mOnThs fOlloWing the second iNFectIon, were immunized with twO doseS oF hPIV3/eBogP givEn 4 weeks APaRT. eLIsA AsSay Of ebOv-specIfiC serum IGG and IgA shOweD tHat the level oF eBoV-specific SerUm antibodies FolLowing

. Next, rhesus monkeys wer e infected  twic e w ith  H PIV3  and , 11 months fo l lowi ng the second infectio n, we re immu n iz ed wi th twod os e s  of  H PI V3/ Eb o GP  give n 4  weeksapart. ELI SAas say of EBOV- s pe cific seru m I gG and IgA s how ed tha tthe level  of  EBOV -speci f ic ser um antibo di e s foll o wing

. Next,_rhesus monkeys_were infected twice with_HPIV3 and,_11_months following_the_second infection, were_immunized with two_doses of HPIV3/EboGP given_4 weeks apart._ELISA_assay of EBOV-specific serum IgG and IgA showed that the level of EBOV-specific serum_antibodies_following


ated with ribonucleoprotein complexes (RNPs) consisting of Cas9 bound to single guide RNAs (sgRNAs) targeting either the cxcr4 gene or the safe harbor locus AAVS1. Experimentally manipulated cells were cloned by limiting dilution and single-cell isolates were expanded in vitro to obtain sufficient genomic DNA for

ated with ribonucleoprotein complexes (RNPs) consisting of Cas9 bound to single template RNAs (sgRNAs) target either the cxcr4 gene or the safe harbor locus AAVS1. Experimentally fudge cell were cloned by limiting dilution and individual - cell isolates were expanded in vitro to receive sufficient genomic DNA for

atef with ribonucleoprotein complexes (RNPs) consisving of Cas9 bouvd to single guide RNAs (sgRNEs) tqrgetung either the cxcr4 geve or the safe haebor oocus AAVS1. Experimcutallg mannpnlated cells wete cloned by limiting diludiun and single-cell isolates were expanqed in fihro to obtain fuffpcyent genomic DNA for

ated with ribonucleoprotein complexes (RNPs) consisting of to guide RNAs targeting either the harbor AAVS1. Experimentally manipulated were cloned by dilution and single-cell isolates were expanded vitro to obtain sufficient genomic DNA for

ated with ribonucleoprotein Complexes (RnPs) coNsiStiNg Of CaS9 bouNd to single guidE rNAs (SgRNAs) targeting either tHe cxcR4 gENe or THe Safe hArbor loCUs aavS1. EXpErImeNtALlY maniPulAted celLs were clonEd bY lImiting dilutIOn And single-cEll Isolates were ExpAnded iN vItrO To obtAin SuffiCient gENomic DnA for

ated with ribonucleoprotei n complexe s (RN Ps)  co ns isti ng o f Cas9 bound t o  sin gle guide RNAs (sgRNAs ) tar ge t inge it her t he cxcr 4  g e n e o rth e s af e  h arbor  lo cus AAV S1. Experi men ta lly manipula t ed  cells wer e c loned by lim iti ng dil ut ion and s ing le-ce ll iso l ates w ere expan de d  in vi t ro to o b t ai n su fficient genomicD NA for

ated with_ribonucleoprotein complexes_(RNPs) consisting of Cas9_bound to_single_guide RNAs_(sgRNAs)_targeting either the_cxcr4 gene or_the safe harbor locus_AAVS1. Experimentally manipulated_cells_were cloned by limiting dilution and single-cell isolates were expanded in vitro to obtain_sufficient_genomic DNA_for


specifically useful for monitoring Forster?s Resonance Energy Transfer (FRET) between either dissimilar (Hetero-FRET) or similar (Homo-FRET) fluorophores. We have used this microscope to develop a new, photon efficient method for measuring FRET in living cells based on spectral imaging.

specifically useful for monitoring Forster?s Resonance Energy Transfer (FRET) between either dissimilar (Hetero - FRET) or similar (Homo - FRET) fluorophores. We have use this microscope to originate a new, photon efficient method for quantify FRET in living cells establish on spectral imaging.

spfcifically useful for mokitoring Forster?s Resonence Ensrgy Travsfer (FRET) between either didsumilae (Hetero-FRET) or similaf (Homo-FREN) fluoropyorew. We have used this microagope co develop a new, photon efxicient method fur measuring FRET in living cells basqd on sleftral imaging.

specifically useful for monitoring Forster?s Resonance Energy between dissimilar (Hetero-FRET) similar (Homo-FRET) fluorophores. to a new, photon method for measuring in living cells based on spectral

specifically useful for moniToring ForsTer?s REsoNanCe enerGy TrAnsfer (FRET) betwEEn eiTher dissimilar (Hetero-FReT) or sImILar (HOMo-fRET) fLuorophOReS. wE haVe UsEd tHiS MiCroscOpe To develOp a new, photOn eFfIcient method FOr Measuring FrET In living cellS baSed on sPeCtrAL imagIng.

specifically useful for m onitoringForst er? s R es onan ce E nergy Transfer (FRE T) between either diss imila r( Hete r o- FRET)  or sim i la r (Ho mo -F RET )f lu oroph ore s. We h ave used t his  m icroscope to de velop a ne w,photon effic ien t meth od  fo r  meas uri ng FR ET inl ivingcells bas ed on spe c tral im a g in g.

specifically_useful for_monitoring Forster?s Resonance Energy_Transfer (FRET)_between_either dissimilar_(Hetero-FRET)_or similar (Homo-FRET)_fluorophores. We have_used this microscope to_develop a new,_photon_efficient method for measuring FRET in living cells based on spectral imaging.


of the FGF20 gene, which modulates hippocampal biology, mRNA expression, verbal episodic memory, and morphology, was shown in T allele carriers to increase HP mRNA expression, had relatively larger HP volume, reduction in verbal episodic memory, and a sharp decline in HP volume with normal aging. From mRNA expression to brain morphology

of the FGF20 gene, which modulates hippocampal biology, mRNA expression, verbal episodic memory, and morphology, was testify in T allele carrier to increase HP mRNA expression, had relatively large HP volume, reduction in verbal episodic memory, and a astute descent in HP volume with normal ripening. From mRNA formula to brain morphology

of the FGF20 gene, which moduuates hippocampco biolmgy, mRHA exprersion, verbal episodic memory, abd moephology, was shown in G allele barriers ro iicrease HP mRNA xspression, had velatnvxly larger HP vplume, reduwtion in verban dpnsodic memory, and a sharp decline in HP volimf with normal wginb. Froj mRNA expression to brain morpholkgy

of the FGF20 gene, which modulates hippocampal expression, episodic memory, morphology, was shown increase mRNA expression, had larger HP volume, in verbal episodic memory, and a decline in HP volume with normal aging. From mRNA expression to brain morphology

of the FGF20 gene, which modulateS hippocampAl bioLogY, mRnA ExprEssiOn, verbal episodIC memOry, and morphology, was shoWn in T AlLEle cARrIers tO increaSE Hp MrNA ExPrEssIoN, HaD relaTivEly largEr HP volume, RedUcTion in verbal EPiSodic memorY, anD a sharp decliNe iN HP volUmE wiTH normAl aGing. FRom mRNa ExpresSion to braIn MOrpholOGy

of the FGF20 gene, whichmodulateshippo cam pal  b iolo gy,mRNA expressio n , ve rbal episodic memory,and m or p holo g y,  wasshown i n  T a lle le  c arr ie r sto in cre ase HPmRNA expre ssi on , had relati v el y larger H P v olume, reduc tio n in v er bal episo dic  memo ry, an d  a sha rp declin ei n HP v o lume wi t h  n orma l aging. From mRN A  e x pression to br ain mo rp h ol o g y

of_the FGF20_gene, which modulates hippocampal_biology, mRNA_expression,_verbal episodic_memory,_and morphology, was_shown in T_allele carriers to increase_HP mRNA expression,_had_relatively larger HP volume, reduction in verbal episodic memory, and a sharp decline in_HP_volume with_normal_aging._From mRNA expression to brain_morphology


gene expression signatures, in combination with comparative functional genomics, constitute an attractive paradigm for defining both the function of oncogenic pathways and the clinically relevant subgroups of human cancers. Transforming growth factor-beta (TGF-beta) is known to exhibit tumor stage dependent suppressive (growth inhibition) and oncogenic (inv

gene expression signatures, in combination with comparative functional genomics, establish an attractive prototype for defining both the function of oncogenic pathways and the clinically relevant subgroup of human cancers. Transforming emergence gene - beta (TGF - beta) is known to expose tumor stage dependent suppressive (emergence inhibition) and oncogenic (inv

geje expression signatures, in combination with cmmparafive funztional genomics, constitute en artracupve paradigm for defiving both the funxtioi of oncogenic pefhways and ths cliuirally relevant xubgroups mf human cancess. Txansforming growth factor-beta (TGF-betw) is knpwj to exhibit tomor xeage dependent suppressive (growth inhigition) end oncogenic (imv

gene expression signatures, in combination with comparative constitute attractive paradigm defining both the the relevant subgroups of cancers. Transforming growth (TGF-beta) is known to exhibit tumor dependent suppressive (growth inhibition) and oncogenic (inv

gene expression signatures, iN combinatiOn witH coMpaRaTive FuncTional genomics, COnstItute an attractive paradIgm foR dEFiniNG bOth thE functiON oF ONcoGeNiC paThWAyS and tHe cLinicalLy relevant SubGrOups of human cANcErs. TransfoRmiNg growth factOr-bEta (TGF-BeTa) iS Known To eXhibiT tumor STage dePendent suPpREssive (GRowth inHIBiTion) And oncogenic (inv

gene expression signature s, in comb inati onwit hcomp arat ive functional geno mics, constitute an at tract iv e  par a di gm fo r defin i ng b oth  t he  fu nc t io n ofonc ogenicpathways a ndth e clinically re levant sub gro ups of human  ca ncers.  T ran s formi nggrowt h fact o r-beta  (TGF-bet a) is kno w n to ex h i bi t tu mor stage depende n ts uppressive (gr owth i nh i bi t i on)  an d oncogeni c(inv

gene_expression signatures,_in combination with comparative_functional genomics,_constitute_an attractive_paradigm_for defining both_the function of_oncogenic pathways and the_clinically relevant subgroups_of_human cancers. Transforming growth factor-beta (TGF-beta) is known to exhibit tumor stage dependent suppressive_(growth_inhibition) and_oncogenic_(inv


tip. As ECM rigidity was increased, the traction peak did not oscillate and remained in the FA center, signifying the frictional slippage regime. We found that perturbing the gradient of paxillin phosphorylation across FA by expressing Y31/118E- or Y31/118F-paxillin

tip. As ECM rigidity was increased, the traction acme did not hover and remained in the FA center, signify the frictional slippage regimen. We found that perturbing the gradient of paxillin phosphorylation across FA by express Y31/118E- or Y31/118F - paxillin

tio. As ECM rigidity was ingreased, the tracjiin pean did hot osciulate and remained in the FA cwnter, signifying the frictiunal slipiage regine. Wt found that pertndbing tmz graslent mh paxillin phoskhorylation dcross FA by efpfedsing Y31/118E- or Y31/118F-paxillin

tip. As ECM rigidity was increased, the did oscillate and in the FA regime. found that perturbing gradient of paxillin across FA by expressing Y31/118E- or

tip. As ECM rigidity was increaSed, the tracTion pEak Did NoT oscIllaTe and remained iN The Fa center, signifying the frIctioNaL SlipPAgE regiMe. We fouND tHAT peRtUrBinG tHE gRadieNt oF paxillIn phosphorYlaTiOn across FA by EXpRessing Y31/118E- oR Y31/118F-Paxillin

tip. As ECM rigidity wasincreased,  thetra cti on  pea k di d not oscillat e  and  remained in the FA ce nter,  s i gnif y in g the  fricti o na l sli pp ag e r eg i me . Wefou nd that  perturbin g t he  gradient of pa xillin pho sph orylation ac ros s FA b yexp r essin g Y 31/11 8E- or Y31/11 8F-paxill in

tip._As ECM_rigidity was increased, the_traction peak_did_not oscillate_and_remained in the_FA center, signifying_the frictional slippage regime._We found that_perturbing_the gradient of paxillin phosphorylation across FA by expressing Y31/118E- or Y31/118F-paxillin


the field will need to re-visit the interpretations placed on crystal structures of TCR-pMHC interactions to explain the self-foreign antigen affinity connection we have uncovered. These data also have important implications for understanding the nature of T cells responding to self-antigens that promote autoimmune disease and for identifying the best subset of

the field will need to re - visit the interpretations rate on quartz glass structures of TCR - pMHC interactions to excuse the self - foreign antigen affinity joining we have uncovered. These data besides give birth important implications for understanding the nature of T cell responding to self - antigens that advertise autoimmune disease and for identifying the best subset of

thf field will need to re-vlsit the interprgtqtions places on cryrtal structures of TCR-pMHC iiterqctiobs to explain the self-woreign ajtigen adfinmty connection wx have ukeoversf. Thzsx data also havg important hmplications fmr uuderstanding the nature of T cells rqspondimg to self-antigegs tnwt pdomote autoimmune disease and for jdentifjing the best subxet of

the field will need to re-visit the on structures of interactions to explain we uncovered. These data have important implications understanding the nature of T cells to self-antigens that promote autoimmune disease and for identifying the best subset of

the field will need to re-visit The interprEtatiOns PlaCeD on cRystAl structures of tcR-pMhC interactions to explaiN the sElF-ForeIGn AntigEn affinITy CONneCtIoN we HaVE uNcoveRed. these daTa also have ImpOrTant implicatIOnS for undersTanDing the naturE of t cells ReSpoNDing tO seLf-antIgens tHAt promOte autoimMuNE diseaSE and for IDEnTifyIng the best subset oF

the field will need to re -visit the  inte rpr eta ti onsplac ed on crystals truc tures of TCR-pMHC inte racti on s  toe xp lainthe sel f -f o r eig nan tig en af finit y c onnecti on we have  un co vered. These da ta also ha veimportant im pli cation sfor under sta nding  the n a ture o f T cells  r e spondi n g to se l f -a ntig ens that promotea ut o immune disease  and f or id e n tif yin g the best  s ubset of

the_field will_need to re-visit the_interpretations placed_on_crystal structures_of_TCR-pMHC interactions to_explain the self-foreign_antigen affinity connection we_have uncovered. These_data_also have important implications for understanding the nature of T cells responding to self-antigens_that_promote autoimmune_disease_and_for identifying the best subset_of


using HLA-I at the ER, GOLGI/TGN and the plasma membrane (PM) was associated with Nef. The binding of Nef was similarly avid for native HLA-I and recombinant HLA-I A2 at the PM. Nef binding to HLA-I at the PM was sensitive to

using HLA - I at the ER, GOLGI / TGN and the plasma membrane (PM) was associated with Nef. The binding of Nef was similarly avid for native HLA - I and recombinant HLA - I A2 at the prime minister. Nef tie to HLA - I at the PM was sensible to

usijg HLA-I at the ER, GOLGI/TNN and the plasmc membrene (PM) sas assoziated with Nef. The binding lf Nef qas similarly avid for native HPA-I and eeconvinant HLA-M A2 at tmz PM. Hcf biudmng to HLA-I at jhe PM was sansitive to

using HLA-I at the ER, GOLGI/TGN and membrane was associated Nef. The binding for HLA-I and recombinant A2 at the Nef binding to HLA-I at the was sensitive to

using HLA-I at the ER, GOLGI/TGN aNd the plasmA membRanE (PM) WaS assOciaTed with Nef. The bINdinG of Nef was similarly avid For naTiVE HLA-i AnD recoMbinant hlA-i a2 At tHe pM. nef BiNDiNg to HlA-I At the PM Was sensitiVe tO

using HLA-I at the ER, GOL GI/TGN and  thepla sma  m embr ane(PM) was assoc i ated  with Nef. The binding  of N ef wass im ilarl y avidf or n ati ve  H LA- Ia nd  reco mbi nant HL A-I A2 atthe  P M. Nef bindi n gto HLA-I a t t he PM was se nsi tive t o

using HLA-I_at the_ER, GOLGI/TGN and the_plasma membrane_(PM)_was associated_with_Nef. The binding_of Nef was_similarly avid for native_HLA-I and recombinant_HLA-I_A2 at the PM. Nef binding to HLA-I at the PM was sensitive to


to the clinical lab pioneered a formal process that solves two of the most vexing and intransigent problems regarding laboratory studies of experimental drug action in cancer patient specimens at academic medical centers: first, because the drugs are experimental, the drug effect assays are highly specialized, and are only used during early clinical drug development,

to the clinical lab pioneered a formal process that solves two of the about exasperating and intransigent problems involve testing ground studies of experimental drug action in cancer affected role specimens at academic medical centers: foremost, because the drug are experimental, the drug effect assays are highly specialized, and are entirely used during early clinical drug development,

to the clinical lab pioneeved a formal proewss thet solvss two ow the most vexing and intranditent kgoblems regarding laburatory snudies of exptrimental drug acvjon in gcncer iatieut specimens at scademic madical centers: fkrdt, because the drugs are experimentwl, the crkg effect assais art hyghlg specialized, and are only used duding eagly clinical drug development,

to the clinical lab pioneered a formal solves of the vexing and intransigent experimental action in cancer specimens at academic centers: first, because the drugs are the drug effect assays are highly specialized, and are only used during early drug development,

to the clinical lab pioneered A formal proCess tHat SolVeS two Of thE most vexing and INtraNsigent problems regardiNg labOrATory STuDies oF experiMEnTAL drUg AcTioN iN CaNcer pAtiEnt specImens at acaDemIc Medical centeRS: fIrst, becausE thE drugs are expEriMental, ThE drUG effeCt aSsays Are higHLy specIalized, anD aRE only uSEd durinG EArLy clInical drug developMEnT,

to the clinical lab pione ered a for mal p roc ess  t hatsolv es two of them ostvexing and intransigen t pro bl e ms r e ga rding  labora t or y stu di es  of  e x pe rimen tal  drug a ction in c anc er  patient spe c im ens at aca dem ic medical c ent ers: f ir st, becau sethe d rugs a r e expe rimental,  t h e drug effecta s sa ys a re highly special i ze d , and are only  useddu r in g ear lyclinical d ru g dev e lopment ,

to_the clinical_lab pioneered a formal_process that_solves_two of_the_most vexing and_intransigent problems regarding_laboratory studies of experimental_drug action in_cancer_patient specimens at academic medical centers: first, because the drugs are experimental, the drug_effect_assays are_highly_specialized,_and are only used during_early clinical drug development,


broad range of LH pulsatility patterns and other features that are being investigated in the context of genetic variants, where identified, in order to increase our understanding of the ontogeny of these disorders. Our phenotyping efforts have identified that uterine anomalies and Chiari type 1 malformations may represent novel non-reproductive features

broad range of LH pulsatility patterns and other feature that are being investigate in the context of genetic variants, where identified, in orderliness to increase our understanding of the ontogeny of these disorder. Our phenotyping efforts have identified that uterine anomaly and Chiari type 1 malformations may represent fresh non - reproductive features

brlad range of LH pulsatillty patterns and other heaturea that afe being investigated in the cintexu of genetic variangs, where pdentifiee, in irder to iidrease our unscrstaudmng of the ontoneny of theve disorders. Ogr pkenotyping efforts have identified trat utetije anomalies agd Cnyari nyke 1 malformations may represent nkvel noi-reproductive fratures

broad range of LH pulsatility patterns and that being investigated the context of order increase our understanding the ontogeny of disorders. Our phenotyping efforts have identified uterine anomalies and Chiari type 1 malformations may represent novel non-reproductive features

broad range of LH pulsatility Patterns anD otheR feAtuReS thaT are Being investigaTEd in The context of genetic varIants, WhERe idENtIfied, In order TO iNCReaSe OuR unDeRStAndinG of The ontoGeny of thesE diSoRders. Our phenOTyPing effortS haVe identified ThaT uteriNe AnoMAlies And chiarI type 1 mALformaTions may rEpREsent nOVel non-rEPRoDuctIve features

broad range of LH pulsati lity patte rns a ndoth er  fea ture s that are bei n g in vestigated in the cont ext o fg enet i cvaria nts, wh e re i den ti fi ed,  i n  o rdertoincreas e our unde rst an ding of theo nt ogeny of t hes e disorders.  Ou r phen ot ypi n g eff ort s hav e iden t ifiedthat uter in e  anoma l ies and C hi aritype 1 malformati o ns may representnovelno n -r e p rod uct ive featur es

broad_range of_LH pulsatility patterns and_other features_that_are being_investigated_in the context_of genetic variants,_where identified, in order_to increase our_understanding_of the ontogeny of these disorders. Our phenotyping efforts have identified that uterine anomalies_and_Chiari type_1_malformations_may represent novel non-reproductive features


de-differentiating to ISCs to regenerate the epithelium under basal and pathological ISC dynamics. Using lineage tracing in vivo and in ex vivo organoids, we show that the enterochromaffin (EC) cell is the predominant EEC with this potential. These studies suggest that an ISC gene-expressing subset

de - differentiating to ISCs to regenerate the epithelium under basal and pathological ISC moral force. use lineage tracing in vivo and in ex vivo organoids, we picture that the enterochromaffin (EC) cellular telephone is the predominant EEC with this potential. These study suggest that an ISC gene - expressing subset

de-fifferentiating to ISCs uo regenerate the epithenium uhder basxl and pathological ISC dynalixs. Usung lineage tracing in vivo and in ex vuvo ieganoids, wx show tmct ths entzrichromaffin (EC) cell is tve predominant EDC with this potential. These studies fuggest tjat an ISC geng-exprtssyng albwet

de-differentiating to ISCs to regenerate the epithelium and ISC dynamics. lineage tracing in organoids, show that the (EC) cell is predominant EEC with this potential. These suggest that an ISC gene-expressing subset

de-differentiating to ISCs to Regenerate The epIthEliUm UndeR basAl and pathologiCAl ISc dynamics. Using lineage tRacinG iN Vivo ANd In ex vIvo orgaNOiDS, We sHoW tHat ThE EnTerocHroMaffin (Ec) cell is the PreDoMinant EEC witH ThIs potentiaL. ThEse studies suGgeSt that An iSC GEne-exPreSsing Subset

de-differentiating to ISC s to regen erate  th e e pi thel iumunder basal an d  pat hological ISC dynamics . Usi ng line a ge  trac ing inv iv o and  i nexvi v oorgan oid s, we s how that t heen terochromaff i n(EC) cellisthe predomin ant  EEC w it h t h is po ten tial.  These studie s suggest  t h at anI SC gene - e xp ress ing subset

de-differentiating_to ISCs_to regenerate the epithelium_under basal_and_pathological ISC_dynamics._Using lineage tracing_in vivo and_in ex vivo organoids,_we show that_the_enterochromaffin (EC) cell is the predominant EEC with this potential. These studies suggest that_an_ISC gene-expressing_subset


and after synthesis and to facilitate interaction of Vif with cellular cofactors required for the degradation of A3G. White blood cells called T lymphocytes play critical roles in immune defense against viruses, bacteria, fungi, protozoa, and cancer cells. They are also involved in allergies/asthma due to the development

and after synthesis and to facilitate interaction of Vif with cellular cofactors required for the abasement of A3G. blank blood cells call T lymphocytes act critical roles in immune defense against virus, bacteria, fungi, protozoa, and cancer cell. They are also involved in allergy / asthma due to the development

anf after synthesis and to facilitate intgrqction of Vir with cdllular cofactors required flr the eegradation of A3G. Whitd blood cvlls callwd T oymphocytes play cvnticam rolzs in immune defgnse against viruses, bactesix, yungi, protozoa, and cancer cells. They are alxo involved in ajlerbyes/aanhna due to the development

and after synthesis and to facilitate interaction with cofactors required the degradation of T play critical roles immune defense against bacteria, fungi, protozoa, and cancer cells. are also involved in allergies/asthma due to the development

and after synthesis and to facIlitate intEractIon Of VIf With CellUlar cofactors rEQuirEd for the degradation of A3g. WhitE bLOod cELlS callEd T lympHOcYTEs pLaY cRitIcAL rOles iN imMune defEnse againsT viRuSes, bacteria, fUNgI, protozoa, aNd cAncer cells. ThEy aRe also InVolVEd in aLleRgies/Asthma DUe to thE developmEnT

and after synthesis and t o facilita te in ter act io n of  Vif  with cellular cofa ctors required for the  degr ad a tion of  A3G.  Whiteb lo o d  ce ll scal le d  T  lymp hoc ytes pl ay critica l r ol es in immune de fense agai nst  viruses, ba cte ria, f un gi, proto zoa , and  cance r  cells . They ar ea lso in v olved i n al lerg ies/asthma due to th e  development

and_after synthesis_and to facilitate interaction_of Vif_with_cellular cofactors_required_for the degradation_of A3G. White_blood cells called T_lymphocytes play critical_roles_in immune defense against viruses, bacteria, fungi, protozoa, and cancer cells. They are also_involved_in allergies/asthma_due_to_the development


contraction dynamics. This work is being prepared for publication Project 2: PROTEOMIC ANALYSIS OF FOCAL ADHESION MATURATION Proteomic Analysis of Myosin II-mediated Focal Adhesion Maturation Reveals a Role for -Pix in Relaxation-mediated Rac1 Activation

contraction dynamics. This work is being prepared for issue Project 2: PROTEOMIC psychoanalysis OF FOCAL attachment MATURATION Proteomic Analysis of Myosin II - mediated Focal Adhesion Maturation reveal a Role for -Pix in rest - mediated Rac1 Activation

cojtraction dynamics. This dork is being ptepared hor pubmication Project 2: PROTEOMIC ANALYSIS OD FOCQL ADHESION MATURATION Proteomib Analysiw of Nyosin II-mxsiated Njcal Wdhevmon Maturation Teveals a Rone for -Pix in Seuaration-mediated Rac1 Activation

contraction dynamics. This work is being prepared Project PROTEOMIC ANALYSIS FOCAL ADHESION MATURATION Focal Maturation Reveals a for -Pix in Rac1 Activation

contraction dynamics. This woRk is being pReparEd fOr pUbLicaTion project 2: PROTEOMic ANAlYSIS OF FOCAL ADHESION MAtURATiOn protEOmIc AnaLysis of mYoSIN II-MeDiAteD FOCaL AdheSioN MaturaTion RevealS a ROlE for -Pix in RelAXaTion-mediatEd RAc1 Activation

contraction dynamics. Thi s work isbeing  pr epa re d fo r pu blication Proj e ct 2 : PROTEOMIC ANALYSIS O F FOC AL ADHE S IO N MAT URATION Pr o t eom ic  A nal ys i sof My osi n II-me diated Foc alAd hesion Matur a ti on Reveals  aRole for -Pi x i n Rela xa tio n -medi ate d Rac 1 Acti v ation

contraction_dynamics. This_work is being prepared_for publication_Project_2: PROTEOMIC_ANALYSIS_OF FOCAL ADHESION_MATURATION Proteomic Analysis_of Myosin II-mediated Focal_Adhesion Maturation Reveals_a_Role for -Pix in Relaxation-mediated Rac1 Activation


N-nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluids in relation to diabetes would be useful. By definition, genes that confer a phenotype when their copy number is changed encode factors that are limiting for physiological processes. In search of dosage-sensitive genes that influence arousal and/or

N - nitroso compounds, arsenic, dioxins, talc, and straight oil machining fluid in relation back to diabetes would be useful. By definition, genes that confer a phenotype when their copy phone number is changed encode factors that are restrict for physiological processes. In search of dose - sensitive genes that charm arousal and/or

N-nltroso compounds, arsenic, dioxins, talc, aue stramght oim machinkng fluids in relation to diebetws woyld be useful. By definktion, genvs that cinfec a phenotype whxh their copy hmmber ms changed encoce factors that are limidivg for physiological processes. In seawch of codage-sensitive denex thaf influence arousal and/or

N-nitroso compounds, arsenic, dioxins, talc, and straight fluids relation to would be useful. a when their copy is changed encode that are limiting for physiological processes. search of dosage-sensitive genes that influence arousal and/or

N-nitroso compounds, arsenic, dIoxins, talc, And stRaiGht OiL macHiniNg fluids in relaTIon tO diabetes would be useful. by defInITion, GEnEs thaT confer A PhENOtyPe WhEn tHeIR cOpy nuMbeR is chanGed encode fActOrS that are limiTInG for physioLogIcal processeS. In Search Of DosAGe-senSitIve geNes thaT InflueNce arousaL aND/or

N-nitroso compounds, arse nic, dioxi ns, t alc , a nd  str aigh t oil machinin g  flu ids in relation to dia betes  w o uldb eusefu l. By d e fi n i tio n,  g ene st ha t con fer  a phen otype when  th ei r copy numbe r  i s changedenc ode factorstha t areli mit i ng fo r p hysio logica l  proce sses. Inse a rch of dosage- s e ns itiv e genes that infl u en c e arousal and/ or

N-nitroso_compounds, arsenic,_dioxins, talc, and straight_oil machining_fluids_in relation_to_diabetes would be_useful. By definition,_genes that confer a_phenotype when their_copy_number is changed encode factors that are limiting for physiological processes. In search of_dosage-sensitive_genes that_influence_arousal_and/or


Based on our evaluation of the tool, which included individual interviews with 85 participants and three focus groups, we have finalized the workbook contents (NHGRI Protocol #12-HG-N023; PI: Laura Koehly). A manuscript describing this process has recently been published. The workbook is currently

Based on our evaluation of the tool, which included individual interviews with 85 participant and three stress groups, we have finalized the workbook content (NHGRI Protocol # 12 - HG - N023; PI: Laura Koehly). A manuscript report this process has recently been published. The workbook is presently

Baded on our evaluation of the tool, which includxd indibidual ivterviews with 85 participants abd theee focus groups, we haxe finalided the wirkbiik contents (NHGRI Ixotockp #12-HG-U023; 'I: Laura Koehly). A manuscrhpt describing tfid process has recently been publishqd. The eogkbook is currgntly

Based on our evaluation of the tool, individual with 85 and three focus workbook (NHGRI Protocol #12-HG-N023; Laura Koehly). A describing this process has recently been The workbook is currently

Based on our evaluation of the Tool, which iNcludEd iNdiViDual InteRviews with 85 partICipaNts and three focus groups, We havE fINaliZEd The woRkbook cONtENTs (NhGrI proToCOl #12-hG-N023; PI: lauRa KoehlY). A manuscriPt dEsCribing this pROcEss has receNtlY been publishEd. THe workBoOk iS CurreNtlY

Based on our evaluation o f the tool , whi chinc lu dedindi vidual intervi e ws w ith 85 participants an d thr ee focu s  g roups , we ha v ef i nal iz ed  th ew or kbook  co ntents(NHGRI Pro toc ol  #12-HG-N023 ;  P I: Laura K oeh ly). A manus cri pt des cr ibi n g thi s p roces s hasr ecentl y been pu bl i shed.T he work b o ok  iscurrently

Based_on our_evaluation of the tool,_which included_individual_interviews with_85_participants and three_focus groups, we_have finalized the workbook_contents (NHGRI Protocol_#12-HG-N023;_PI: Laura Koehly). A manuscript describing this process has recently been published. The workbook_is_currently


. These findings have been described in a manuscript that has been submitted for publication. These results have recently been published in the Journal of Biological Chemistry. Studies intended to delineate the mechanism(s) by which EpCAM stabilizes selected claudins are in progress. We have also begun to propagate mouse intestinal organoids and

. These findings have been described in a manuscript that has been submitted for publication. These result have recently been publish in the Journal of Biological Chemistry. Studies intended to delineate the mechanism(s) by which EpCAM brace selected claudins are in progress. We have besides begun to propagate mouse intestinal organoids and

. Thfse findings have been dtscribed in a manosxript vhat haa been sjbmitted for publication. Thede resuots have recently been publishef in the Joucnal of Biologicem Chemistry. Sfmdies mntended to dellneate the kechanism(s) by fhkck EpCAM stabilizes selected claudins are in pgogress. We havg alsp beghn to propagate mouse intestinal odganoidv and

. These findings have been described in that been submitted publication. These results the of Biological Chemistry. intended to delineate mechanism(s) by which EpCAM stabilizes selected are in progress. We have also begun to propagate mouse intestinal organoids and

. These findings have been descRibed in a maNuscrIpt ThaT hAs beEn suBmitted for publICatiOn. These results have receNtly bEeN PublIShEd in tHe JournAL oF bIolOgIcAl CHeMIsTry. StUdiEs intenDed to delinEatE tHe mechanism(s) BY wHich EpCAM sTabIlizes selectEd cLaudinS aRe iN ProgrEss. we havE also bEGun to pRopagate mOuSE intesTInal orgANOiDs anD

. These findings have been  described  in a  ma nus cr iptthat  has been subm i tted  for publication. Thes e res ul t s ha v erecen tly bee n  p u b lis he dinth e  J ourna l o f Biolo gical Chem ist ry . Studies in t en ded to del ine ate the mech ani sm(s)by  wh i ch Ep CAM  stab ilizes select ed claudi ns are in progres s .  W e ha ve also begun top ro p agate mouse in testin al or g a noi dsand

. These_findings have_been described in a_manuscript that_has_been submitted_for_publication. These results_have recently been_published in the Journal_of Biological Chemistry._Studies_intended to delineate the mechanism(s) by which EpCAM stabilizes selected claudins are in progress._We_have also_begun_to_propagate mouse intestinal organoids and


treatment since the study stopped. A less uniform response to rilonacept was observed in 2 patients, one of them was subsequently switched to the commercially available IL-6 blocking agent tocilizumab. BEHCETS DISEASE A cohort of patients with Behcets disease has been recruited by Dr. Henderson and the

treatment since the study stopped. A less uniform reception to rilonacept was observe in 2 patients, one of them was subsequently switch to the commercially available IL-6 obstruct agent tocilizumab. BEHCETS DISEASE A cohort of affected role with Behcets disease has been recruit by Dr. Henderson and the

trfatment since the study rtopped. A less onuform cesponss to rilunacept was observed in 2 patmentw, one of them was subsequengly switcjed to tye cinmercially available IL-6 gpocknnj agent tocilizomab. BEHCETS DISEASE A cohmrg lf patients with Behcets disease haf been tefruited by Dr. Rendtrsjn ahd the

treatment since the study stopped. A less to was observed 2 patients, one to commercially available IL-6 agent tocilizumab. BEHCETS A cohort of patients with Behcets has been recruited by Dr. Henderson and the

treatment since the study stoPped. A less uNiforM reSpoNsE to rIlonAcept was observED in 2 pAtients, one of them was subSequeNtLY swiTChEd to tHe commeRCiALLy aVaIlAblE Il-6 BlOckinG agEnt tociLizumab. BEHcETs DiSEASE A cohorT Of Patients wiTh BEhcets diseasE haS been rEcRuiTEd by DR. HeNdersOn and tHE

treatment since the study  stopped.A les s u nif or m re spon se to rilonace p t wa s observed in 2 patien ts, o ne of t h em  wassubsequ e nt l y  sw it ch edto th e com mer ciallyavailableIL- 6blocking age n ttocilizuma b.BEHCETS DISE ASE  A coh or t o f  pati ent s wit h Behc e ts dis ease hasbe e n recr u ited by D r.  Hen derson and the

treatment_since the_study stopped. A less_uniform response_to_rilonacept was_observed_in 2 patients,_one of them_was subsequently switched to_the commercially available_IL-6_blocking agent tocilizumab. BEHCETS DISEASE A cohort of patients with Behcets disease has been_recruited_by Dr._Henderson_and_the


ranasal (IN) and intratracheal (IT) routes was immunogenic and protective against SARS challenge in African green monkeys (AGM). We also previously evaluated HPIV3 as a vector to express the single glycoprotein GP of Ebola virus (EBOV). This construct was highly immunogenic and completely protective

ranasal (IN) and intratracheal (IT) routes was immunogenic and protective against SARS challenge in African green monkeys (AGM). We also previously measure HPIV3 as a vector to carry the single glycoprotein GP of Ebola virus (EBOV). This construct was highly immunogenic and completely protective

ranwsal (IN) and intratracheau (IT) routes was immunojenic ahd proteztive against SARS challenge ib Afrucan green monkeys (AGM). We also ireviouslt eveluated HPIV3 as e vector to exlvess chx single glycoptotein GP of Ebola virus (ETOX). Chis construct was highly immunogenis and cpmoletely protecjive

ranasal (IN) and intratracheal (IT) routes was protective SARS challenge African green monkeys HPIV3 a vector to the single glycoprotein of Ebola virus (EBOV). This construct highly immunogenic and completely protective

ranasal (IN) and intratracheal (iT) routes waS immuNogEniC aNd prOtecTive against SARs ChalLenge in African green monKeys (AgM). wE alsO PrEviouSly evalUAtED hPIv3 aS a VecToR To ExpreSs tHe singlE glycoprotEin gP Of Ebola virus (ebOv). This constRucT was highly imMunOgenic AnD coMPleteLy pRotecTive

ranasal (IN) and intratrac heal (IT)route s w asim muno geni c and protecti v e ag ainst SARS challenge i n Afr ic a n gr e en  monk eys (AG M ). W e a ls opre vi o us ly ev alu ated HP IV3 as a v ect or  to expresst he  single gl yco protein GP o f E bola v ir us( EBOV) . T his c onstru c t washighly im mu n ogenic and com p l et elyprotective

ranasal (IN)_and intratracheal_(IT) routes was immunogenic_and protective_against_SARS challenge_in_African green monkeys_(AGM). We also_previously evaluated HPIV3 as_a vector to_express_the single glycoprotein GP of Ebola virus (EBOV). This construct was highly immunogenic and_completely_protective


, or linked to pathogenesis or host range. Each P-MLV has an E-MLV backbone with P- or X-ERV replacements that together cover 100% of the recombinant genomes, with different substitution patterns for X- and P-ERVs. Two segments are always replaced, in envelope (Env): the

, or linked to pathogenesis or host range. Each P - MLV has an E - MLV spine with P- or X - ERV replacements that in concert cover 100% of the recombinant genomes, with unlike substitution patterns for X- and phosphorus - ERVs. Two segments are always substitute, in envelope (Env ): the

, or linked to pathogenesis ur host range. Ecxh P-MLT has ah E-MLV bxckbone with P- or X-ERV replaremebts tyat together cover 100% of the recolbinant tenonws, with dihrerent substifmtion 'atterns for X- snd P-ERVs. Dwo segments ase apways replaced, in envelope (Env): the

, or linked to pathogenesis or host P-MLV an E-MLV with P- or 100% the recombinant genomes, different substitution patterns X- and P-ERVs. Two segments are replaced, in envelope (Env): the

, or linked to pathogenesis or hOst range. EaCh P-MLv haS an e-MlV baCkboNe with P- or X-ERV rEPlacEments that together coveR 100% of thE rECombINaNt genOmes, witH DiFFEreNt SuBstItUTiOn patTerNs for X- aNd P-ERVs. Two SegMeNts are always REpLaced, in envEloPe (Env): the

, or linked to pathogenesi s or hostrange . E ach  P -MLV  has  an E-MLV back b onewith P- or X-ERV repla cemen ts that to gethe r cover 10 0 %  of  t he  re co m bi nantgen omes, w ith differ ent  s ubstitutionp at terns forX-and P-ERVs.Two  segme nt s a r e alw ays  repl aced,i n enve lope (Env ): the

, or_linked to_pathogenesis or host range._Each P-MLV_has_an E-MLV_backbone_with P- or_X-ERV replacements that_together cover 100% of_the recombinant genomes,_with_different substitution patterns for X- and P-ERVs. Two segments are always replaced, in envelope_(Env):_the


A direct relationship exists between membrane-associated ARTS-1 protein levels and concordant changes in the release of soluble TNFR1. Cells over-expressing ARTS-1 demonstrated increased soluble TNFR1 release and decreased membrane-associated TNFR1, while cells expressing anti-sense ARTS-1 mRNA demonstrated decreased

A direct relationship exists between membrane - associated ARTS-1 protein degree and accordant changes in the release of soluble TNFR1. cell all over - expressing ARTS-1 demonstrated increased soluble TNFR1 acquittance and decreased membrane - associated TNFR1, while cell expressing anti - sense ARTS-1 mRNA demonstrated decrease

A firect relationship exisus between membrauw-assocmated ADTS-1 protdin levels and concordant chengew in uke release of solubld TNFR1. Cepls over-wxprtssing ARTS-1 demonstrated lucreaacd sonnble TNFR1 releaxe and decseased membrana-arslciated TNFR1, while cells expressing anti-semsf ARTS-1 mRNA deionsuraeed svcveased

A direct relationship exists between membrane-associated ARTS-1 and changes in release of soluble increased TNFR1 release and membrane-associated TNFR1, while expressing anti-sense ARTS-1 mRNA demonstrated decreased

A direct relationship exists Between memBrane-AssOciAtEd ARtS-1 prOtein levels and COncoRdant changes in the releaSe of sOlUBle TnfR1. cells Over-expREsSINg ArTs-1 dEmoNsTRaTed inCreAsed solUble TNFR1 reLeaSe And decreased MEmBrane-assocIatEd TNFR1, while cEllS expreSsIng ANti-seNse aRTS-1 mrNA demONstratEd decreasEd

A direct relationship exi sts betwee n mem bra ne- as soci ated  ARTS-1 protei n  lev els and concordant cha ngesin ther el easeof solu b le T NFR 1.  C ell so ve r-exp res sing AR TS-1 demon str at ed increased so luble TNFR 1 r elease and d ecr easedme mbr a ne-as soc iated  TNFR1 ,  while  cells ex pr e ssinga nti-sen s e  A RTS- 1 mRNA demonstrat e dd ecreased

A_direct relationship_exists between membrane-associated ARTS-1_protein levels_and_concordant changes_in_the release of_soluble TNFR1. Cells_over-expressing ARTS-1 demonstrated increased_soluble TNFR1 release_and_decreased membrane-associated TNFR1, while cells expressing anti-sense ARTS-1 mRNA demonstrated decreased


activity may regulate hippocampal electrical oscillations, which arise from coordinated activity among distinct populations of neurons and are associated with cognitive functions. Using the controlled experimental system of excitatory and inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to manipulate CA2 neuronal activity in mice, we studied hippocampal-pref

activity may regulate hippocampal electrical oscillations, which rebel from coordinated natural process among distinct populations of neurons and are consort with cognitive functions. Using the manipulate experimental organization of excitatory and inhibitory Designer receptor Exclusively Activated by couturier Drugs (DREADDs) to manipulate CA2 neural activity in mice, we studied hippocampal - pref

achivity may regulate hippucampal electrieql oscmllatiohs, which arise from coordinated actitity amont distinct populations of neurojs and aee awwociated wmfh cognlcive rmnctimis. Using the coktrolled ex[erimental sysdeo lf excitatory and inhibitory Designqr Receltlrs Exclusiveli Actpvwted by Designer Drugs (DREADDs) to manilulate BA2 neuronal activoty in mice, we studied hipoocalpal-pref

activity may regulate hippocampal electrical oscillations, which coordinated among distinct of neurons and Using controlled experimental system excitatory and inhibitory Receptors Exclusively Activated by Designer Drugs to manipulate CA2 neuronal activity in mice, we studied hippocampal-pref

activity may regulate hippocAmpal electRical OscIllAtIons, WhicH arise from coorDInatEd activity among distincT popuLaTIons OF nEuronS and are ASsOCIatEd WiTh cOgNItIve fuNctIons. UsiNg the contrOllEd Experimental SYsTem of excitAtoRy and inhibitOry designEr recEPtors excLusivEly ActIVated bY Designer drUGs (DREAdds) to manIPUlAte Ca2 neuronal activity IN mICe, we studied hipPocampAl-PReF

activity may regulate hip pocampal e lectr ica l o sc illa tion s, which arise from  coordinated activityamong  d i stin c tpopul ationso fn e uro ns  a ndar e  a ssoci ate d withcognitivefun ct ions. Usingt he  controlle d e xperimentalsys tem of  e xci t atory  an d inh ibitor y  Desig ner Recep to r s Excl u sivelyA c ti vate d by Designer Dru g s( DREADDs) to ma nipula te CA 2 neu ron al activit yin mi c e, we s t ud i e d  hi p pocampal-pref

activity_may regulate_hippocampal electrical oscillations, which_arise from_coordinated_activity among_distinct_populations of neurons_and are associated_with cognitive functions. Using_the controlled experimental_system_of excitatory and inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to manipulate_CA2_neuronal activity_in_mice,_we studied hippocampal-pref


P labeling to identify SAMHD1 as a phosphoprotein, both endogenously in THP-1 cells and after exogenous expression in HeLa cells. Several amino acids in SAMHD1 were identified to be sites of phosphorylation using direct mass spectrometry Mutation of these residues to alanine, to prevent phosphorylation, or to glutamic

P labeling to identify SAMHD1 as a phosphoprotein, both endogenously in THP-1 cells and after exogenous expression in HeLa cell. respective amino acids in SAMHD1 were identified to be web site of phosphorylation use direct mass spectroscopy Mutation of these residues to alanine, to prevent phosphorylation, or to glutamic

P lwbeling to identify SAMHA1 as a phosphoptorein, bmth ensogenousuy in THP-1 cells and after exlgwnous expression in HeLa ceuls. Severwl amino acivs in SAMHD1 were identiflzd to ne sicew of phosphorykation usitg direct mass soeetrometry Mutation of these residues to alamije, to prevent khospnjrylzniin, or to glutamic

P labeling to identify SAMHD1 as a endogenously THP-1 cells after exogenous expression acids SAMHD1 were identified be sites of using direct mass spectrometry Mutation of residues to alanine, to prevent phosphorylation, or to glutamic

P labeling to identify SAMHD1 aS a phosphopRoteiN, boTh eNdOgenOuslY in THP-1 cells and AFter Exogenous expression in HELa ceLlS. seveRAl Amino Acids in saMhd1 WerE iDeNtiFiED tO be siTes Of phospHorylation UsiNg Direct mass spECtRometry MutAtiOn of these resIduEs to alAnIne, TO prevEnt PhospHorylaTIon, or tO glutamic

P labeling to identify SAM HD1 as a p hosph opr ote in , bo th e ndogenously in THP- 1 cells and after exog enous  e x pres s io n inHeLa ce l ls . Sev er al  am in o  a cidsinSAMHD1were ident ifi ed  to be sites of  phosphory lat ion using di rec t mass  s pec t romet ryMutat ion of theseresiduesto alanin e , to pr e v en t ph osphorylation, or to glutamic

P labeling_to identify_SAMHD1 as a phosphoprotein,_both endogenously_in_THP-1 cells_and_after exogenous expression_in HeLa cells._Several amino acids in_SAMHD1 were identified_to_be sites of phosphorylation using direct mass spectrometry Mutation of these residues to alanine,_to_prevent phosphorylation,_or_to_glutamic


the effect of ions on the structure and dynamic properties of synthetic and biopolymers we developed a multi-scale experimental framework by combining high-resolution techniques, such as small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), and static light scattering (SLS), with macroscopic methods

the effect of ions on the structure and dynamic place of synthetic and biopolymers we modernize a multi - scale experimental framework by combining high - resoluteness techniques, such as small - slant X - ray scattering (SAXS), minor - angle neutron scattering (SANS), and electrostatic light scattering (SLS), with macroscopic method acting

thf effect of ions on the rtructure and dinqmic pcopertiss of syvthetic and biopolymers we dxveliped q multi-scale experimengal frameaork by xombmning high-resoluvjon tecmuiquea, suck es small-angle X-tay scatteritg (SAXS), small-atgue neutron scattering (SANS), and static light xcwttering (SLS), wyth kwcroabokic methods

the effect of ions on the structure properties synthetic and we developed a high-resolution such as small-angle scattering (SAXS), small-angle scattering (SANS), and static light scattering with macroscopic methods

the effect of ions on the strucTure and dynAmic pRopErtIeS of sYnthEtic and biopolyMErs wE developed a multi-scale eXperiMeNTal fRAmEwork By combiNInG HIgh-ReSoLutIoN TeChniqUes, Such as sMall-angle X-Ray ScAttering (SAXS), SMaLl-angle neuTroN scattering (SaNS), And staTiC liGHt scaTteRing (SlS), with MAcroscOpic methoDs

the effect of ions on the  structure  anddyn ami cprop erti es of syntheti c  and  biopolymers we develo ped a  m u lti- s ca le ex perimen t al f ram ew or k b yc om binin g h igh-res olution te chn iq ues, such as sm all-angleX-r ay scatterin g ( SAXS),  s mal l -angl e n eutro n scat t ering(SANS), a nd static light s c a tt erin g (SLS), with mac r os c opic methods

the_effect of_ions on the structure_and dynamic_properties_of synthetic_and_biopolymers we developed_a multi-scale experimental_framework by combining high-resolution_techniques, such as_small-angle_X-ray scattering (SAXS), small-angle neutron scattering (SANS), and static light scattering (SLS), with macroscopic_methods


fail compliance sensing regime and a frictional slippage regime as described in the clutch oscillation model (Chan and Odde, 2008). In the load and fail regime, the position of peak traction within the FA resided on average at the distal FA tip, but oscillated over time towards the FA center and back to the

fail compliance sensing regime and a frictional slippage regime as trace in the clutch cycle model (Chan and Odde, 2008). In the load and fail government, the status of peak traction within the FA resided on median at the distal FA point, but oscillated over time towards the FA center and back to the

faip compliance sensing reglme and a frictional slmppage degime ar described in the clutch osrillqtion model (Chan and Odde, 2008). Kn the lowd and fqil cegime, the positmkn of pcck trzgtion xithin the FA rgsided on avarage at the dhsgap FA tip, but oscillated over time tjwards yhf FA center anq babk to fhe

fail compliance sensing regime and a frictional as in the oscillation model (Chan load fail regime, the of peak traction the FA resided on average at distal FA tip, but oscillated over time towards the FA center and back the

fail compliance sensing regiMe and a fricTionaL slIppAgE regIme aS described in thE ClutCh oscillation model (Chan And OdDe, 2008). iN the LOaD and fAil regiME, tHE PosItIoN of PeAK tRactiOn wIthin thE FA resided On aVeRage at the disTAl fA tip, but osCilLated over timE toWards tHe fA cENter aNd bAck to The

fail compliance sensing re gime and a  fric tio nal  s lipp ageregime as desc r ibed  in the clutch oscilla tionmo d el ( C ha n and  Odde,2 00 8 ) . I nth e l oa d  a nd fa ilregime,  the posit ion  o f peak tract i on  within th e F A resided on  av erageat  th e  dist alFA ti p, but oscill ated over  t i me tow a rds the F Acent er and back to th e

fail compliance_sensing regime_and a frictional slippage_regime as_described_in the_clutch_oscillation model (Chan_and Odde, 2008)._In the load and_fail regime, the_position_of peak traction within the FA resided on average at the distal FA tip,_but_oscillated over_time_towards_the FA center and back_to the


signature showed significantly (P <0.005) shortened mean survival time (16.25.3 months) compared to patients with the early TGF-beta signature (60.716.1 months). Significantly, tumors expressing the late TGF-beta-responsive genes displayed invasive phenotype and increased tumor recurrence. Also

signature showed significantly (P & lt;0.005) shorten base survival time (16.25.3 months) compared to affected role with the early TGF - beta signature (60.716.1 months). importantly, tumors expressing the late TGF - beta - reactive gene displayed invasive phenotype and increase tumor recurrence. Also

sihnature showed significaktly (P <0.005) shorteuwd meai survibal time (16.25.3 months) compared to patientd qith uke early TGF-beta sigvature (60.716.1 mlnths). Sitnifmcantly, tumors eelressinn the pate VGF-beta-responsiye genes divplayed invasiee pkenotype and increased tumor recurregce. Alsp

signature showed significantly (P <0.005) shortened mean (16.25.3 compared to with the early tumors the late TGF-beta-responsive displayed invasive phenotype increased tumor recurrence. Also

signature showed significanTly (P <0.005) shorTened MeaN suRvIval Time (16.25.3 Months) compared TO patIents with the early TGF-beTa sigNaTUre (60.716.1 mONtHs). SigNificanTLy, TUMorS eXpResSiNG tHe latE TGf-beta-reSponsive geNes DiSplayed invasIVe Phenotype aNd iNcreased tumoR reCurrenCe. alsO

signature showed signific antly (P & lt;0. 005 ) s ho rten ed m ean survival t i me ( 16.25.3 months) compar ed to  p a tien t swiththe ear l yT G F-b et asig na t ur e (60 .71 6.1 mon ths). Sign ifi ca ntly, tumors ex pressing t helate TGF-bet a-r espons iv e g e nes d isp layed  invas i ve phe notype an di ncreas e d tumor r ec urre nce. Also

signature_showed significantly_(P <0.005) shortened mean_survival time_(16.25.3_months) compared_to_patients with the_early TGF-beta signature_(60.716.1 months). Significantly, tumors_expressing the late_TGF-beta-responsive_genes displayed invasive phenotype and increased tumor recurrence. Also


ending success of these proof-of-concept experiments, options will be explored to develop this concept clinically. The mechanisms underlying the profound modulation of parasite antigen-specific human T cell responses in lymphatic filariasis have been addressed by demonstrating the multiple pathways involved. In terms of APC dysfunction, human monocytes from patients with patent fil

ending success of these proof - of - concept experiments, choice will be explore to develop this concept clinically. The mechanisms underlying the heavy modulation of parasite antigen - specific human T cellular telephone responses in lymphatic filariasis have been addressed by demonstrating the multiple nerve pathway involved. In terms of APC dysfunction, human monocyte from patients with patent fil

endlng success of these prouf-of-concept expgruments, optiohs will ce explored to develop this roncwpt coinically. The mechanisos underljing the profiynd modulavjon of icrasifc antngxn-specific humak T cell revponses in lym[hxtnc filariasis have been addressed by demonsyrwting the multyple [athsays involved. In terms of APC dysfhnction, human monocyyes from patients with patfnt vil

ending success of these proof-of-concept experiments, options explored develop this clinically. The mechanisms parasite human T cell in lymphatic filariasis been addressed by demonstrating the multiple involved. In terms of APC dysfunction, human monocytes from patients with patent fil

ending success of these proof-Of-concept eXperiMenTs, oPtIons Will Be explored to deVElop This concept clinically. THe mecHaNIsms UNdErlyiNg the prOFoUND moDuLaTioN oF PaRasitE anTigen-spEcific humaN T cElL responses in LYmPhatic filaRiaSis have been aDdrEssed bY dEmoNStratIng The muLtiple PAthwayS involved. in TErms of apC dysfuNCTiOn, huMan monocytes from pATiENts with patent fIl

ending success of these pr oof-of-con ceptexp eri me nts,  opt ions will be e x plor ed to develop this con ceptcl i nica l ly . The  mechan i sm s und er ly ing  t h eprofo und  modula tion of pa ras it e antigen-sp e ci fic humanT c ell response s i n lymp ha tic filar ias is ha ve bee n  addre ssed by d em o nstrat i ng them u lt iple  pathways involve d .I n terms of APC  dysfu nc t io n ,  hu man  monocytes  f rom p a tientsw it h p ate n t fil

ending success_of these_proof-of-concept experiments, options will_be explored_to_develop this_concept_clinically. The mechanisms_underlying the profound_modulation of parasite antigen-specific_human T cell_responses_in lymphatic filariasis have been addressed by demonstrating the multiple pathways involved. In terms_of_APC dysfunction,_human_monocytes_from patients with patent fil


2 by HIV-1 Vpu is mediated by cytoplasmic domain interactions. We knew that Vpu encoded by NL4-3, a widely used HIV-1 laboratory strain, antagonizes human BST-2 but not monkey or murine BST-2 leading to the impression that BST-2 antagonism by V

2 by HIV-1 Vpu is mediated by cytoplasmic domain interactions. We knew that Vpu encode by NL4 - 3, a wide practice HIV-1 laboratory strain, antagonize human BST-2 but not monkey or murine BST-2 leading to the mental picture that BST-2 antagonism by V

2 by HIV-1 Vpu is mediated by gytoplasmic domanb intecactiona. We kned that Vpu encoded by NL4-3, a wmdelt usee HIV-1 laboratory straiv, antagonpzes humab BSU-2 but not monkey or murinc BST-2 peadnnj to the impresxion that TST-2 antagonism bh R

2 by HIV-1 Vpu is mediated by interactions. knew that encoded by NL4-3, strain, human BST-2 but monkey or murine leading to the impression that BST-2 by V

2 by HIV-1 Vpu is mediated by cytopLasmic domaIn intEraCtiOnS. We kNew tHat Vpu encoded bY nL4-3, a wIdely used HIV-1 laboratory StraiN, aNTagoNIzEs humAn BST-2 buT NoT MOnkEy Or MurInE bSt-2 leadIng To the imPression thAt BsT-2 Antagonism by v

2 by HIV-1 Vpu is mediated  by cytopl asmic  do mai ninte ract ions. We knewt hatVpu encoded by NL4-3,a wid el y  use d  H IV-1laborat o ry s tra in ,ant ag o ni zes h uma n BST-2  but not m onk ey  or murine B S T- 2 leadingtothe impressi onthat B ST -2a ntago nis m byV

2 by_HIV-1 Vpu_is mediated by cytoplasmic_domain interactions._We_knew that_Vpu_encoded by NL4-3,_a widely used_HIV-1 laboratory strain, antagonizes_human BST-2 but_not_monkey or murine BST-2 leading to the impression that BST-2 antagonism by V


malarial coinfections) and to mycobacterial antigens (in filarial/latent tuberculosis coinfections). Lymphatic filarial disease manifested by overt, morbid clinical pathology, characterized by swelling of the scrotal area and limb edema (hydrocele, elephantiasis, lymphedema) has been

malarial coinfections) and to mycobacterial antigens (in filarial / latent tuberculosis coinfections). Lymphatic filarial disease manifested by overt, morbid clinical pathology, characterized by bulge of the scrotal sphere and limb edema (hydrocele, elephantiasis, lymphedema) has been

malwrial coinfections) and tu mycobacterial antigeis (in fjlarial/lxtent tuberculosis coinfectilnw). Lymkkatic filarial diseare manifedted by iveru, morbid clinical patholonv, chadwctexived by swelling of the scsotal area and lkmy edema (hydrocele, elephantiasis, lympredema) nad been

malarial coinfections) and to mycobacterial antigens (in coinfections). filarial disease by overt, morbid of scrotal area and edema (hydrocele, elephantiasis, has been

malarial coinfections) and to MycobacterIal anTigEns (In FilaRial/Latent tuberculOSis cOinfections). Lymphatic fiLariaL dISeasE MaNifesTed by ovERt, MORbiD cLiNicAl PAtHologY, chAracterIzed by swelLinG oF the scrotal aREa And limb edeMa (hYdrocele, elepHanTiasis, LyMphEDema) hAs bEen

malarial coinfections) and  to mycoba cteri alant ig ens(infilarial/laten t  tub erculosis coinfections ). Ly mp h atic fi laria l disea s em a nif es te d b yo ve rt, m orb id clin ical patho log y,  characteriz e dby swellin g o f the scrota l a rea an dlim b  edem a ( hydro cele,e lephan tiasis, l ym p hedema )  has be e n

malarial coinfections)_and to_mycobacterial antigens (in filarial/latent_tuberculosis coinfections)._Lymphatic_filarial disease_manifested_by overt, morbid_clinical pathology, characterized_by swelling of the_scrotal area and_limb_edema (hydrocele, elephantiasis, lymphedema) has been


that transfection of active Rac1 (Rac1V12) induced PKC- and integrin-dependent myosin IIA phosphoryation on Ser 1916. Live cell imaging of GFP-myosin IIA revealed that Rac1 activation promotes rapid assembly, motion, and turnover of myosin IIA minifilaments, as well as

that transfection of active Rac1 (Rac1V12) induced PKC- and integrin - dependent myosin IIA phosphoryation on Ser 1916. Live cell imagination of GFP - myosin IIA reveal that Rac1 activation promotes rapid fabrication, movement, and turnover of myosin IIA minifilaments, as well as

thwt transfection of activt Rac1 (Rac1V12) induceb PKC- aid intefrin-depevdent myosin IIA phosphoryatmon in See 1916. Live cell imaging ow GFP-myospn IIA recealtd that Rac1 activefion promotes vapid essembly, motion, and turnoeer of myosin HIX linifilaments, as well as

that transfection of active Rac1 (Rac1V12) induced integrin-dependent IIA phosphoryation Ser 1916. Live revealed Rac1 activation promotes assembly, motion, and of myosin IIA minifilaments, as well

that transfection of active RAc1 (Rac1V12) induCed PKc- anD inTeGrin-DepeNdent myosin IIA PHospHoryation on Ser 1916. Live cell ImagiNg OF GFP-MYoSin IIa revealED tHAT RaC1 aCtIvaTiON pRomotEs rApid assEmbly, motioN, anD tUrnover of myoSIn iIA minifilAmeNts, as well as

that transfection of acti ve Rac1 (R ac1V1 2)ind uc ed P KC-and integrin-d e pend ent myosin IIA phospho ryati on on S e r1916.  Live c e ll i mag in gofGF P -m yosin  II A revea led that R ac1  a ctivation pr o mo tes rapidass embly, motio n,and tu rn ove r  of m yos in II A mini f ilamen ts, as we ll as

that_transfection of_active Rac1 (Rac1V12) induced_PKC- and_integrin-dependent_myosin IIA_phosphoryation_on Ser 1916._Live cell imaging_of GFP-myosin IIA revealed_that Rac1 activation_promotes_rapid assembly, motion, and turnover of myosin IIA minifilaments, as well as


8(+) T cells compared to that of unexposed monocytes. Similar to results with IL-4, exposure of monocytes to live mf induced upregulation of CCL15, CCL17, CCL18, CCL22, CD274, and CD273 and downregulation of Toll-like receptor 3 (TLR3), TLR5

8(+) T cells compared to that of unexposed monocytes. exchangeable to result with IL-4, exposure of monocytes to live mf induce upregulation of CCL15, CCL17, CCL18, CCL22, CD274, and CD273 and downregulation of Toll - like sense organ 3 (TLR3), TLR5

8(+) T fells compared to that on unexposed monoettes. Smmilar fo resulgs with IL-4, exposure of monocbtes to luve mf induced upregulxtion of BCL15, CCL17, CXL18, CRL22, CD274, and CD273 and downregmjatikk of Cool-like receptot 3 (TLR3), TLR5

8(+) T cells compared to that of Similar results with exposure of monocytes of CCL17, CCL18, CCL22, and CD273 and of Toll-like receptor 3 (TLR3), TLR5

8(+) T cells compared to that of uneXposed monoCytes. simIlaR tO resUlts With IL-4, exposure OF monOcytes to live mf induced uPreguLaTIon oF cCl15, CCL17, CcL18, CCL22, CD274, ANd cd273 And DoWnRegUlATiOn of TOll-Like recEptor 3 (TLR3), TLr5

8(+) T cells compared to t hat of une xpose d m ono cy tes.  Sim ilar to result s  wit h IL-4, exposure of mo nocyt es to l i ve  mf i nducedu pr e g ula ti on  of  C C L1 5, CC L17 , CCL18 , CCL22, C D27 4,  and CD273 a n ddownregula tio n of Toll-li kerecept or  3( TLR3) , T LR5

8(+) T_cells compared_to that of unexposed_monocytes. Similar_to_results with_IL-4,_exposure of monocytes_to live mf_induced upregulation of CCL15,_CCL17, CCL18, CCL22,_CD274,_and CD273 and downregulation of Toll-like receptor 3 (TLR3), TLR5


provided evidence that families are a social context for which social network based interventions may be particularly effective in motivating the dissemination of genomic risk information and engaging families in cooperative approaches to facilitate positive adaptation to disease risk. However, not much is known about other social spheres in which health information is exchanged that may be leveraged in network

provided evidence that families are a social context for which social network based interposition may be peculiarly effective in motivating the dissemination of genomic hazard information and engage families in cooperative approach to facilitate positive adaptation to disease hazard. However, not much is know about other social sector in which health information is exchanged that may be leverage in net

prlvided evidence that famllies are a socico contxxt for which sucial network based intervenvionw may be particularly effecgive in mltivatint tht dissemination oh genomig risi infmcmation and engsging faminies in cooperdtkvz approaches to facilitate positive wdaptatooj to disease rysk. Njwevsg, kot much is known about other sodial spieres in which nealth information is exchwngef that may be levegaged in nejsorh

provided evidence that families are a social which network based may be particularly of risk information and families in cooperative to facilitate positive adaptation to disease However, not much is known about other social spheres in which health information exchanged that may be leveraged in network

provided evidence that familIes are a socIal coNteXt fOr WhicH socIal network baseD InteRventions may be particulArly eFfECtivE In MotivAting thE DiSSEmiNaTiOn oF gENoMic riSk iNformatIon and engaGinG fAmilies in cooPErAtive approAchEs to facilitaTe pOsitivE aDapTAtion To dIseasE risk. HOWever, nOt much is kNoWN about OTher socIAL sPherEs in which health inFOrMAtion is exchangEd that MaY Be LEVerAgeD in network

provided evidence that fa milies are  a so cia l c on text  for  which socialn etwo rk based interventions  maybe part i cu larly  effect i ve i n m ot iv ati ng th e dis sem ination  of genomi c r is k informatio n  a nd engagin g f amilies in c oop erativ eapp r oache s t o fac ilitat e  posit ive adapt at i on tod iseaser i sk . Ho wever, not much i s  k n own about othe r soci al sp h e res  in  which hea lt h inf o rmation is e x cha n ged that maybe leverage d  in  netwo rk

provided_evidence that_families are a social_context for_which_social network_based_interventions may be_particularly effective in_motivating the dissemination of_genomic risk information_and_engaging families in cooperative approaches to facilitate positive adaptation to disease risk. However, not_much_is known_about_other_social spheres in which health_information is exchanged that may_be leveraged_in network


adhesion using human intestinal epithelial cells as a model system. We have determined that EpCAM acts in part by binding tightly to the tight junction-associated protein claudin-7. This interaction sequesters claudin-7 distinctly away from tight junctions and protects claudin-7 and associated claudin-1

adhesion using human intestinal epithelial cells as a model arrangement. We have determine that EpCAM acts in part by binding tightly to the compressed junction - associated protein claudin-7. This interaction seclude claudin-7 distinctly off from tight junctions and protects claudin-7 and associated claudin-1

adjesion using human intesuinal epithelial ewlls av a mosel systdm. We have determined that E'CAM acts in part by binding tiehtly to nhe tight junrtion-associated 'dotein gjaudjk-7. Thiv interaction sgquesters cldudin-7 distinctny acay from tight junctions and protectf claudon-7 and associateq clstdin-1

adhesion using human intestinal epithelial cells as system. have determined EpCAM acts in the junction-associated protein claudin-7. interaction sequesters claudin-7 away from tight junctions and protects and associated claudin-1

adhesion using human intestiNal epithelIal ceLls As a MoDel sYsteM. We have determiNEd thAt EpCAM acts in part by binDing tIgHTly tO ThE tighT junctiON-aSSOciAtEd ProTeIN cLaudiN-7. ThIs interAction sequEstErS claudin-7 distINcTly away froM tiGht junctions And ProtecTs ClaUDin-7 anD asSociaTed claUDin-1

adhesion using human inte stinal epi theli alcel ls  asa mo del system. We have  determined that EpCAM  acts  i n  par t  b y bin ding ti g ht l y  to  t he  ti gh t  j uncti on- associa ted protei n c la udin-7. This in teractionseq uesters clau din -7 dis ti nct l y awa y f rom t ight j u nction s and pro te c ts cla u din-7 a n d  a ssoc iated claudin-1

adhesion_using human_intestinal epithelial cells as_a model_system._We have_determined_that EpCAM acts_in part by_binding tightly to the_tight junction-associated protein_claudin-7._This interaction sequesters claudin-7 distinctly away from tight junctions and protects claudin-7 and associated_claudin-1


-based interventions. To this end, we have developed an assessment tool to be used for large scale collection of social network information from participants that will identify social network typologies that might be used to tailor health promotion interventions. A description of these data was recently presented at the annual meeting of the International Network of Social Network Analysis

-based interventions. To this end, we have developed an assessment cock to be use for large scale collection of social net information from participants that will identify social net typology that might be used to tailor health promotion interventions. A description of these data was recently present at the annual meeting of the International Network of Social Network Analysis

-basfd interventions. To this end, we have derwloped an asaessment tool to be used for large srale colltbtion of social netwofk informwtion frim perticipants that will idcutify docicl network typolpgies that might be used tu cailor health promotion interventionf. A desvrlption of thesg dats was gegently presented at the annual mseting mf the Internstional Network of Social Jetwlrk Analysis

-based interventions. To this end, we have assessment to be for large scale from that will identify network typologies that be used to tailor health promotion A description of these data was recently presented at the annual meeting of International Network of Social Network Analysis

-based interventions. To this eNd, we have deVelopEd aN asSeSsmeNt toOl to be used for lARge sCale collection of social NetwoRk INforMAtIon frOm partiCIpANTs tHaT wIll IdENtIfy soCiaL networK typologieS thAt Might be used tO TaIlor health ProMotion intervEntIons. A dEsCriPTion oF thEse daTa was rECently Presented At THe annuAL meetinG OF tHe InTernational NetworK Of sOcial Network AnAlysis

-based interventions. To t his end, w e hav e d eve lo pedan a ssessment tool to b e used for large scale  coll ec t iono fsocia l netwo r ki n for ma ti onfr o mparti cip ants th at will id ent if y social net w or k typologi esthat might b e u sed to  t ail o r hea lth  prom otioni nterve ntions. A  d e script i on of t h e se  dat a was recently pr e se n ted at the ann ual me et i ng o f t heInternatio na l Net w ork ofS oc i a l  Ne t work Analysis

-based interventions._To this_end, we have developed_an assessment_tool_to be_used_for large scale_collection of social_network information from participants_that will identify_social_network typologies that might be used to tailor health promotion interventions. A description of_these_data was_recently_presented_at the annual meeting of_the International Network of Social_Network Analysis


immune surveillance may contribute to a rapid selection of tumor clones at the early stages of hepatocarcinogenesis. This aspect is under investigation. To study the in vivo effects of DLC1 deficiency, we had previously generated a Dlc1 knockout mouse strain. Homozygous mutant embryos died by 10 days of gestation with defects in several

immune surveillance may contribute to a rapid selection of tumor clones at the early stages of hepatocarcinogenesis. This view is under probe. To study the in vivo effects of DLC1 lack, we had previously render a Dlc1 knockout mouse strain. Homozygous mutant embryo die by 10 days of gestation with defects in several

imlune surveillance may coktribute to a rakie selertion or tumor zlones at the early stages oh hepatocqrcinogenesis. This aspdct is unfer invewtigetion. To study tis in viyj efrccts mh DLC1 deficienci, we had preeiously generadea c Dlc1 knockout mouse strain. Homozygots mutamt embryos died fy 10 cwys kf gestation with defects in severzl

immune surveillance may contribute to a rapid tumor at the stages of hepatocarcinogenesis. To the in vivo of DLC1 deficiency, had previously generated a Dlc1 knockout strain. Homozygous mutant embryos died by 10 days of gestation with defects in

immune surveillance may contRibute to a rApid sEleCtiOn Of tuMor cLones at the earlY StagEs of hepatocarcinogenesIs. ThiS aSPect IS uNder iNvestigATiON. to sTuDy The In VIvO effeCts Of DLC1 deFiciency, we Had PrEviously geneRAtEd a Dlc1 knocKouT mouse strain. homOzygouS mUtaNT embrYos Died bY 10 days oF GestatIon with deFeCTs in seVEral

immune surveillance may c ontributeto arap idse lect ionof tumor clone s  atthe early stages of he patoc ar c inog e ne sis.This as p ec t isun de r i nv e st igati on.  To stu dy the inviv oeffects of D L C1  deficienc y,we had previ ous ly gen er ate d  a Dl c1knock out mo u se str ain. Homo zy g ous mu t ant emb r y os  die d by 10 days of g e st a tion with defe cts in  s e ve r a l

immune_surveillance may_contribute to a rapid_selection of_tumor_clones at_the_early stages of_hepatocarcinogenesis. This aspect_is under investigation. To_study the in_vivo_effects of DLC1 deficiency, we had previously generated a Dlc1 knockout mouse strain. Homozygous_mutant_embryos died_by_10_days of gestation with defects_in several


well blocked the DNA synthesis of HBVETV-RL180M/S202G/M204V, giving an IC50 value of 2,657. We then asked whether CMCP blocked the replication of HBV in hu-liver-chimeric mice. In 8 weeks following the inoculation of such mice with HBV

well blocked the DNA synthesis of HBVETV - RL180M / S202G / M204V, giving an IC50 value of 2,657. We then ask whether CMCP block the replication of HBV in hu - liver - chimeric mice. In 8 weeks postdate the inoculation of such mice with HBV

wepl blocked the DNA synthtsis of HBVETV-RL180M/S202G/M204V, giting an IC50 valud of 2,657. We then asked whether RMCP blocjed the replication of HBV in hl-liver-chinerir mice. In 8 weeks followiky the lnocunetion of such mlce with HBE

well blocked the DNA synthesis of HBVETV-RL180M/S202G/M204V, IC50 of 2,657. then asked whether HBV hu-liver-chimeric mice. In weeks following the of such mice with HBV

well blocked the DNA synthesiS of HBVETV-Rl180M/S202G/M204v, giVinG aN IC50 vAlue Of 2,657. We then asked wHEtheR CMCP blocked the replicaTion oF Hbv in hU-LiVer-chImeric mICe. iN 8 WeeKs FoLloWiNG tHe inoCulAtion of Such mice wiTh HbV

well blocked the DNA synt hesis of H BVETV -RL 180 M/ S202 G/M2 04V, giving an IC50  value of 2,657. We th en as ke d  whe t he r CMC P block e dt h e r ep li cat io n  o f HBV  in  hu-liv er-chimeri c m ic e. In 8 week s  f ollowing t heinoculationofsuch m ic e w i th HB V

well_blocked the_DNA synthesis of HBVETV-RL180M/S202G/M204V,_giving an_IC50_value of_2,657._We then asked_whether CMCP blocked_the replication of HBV_in hu-liver-chimeric mice._In_8 weeks following the inoculation of such mice with HBV


inhibiting compensatory endocytosis. This application extends follow-up of old and very-old persons who have received cognitive interventions as part of ACTIVE (Advanced Cognitive Training for independent and Vital Elderly). Findings at five years indicate the effects of the intervention on cognitive abilities are durable and that these intervention effects nave transferred to

inhibiting compensatory endocytosis. This application extends follow - up of old and very - previous person who have received cognitive interventions as part of ACTIVE (Advanced Cognitive Training for autonomous and Vital Elderly). Findings at five years indicate the effect of the intervention on cognitive abilities are durable and that these interposition effects nave transferred to

injibiting compensatory enaocytosis. This cpplicavion exfends foulow-up of old and very-old pecsonw who have received cognitixe intervvntions aw pact of ACTIVE (Advehced Conuitivs Trannmng for indepencent and Vhtal Elderly). Fhnaiugs at five years indicate the effeces of tne intervention jn cpdnitjne abilities are durable and thzt thest intervention effrcts nave transferred to

inhibiting compensatory endocytosis. This application extends follow-up and persons who received cognitive interventions Cognitive for independent and Elderly). Findings at years indicate the effects of the on cognitive abilities are durable and that these intervention effects nave transferred to

inhibiting compensatory endOcytosis. ThIs appLicAtiOn ExteNds fOllow-up of old anD Very-Old persons who have receiVed coGnITive INtErvenTions as PArT OF ACtIvE (advAnCEd cogniTivE TrainiNg for indepEndEnT and Vital EldERlY). Findings aT fiVe years indicAte The effEcTs oF The inTerVentiOn on coGNitive Abilities ArE DurablE And that THEsE intErvention effects nAVe TRansferred to

inhibiting compensatory e ndocytosis . Thi s a ppl ic atio n ex tends follow-u p  ofold and very-old perso ns wh oh aver ec eived  cognit i ve i nte rv en tio ns as  part  of  ACTIVE  (Advanced  Co gn itive Traini n gfor indepe nde nt and Vital  El derly) .Fin d ingsatfiveyearsi ndicat e the eff ec t s of t h e inter v e nt ionon cognitive abil i ti e s are durableand th at th e s e i nte rvention e ff ectsn ave tra n sf e r r edt o

inhibiting_compensatory endocytosis._This application extends follow-up_of old_and_very-old persons_who_have received cognitive_interventions as part_of ACTIVE (Advanced Cognitive_Training for independent_and_Vital Elderly). Findings at five years indicate the effects of the intervention on cognitive_abilities_are durable_and_that_these intervention effects nave transferred_to


with 3 different infectious agents, revealing that CD5hi T cells dominated in the memory pool over CD5 lo cells after resolution of the infectious process, that in older mice, the nave T cell pool is relatively depleted and the memory pool enriched in CD5hi T cells, and that a similar shift between in the

with 3 different infectious agents, revealing that CD5hi T cells dominate in the memory pond over CD5 lo cells after resolution of the infectious process, that in elder mice, the nave T cell consortium is relatively consume and the memory pool enriched in CD5hi T cells, and that a similar shift between in the

wihh 3 different infectious agents, revealiut that CD5hi F cells aominated in the memory pool ocer CE5 lo cells after resoljtion of nhe infecriouw process, tizt in older mjge, thz iave T cell pook is relathvely depleted avd the memory pool enriched in CD5hi T cells, snf that a similwr snyft gvtceen in the

with 3 different infectious agents, revealing that cells in the pool over CD5 the process, that in mice, the nave cell pool is relatively depleted and memory pool enriched in CD5hi T cells, and that a similar shift between the

with 3 different infectious agEnts, revealIng thAt Cd5hi t cElls DomiNated in the memoRY pooL over CD5 lo cells after resOlutiOn OF the INfEctioUs proceSS, tHAT in OlDeR miCe, THe Nave T CelL pool is Relatively DepLeTed and the memORy Pool enrichEd iN CD5hi T cells, aNd tHat a siMiLar SHift bEtwEen in The

with 3 different infectio us agents,  reve ali ngth at C D5hi  T cells domin a tedin the memory pool ove r CD5  l o  cel l safter  resolu t io n ofth einf ec t io us pr oce ss, tha t in older  mi ce , the nave T ce ll pool is  re latively dep let ed and  t hem emory  po ol en riched in CD5 hi T cell s, and th a t a sim i l ar  shi ft between in the

with_3 different_infectious agents, revealing that_CD5hi T_cells_dominated in_the_memory pool over_CD5 lo cells_after resolution of the_infectious process, that_in_older mice, the nave T cell pool is relatively depleted and the memory pool_enriched_in CD5hi_T_cells,_and that a similar shift_between in the


low-dose PCB studies continue to suggest adverse effects in animals this would strongly support the biologic plausibility that background-level PCB exposure in humans could have similar consequences. We considered the importance of assessing endocrine disruption in a large new birth cohort that has been proposed, the National Children's Study (NCS). We believe

low - dose PCB studies continue to indicate adverse effect in animals this would strongly support the biological plausibility that background - level PCB exposure in world could have similar consequence. We considered the importance of assessing endocrine gland disruption in a large raw parturition cohort that has been proposed, the National Children's Study (NCS). We believe

loa-dose PCB studies continme to suggest adrwrse ehfects jn animaus this would strongly suppoct tye biilogic plausibility thxt backgrlund-leveo PCU exposure in humans could havs simnler consequences. We considared the impordavcz of assessing endocrine disruption yn a latgf new birth corort ehat has been proposed, the National Chjldren's Study (NCS). We believe

low-dose PCB studies continue to suggest adverse animals would strongly the biologic plausibility humans have similar consequences. considered the importance assessing endocrine disruption in a large birth cohort that has been proposed, the National Children's Study (NCS). We believe

low-dose PCB studies continue To suggest aDversE efFecTs In anImalS this would stroNGly sUpport the biologic plausIbiliTy THat bACkGrounD-level Pcb eXPOsuRe In HumAnS CoUld haVe sImilar cOnsequenceS. We CoNsidered the iMPoRtance of asSesSing endocrinE diSruptiOn In a LArge nEw bIrth cOhort tHAt has bEen proposEd, THe NatiONal ChilDREn'S StuDy (NCS). We believe

low-dose PCB studies cont inue to su ggest  ad ver se  eff ects  in animals th i s wo uld strongly support t he bi ol o gicp la usibi lity th a tb a ckg ro un d-l ev e lPCB e xpo sure in  humans co uld  h ave similarc on sequences.  We  consideredthe  impor ta nce of as ses singendocr i ne dis ruption i na  large new bir t h  c ohor t that has been p r op o sed, the Natio nal Ch il d re n ' s S tud y (NCS). W ebelie v e

low-dose_PCB studies_continue to suggest adverse_effects in_animals_this would_strongly_support the biologic_plausibility that background-level_PCB exposure in humans_could have similar_consequences._We considered the importance of assessing endocrine disruption in a large new birth cohort_that_has been_proposed,_the_National Children's Study (NCS). We_believe


maintains ISCs. Similar to our previous work in the duodenum of mice, we wondered if the EC cells in the distal SI that reside below +4 position were derived from reserve ISCs and were susceptible to tumorigenesis in Familial SI-NET patients. Presently, it is unknown whether there is a subset

maintains ISCs. Similar to our previous work in the duodenum of mouse, we wonder if the EC cells in the distal SI that reside below +4 position were derive from reserve ISCs and were susceptible to tumorigenesis in Familial SI - NET patients. soon, it is unknown whether there is a subset

malntains ISCs. Similar to uur previous wotk in thx duodehum of mkce, we wondered if the EC ceplw in uke distal SI that reride beloa +4 posituon xere derived from reservc ISCa and xere susceptiblg to tumoriganesis in Faminixl SI-NET patients. Presently, it is unkgown whrtjer there is a subxqt

maintains ISCs. Similar to our previous work duodenum mice, we if the EC that below +4 position derived from reserve and were susceptible to tumorigenesis in SI-NET patients. Presently, it is unknown whether there is a subset

maintains ISCs. Similar to our Previous woRk in tHe dUodEnUm of Mice, We wondered if thE eC ceLls in the distal SI that reSide bElOW +4 posITiOn werE deriveD FrOM ResErVe iSCS aND wEre suScePtible tO tumorigenEsiS iN Familial SI-Net pAtients. PreSenTly, it is unknoWn wHether ThEre IS a subSet

maintains ISCs. Similar t o our prev iouswor k i ntheduod enum of mice,w e wo ndered if the EC cells  in t he dist a lSI th at resi d eb e low  + 4pos it i on  were  de rived f rom reserv e I SC s and were s u sc eptible to  tu morigenesisinFamili al  SI - NET p ati ents.  Prese n tly, i t is unkn ow n  wheth e r there i sa su bset

maintains_ISCs. Similar_to our previous work_in the_duodenum_of mice,_we_wondered if the_EC cells in_the distal SI that_reside below +4_position_were derived from reserve ISCs and were susceptible to tumorigenesis in Familial SI-NET patients._Presently,_it is_unknown_whether_there is a subset


the molecular details of two novel regulatory pathways controlling early signaling by the T cell receptor (SHP-1 phosphatase dependent negative control and MAPK mediated positive control) and a full mathematical computer description of T cell receptor (TCR) signaling that incorporates these novel regulatory pathways. Over the past several years we have focused on using the

the molecular details of two novel regulatory pathways operate early on signaling by the T cell sense organ (SHP-1 phosphatase dependent minus control and MAPK mediated cocksure control) and a full numerical calculator description of T cell sense organ (TCR) signaling that incorporates these fresh regulatory pathways. Over the past several years we have focused on using the

thf molecular details of tdo novel regulajoey patiways ckntrollivg early signaling by the T rell receknor (SHP-1 phosphatase ddpendent jegative conurol and MAPK medmzted positive gontrmo) and a full msthematican computer deswrkpcion of T cell receptor (TCR) signalind that onforporates thefe npdel dvgmlatory pathways. Over the past ssveral jears we have focised on using the

the molecular details of two novel regulatory early by the cell receptor (SHP-1 MAPK positive control) and full mathematical computer of T cell receptor (TCR) signaling incorporates these novel regulatory pathways. Over the past several years we have focused using the

the molecular details of two nOvel regulaTory pAthWayS cOntrOlliNg early signaliNG by tHe T cell receptor (SHP-1 phosPhataSe DEpenDEnT negaTive conTRoL ANd MaPk mEdiAtED pOsitiVe cOntrol) aNd a full matHemAtIcal computer DEsCription of t ceLl receptor (TCr) siGnalinG tHat INcorpOraTes thEse novEL regulAtory pathWaYS. Over tHE past seVERaL yeaRs we have focused on USiNG the

the molecular details oftwo novelregul ato rypa thwa ys c ontrolling ear l y si gnaling by the T cellrecep to r  (SH P -1  phos phatase de p e nde nt  n ega ti v econtr oland MAP K mediated  po si tive control )  a nd a fullmat hematical co mpu ter de sc rip t ion o f T  cell  recep t or (TC R) signal in g  thati ncorpor a t es  the se novel regulato r yp athways. Overthe pa st se v e ral  ye ars we hav efocus e d on us i ng t h e

the_molecular details_of two novel regulatory_pathways controlling_early_signaling by_the_T cell receptor_(SHP-1 phosphatase dependent_negative control and MAPK_mediated positive control)_and_a full mathematical computer description of T cell receptor (TCR) signaling that incorporates these_novel_regulatory pathways._Over_the_past several years we have_focused on using the


served as referents. We studied serum TCDD level in relation to red blood cell count, white blood cell count, hemoglobin, hematocrit, mean corpuscular volume, platelet count, and erythrocyte sedimentation rate at each of four physical examinations over 10 years. We measured TCDD serum level in

served as referents. We studied serum TCDD level in relation back to crimson blood cell count, white lineage cell count, hemoglobin, hematocrit, mean corpuscular book, platelet count, and erythrocyte deposit rate at each of four physical examinations over 10 years. We measured TCDD serum horizontal surface in

segved as referents. We stuaied serum TCDD level mn relafion to fed blood cell count, white bpoid ceol count, hemoglobin, heoatocrit, lean corpuscnlar volume, platxmet coukc, and crythxoryte sedimentatlon rate at each of four [hhsncal examinations over 10 years. We meafured TVDF serum level yn

served as referents. We studied serum TCDD relation red blood count, white blood corpuscular platelet count, and sedimentation rate at of four physical examinations over 10 We measured TCDD serum level in

served as referents. We studieD serum TCDD Level In rElaTiOn to Red bLood cell count, wHIte bLood cell count, hemoglobiN, hemaToCRit, mEAn CorpuScular vOLuME, PlaTeLeT coUnT, AnD erytHroCyte sedImentation RatE aT each of four pHYsIcal examinAtiOns over 10 years. we mEasureD TcDD SErum lEveL in

served as referents. We s tudied ser um TC DDlev el  inrela tion to red bl o od c ell count, white blood  cell  c o unt, he moglo bin, he m at o c rit ,me anco r pu scula r v olume,platelet c oun t,  and erythro c yt e sediment ati on rate at e ach  of fo ur  ph y sical  ex amina tionso ver 10  years. W em easure d  TCDD s e r um  lev el in

served_as referents._We studied serum TCDD_level in_relation_to red_blood_cell count, white_blood cell count,_hemoglobin, hematocrit, mean corpuscular_volume, platelet count,_and_erythrocyte sedimentation rate at each of four physical examinations over 10 years. We measured_TCDD_serum level_in


demonstrate that TNF bioactivity may down-regulate allergen-mediated asthmatic airway inflammation in patients with mild-to-moderate asthma. Ongoing investigations are aimed at elucidating further the molecular mechanisms that modulate TNFR1 release to the extracellular compartment. HIV/AIDS is a major cause of global morbidity and

demonstrate that TNF bioactivity may down - regulate allergen - mediated asthmatic airway inflammation in patient with meek - to - moderate asthma. Ongoing investigations are aimed at elucidating far the molecular mechanisms that modulate TNFR1 passing to the extracellular compartment. HIV / AIDS is a major causal agent of global morbidity and

delonstrate that TNF bioacuivity may down-reyylate ellergeh-mediatea asthmatic airway inflammatmon un paupents with mild-to-modefate asthla. Ongoibg iivestigations arx aimed at eludldatiug further the mplecular machanisms that mudblate TNFR1 release to the extracellujar comlagtment. HIV/AIDS is s majkg gause of global morbidity and

demonstrate that TNF bioactivity may down-regulate allergen-mediated inflammation patients with asthma. Ongoing investigations the mechanisms that modulate release to the compartment. HIV/AIDS is a major cause global morbidity and

demonstrate that TNF bioactiVity may dowN-reguLatE alLeRgen-MediAted asthmatic aIRway Inflammation in patients With mIlD-To-moDErAte asThma. OngOInG INveStIgAtiOnS ArE aimeD at ElucidaTing furtheR thE mOlecular mechANiSms that modUlaTe TNFR1 releasE to The extRaCelLUlar cOmpArtmeNt. HIV/AidS is a mAjor cause Of GLobal mORbidity AND

demonstrate that TNF bioa ctivity ma y dow n-r egu la te a ller gen-mediated a s thma tic airway inflammatio n inpa t ient s  w ith m ild-to- m od e r ate  a st hma .O ng oinginv estigat ions are a ime dat elucidati n gfurther th e m olecular mec han isms t ha t m o dulat e T NFR1releas e  to th e extrace ll u lar co m partmen t .  H IV/A IDS is a major ca u se of global morb idityan d

demonstrate_that TNF_bioactivity may down-regulate allergen-mediated_asthmatic airway_inflammation_in patients_with_mild-to-moderate asthma. Ongoing_investigations are aimed_at elucidating further the_molecular mechanisms that_modulate_TNFR1 release to the extracellular compartment. HIV/AIDS is a major cause of global morbidity_and


occupied chemoattractant receptors. Chemotaxis inhibition following short-term LPS treatment didnt result from downmodulation of signaling receptors or from inordinate increase in adhesion through integrin activation. However, chemokine stimulation of LPS treated monocytes displayed circumferential accumulation of activated integrin and F-actin polymers resulting from global recruitment of EPAC leading

occupied chemoattractant receptors. Chemotaxis inhibition following light - condition LPS treatment did nt result from downmodulation of signaling sense organ or from inordinate increase in attachment through integrin energizing. However, chemokine stimulation of LPS treated monocytes displayed circumferential accumulation of activate integrin and F - actin polymers resulting from ball-shaped recruitment of EPAC leading

ocfupied chemoattractant rtceptors. Chemotaxnw inhiuition rollowine short-term LPS treatment divnt eesulu from downmodulatiun of sigjaling rwcepuors or from inorvjnate ikereass in cdiesion through lntegrin acdivation. Howevar, ckemokine stimulation of LPS treated ionocytrs displayed cirsumftregtiam accumulation of activated integrjn and H-actin polymers resulting from global recguitlent of EPAC leadijg

occupied chemoattractant receptors. Chemotaxis inhibition following short-term didnt from downmodulation signaling receptors or through activation. However, chemokine of LPS treated displayed circumferential accumulation of activated integrin F-actin polymers resulting from global recruitment of EPAC leading

occupied chemoattractant reCeptors. CheMotaxIs iNhiBiTion FollOwing short-term lpS trEatment didnt result from DownmOdULatiON oF signAling reCEpTORs oR fRoM inOrDInAte inCreAse in adHesion throUgh InTegrin activaTIoN. However, chEmoKine stimulatIon Of LPS tReAteD MonocYteS dispLayed cIRcumfeRential acCuMUlatioN Of activATEd InteGrin and F-actin polyMErS Resulting from gLobal rEcRUiTMEnt Of EpAC leading

occupied chemoattractantreceptors.  Chem ota xis  i nhib itio n following sh o rt-t erm LPS treatment didn t res ul t  fro m  d ownmo dulatio n  o f sig na li ngre c ep torsorfrom in ordinate i ncr ea se in adhesi o nthrough in teg rin activati on.  Howev er , c h emoki nestimu lation of LPS  treatedmo n ocytes display e d  c ircu mferential accumu l at i on of activate d inte gr i na n d F -ac tin polyme rs  resu l ting fr o mg l o bal recruitment o f EPAC lead i ng

occupied_chemoattractant receptors._Chemotaxis inhibition following short-term_LPS treatment_didnt_result from_downmodulation_of signaling receptors_or from inordinate_increase in adhesion through_integrin activation. However,_chemokine_stimulation of LPS treated monocytes displayed circumferential accumulation of activated integrin and F-actin polymers_resulting_from global_recruitment_of_EPAC leading


of direct drug action on the DNA methyltransferases that play major roles in controlling DNA methylation and abnormal gene silencing in cancers, and drug action on the enzyme topoisomerase I which is already a validated therapeutic target via the market approval of the camptothecins. Outsourcing the final steps of the defined,

of direct drug action on the DNA methyltransferases that play major function in operate DNA methylation and abnormal gene silencing in cancers, and drug action on the enzyme topoisomerase I which is already a validate therapeutic target via the marketplace blessing of the camptothecins. Outsourcing the final steps of the defined,

of direct drug action on tme DNA methyltrauwferasxs that play magor roles in controlling DNA mwthylqtion and abnormal gend silencijg in cabcerw, and drug edtion ok the cnzymz vopoisomerase I which is dlready a valigageb therapeutic target via the market wpprovak lf the camptotrecimf. Oufsourcing the final steps of the dsfined,

of direct drug action on the DNA play roles in DNA methylation and and action on the topoisomerase I which already a validated therapeutic target via market approval of the camptothecins. Outsourcing the final steps of the defined,

of direct drug action on the DNa methyltraNsferAseS thAt Play MajoR roles in controLLing dNA methylation and abnorMal geNe SIlenCInG in caNcers, anD DrUG ActIoN oN thE eNZyMe topOisOmerase i which is alReaDy A validated thERaPeutic targEt vIa the market aPprOval of ThE caMPtothEciNs. OutSourciNG the fiNal steps oF tHE definED,

of direct drug action onthe DNA me thylt ran sfe ra sesthat  play major ro l es i n controlling DNA meth ylati on anda bn ormal  gene s i le n c ing  i ncan ce r s,  anddru g actio n on the e nzy me  topoisomera s eI which is  al ready a vali dat ed the ra peu t ic ta rge t via  the m a rket a pproval o ft he cam p totheci n s .Outs ourcing the final st e ps of the defi ned,

of_direct drug_action on the DNA_methyltransferases that_play_major roles_in_controlling DNA methylation_and abnormal gene_silencing in cancers, and_drug action on_the_enzyme topoisomerase I which is already a validated therapeutic target via the market approval_of_the camptothecins._Outsourcing_the_final steps of the defined,


2 cytoplasmic domain and partially neutralized the ability of this BST-2 variant to inhibit viral release. Interaction of Vpu and rhesus BST-2 involved a five-residue motif in the cytoplasmic domain of BST-2 previously identified as important for antagonism of monkey and great ape BST

2 cytoplasmic domain and partially neutralized the ability of this BST-2 variant to inhibit viral dismissal. Interaction of Vpu and rhesus BST-2 imply a five - residue motif in the cytoplasmic domain of BST-2 previously name as important for antagonism of imp and great ape BST

2 cyhoplasmic domain and paruially neutralizeb the auility kf this CST-2 variant to inhibit viral rwleast. Interaction of Vpj and rhedus BST-2 unvooced a five-cssidue motif jk the rytoplasmic domsin of BST-2 previously idangiyied as important for antagonism of ionkey snf great ape BSJ

2 cytoplasmic domain and partially neutralized the this variant to viral release. Interaction involved five-residue motif in cytoplasmic domain of previously identified as important for antagonism monkey and great ape BST

2 cytoplasmic domain and partiAlly neutraLized The AbiLiTy of This bST-2 variant to inHIbit Viral release. InteractioN of VpU aND rheSUs bST-2 inVolved a FIvE-REsiDuE mOtiF iN ThE cytoPlaSmic domAin of BST-2 prEviOuSly identifieD As Important fOr aNtagonism of mOnkEy and gReAt aPE BST

2 cytoplasmic domain and p artially n eutra liz edth e ab ilit y of this BST- 2  var iant to inhibit viralrelea se .  Int e ra ction  of Vpu an d rhe su sBST -2 in volve d a  five-r esidue mot ifin  the cytopla s mi c domain o f B ST-2 previou sly  ident if ied as im por tantfor an t agonis m of monk ey and gr e at apeB S T

2 cytoplasmic_domain and_partially neutralized the ability_of this_BST-2_variant to_inhibit_viral release. Interaction_of Vpu and_rhesus BST-2 involved a_five-residue motif in_the_cytoplasmic domain of BST-2 previously identified as important for antagonism of monkey and great_ape_BST