, at comparable Vif levels, CBF further enhanced A3G degradation suggesting that CBF facilitates A3G degradation by increasing the levels of Vif and by independently augmenting the ability of Vif to target A3G for degradation. We propose that CBF acts like a chaperone to stabilize Vif during

, at comparable Vif levels, CBF further enhanced A3 G degradation suggest that CBF facilitate A3 G degradation by increasing the grade of Vif and by independently augmenting the ability of Vif to target A3 G for abasement. We propose that CBF acts like a chaperone to brace Vif during

, at comparable Vif levels, CNF further enhanewd A3G vegradafion sugeesting that CBF facilitates A3T degeadation by increasing the leveps of Vid anv by independently augmekcing fme abnlmty of Vif to tsrget A3G fmr degradation. Wd 'ropose that CBF acts like a chaperoge to syahilize Vif duryng

, at comparable Vif levels, CBF further degradation that CBF A3G degradation by and independently augmenting the of Vif to A3G for degradation. We propose that acts like a chaperone to stabilize Vif during

, at comparable Vif levels, CBF fUrther enhaNced A3g deGraDaTion SuggEsting that CBF fACiliTates A3G degradation by inCreasInG The lEVeLs of VIf and by INdEPEndEnTlY auGmENtIng thE abIlity of vif to targeT A3G FoR degradation. wE pRopose that cBF Acts like a chaPerOne to sTaBilIZe Vif DurIng

, at comparable Vif levels , CBF furt her e nha nce dA3Gdegr adation sugges t ingthat CBF facilitates A 3G de gr a dati o nby in creasin g  t h e  le ve ls  of  V i fand b y i ndepend ently augm ent in g the abilit y  o f Vif to t arg et A3G for d egr adatio n.  We propo sethatCBF ac t s like  a chaper on e  to st a bilizeV i fduri ng

, at_comparable Vif_levels, CBF further enhanced_A3G degradation_suggesting_that CBF_facilitates_A3G degradation by_increasing the levels_of Vif and by_independently augmenting the_ability_of Vif to target A3G for degradation. We propose that CBF acts like a_chaperone_to stabilize_Vif_during


multiple strains is to investigate genetic diversity suggested by observed phenotypic and/or genetic diversity Our current work aims to understand the social mechanisms underlying the dissemination of family risk information and cooperative adaptation to shared risk. We examine these processes across several different disease contexts, representing highly penetrant, genetic disorders as well as more common, complex diseases

multiple strains is to investigate genetic diversity suggested by ascertained phenotypic and/or familial diversity Our current work drive to sympathize the social mechanisms underlying the dissemination of class risk information and concerted adaptation to shared risk. We test these processes across several unlike disease contexts, representing highly penetrant, familial disorders as well as more coarse, complex diseases

muptiple strains is to invtstigate genetic buversivy suggssted by observed phenotypic and/or gxnetuc dicersity Our current wofk aims tl undersrand rhe social mechanisms unscrlyiug the disseminajion of faminy risk informdtkou and cooperative adaptation to sharqd risk. Wf examine thesg probefses across several different disease dontextv, representinb highly penetrant, genetic dislrders as well as lore common, com[oex diseases

multiple strains is to investigate genetic diversity observed and/or genetic Our current work mechanisms the dissemination of risk information and adaptation to shared risk. We examine processes across several different disease contexts, representing highly penetrant, genetic disorders as well more common, complex diseases

multiple strains is to investIgate genetIc divErsIty SuGgesTed bY observed phenoTYpic And/or genetic diversity OUr curReNT worK AiMs to uNderstaND tHE SocIaL mEchAnISmS undeRlyIng the dIsseminatiOn oF fAmily risk infORmAtion and coOpeRative adaptaTioN to shaReD riSK. We exAmiNe theSe procESses acRoss severAl DIffereNT diseasE COnTextS, representing highLY pENetrant, genetic DisordErS As WELl aS moRe common, coMpLex diSEases

multiple strains is to in vestigategenet icdiv er sity  sug gested by obse r vedphenotypic and/or gene tic d iv e rsit y  O ur cu rrent w o rk a ims  t ound er s ta nd th e s ocial m echanismsund er lying the di s se mination o f f amily risk i nfo rmatio nand coope rat ive a daptat i on toshared ri sk .  We ex a mine th e s eproc esses across seve r al different dise ase co nt e xt s ,  re pre senting hi gh ly pe n etrant, ge n e t icd isorders as w ell as more com mon, c om ple x  disea ses

multiple_strains is_to investigate genetic diversity_suggested by_observed_phenotypic and/or_genetic_diversity Our current_work aims to_understand the social mechanisms_underlying the dissemination_of_family risk information and cooperative adaptation to shared risk. We examine these processes across_several_different disease_contexts,_representing_highly penetrant, genetic disorders as_well as more common, complex_diseases


we showed that both the recycling cell surface receptor and the nascent receptor in transit to the plasma membrane were susceptible to intra-cellular retention and degradation by HIV-1 Nef (J Cell Biology, 163, 1281, 2003 and J Biol Chem. 280, 7413, 2005). Nef is thought to mediate

we showed that both the recycling cell surface receptor and the nascent sense organ in passage to the plasma membrane were susceptible to intra - cellular retention and degradation by HIV-1 Nef (J Cell Biology, 163, 1281, 2003 and J Biol Chem. 280, 7413, 2005). Nef is think to intercede

we showed that both the regycling cell suryqce rereptor znd the vascent receptor in transit vo tye plqsma membrane were suszeptible no intra-cwlluoqr retention and dcyradaflon bv IIV-1 Nef (J Cell Niology, 163, 1281, 2003 dnd J Biol Chek. 280, 7413, 2005). Nef is thought to mediate

we showed that both the recycling cell and nascent receptor transit to the intra-cellular and degradation by Nef (J Cell 163, 1281, 2003 and J Biol 280, 7413, 2005). Nef is thought to mediate

we showed that both the recyclIng cell surFace rEcePtoR aNd thE nasCent receptor in TRansIt to the plasma membrane wEre suScEPtibLE tO intrA-cellulAR rETEntIoN aNd dEgRAdAtion By HiV-1 Nef (J CEll Biology, 163, 1281, 2003 And j BIol Chem. 280, 7413, 2005). Nef is THoUght to mediAte

we showed that both the r ecycling c ell s urf ace  r ecep torand the nascen t  rec eptor in transit to th e pla sm a  mem b ra ne we re susc e pt i b leto  i ntr a- c el lular  re tention  and degra dat io n by HIV-1 N e f(J Cell Bi olo gy, 163, 128 1,2003 a nd  JB iol C hem . 280 , 7413 ,  2005) . Nef isth o ught t o  mediat e

we_showed that_both the recycling cell_surface receptor_and_the nascent_receptor_in transit to_the plasma membrane_were susceptible to intra-cellular_retention and degradation_by_HIV-1 Nef (J Cell Biology, 163, 1281, 2003 and J Biol Chem. 280, 7413,_2005)._Nef is_thought_to_mediate


(hu-liver-chimeric) mice. CAdA and CdG were also potent against a highly entecavir (ETV)-resistant HBV variant containing three critical amino acid substitutions: L180M, S202G, and M204V (HBVL180M/S202G/ M

(hu - liver - chimeric) mice. CAdA and CdG were also potent against a highly entecavir (ETV)-resistant HBV variant containing three critical amino acid substitution: L180 M, S202 G, and M204V (HBVL180M / S202G/ M

(hu-piver-chimeric) mice. CAdA xnd CdG were also poteit agaihst a hiehly entecavir (ETV)-resistant IBV cariabt containing three crktical ampno acid wubsuitutions: L180M, S202G, ais M204V (HBYJ180M/S202G/ L

(hu-liver-chimeric) mice. CAdA and CdG were also a entecavir (ETV)-resistant variant containing three S202G, M204V (HBVL180M/S202G/ M

(hu-liver-chimeric) mice. CAdA anD CdG were alSo potEnt AgaInSt a hIghlY entecavir (ETV)-rESistAnt HBV variant containinG threE cRIticAL aMino aCid subsTItUTIonS: L180m, S202g, anD M204v (hBvL180M/S202G/ m

(hu-liver-chimeric) mice.  CAdA andCdG w ere  al so  pot entagainst a high l y en tecavir (ETV)-resistan t HBV  v a rian t  c ontai ning th r ee c rit ic al  am in o  a cid s ubs titutio ns: L180M,  S2 02 G, and M204V (H BVL180M/S2 02G / M

(hu-liver-chimeric)_mice. CAdA_and CdG were also_potent against_a_highly entecavir_(ETV)-resistant_HBV variant containing_three critical amino_acid substitutions: L180M, S202G,_and M204V (HBVL180M/S202G/_M


izes the plasma membrane. This allowed us to determine the fundamental organization of the exocytic membrane system and how specific molecular components responsible for vesicle trafficking and fusion assemble together and function. Specifically, we have been using two-color TIRF microscopy and high-throughput image analysis to detect and characterize over 80 different proteins that have

izes the plasma membrane. This allowed us to determine the fundamental organization of the exocytic membrane arrangement and how specific molecular component responsible for vesicle trafficking and fusion assemble in concert and function. Specifically, we have been using two - color TIRF microscopy and eminent - throughput image analysis to detect and qualify over 80 unlike proteins that have

ized the plasma membrane. Thls allowed us to determmne the fundamevtal organization of the exorytix memvrane system and how soecific mllecular comkonents responsible for vcficls trayfmcking and fusipn assembla together and fjnetion. Specifically, we have been usind two-cokog TIRF microscjpy sgd hjgh-throughput image analysis to defect anv characterize pver 80 different proteins tjat jave

izes the plasma membrane. This allowed us the organization of exocytic membrane system responsible vesicle trafficking and assemble together and Specifically, we have been using two-color microscopy and high-throughput image analysis to detect and characterize over 80 different proteins have

izes the plasma membrane. This Allowed us tO deteRmiNe tHe FundAmenTal organizatioN Of thE exocytic membrane systeM and hOw SPeciFIc MolecUlar comPOnENTs rEsPoNsiBlE FoR vesiCle TrafficKing and fusIon AsSemble togethER aNd function. speCifically, we hAve Been usInG twO-Color tIRf micrOscopy ANd high-ThroughpuT iMAge anaLYsis to dETEcT and Characterize over 80 dIFfERent proteins thAt have

izes the plasma membrane.This allow ed us  to  de te rmin e th e fundamentalo rgan ization of the exocyti c mem br a ne s y st em an d how s p ec i f icmo le cul ar co mpone nts  respon sible forves ic le trafficki n gand fusion  as semble toget her  and f un cti o n. Sp eci fical ly, we have b een using  t w o-colo r  TIRF m i c ro scop y and high-throug h pu t  image analysi s to d et e ct a ndcha racterizeov er 80 differe n tp r o tei n s that have

izes the_plasma membrane._This allowed us to_determine the_fundamental_organization of_the_exocytic membrane system_and how specific_molecular components responsible for_vesicle trafficking and_fusion_assemble together and function. Specifically, we have been using two-color TIRF microscopy and high-throughput_image_analysis to_detect_and_characterize over 80 different proteins_that have


patients with premature reactivation of hypothalamic GnRH secretion, resulting in idiopathic central precocious puberty (CPP). There is evidence that familial cases account for anywhere from 20-45% of CPP, with most studies describing autosomal dominant inheritance patterns. Far less is known about the molecular basis of CPP, and candidate

patients with premature reactivation of hypothalamic GnRH secretion, resulting in idiopathic central precocious puberty (CPP). There be evidence that familial case account for anywhere from 20 - 45% of CPP, with most studies describing autosomal prevailing inheritance patterns. Far less is known about the molecular basis of CPP, and campaigner

pahients with premature rexctivation of hipithalakic GnDH secregion, resulting in idiopathic cwntrao precocious puberty (COP). There ps evidenxe tiat familial casxa accoukc for wnywkece from 20-45% of CPP, with most studies descrhbkny autosomal dominant inheritance pateerns. Fsr less is known abolt the molecular basis of CPP, and candidzte

patients with premature reactivation of hypothalamic GnRH in central precocious (CPP). There is for from 20-45% of with most studies autosomal dominant inheritance patterns. Far less known about the molecular basis of CPP, and candidate

patients with premature reacTivation of HypotHalAmiC GNRH sEcreTion, resulting iN IdioPathic central precociouS pubeRtY (cPP). THErE is evIdence tHAt FAMilIaL cAseS aCCoUnt foR anYwhere fRom 20-45% of CPP, wiTh mOsT studies descRIbIng autosomAl dOminant inherItaNce patTeRns. fAr lesS is Known About tHE molecUlar basis Of cpP, and cANdidate

patients with premature r eactivatio n ofhyp oth al amic  GnR H secretion, r e sult ing in idiopathic cent ral p re c ocio u spuber ty (CPP ) .T h ere  i sevi de n ce  that  fa milialcases acco unt  f or anywheref ro m 20-45% o f C PP, with mos t s tudies  d esc r ibing  au tosom al dom i nant i nheritanc ep attern s . Far l e s sis k nown about the mo l ec u lar basis of C PP, an dc an d i dat e

patients_with premature_reactivation of hypothalamic GnRH_secretion, resulting_in_idiopathic central_precocious_puberty (CPP). There_is evidence that_familial cases account for_anywhere from 20-45%_of_CPP, with most studies describing autosomal dominant inheritance patterns. Far less is known about_the_molecular basis_of_CPP,_and candidate


Fc substrate. In addition, N-TACE18-54 inhibited constitutive TNFR2 shedding from a human monocytic cell line by 42%. A 19-amino acid, leucine-rich domain, corresponding to TACE amino acids 30 to 48, demonstrated partial inhibitory activity. Thus, we identified a sub-domain

Fc substrate. In addition, N - TACE18 - 54 inhibited constitutive TNFR2 shedding from a human monocytic cellular telephone credit line by 42% . A 19 - amino acid, leucine - rich domain, correspond to TACE amino acid 30 to 48, demonstrated partial inhibitory activeness. therefore, we identified a sub - domain

Fc dubstrate. In addition, N-TXCE18-54 inhibited constituvive TNRR2 sheddkng from a human monocytic cxll oine vy 42%. A 19-amino acid, leucive-rich dolain, coreespibding to TEDE amino acida 30 to 48, demonstrated kartial inhititory activitf. Ghbs, we identified a sub-domain

Fc substrate. In addition, N-TACE18-54 inhibited constitutive from human monocytic line by 42%. corresponding TACE amino acids to 48, demonstrated inhibitory activity. Thus, we identified a

Fc substrate. In addition, N-TACe18-54 inhibited ConstItuTivE TnFR2 sHeddIng from a human mONocyTic cell line by 42%. A 19-amino aciD, leucInE-Rich DOmAin, coRresponDInG TO TAcE AmIno AcIDs 30 To 48, demOnsTrated pArtial inhiBitOrY activity. ThuS, We Identified A suB-domain

Fc substrate. In addition,  N-TACE18- 54 in hib ite dcons titu tive TNFR2 she d ding  from a human monocyti c cel ll ineb y42%.A 19-am i no a cid ,le uci ne - ri ch do mai n, corr espondingtoTA CE amino aci d s30 to 48,dem onstrated pa rti al inh ib ito r y act ivi ty. T hus, w e  ident ified a s ub - domain

Fc substrate._In addition,_N-TACE18-54 inhibited constitutive TNFR2_shedding from_a_human monocytic_cell_line by 42%._A 19-amino acid,_leucine-rich domain, corresponding to_TACE amino acids_30_to 48, demonstrated partial inhibitory activity. Thus, we identified a sub-domain


in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects. MC3R(hDM/hDM) bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiated into adipocytes that accumulated more triglyceride than MC3R(hWT/

in MC3R(hDM / hDM) mice and MC3R(hDM / hDM) human subjects. MC3R(hDM / hDM) bone- and adipose tissue - derived mesenchymal stem cell (MSCs) differentiate into adipocytes that accumulated more triglyceride than MC3R(hWT/

in MC3R(hDM/hDM) mice and MC3R(hAM/hDM) human sublwcts. MR3R(hDM/hDJ) bone- avd adipose tissue-derived mesxnchtmal wtem cells (MSCs) differdntiated pnto adipicytts that accumulatxs more bxiglydcride vhan MC3R(hWT/

in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects. and tissue-derived mesenchymal cells (MSCs) differentiated triglyceride MC3R(hWT/

in MC3R(hDM/hDM) mice and MC3R(hDM/hdM) human subJects. mC3R(HDM/HDm) bonE- and Adipose tissue-dERiveD mesenchymal stem cells (MsCs) diFfERentIAtEd intO adipocYTeS THat AcCuMulAtED mOre trIglYceride Than MC3R(hWT/

in MC3R(hDM/hDM) mice and  MC3R(hDM/ hDM)hum ansu bjec ts.MC3R(hDM/hDM)b one-  and adipose tissue-de rived  m e senc h ym al st em cell s  ( M S Cs)  d if fer en t ia ted i nto  adipoc ytes thatacc um ulated moret ri glyceridetha n MC3R(hWT/

in_MC3R(hDM/hDM) mice_and MC3R(hDM/hDM) human subjects._MC3R(hDM/hDM) bone-_and_adipose tissue-derived_mesenchymal_stem cells (MSCs)_differentiated into adipocytes_that accumulated more triglyceride_than MC3R(hWT/


the chemotactic function of neutrophils differentiated from these progenitor cells in vitro. Transplantation of FV-hCD18-transduced LAD-1 HSPCs into immuno-deficient (NSG) mice resulted in high-level, clinically relevant gene marking levels in vivo. The average percentages of human cells expressing CD18

the chemotactic function of neutrophils differentiated from these progenitor cells in vitro. Transplantation of FV - hCD18 - transduce LAD-1 HSPCs into immuno - insufficient (NSG) mouse resulted in eminent - grade, clinically relevant gene marking levels in vivo. The median share of human cells express CD18

thf chemotactic function on neutrophils diyderentmated fdom thesd progenitor cells in vitro. Vranwplanuction of FV-hCD18-transdjced LAD-1 JSPCs inro innuno-deficixht (NSG) mice rsdultzd in high-level, glinically selevant gene kafknng levels in vivo. The average percegtages pf human cells evprexfing BD18

the chemotactic function of neutrophils differentiated from cells vitro. Transplantation FV-hCD18-transduced LAD-1 HSPCs in clinically relevant gene levels in vivo. average percentages of human cells expressing

the chemotactic function of nEutrophils DiffeRenTiaTeD froM theSe progenitor ceLLs in Vitro. Transplantation of fV-hCD18-TrANsduCEd lAD-1 HSpCs into IMmUNO-deFiCiEnt (nSg) MiCe resUltEd in higH-level, clinIcaLlY relevant genE MaRking levelS in Vivo. The averaGe pErcentAgEs oF Human CelLs expRessinG cD18

the chemotactic functionof neutrop hilsdif fer en tiat ed f rom these prog e nito r cells in vitro. Tran splan ta t iono fFV-hC D18-tra n sd u c edLA D- 1 H SP C sintoimm uno-def icient (NS G)mi ce resultedi nhigh-level , c linically re lev ant ge ne  ma r kinglev els i n vivo .  The a verage pe rc e ntages of huma n ce llsexpressing CD18

the_chemotactic function_of neutrophils differentiated from_these progenitor_cells_in vitro._Transplantation_of FV-hCD18-transduced LAD-1_HSPCs into immuno-deficient_(NSG) mice resulted in_high-level, clinically relevant_gene_marking levels in vivo. The average percentages of human cells expressing CD18


[unreadable] In addition to removing the PPT primer from the plus strand, RNase H is known to remove the primer from the 5? end of the minus strand DNA. Tf1 uses a unique mechanism of self-priming to initiate reverse transcription. Instead of using a tRNA, Tf1 primes minus strand

[ unreadable ] In addition to removing the PPT primer from the plus strand, RNase H is know to absent the primer from the 5? end of the minus strand DNA. Tf1 use a unique mechanism of self - priming to originate reverse transcription. alternatively of using a tRNA, Tf1 primes minus strand

[ungeadable] In addition to vemoving the PPT primer from fhe plus strand, RNase H is known to cemoce tht primer from the 5? dnd of thv minus srranv DNA. Tf1 uses a nhique mcehanial of welf-priming to initiate severse transcsiotnon. Instead of using a tRNA, Tf1 primef minus shrand

[unreadable] In addition to removing the PPT the strand, RNase is known to 5? of the minus DNA. Tf1 uses unique mechanism of self-priming to initiate transcription. Instead of using a tRNA, Tf1 primes minus strand

[unreadable] In addition to remOving the PPt primEr fRom ThE pluS strAnd, RNase H is knoWN to rEmove the primer from the 5? eNd of tHe MInus STrAnd DNa. Tf1 uses A UnIQUe mEcHaNisM oF SeLf-priMinG to initIate reversE trAnScription. InsTEaD of using a trNA, tf1 primes minuS stRand

[unreadable] In additionto removin g the  PP T p ri merfrom  the plus stra n d, R Nase H is known to rem ove t he prim e rfromthe 5?e nd o f t he  m inu ss tr and D NA.  Tf1 us es a uniqu e m ec hanism of se l f- priming to  in itiate rever setransc ri pti o n. In ste ad of  using a tRNA , Tf1 pri me s  minus strand

[unreadable]_In addition_to removing the PPT_primer from_the_plus strand,_RNase_H is known_to remove the_primer from the 5?_end of the_minus_strand DNA. Tf1 uses a unique mechanism of self-priming to initiate reverse transcription. Instead_of_using a_tRNA,_Tf1_primes minus strand


from degradation in lysosomes. In the absence of EpCAM, whole cell levels of claudin-7 and claudin-1 decrease dramatically but remaining claudin-7 and claudin-1 becomes tight junction-associated. This results in increased tight junction avidity and increased trans-epithelial electrical resistance

from degradation in lysosomes. In the absence of EpCAM, whole cell degree of claudin-7 and claudin-1 decrease dramatically but remain claudin-7 and claudin-1 becomes tight junction - consort. This results in increased close articulation avidity and increased trans - epithelial electrical resistance

frlm degradation in lysosooes. In the abseuxe of XpCAM, wgole celu levels of claudin-7 and clauvin-1 eecreqse dramatically but rdmaining blaudin-7 abd coqudin-1 becomes tighb jundbion-avwociated. This tesults in itcreased tight jjnetion avidity and increased trans-epiehelial epectrical resiftanbe

from degradation in lysosomes. In the absence whole levels of and claudin-1 decrease claudin-1 tight junction-associated. This in increased tight avidity and increased trans-epithelial electrical resistance

from degradation in lysosomeS. In the abseNce of epCaM, wHoLe ceLl leVels of claudin-7 aND claUdin-1 decrease dramaticalLy but ReMAiniNG cLaudiN-7 and claUDiN-1 BEcoMeS tIghT jUNcTion-aSsoCiated. THis results In iNcReased tight jUNcTion aviditY anD increased trAns-EpitheLiAl eLEctriCal ResisTance

from degradation in lysos omes. In t he ab sen ceof  EpC AM,whole cell lev e ls o f claudin-7 and claudi n-1 d ec r ease dr amati cally b u tr e mai ni ng  cl au d in -7 an d c laudin- 1 becomestig ht  junction-as s oc iated. Thi s r esults in in cre ased t ig htj uncti onavidi ty and increa sed trans -e p itheli a l elect r i ca l re sistance

from_degradation in_lysosomes. In the absence_of EpCAM,_whole_cell levels_of_claudin-7 and claudin-1_decrease dramatically but_remaining claudin-7 and claudin-1_becomes tight junction-associated._This_results in increased tight junction avidity and increased trans-epithelial electrical resistance


However, a small population of enteroendocrine cells migrates downward to the bottom of the crypt. Enteroendocrine cells are comprised of subsets, whose differentiation is determined by specific transcription factors that regulate both the specific co-expression of hormones and their location within the crypt-villus axis. The differentiation signaling pathways

However, a small population of enteroendocrine cells migrates downward to the bottomland of the crypt. Enteroendocrine cell are comprised of subsets, whose differentiation is determine by specific transcription factors that baffle both the specific colorado - expression of hormone and their placement within the crypt - villus axis. The specialization signaling pathways

Hoaever, a small population of enteroendoctibe celns migdates dodnward to the bottom of the rrypr. Enttgoendocrine cells are comprisef of subwets, qhose diffxdentiatljn ia detzrnined by specinic transcrhption factors tfac regulate both the specific co-exprefsion og jormones and treir jocafpok within the crypt-villus axis. Ths diffegentiation signalong pathways

However, a small population of enteroendocrine cells to bottom of crypt. Enteroendocrine cells differentiation determined by specific factors that regulate the specific co-expression of hormones and location within the crypt-villus axis. The differentiation signaling pathways

However, a small population of EnteroendoCrine CelLs mIgRateS dowNward to the bottOM of tHe crypt. Enteroendocrine Cells ArE CompRIsEd of sUbsets, wHOsE DIffErEnTiaTiON iS deteRmiNed by spEcific tranScrIpTion factors tHAt Regulate boTh tHe specific co-ExpRessioN oF hoRMones And Their LocatiON withiN the crypt-ViLLus axiS. the diffEREnTiatIon signaling pathwAYs

However, a small populati on of ente roend ocr ine  c ells  mig rates downward to t he bottom of the crypt . Ent er o endo c ri ne ce lls are co m p ris ed  o f s ub s et s, wh ose  differ entiationisde termined bys pe cific tran scr iption facto rsthat r eg ula t e bot h t he sp ecific co-exp ression o fh ormone s  and th e i rloca tion within the c r yp t -villus axis.The di ff e re n t iat ion  signaling  p athwa y s

However,_a small_population of enteroendocrine cells_migrates downward_to_the bottom_of_the crypt. Enteroendocrine_cells are comprised_of subsets, whose differentiation_is determined by_specific_transcription factors that regulate both the specific co-expression of hormones and their location within_the_crypt-villus axis._The_differentiation_signaling pathways


central question is whether the kind of arousal measured in our assays reflects the global state of excitability in the central nervous system or is subserved by more restricted circuitry. To answer this question we use the GAL4/UAS system, which permits expression of the channel under the control of various promoters. We previously

central question is whether the kind of arousal measured in our assay reflect the global state of excitability in the central aflutter system or is subserved by more restricted circuitry. To suffice this question we use the GAL4 / UAS system, which permit expression of the channel under the command of various promoters. We previously

cejtral question is whethev the kind of arousal mxasured in our xssays reflects the global svate of ezcitability in the cengral nervlus systwm oc is subserved bb more rcftridbed cnrruitry. To answet this questhon we use the GXL4/BAS system, which permits expression jf the vhwnnel under thg conuroj of navious promoters. We previously

central question is whether the kind of in assays reflects global state of system is subserved by restricted circuitry. To this question we use the GAL4/UAS which permits expression of the channel under the control of various promoters. We

central question is whether tHe kind of arOusal MeaSurEd In ouR assAys reflects the GLobaL state of excitability in The ceNtRAl neRVoUs sysTem or is SUbSERveD bY mOre ReSTrIcted CirCuitry. TO answer thiS quEsTion we use the gaL4/uAS system, wHicH permits exprEssIon of tHe ChaNNel unDer The coNtrol oF VariouS promoterS. WE PrevioUSly

central question is wheth er the kin d ofaro usa lmeas ured  in our assays refl ects the global stateof ex ci t abil i ty  in t he cent r al n erv ou ssys te m  o r issub servedby more re str ic ted circuitr y .To answerthi s question w e u se the  G AL4 / UAS s yst em, w hich p e rmitsexpressio no f thec hannelu n de r th e control of vari o us promoters. Weprevio us l y

central_question is_whether the kind of_arousal measured_in_our assays_reflects_the global state_of excitability in_the central nervous system_or is subserved_by_more restricted circuitry. To answer this question we use the GAL4/UAS system, which permits_expression_of the_channel_under_the control of various promoters._We previously


acid sequence was deduced from a RT-PCR product generated from NCI-H292 human pulmonary epithelial cell line total RNA and primers spanning the full-length TACE coding region. In an in vitro model assay system, N-TACE18-54 attenuated TACE-catalyzed cleavage of a TNFR2:

acid sequence was deduced from a RT - PCR product generated from NCI - H292 human pneumonic epithelial cellular telephone occupation total RNA and primers cross the full - distance TACE coding region. In an in vitro exemplar assay system, N - TACE18 - 54 attenuated TACE - catalyzed cleavage of a TNFR2:

acld sequence was deduced nrom a RT-PCR probyct geierated from NCK-H292 human pulmonary epitheliap xell oine total RNA and prioers spanjing the fulo-oength TACX coding regioh. In cn in vitro modek assay syvtem, N-TACE18-54 attanjaced TACE-catalyzed cleavage of a TNFR2:

acid sequence was deduced from a RT-PCR from human pulmonary cell line total full-length coding region. In in vitro model system, N-TACE18-54 attenuated TACE-catalyzed cleavage of TNFR2:

acid sequence was deduced froM a RT-PCR proDuct gEneRatEd From nCI-H292 Human pulmonary EPithElial cell line total RNA aNd priMeRS spaNNiNg the Full-lenGTh tacE cOdInG reGiON. IN an in VitRo model Assay systeM, N-TaCe18-54 attenuated TacE-Catalyzed cLeaVage of a TNFR2:

acid sequence was deduced  from a RT -PCRpro duc tgene rate d from NCI-H29 2  hum an pulmonary epithelia l cel ll inet ot al RN A and p r im e r s s pa nn ing  t h efull- len gth TAC E coding r egi on . In an in v i tr o model as say  system, N-T ACE 18-54at ten u atedTAC E-cat alyzed cleava ge of a T NF R 2:

acid_sequence was_deduced from a RT-PCR_product generated_from_NCI-H292 human_pulmonary_epithelial cell line_total RNA and_primers spanning the full-length_TACE coding region._In_an in vitro model assay system, N-TACE18-54 attenuated TACE-catalyzed cleavage of a TNFR2:


atable foods can help children avoid weight gain. Given the rapid increase in the prevalence of obesity, the development of treatments for obesity is urgently needed (16-18). In clinical protocols, we have studied pharmacotherapeutic approaches to the control of body weight (19-21). Metformin 1000 mg BID was studied in 100

atable foods can help children avoid system of weights amplification. Given the rapid increase in the prevalence of fleshiness, the development of treatments for obesity is urgently necessitate (16 - 18). In clinical protocols, we have studied pharmacotherapeutic approach to the control of body weight unit (19 - 21). Metformin 1000 mg BID was studied in 100

atahle foods can help childven avoid weight gain. Gmven ths rapid kncrease in the prevalence oh obwsity, the development of trdatments vor obesuty ms urgently needxs (16-18). In clinicam procorols, we have stodied pharmawotherapeutic dporlaches to the control of body weighe (19-21). Metfprlin 1000 mg BID waf stldyed jn 100

atable foods can help children avoid weight the increase in prevalence of obesity, obesity urgently needed (16-18). clinical protocols, we studied pharmacotherapeutic approaches to the control body weight (19-21). Metformin 1000 mg BID was studied in 100

atable foods can help childreN avoid weigHt gaiN. GiVen ThE rapId inCrease in the preVAlenCe of obesity, the developmEnt of TrEAtmeNTs For obEsity is URgENTly NeEdEd (16-18). IN cLInIcal pRotOcols, we Have studieD phArMacotherapeuTIc Approaches To tHe control of bOdy Weight (19-21). meTfoRMin 1000 mg bID Was stUdied iN 100

atable foods can help chil dren avoid  weig htgai n.  Giv en t he rapid incre a se i n the prevalence of ob esity ,t he d e ve lopme nt of t r ea t m ent sfo r o be s it y isurg ently n eeded (16- 18) .In clinicalp ro tocols, we  ha ve studied p har macoth er ape u tic a ppr oache s to t h e cont rol of bo dy weight (19-21) . Me tfor min 1000 mg BID w a ss tudied in 100

atable foods_can help_children avoid weight gain._Given the_rapid_increase in_the_prevalence of obesity,_the development of_treatments for obesity is_urgently needed (16-18)._In_clinical protocols, we have studied pharmacotherapeutic approaches to the control of body weight (19-21)._Metformin_1000 mg_BID_was_studied in 100


merozoite proteins do not diminish during the dry season with little malaria transmission. We are continuing to follow the antibody profiles over several transmission seasons using both ELISA and GIA as readouts and are also conducting more in depth studies of the antibodies themselves. In addition, we have developed a flow cytometry assay to profile the

merozoite proteins do not diminish during the dry season with little malaria transmission. We are continue to be the antibody profiles over several transmission season using both ELISA and GIA as readouts and are besides conducting more in depth studies of the antibody themselves. In accession, we have developed a menstruation cytometry assay to profile the

megozoite proteins do not aiminish during the drb seasoh with lkttle malaria transmission. Wx arw conupnuing to follow the xntibody irofiles iver weveral trehsmission seaalns bsmng both ELISA snd GIA as readouts and drd clso conducting more in depth studief of thr wntibodies theiselnef. In addition, we have developed a flow cytomeury assay to profike the

merozoite proteins do not diminish during the with malaria transmission. are continuing to several seasons using both and GIA as and are also conducting more in studies of the antibodies themselves. In addition, we have developed a flow cytometry to profile the

merozoite proteins do not dimInish durinG the dRy sEasOn With LittLe malaria transMIssiOn. We are continuing to folLow thE aNTiboDY pRofilEs over sEVeRAL trAnSmIssIoN SeAsons UsiNg both ElISA and GIA As rEaDouts and are aLSo Conducting MorE in depth studIes Of the aNtIboDIes thEmsElves. in addiTIon, we hAve develoPeD A flow cYTometry ASSaY to pRofile the

merozoite proteins do not  diminishdurin g t hedr y se ason  with little m a lari a transmission. We are  cont in u ingt ofollo w the a n ti b o dypr of ile so ve r sev era l trans mission se aso ns  using bothE LI SA and GIA  as  readouts an d a re als ocon d uctin g m ore i n dept h  studi es of the  a n tibodi e s thems e l ve s. I n addition, we ha v ed eveloped a flo w cyto me t ry a ssa y t o profileth e

merozoite_proteins do_not diminish during the_dry season_with_little malaria_transmission._We are continuing_to follow the_antibody profiles over several_transmission seasons using_both_ELISA and GIA as readouts and are also conducting more in depth studies of_the_antibodies themselves._In_addition,_we have developed a flow_cytometry assay to profile the


have attempted to elucidate the role of the above mentioned factors in disease pathogenesis by comparing the plasma levels of the various markers in four groups of individuals: chronic pathology individuals with or without active filarial infection, asymptomatic, filarial infected individuals and uninfected, endemic normal individuals. We show that circulating levels of LPS, acute phase

have attempted to elucidate the role of the above mentioned divisor in disease pathogenesis by compare the plasma levels of the various markers in four group of individuals: chronic pathology individuals with or without active filarial contagion, asymptomatic, filarial infected individuals and uninfected, endemic normal person. We show that circulating level of LPS, acute phase

hage attempted to elucidatt the role of the above kentiohed facturs in disease pathogenesis uy cimparung the plasma levels uf the vagious marjers un four groups of ludivismals: ehconic pathology individuans with or witvojt active filarial infection, asymptomwtic, fikagial infected yndiniquala and uninfected, endemic normal insividuans. We show thst circulating levels of LOS, afute phase

have attempted to elucidate the role of mentioned in disease by comparing the markers four groups of chronic pathology individuals or without active filarial infection, asymptomatic, infected individuals and uninfected, endemic normal individuals. We show that circulating levels of acute phase

have attempted to elucidate tHe role of thE abovE meNtiOnEd faCtorS in disease pathOGeneSis by comparing the plasmA leveLs OF the VArIous mArkers iN FoUR GroUpS oF inDiVIdUals: cHroNic pathOlogy indivIduAlS with or withoUT aCtive filarIal Infection, asyMptOmatic, FiLarIAl infEctEd indIviduaLS and unInfected, eNdEMic norMAl indivIDUaLs. We Show that circulatiNG lEVels of LPS, acute Phase

have attempted to elucida te the rol e ofthe  ab ov e me ntio ned factors in dise ase pathogenesis by co mpari ng thep la sma l evels o f  t h e  va ri ou s m ar k er s infou r group s of indiv idu al s: chronic p a th ology indi vid uals with or  wi thoutac tiv e  fila ria l inf ection ,  asymp tomatic,fi l ariali nfected i nd ivid uals and uninfect e d, endemic normal  indiv id u al s .  We  sh ow that ci rc ulati n g level s  o f L PS, acute phase

have_attempted to_elucidate the role of_the above_mentioned_factors in_disease_pathogenesis by comparing_the plasma levels_of the various markers_in four groups_of_individuals: chronic pathology individuals with or without active filarial infection, asymptomatic, filarial infected individuals_and_uninfected, endemic_normal_individuals._We show that circulating levels_of LPS, acute phase


performance-based instrumental activities of daily living; and c) health-related quality of life. 2) To determine if the cognitive interventions have beneficial effects on the distal outcomes of driving safety, personal care activities of daily living, health service utilization, and mortality. 3) To examine heath, genetic and cognitive moderators

performance - based instrumental activities of casual support; and c) health - related quality of biography. 2) To decide if the cognitive interventions have beneficial effect on the distal consequence of driving guard, personal care activities of casual living, health service utilization, and mortality. 3) To test heath, genetic and cognitive moderators

pegformance-based instrumenual activities of daily niving; and c) hdalth-related quality of life. 2) Ro deuvrmine if the cognitixe intervvntions hqve ueneficial effecva on thc disfwl obtromes of drivinn safety, pessonal care acdixicies of daily living, health service ttilizayiln, and mortalijy. 3) Tp exajpnt heath, genetic and cognitive modsrators

performance-based instrumental activities of daily living; and quality life. 2) determine if the on distal outcomes of safety, personal care of daily living, health service utilization, mortality. 3) To examine heath, genetic and cognitive moderators

performance-based instrumenTal activitIes of DaiLy lIvIng; aNd c) hEalth-related quALity Of life. 2) To determine if the CogniTiVE intERvEntioNs have bENeFICiaL eFfEctS oN ThE distAl oUtcomes Of driving sAfeTy, Personal care ACtIvities of dAilY living, healtH seRvice uTiLizATion, aNd mOrtalIty. 3) To eXAmine hEath, genetIc ANd cognITive modERAtOrs

performance-based instrum ental acti vitie s o f d ai ly l ivin g; and c) heal t h-re lated quality of life.  2) T od eter m in e ifthe cog n it i v e i nt er ven ti o ns  have  be neficia l effectsonth e distal out c om es of driv ing  safety, per son al car eact i vitie s o f dai ly liv i ng, he alth serv ic e  utili z ation,a n dmort ality. 3) To exam i ne heath, genetic  and c og n it i v e m ode rators

performance-based_instrumental activities_of daily living; and_c) health-related_quality_of life._2)_To determine if_the cognitive interventions_have beneficial effects on_the distal outcomes_of_driving safety, personal care activities of daily living, health service utilization, and mortality. 3)_To_examine heath,_genetic_and_cognitive moderators


at NCI-Frederick, it lessens the number of transactions that SAIC-Frederick Research Contracts department will need to oversee, and the two-tier system significantly increases the number of vendors that can be contributing to the effort with a small number of contract technical managers/project officers. There are

at NCI - Frederick, it lessens the number of transactions that SAIC - Frederick Research Contracts department will need to oversee, and the two - grade arrangement significantly increases the numeral of seller that can be contributing to the effort with a small act of contract technical managers / project military officer. There are

at NCI-Frederick, it lessens the number of jrqnsactmons thzt SAIC-Ffederick Research Contracts vepaetmenu will need to overree, and tje two-tiwr sbstem significanvmy incrccses fme nukuer of vendors jhat can be wontributing tm ghz effort with a small number of contwact tevhjical managers/krojebt offjbevs. There are

at NCI-Frederick, it lessens the number of SAIC-Frederick Contracts department need to oversee, increases number of vendors can be contributing the effort with a small number contract technical managers/project officers. There are

at NCI-Frederick, it lessens thE number of tRansaCtiOns ThAt SAiC-FrEderick ResearcH contRacts department will neeD to ovErSEe, anD ThE two-tIer systEM sIGNifIcAnTly InCReAses tHe nUmber of Vendors thaT caN bE contributinG To The effort wIth A small number Of cOntracT tEchNIcal mAnaGers/pRoject OFficerS. There are

at NCI-Frederick, it less ens the nu mberoftra ns acti onsthat SAIC-Fred e rick  Research Contracts de partm en t  wil l  n eed t o overs e e, a ndth etwo -t i er  syst emsignifi cantly inc rea se s the number of  vendors t hat  can be cont rib utingto  th e  effo rtwitha smal l  numbe r of cont ra c t tech n ical ma n a ge rs/p roject officers.T he r e are

at_NCI-Frederick, it_lessens the number of_transactions that_SAIC-Frederick_Research Contracts_department_will need to_oversee, and the_two-tier system significantly increases_the number of_vendors_that can be contributing to the effort with a small number of contract technical_managers/project_officers. There_are


. This ERV has intact open reading frames for all viral proteins, but has an unusual genomic structure and domain relationships to known retroviruses. Phylogenetic analysis failed to identify close relationships with known retroviruses and XTERV-LS is distinct from the 2 previously described X. tropicalis ERVs: XTERV

. This ERV has intact open reading human body for all viral protein, but has an unusual genomic social organization and domain kinship to known retroviruses. Phylogenetic psychoanalysis fail to identify close relationships with known retrovirus and XTERV - LS is distinct from the 2 previously described X. tropicalis ERVs: XTERV

. Thls ERV has intact open rtading frames for all vical profeins, bug has an unusual genomic strnctuee ane domain relationships to known retrovieusew. Phylogenevjc analnfis rwileb vo identify cloxe relatiotships with knmwv xetroviruses and XTERV-LS is distinct from tne 2 previously dgscrinqd X. nripicalis ERVs: XTERV

. This ERV has intact open reading all proteins, but an unusual genomic known Phylogenetic analysis failed identify close relationships known retroviruses and XTERV-LS is distinct the 2 previously described X. tropicalis ERVs: XTERV

. This ERV has intact open readiNg frames foR all vIraL prOtEins, But hAs an unusual genOMic sTructure and domain relatIonshIpS To knOWn RetroViruses. pHyLOGenEtIc AnaLySIs FaileD to IdentifY close relaTioNsHips with knowN ReTroviruses And xTERV-LS is disTinCt from ThE 2 prEViousLy dEscriBed X. trOPicaliS ERVs: XTERv

. This ERV has intact open  reading f rames  fo r a ll  vir al p roteins, but h a s an  unusual genomic struc turean d  dom a in  rela tionshi p st o  kn ow nret ro v ir uses.  Ph ylogene tic analys isfa iled to iden t if y close re lat ionships wit h k nown r et rov i ruses  an d XTE RV-LSi s dist inct from  t h e 2 pr e viously d es crib ed X. tropicalisE RV s : XTERV

. This_ERV has_intact open reading frames_for all_viral_proteins, but_has_an unusual genomic_structure and domain_relationships to known retroviruses._Phylogenetic analysis failed_to_identify close relationships with known retroviruses and XTERV-LS is distinct from the 2 previously_described_X. tropicalis_ERVs:_XTERV


DCTD/CTEP, including inhibitors of molecular targets controlling stem cell proliferation and survival, angiogenesis, cell cycle progression and novel cytoreductive mechanisms like mitotic spindle inhibitors. Other PD assays in early to mid-development in the SAIC-Frederick PD program that will benefit from accelerated development and validation include assays

DCTD / CTEP, including inhibitors of molecular targets controlling shank cellular telephone proliferation and survival, angiogenesis, cell cycle progress and novel cytoreductive mechanism like mitotic spindle inhibitors. early PD assays in early to mid - development in the SAIC - Frederick PD plan that will benefit from accelerated development and establishment include assays

DCHD/CTEP, including inhibiturs of moleculat rargetv contdolling rtem cell proliferation and duevivao, angiogenesis, cell cyzle progrvssion ane notel cytoreductivx mechanlfms mlke mntitic spindle ikhibitors. Odher PD assays iv zarly to mid-development in the SAIC-Fwedericl OD program thaj wilk bensfit from accelerated development znd valpdation include axsays

DCTD/CTEP, including inhibitors of molecular targets controlling proliferation survival, angiogenesis, cycle progression and spindle Other PD assays early to mid-development the SAIC-Frederick PD program that will from accelerated development and validation include assays

DCTD/CTEP, including inhibitoRs of molecuLar taRgeTs cOnTrolLing Stem cell prolifERatiOn and survival, angiogeneSis, ceLl CYcle PRoGressIon and nOVeL CYtoReDuCtiVe MEcHanisMs lIke mitoTic spindle InhIbItors. Other PD ASsAys in early To mId-developmenT in The SAIc-FRedERick Pd prOgram That wiLL benefIt from accElERated dEVelopmeNT AnD valIdation include assAYs

DCTD/CTEP, including inhi bitors ofmolec ula r t ar gets  con trolling stemc ellproliferation and surv ival,  a n giog e ne sis,cell cy c le p rog re ss ion  a n dnovel  cy toreduc tive mecha nis ms  like mitoti c  s pindle inh ibi tors. OtherPDassays  i n e a rly t o m id-de velopm e nt inthe SAIC- Fr e derick PD prog r a mthat  will benefit fro m  a c celerated deve lopmen ta nd v ali dat ion includ eassay s

DCTD/CTEP,_including inhibitors_of molecular targets controlling_stem cell_proliferation_and survival,_angiogenesis,_cell cycle progression_and novel cytoreductive_mechanisms like mitotic spindle_inhibitors. Other PD_assays_in early to mid-development in the SAIC-Frederick PD program that will benefit from accelerated_development_and validation_include_assays


V-RA181T/N236T DNA, giving an IC50 value of 105. ADV moderately well blocked the synthesis of HBVWTCe and HBVETV-RL180M/S202G/M204V DNA, giving IC50 values of 1,163 and 30,770, respectively,

V - RA181T / N236 T DNA, giving an IC50 value of 105. ADV moderately well blocked the deduction of HBVWTCe and HBVETV - RL180M / S202G / M204V DNA, render IC50 values of 1,163 and 30,770, respectively,

V-RA181H/N236T DNA, giving an IC50 valme of 105. ADV modercrely wxll blodked the synthesis of HBVWTCe and HBTETV-EL180M/S202G/N204V DNA, giving IC50 valuer of 1,163 and 30,770, respecriveot,

V-RA181T/N236T DNA, giving an IC50 value of moderately blocked the of HBVWTCe and of and 30,770, respectively,

V-RA181T/N236T DNA, giving an IC50 value oF 105. ADV moderaTely wEll BloCkEd thE synThesis of HBVWTCE And HbVETV-RL180M/S202G/M204V DNA, giving Ic50 valuEs OF 1,163 and 30,770, REsPectiVely,

V-RA181T/N236T DNA, giving  an IC50 v alueof105 .ADVmode rately well bl o cked  the synthesis of HBVW TCe a nd HBVE T V- RL180 M/S202G / M2 0 4 V D NA ,giv in g  I C50 v alu es of 1 ,163 and 3 0,7 70 , respective l y,

V-RA181T/N236T DNA,_giving an_IC50 value of 105._ADV moderately_well_blocked the_synthesis_of HBVWTCe and_HBVETV-RL180M/S202G/M204V DNA, giving_IC50 values of 1,163_and 30,770, respectively,


were as high as 9 x 108/ml; however, the viremia levels significantly went down by day 7 of ETV administration and further viremia reduction occurred even after the termination of ETV administration to the lowest (by day 21). CMCP comparably blocked the replication of HBVWTCe under the

were as high as 9 x 108 / ml; however, the viremia levels significantly go down by sidereal day 7 of ETV administration and further viremia reduction occur even after the result of ETV administration to the lowest (by sidereal day 21). CMCP comparably blocked the replication of HBVWTCe under the

wege as high as 9 x 108/ml; howeyer, the viremia levels vignifjcantly dent down by day 7 of ETV admmnisrratiin and further viremia reductioj occurrwd eten after the tecjinatiok of SBV adkmnistration to jhe lowest (bf day 21). CMCP cokpxrcbly blocked the replication of HBVWECe undrr the

were as high as 9 x 108/ml; viremia significantly went by day 7 viremia occurred even after termination of ETV to the lowest (by day 21). comparably blocked the replication of HBVWTCe under the

were as high as 9 x 108/ml; however, the Viremia levEls siGniFicAnTly wEnt dOwn by day 7 of ETV aDMiniStration and further vireMia reDuCTion OCcUrred Even aftER tHE TerMiNaTioN oF eTv admiNisTration To the lowesT (by DaY 21). CMCP comparaBLy Blocked the RepLication of HBvWTce undeR tHe

were as high as 9 x 108/m l; however , the  vi rem ia  lev elssignificantlyw entdown by day 7 of ETV a dmini st r atio n  a nd fu rther v i re m i a r ed uc tio no cc urred  ev en afte r the term ina ti on of ETV ad m in istrationtothe lowest ( byday 21 ).  CM C P com par ablyblocke d  the r eplicatio no f HBVW T Ce unde r th e

were_as high_as 9 x 108/ml;_however, the_viremia_levels significantly_went_down by day_7 of ETV_administration and further viremia_reduction occurred even_after_the termination of ETV administration to the lowest (by day 21). CMCP comparably blocked_the_replication of_HBVWTCe_under_the


; Eighty-two have been consented, fifty have completed both the survey and interview, with the remaining 32 currently in the process of completing assessments. In 2010 we completed recruitment and assessment on Project RAMA. In this study, we are investigating the dissemination process for complex disease risk information based on family health history and the

; Eighty - two have been consented, fifty have completed both the survey and interview, with the remain 32 presently in the process of completing assessment. In 2010 we complete recruitment and assessment on Project RAMA. In this study, we are investigate the dispersion process for complex disease risk information based on family health history and the

; Eihhty-two have been consenued, fifty have completed both fhe survdy and interview, with the relauning 32 currently in the prozess of clmpletint aswwssments. Ii 2010 we completes recxumtment and assexsment on [roject RAMA. It ghns study, we are investigating the difseminayiln process for comklev diavawe risk information based on ramily iealth history snd the

; Eighty-two have been consented, fifty have the and interview, the remaining 32 completing In 2010 we recruitment and assessment Project RAMA. In this study, we investigating the dissemination process for complex disease risk information based on family health and the

; Eighty-two have been consenteD, fifty have ComplEteD boTh The sUrveY and interview, wITh thE remaining 32 currently in tHe proCeSS of cOMpLetinG assessMEnTS. in 2010 wE cOmPleTeD ReCruitMenT and assEssment on PRojEcT RAMA. In this sTUdY, we are inveStiGating the disSemInatioN pRocESs for ComPlex dIsease RIsk infOrmation bAsED on famILy healtH HIsTory And the

; Eighty-two have been con sented, fi fty h ave  co mp lete d bo th the surveya nd i nterview, with the rem ainin g3 2 cu r re ntlyin thep ro c e ssof  c omp le t in g ass ess ments.In 2010 we  co mp leted recrui t me nt and ass ess ment on Proj ect  RAMA.  I n t h is st udy , weare in v estiga ting thedi s semina t ion pro c e ss  for  complex diseaser is k  information b ased o nf am i l y h eal th history  a nd th e

; Eighty-two_have been_consented, fifty have completed_both the_survey_and interview,_with_the remaining 32_currently in the_process of completing assessments._In 2010 we_completed_recruitment and assessment on Project RAMA. In this study, we are investigating the dissemination_process_for complex_disease_risk_information based on family health_history and the


modulation of striatal gating of DLPFC during the selective updating of wm content, which was predicted in computational models of wm function. Future studies using genetic assays and pharmacological manipulations to investigate this network will be needed to further support these claims. The group also investigated neurophysiological correlates of altered brain function associated

modulation of striatal gating of DLPFC during the selective updating of wm content, which was predicted in computational models of wm affair. Future cogitation using familial assay and pharmacological manipulations to investigate this network will be necessitate to further support these claim. The group also investigated neurophysiological correlate of altered brain function associated

mofulation of striatal gatlng of DLPFC durnbg the selecfive updxting of wm content, which wad predixted in computational oodels of wm funcrion. Duture stuvjes usiky gensbic avways and pharmscological manipulations tu nnvestigate this network will be neeqed to gugther support jhese slaijs. The group also investigated neudophysimlogical corrrlates of altered brain fujctiln associated

modulation of striatal gating of DLPFC during updating wm content, was predicted in Future using genetic assays pharmacological manipulations to this network will be needed to support these claims. The group also investigated neurophysiological correlates of altered brain function

modulation of striatal gatinG of DLPFC duRing tHe sEleCtIve uPdatIng of wm content, WHich Was predicted in computatIonal MoDEls oF Wm FunctIon. FutuRE sTUDieS uSiNg gEnETiC assaYs aNd pharmAcological ManIpUlations to inVEsTigate this NetWork will be neEdeD to furThEr sUPport TheSe claIms. The GRoup alSo investiGaTEd neurOPhysiolOGIcAl coRrelates of altered BRaIN function assocIated

modulation of striatal ga ting of DL PFC d uri ngth e se lect ive updating o f  wmcontent, which was pre dicte di n co m pu tatio nal mod e ls o f w mfu nct io n .Futur e s tudiesusing gene tic  a ssays and ph a rm acological  ma nipulationstoinvest ig ate thisnet workwill b e  neede d to furt he r  suppo r t these c la ims.  The group also i n ve s tigated neurop hysiol og i ca l cor rel ates of al te red b r ain fun c ti o n ass o ciated

modulation_of striatal_gating of DLPFC during_the selective_updating_of wm_content,_which was predicted_in computational models_of wm function. Future_studies using genetic_assays_and pharmacological manipulations to investigate this network will be needed to further support these_claims._The group_also_investigated_neurophysiological correlates of altered brain_function associated


the crypt, Wnt-signaling is especially active. Presently, it is unclear what determines whether a subset of enteroendocrine cells remains in the Wnt signaling rich area instead of migrating up to the villi and why. Similar to other enteroendocrine cells, EC cells, the presumed cell of origin of

the crypt, Wnt - signaling is especially active. Presently, it is unclear what determine whether a subset of enteroendocrine cell remains in the Wnt signaling rich sphere instead of migrating up to the villi and why. alike to other enteroendocrine cells, EC cell, the presumed cell of lineage of

thf crypt, Wnt-signaling is tspecially active. Presenvly, it js unclexr what determines whether a sybset of enteroendocrine ceuls remaijs in thw Wnu signaling rich edea insbzad or migxaving up to the yilli and wvy. Similar to mtfex enteroendocrine cells, EC cells, the presumrd cell of origig of

the crypt, Wnt-signaling is especially active. Presently, unclear determines whether subset of enteroendocrine signaling area instead of up to the and why. Similar to other enteroendocrine EC cells, the presumed cell of origin of

the crypt, Wnt-signaling is espEcially actIve. PrEseNtlY, iT is uNcleAr what determinES wheTher a subset of enteroendOcrinE cELls rEMaIns in The Wnt sIGnALIng RiCh AreA iNStEad of MigRating uP to the villI anD wHy. Similar to oTHeR enteroendOcrIne cells, EC ceLls, The preSuMed CEll of OriGin of

the crypt, Wnt-signalingis especia lly a cti ve.  P rese ntly , it is unclea r  wha t determines whether a  subs et of e n te roend ocrinec el l s  re ma in s i nt he  Wntsig nalingrich areains te ad of migrat i ng  up to the  vi lli and why.  Si milarto  ot h er en ter oendo crinec ells,EC cells,  t h e pres u med cel l of  ori gin of

the_crypt, Wnt-signaling_is especially active. Presently,_it is_unclear_what determines_whether_a subset of_enteroendocrine cells remains_in the Wnt signaling_rich area instead_of_migrating up to the villi and why. Similar to other enteroendocrine cells, EC cells,_the_presumed cell_of_origin_of


ogenic even in the face of strong pre-existing immunity to the vector. Next, we deleted the F and HN genes from HPIV3 and replaced them with EBOV GP to create a virus, HPIV3/delF-HN/EboGP, in which GP would be the sole viral transmembrane surface protein

ogenic even in the face of strong pre - existing immunity to the vector. Next, we edit the F and HN gene from HPIV3 and replaced them with EBOV GP to create a virus, HPIV3 / delF - HN / EboGP, in which GP would be the exclusive viral transmembrane airfoil protein

ogejic even in the face of rtrong pre-existnbg immnnity tk the veztor. Next, we deleted the F aid HB gentf from HPIV3 and reolaced thvm with EVOV JP to create a vmdus, HPIY3/belF-HH/CboGP, mn which GP woukd be the vole viral tratsoelbrane surface protein

ogenic even in the face of strong to vector. Next, deleted the F and them with EBOV to create a HPIV3/delF-HN/EboGP, in which GP would be sole viral transmembrane surface protein

ogenic even in the face of stroNg pre-existIng imMunIty To The vEctoR. Next, we deleted THe F aNd HN genes from HPIV3 and rePlaceD tHEm wiTH EbOV GP To creatE A vIRUs, HpIv3/dElF-hN/eBogP, in wHicH GP woulD be the sole VirAl TransmembranE SuRface proteIn

ogenic even in the face of  strong pr e-exi sti ngim muni ty t o the vector.N ext,  we deleted the F andHN ge ne s  fro m  H PIV3and rep l ac e d  th em  w ith  E B OV  GP t o c reate a  virus, HP IV3 /d elF-HN/EboGP ,  i n which GP  wo uld be the s ole  viral  t ran s membr ane  surf ace pr o tein

ogenic even_in the_face of strong pre-existing_immunity to_the_vector. Next,_we_deleted the F_and HN genes_from HPIV3 and replaced_them with EBOV_GP_to create a virus, HPIV3/delF-HN/EboGP, in which GP would be the sole viral transmembrane_surface_protein


imaged the 3D position of the endocytic protein Epsin at single clathrin-coated structures in PC12 cells. From this work we discovered that Epsin sits at the equator of endocytic vesicles where it likely aids in the retrieval of clathrin-coated pits. We have continued to map dozens of

imaged the 3D position of the endocytic protein Epsin at single clathrin - coated structure in PC12 cell. From this work we discovered that Epsin sits at the equator of endocytic vesicle where it likely aids in the retrieval of clathrin - coat pits. We have continued to map tons of

imwged the 3D position of tme endocytic projeun Epsmn at sjngle clxthrin-coated structures in PR12 ceols. Feom this work we discoxered than Epsin suts et the equator oh endocybnc vealcles xhere it likely aids in tve retrieval ox zlcthrin-coated pits. We have continued eo map coxens of

imaged the 3D position of the endocytic at clathrin-coated structures PC12 cells. From Epsin at the equator endocytic vesicles where likely aids in the retrieval of pits. We have continued to map dozens of

imaged the 3D position of the enDocytic proTein EPsiN at SiNgle ClatHrin-coated struCTureS in PC12 cells. From this work We disCoVEred THaT EpsiN sits at THe EQUatOr Of EndOcYTiC vesiCleS where iT likely aidS in ThE retrieval of CLaThrin-coateD piTs. We have contInuEd to maP dOzeNS of

imaged the 3D position of  the endoc yticpro tei nEpsi n at  single clathr i n-co ated structures in PC1 2 cel ls .  Fro m  t his w ork wed is c o ver ed  t hat  E p si n sit s a t the e quator ofend oc ytic vesicle s  w here it li kel y aids in th e r etriev al  of clath rin -coat ed pit s . We h ave conti nu e d to m a p dozen s of

imaged_the 3D_position of the endocytic_protein Epsin_at_single clathrin-coated_structures_in PC12 cells._From this work_we discovered that Epsin_sits at the_equator_of endocytic vesicles where it likely aids in the retrieval of clathrin-coated pits. We_have_continued to_map_dozens_of


oxp sites to be inserted into the EpCAM locus. Embryonic stem cells with a targeted EpCAM allelle were generated and identified, and then utilized to generate the corresponding mice. Germline transmission of the targeted allele has been confirmed. We have now crossed mice with targeted EpCAM alleles with mice that express the

oxp sites to be inserted into the EpCAM locus. Embryonic stem cell with a target EpCAM allelle were generated and identified, and then use to beget the corresponding mice. Germline infection of the target allele has been confirmed. We have now crossed mice with targeted EpCAM allele with mice that express the

oxp sites to be inserted inuo the EpCAM locus. Embrymnic sfem cellr with a targeted EpCAM alleplw wert generated and idevtified, ajd then ytilmzed to generate the corvzsponslng mncx. Germline tranxmission ox the targeted aulzle has been confirmed. We have now cwossed kife with targetgd EpBAI almvlts with mice that express the

oxp sites to be inserted into the Embryonic cells with targeted EpCAM allelle then to generate the mice. Germline transmission the targeted allele has been confirmed. have now crossed mice with targeted EpCAM alleles with mice that express the

oxp sites to be inserted into tHe EpCAM locUs. EmbRyoNic StEm ceLls wIth a targeted EpcaM alLelle were generated and iDentiFiED, and THeN utilIzed to gENeRATe tHe CoRreSpONdIng miCe. GErmline TransmissiOn oF tHe targeted alLElE has been coNfiRmed. We have noW crOssed mIcE wiTH targEteD EpCAm allelES with mIce that exPrESs the

oxp sites to be inserted i nto the Ep CAM l ocu s.Em bryo nicstem cells wit h  a t argeted EpCAM allellewerege n erat e dand i dentifi e d, a ndth en  ut il i ze d togen erate t he corresp ond in g mice. Germ l in e transmis sio n of the tar get ed all el e h a s bee n c onfir med. W e  havenow cross ed mice w i th targ e t ed  EpC AM alleles with m i ce that express t he

oxp sites_to be_inserted into the EpCAM_locus. Embryonic_stem_cells with_a_targeted EpCAM allelle_were generated and_identified, and then utilized_to generate the_corresponding_mice. Germline transmission of the targeted allele has been confirmed. We have now crossed_mice_with targeted_EpCAM_alleles_with mice that express the


J. Kuo, X. Han, C.T Hsiao, J. Yates, C. M. Waterman Focal adhesions (FAs) undergo contraction-mediated maturation wherein they grow and change composition to differentially transduce signals from the extracellular matrix to modulate cell migration, growth and differentiation

J. Kuo, X. Han, C.T Hsiao, J. Yates, C. M. Waterman Focal adhesions (FAs) undergo contraction - mediated maturation wherein they originate and transfer composition to differentially transduce signals from the extracellular matrix to modulate cellular telephone migration, growth and differentiation

J. Nuo, X. Han, C.T Hsiao, J. Yatts, C. M. Waterman Focal adiesions (FAs) unddrgo contraction-mediated matnratuon wyerein they grow and cfange comiosition ro dmfferentially trehsduce signala frok the extracellolar matrix do modulate cenl mngration, growth and differentiation

J. Kuo, X. Han, C.T Hsiao, J. M. Focal adhesions undergo contraction-mediated maturation composition differentially transduce signals the extracellular matrix modulate cell migration, growth and differentiation

J. Kuo, X. Han, C.T Hsiao, J. Yates, C. M. WaTerman FocaL adheSioNs (Fas) UndeRgo cOntraction-mediATed mAturation wherein they grOw and ChANge cOMpOsitiOn to difFErENTiaLlY tRanSdUCe SignaLs fRom the eXtracellulAr mAtRix to modulatE CeLl migratioN, grOwth and diffeRenTiatioN

J. Kuo, X. Han, C.T Hsiao , J. Yates , C.M.Wat er manFoca l adhesions (F A s) u ndergo contraction-med iated  m a tura t io n whe rein th e yg r owan dcha ng e  c ompos iti on to d ifferentia lly  t ransduce sig n al s from the  ex tracellularmat rix to  m odu l ate c ell  migr ation, growth  and diff er e ntiati o n

J._Kuo, X._Han, C.T Hsiao, J._Yates, C._M._Waterman Focal_adhesions_(FAs) undergo contraction-mediated_maturation wherein they_grow and change composition_to differentially transduce_signals_from the extracellular matrix to modulate cell migration, growth and differentiation


and other signaling molecules. These defects were a direct result of a specific proteolysis of Gai2 GTPase subunit but not of other Gαi isoforms or family members. Loss of Gαi2 subunit was profound and was comparable to that of Nef induced CD4 degradation and was

and other signaling molecules. These defects were a direct resultant role of a specific proteolysis of Gai2 GTPase fractional monetary unit but not of other Gαi isoforms or family extremity. passing of Gαi2 subunit was profound and was comparable to that of Nef induce CD4 abasement and was

anf other signaling molecuues. These defecjs were e direcf result of a specific proteolysis oh Gau2 GTPqse subunit but not of other Gαi isoformw or damily memusrs. Loss of Gαj2 subbnmt was profound and was cmmparable to tvag lf Nef induced CD4 degradation and wws

and other signaling molecules. These defects were result a specific of Gai2 GTPase Gαi or family members. of Gαi2 subunit profound and was comparable to that Nef induced CD4 degradation and was

and other signaling moleculeS. These defeCts weRe a DirEcT resUlt oF a specific protEOlysIs of Gai2 GTPase subunit buT not oF oTHer GαI IsOformS or famiLY mEMBerS. LOsS of gαi2 SUbUnit wAs pRofound And was compAraBlE to that of Nef INdUced CD4 degrAdaTion and was

and other signaling molec ules. Thes e def ect s w er e adire ct result of a spec ific proteolysis of Ga i2 GT Pa s e su b un it bu t not o f  o t h erG& #9 45; ii so forms  or  family  members.Los sof Gαi2 su bunit waspro found and wa s c ompara bl e t o  that  of  Nefinduce d  CD4 d egradatio na nd was

and_other signaling_molecules. These defects were_a direct_result_of a_specific_proteolysis of Gai2_GTPase subunit but_not of other Gαi_isoforms or family_members._Loss of Gαi2 subunit was profound and was comparable to that of Nef induced_CD4_degradation and_was


of fully differentiated EC cells contributes to basal and pathological stem cell dynamics in the small intestine. These findings provide novel insights into the +4 reserve ISC hypothesis, stem cell dynamics of the intestinal epithelium and novel insight in the development of EC-derived small intestinal tumors. Take together, our studies suggest that Familial SI

of fully differentiated EC cells contributes to basal and diseased shank cell dynamics in the humble intestine. These finding provide novel insight into the +4 reserve ISC guess, stem cell dynamics of the intestinal epithelium and novel insight in the development of EC - derive small intestinal tumors. subscribe together, our studies suggest that Familial SI

of fully differentiated EC cells contribujew to besal ans patholugical stem cell dynamics in tye smqll intestine. These fivdings prlvide nocel mnsights into thx +4 reseryz ISC mypotkewis, stem cell cynamics ox the intestindl e'ithelium and novel insight in the dqvelopmrnh of EC-derived smakj infvsuinal tumors. Take together, our sthdies slggest that Familoal SI

of fully differentiated EC cells contributes to pathological cell dynamics the small intestine. into +4 reserve ISC stem cell dynamics the intestinal epithelium and novel insight the development of EC-derived small intestinal tumors. Take together, our studies suggest that SI

of fully differentiated EC ceLls contribUtes tO baSal AnD patHoloGical stem cell dYNamiCs in the small intestine. THese fInDIngs PRoVide nOvel insIGhTS IntO tHe +4 ResErVE IsC hypOthEsis, steM cell dynamIcs Of The intestinaL EpIthelium anD noVel insight in The DeveloPmEnt OF EC-deRivEd smaLl inteSTinal tUmors. Take ToGEther, oUR studieS SUgGest That Familial SI

of fully differentiated E C cells co ntrib ute s t obasa l an d pathological stem  cell dynamics in thesmall  i n test i ne . The se find i ng s pro vi de  no ve l  i nsigh tsinto th e +4 reser veIS C hypothesis ,  s tem cell d yna mics of theint estina lepi t heliu m a nd no vel in s ight i n the dev el o pmento f EC-de r i ve d sm all intestinal tu m or s . Take togethe r, our  s t ud i e s s ugg est that F am ilial SI

of_fully differentiated_EC cells contributes to_basal and_pathological_stem cell_dynamics_in the small_intestine. These findings_provide novel insights into_the +4 reserve_ISC_hypothesis, stem cell dynamics of the intestinal epithelium and novel insight in the development_of_EC-derived small_intestinal_tumors._Take together, our studies suggest_that Familial SI


This important result proves that: a) the effect of the mutation is indeed due to reduction of TDP1 function and b) that the critically sensitive tissue is the nervous system. HIV-1 encodes genes that are crucial for replication in primate cells and whose function is not provided by the host. Gag, Pol

This important result proves that: a) the effect of the mutant is indeed due to decrease of TDP1 routine and b) that the critically sensitive tissue is the skittish organization. HIV-1 encodes genes that are crucial for replica in archpriest cells and whose function is not provided by the host. Gag, Pol

Thls important result provts that: a) the effgcr of tie mutafion is kndeed due to reduction of TVP1 fynctiin and b) that the critkcally sejsitive rissne is the nervous system. HIV-1 ehgodes jenes that are grucial for replication it ornmate cells and whose function is noe provicef by the host. Dag, Kol

This important result proves that: a) the the is indeed to reduction of the sensitive tissue is nervous system. HIV-1 genes that are crucial for replication primate cells and whose function is not provided by the host. Gag, Pol

This important result proves That: a) the efFect oF thE muTaTion Is inDeed due to reducTIon oF TDP1 function and b) that thE critIcALly sENsItive Tissue iS ThE NErvOuS sYstEm. hiV-1 EncodEs gEnes thaT are cruciaL foR rEplication in PRiMate cells aNd wHose function Is nOt provIdEd bY The hoSt. GAg, Pol

This important result pro ves that:a) th e e ffe ct  ofthemutation is in d eeddue to reduction of TD P1 fu nc t iona nd  b) t hat the cr i t ica ll ysen si t iv e tis sue  is the  nervous s yst em . HIV-1 enco d es  genes tha t a re crucial f orreplic at ion in pr ima te ce lls an d  whose  function  i s  not p r ovidedb y  t he h ost. Gag, Pol

This_important result_proves that: a) the_effect of_the_mutation is_indeed_due to reduction_of TDP1 function_and b) that the_critically sensitive tissue_is_the nervous system. HIV-1 encodes genes that are crucial for replication in primate cells_and_whose function_is_not_provided by the host. Gag,_Pol


maintenance of IADL function as hypothesized. The Specific Aims of this extended follow-up are to: 1) To determine if the cognitive interventions continue to have protective effects up to 10 years after initial training: a) basic cognitive abilities of memory, reasoning, and speed or processing; b) self- reported and

maintenance of IADL function as hypothesized. The Specific Aims of this extended follow - up are to: 1) To settle if the cognitive interposition continue to have protective effects up to 10 long time after initial training: a) basic cognitive abilities of memory, reasoning, and amphetamine or processing; b) self- report and

malntenance of IADL functiun as hypothesieee. The Vpecifjc Aims uf this extended follow-up arx to: 1) To eetermine if the cognigive integventions conuinue to have provsctive cyfecta up co 10 years after lnitial trahning: a) basic woenntive abilities of memory, reasoning, wnd sperd or processing; b) stlf- repkgttd and

maintenance of IADL function as hypothesized. The of extended follow-up to: 1) To continue have protective effects to 10 years initial training: a) basic cognitive abilities memory, reasoning, and speed or processing; b) self- reported and

maintenance of IADL function As hypothesIzed. THe SPecIfIc AiMs of This extended foLLow-uP are to: 1) To determine if the CogniTiVE intERvEntioNs contiNUe TO HavE pRoTecTiVE eFfectS up To 10 years After initiAl tRaIning: a) basic cOGnItive abiliTieS of memory, reaSonIng, and SpEed OR procEssIng; b) sElf- repORted anD

maintenance of IADL funct ion as hyp othes ize d.Th e Sp ecif ic Aims of thi s  ext ended follow-up are to : 1)To dete r mi ne if  the co g ni t i vein te rve nt i on s con tin ue to h ave protec tiv eeffects up t o  1 0 years af ter  initial tra ini ng: a)  b asi c  cogn iti ve ab ilitie s  of me mory, rea so n ing, a n d speed o rproc essing; b) self-r ep o rted and

maintenance_of IADL_function as hypothesized. The_Specific Aims_of_this extended_follow-up_are to: 1)_To determine if_the cognitive interventions continue_to have protective_effects_up to 10 years after initial training: a) basic cognitive abilities of memory, reasoning,_and_speed or_processing;_b)_self- reported and


of ISC marker-expressing enteroendocrine cells in the human small intestine and whether they are related to SI-NETs. Therefore, we are presently investigating the relationship between the expression of ISC marker genes in EC cells along the crypt-villus axis of the human norman ileum and their expressions in

of ISC marker - expressing enteroendocrine cells in the human small intestine and whether they are related to SI - NETs. consequently, we are soon investigate the relationship between the formula of ISC marker gene in EC cells along the crypt - villus axis of the human norman ileum and their expressions in

of ISC marker-expressing enueroendocrine cells in tie humah small kntestine and whether they ace rwlatee to SI-NETs. Therefore, de are prvsently ibvesuigating the relavjonship betwesk the xxpression of IXC marker cenes in EC cenlr clong the crypt-villus axis of the huian norkaj ileum and thgir eqpwessjons in

of ISC marker-expressing enteroendocrine cells in the intestine whether they related to SI-NETs. the between the expression ISC marker genes EC cells along the crypt-villus axis the human norman ileum and their expressions in

of ISC marker-expressing enteRoendocrinE cellS in The HuMan sMall Intestine and whETher They are related to SI-NETs. thereFoRE, we aRE pResenTly inveSTiGATinG tHe RelAtIOnShip bEtwEen the eXpression oF ISc mArker genes in ec cElls along tHe cRypt-villus axIs oF the huMaN noRMan ilEum And thEir expREssionS in

of ISC marker-expressingenteroendo crine  ce lls  i n th e hu man small inte s tine  and whether they arerelat ed to S I -N ETs.Therefo r e, w e a re  p res en t ly  inve sti gatingthe relati ons hi p between th e  e xpressionofISC marker g ene s in E Ccel l s alo ngthe c rypt-v i llus a xis of th eh uman n o rman il e u mandtheir expressions in

of_ISC marker-expressing_enteroendocrine cells in the_human small_intestine_and whether_they_are related to_SI-NETs. Therefore, we_are presently investigating the_relationship between the_expression_of ISC marker genes in EC cells along the crypt-villus axis of the human_norman_ileum and_their_expressions_in


year outcome data in 26 patients with NOMID who have been receiving escalating doses of anakinra. The initially observed good clinical response to anakinra persists, the drug is overall well tolerated. In most patients hearing and vision was persevered over 3 and 5 years, however patients who experienced hearing loss on

year outcome data in 26 patients with NOMID who have been pick up escalate doses of anakinra. The initially observed beneficial clinical answer to anakinra persists, the drug is overall well tolerated. In most patients hear and imagination was persevered over 3 and 5 old age, however patients who experienced hear loss on

yewr outcome data in 26 patitnts with NOMID wki have been deceivine escalating doses of anakinca. Tye inutially observed good zlinical gesponse ro aiakinra persists, the drun is kyeraln well toleratec. In most [atients hearitg aud vision was persevered over 3 and 5 rears, hpwfver patients rho txpqriehbeb hearing loss on

year outcome data in 26 patients with have receiving escalating of anakinra. The to persists, the drug overall well tolerated. most patients hearing and vision was over 3 and 5 years, however patients who experienced hearing loss on

year outcome data in 26 patients With NOMID wHo havE beEn rEcEiviNg esCalating doses oF AnakInra. The initially observEd gooD cLInicAL rEsponSe to anaKInRA PerSiStS, thE dRUg Is oveRalL well toLerated. In mOst PaTients hearinG AnD vision was PerSevered over 3 aNd 5 yEars, hoWeVer PAtienTs wHo expEriencED heariNg loss on

year outcome data in 26 p atients wi th NO MID  wh ohave  bee n receiving es c alat ing doses of anakinra.  Thein i tial l yobser ved goo d  c l i nic al  r esp on s eto an aki nra per sists, the  dr ug  is overallw el l tolerate d.In most pati ent s hear in g a n d vis ion  waspersev e red ov er 3 and5y ears,h oweverp a ti ents  who experiencedh ea r ing loss on

year_outcome data_in 26 patients with_NOMID who_have_been receiving_escalating_doses of anakinra._The initially observed_good clinical response to_anakinra persists, the_drug_is overall well tolerated. In most patients hearing and vision was persevered over 3_and_5 years,_however_patients_who experienced hearing loss on


providing a clinically relevant alternative to IN administration. In summary, NDV has considerable potential for further development as a highly attenuated vector for human vaccine use. NDV represents serotype 1 of the avian paramyxoviruses (APMV). There are 8 other serotypes, namely APMV2-9. We have initiated

providing a clinically relevant alternative to IN administration. In summary, NDV has considerable electric potential for further growth as a highly attenuated vector for human vaccine use. NDV represent serotype 1 of the avian paramyxovirus (APMV). There are 8 other serotypes, namely APMV2 - 9. We have initiated

prlviding a clinically reltvant alternative to IN edminisfration. Kn summary, NDV has consideraule potenupal for further develupment as a highlt atuenuated vector for human vaccihc use. IDV represents xerotype 1 mf the avian pdrxmvxoviruses (APMV). There are 8 other serjtypes, malely APMV2-9. We hwve pnytiafvd

providing a clinically relevant alternative to IN summary, has considerable for further development for vaccine use. NDV serotype 1 of avian paramyxoviruses (APMV). There are 8 serotypes, namely APMV2-9. We have initiated

providing a clinically relevAnt alternaTive tO IN AdmInIstrAtioN. In summary, NDV hAS conSiderable potential for fUrtheR dEVeloPMeNt as a Highly aTTeNUAteD vEcTor FoR HuMan vaCciNe use. NDv representS seRoType 1 of the aviAN pAramyxovirUseS (APMV). There arE 8 otHer serOtYpeS, NamelY APmV2-9. We hAve iniTIated

providing a clinically re levant alt ernat ive  to  I N ad mini stration. In s u mmar y, NDV has considerabl e pot en t ialf or  furt her dev e lo p m ent  a sa h ig h ly  atte nua ted vec tor for hu man  v accine use.N DV  represent s s erotype 1 of  th e avia npar a myxov iru ses ( APMV). Thereare 8 oth er seroty p es, nam e l yAPMV 2-9. We have init i at e d

providing_a clinically_relevant alternative to IN_administration. In_summary,_NDV has_considerable_potential for further_development as a_highly attenuated vector for_human vaccine use._NDV_represents serotype 1 of the avian paramyxoviruses (APMV). There are 8 other serotypes, namely_APMV2-9._We have_initiated


are from merozoites, antigens present on the surface of the infected red cell have significant advantages as targets because of their exposure to the serum for long periods. However, the antigenic complexity and diversity of the known surface molecules (e.g., PfEMP1) have proven daunting for vaccine development. To

are from merozoites, antigens present on the surface of the infected red cellular telephone take significant advantages as target because of their photograph to the serum for long periods. However, the antigenic complexity and diverseness of the known surface molecules (e.g., PfEMP1) have prove daunting for vaccine development. To

arf from merozoites, antigeks present on thg wurfacx of ths infectdd red cell have significant aevantqges as targets becausd of theig exposurw to rhe serum hkr long periosd. Hoceter, the antigenlc complexidy and diversidy oy the known surface molecules (e.g., PfEIP1) have pgoven daunting for daccjne development. To

are from merozoites, antigens present on the the red cell significant advantages as to serum for long However, the antigenic and diversity of the known surface (e.g., PfEMP1) have proven daunting for vaccine development. To

are from merozoites, antigens Present on tHe surFacE of ThE infEcteD red cell have siGNifiCant advantages as targetS becaUsE Of thEIr ExposUre to thE SeRUM foR lOnG peRiODs. howevEr, tHe antigEnic compleXitY aNd diversity oF ThE known surfAce Molecules (e.g., PFEMp1) have pRoVen DAuntiNg fOr vacCine deVElopmeNt. To

are from merozoites, anti gens prese nt on  th e s ur face  ofthe infected r e d ce ll have significant ad vanta ge s  ast ar getsbecause of t hei rex pos ur e  t o the  se rum for  long peri ods .However, the an tigenic co mpl exity and di ver sity o fthe known  su rface  molec u les (e .g., PfEM P1 )  havep roven d a u nt ingfor vaccine devel o pm e nt. To

are_from merozoites,_antigens present on the_surface of_the_infected red_cell_have significant advantages_as targets because_of their exposure to_the serum for_long_periods. However, the antigenic complexity and diversity of the known surface molecules (e.g., PfEMP1)_have_proven daunting_for_vaccine_development. To


treatment. These data suggest that treatment with anakinra not only controls disease symptoms and inflammatory blood markers but can also prevent the progression of organ damage. Studies to assess the prevention of any organ damage in very young children are ongoing. 2. Disability on treatment with anakinra significantly improvement and persisted up to 3 and

treatment. These data suggest that treatment with anakinra not merely operate disease symptoms and inflammatory blood marker but can also prevent the progression of harmonium wrong. Studies to measure the prevention of any organ damage in very unseasoned children are ongoing. 2. Disability on treatment with anakinra importantly improvement and persisted up to 3 and

trfatment. These data suggert that treatmeur with anakihra not unly controls disease symptols and unflammatory blood maryers but ban also prevtnt the progression of orncn dajwge. Vvudies to assesx the prevantion of any mreau damage in very young children are jngoing. 2. Fisability on jreatkqnt sptm anakinra significantly improvejent anv persisted up yo 3 and

treatment. These data suggest that treatment with only disease symptoms inflammatory blood markers progression organ damage. Studies assess the prevention any organ damage in very young are ongoing. 2. Disability on treatment with anakinra significantly improvement and persisted up 3 and

treatment. These data suggest That treatmEnt wiTh aNakInRa noT onlY controls diseaSE symPtoms and inflammatory blOod maRkERs buT CaN also Prevent THe PROgrEsSiOn oF oRGaN damaGe. STudies tO assess the PreVeNtion of any orGAn Damage in veRy yOung children Are OngoinG. 2. DIsaBIlity On tReatmEnt witH AnakinRa signifiCaNTly impROvement AND pErsiSted up to 3 and

treatment. These data sug gest thattreat men t w it h an akin ra not only co n trol s disease symptoms and  infl am m ator y  b loodmarkers bu t can  a ls o p re v en t the  pr ogressi on of orga n d am age. Studies to  assess th e p revention of  an y orga ndam a ge in  ve ry yo ung ch i ldrenare ongoi ng .  2. Di s ability o ntrea tment with anakin r as ignificantly i mprove me n ta n d p ers isted up t o3 and

treatment._These data_suggest that treatment with_anakinra not_only_controls disease_symptoms_and inflammatory blood_markers but can_also prevent the progression_of organ damage._Studies_to assess the prevention of any organ damage in very young children are ongoing._2._Disability on_treatment_with_anakinra significantly improvement and persisted_up to 3 and


EpCAM-expressing Langerhans cells after antigen-induced activation. This results in decreased migration of Langerhans cells from skin to regional lymph nodes and enhanced contact sensitivity reactions. These results definitively linking Langerhans cell migration to function and support the concept that Langerhans cells have a anti

EpCAM - expressing Langerhans cells after antigen - induced activation. This result in decrease migration of Langerhans cells from skin to regional lymph nodes and enhance contact sensitivity reactions. These resultant role definitively yoke Langerhans cell migration to serve and support the concept that Langerhans cells get a anti

EpFAM-expressing Langerhans cells after anjiten-indnced acfivation. This results in decreased mmgrarion if Langerhans cells frum skin tl regionql lbmph nodes and eiganced gjntadb senvmtivity reactioks. These revults definitieeuy linking Langerhans cell migration eo funcyiln and support the soncsit that Langerhans cells have a anti

EpCAM-expressing Langerhans cells after antigen-induced activation. This decreased of Langerhans from skin to contact reactions. These results linking Langerhans cell to function and support the concept Langerhans cells have a anti

EpCAM-expressing Langerhans Cells after AntigEn-iNduCeD actIvatIon. This results IN decReased migration of LangeRhans CeLLs frOM sKin to RegionaL LyMPH noDeS aNd eNhANcEd conTacT sensitIvity reactIonS. THese results dEFiNitively liNkiNg Langerhans CelL migraTiOn tO FunctIon And suPport tHE concePt that LanGeRHans ceLLs have a ANTi

EpCAM-expressing Langerha ns cells a fterant ige n- indu cedactivation. Th i s re sults in decreased mig ratio no f La n ge rhans  cellsf ro m ski nto  re gi o na l lym phnodes a nd enhance d c on tact sensiti v it y reaction s.These result s d efinit iv ely linki ngLange rhansc ell mi gration t of unctio n  and su p p or t th e concept that La n ge r hans cells hav e a an ti

EpCAM-expressing_Langerhans cells_after antigen-induced activation. This_results in_decreased_migration of_Langerhans_cells from skin_to regional lymph_nodes and enhanced contact_sensitivity reactions. These_results_definitively linking Langerhans cell migration to function and support the concept that Langerhans cells_have_a anti


may improve glucose tolerance in children. In non-overweight children, we found that Interrupting sitting resulted in a 32% lower insulin Area Under the Curve (AUC; P <.001), 17% lower C-peptide AUC (P <.001), and 7% lower glucose AUC (P =.018

may improve glucose tolerance in children. In non - overweight child, we discover that Interrupting sitting resulted in a 32% lower insulin Area Under the Curve (united self-defense force of colombia; P < .001), 17% lower C - peptide united self-defense force of colombia (phosphorus < .001), and 7% lower glucose AUC (P = .018

maj improve glucose tolerakce in children. Nb non-oterweiggt childfen, we found that Interruptiig suttint resulted in a 32% lower insulin Wrea Undwr tie Curve (AUC; P <.001), 17% lower C-izptids AUC (' <.001), and 7% lower gkucose AUC (P =.018

may improve glucose tolerance in children. In we that Interrupting resulted in a the (AUC; P <.001), lower C-peptide AUC <.001), and 7% lower glucose AUC =.018

may improve glucose tolerancE in childreN. In noN-ovErwEiGht cHildRen, we found that iNterRupting sitting resulted In a 32% loWeR InsuLIn area UNder the cUrVE (aUC; p <.001), 17% lOwEr C-PePTiDe AUC (p <.001), anD 7% lower gLucose AUC (P =.018

may improve glucose toler ance in ch ildre n.Inno n-ov erwe ight children, we f ound that Interrupting  sitt in g  res u lt ed in  a 32%l ow e r  in su li n A re a  U nderthe  Curve(AUC; P <. 001 ),  17% lower C - pe ptide AUC(P<.001), and7%lowergl uco s e AUC  (P  =.01 8

may_improve glucose_tolerance in children. In_non-overweight children,_we_found that_Interrupting_sitting resulted in_a 32% lower_insulin Area Under the_Curve (AUC; P_<.001),_17% lower C-peptide AUC (P <.001), and 7% lower glucose AUC (P =.018


the manufacture of PCBs has been banned worldwide, they persist in measurable amounts in nearly everyone in developed countries. Animal and human data suggest that PCBs interfere with thyroid hormone metabolism and are neurotoxic even at levels found in background-exposed humans. Epidemiologic data on health effects guide advisories regarding fish consumption and are

the manufacture of PCBs has been banned worldwide, they persist in measurable amounts in about everyone in modernize countries. Animal and human data suggest that PCBs intervene with thyroid hormone metabolism and are neurotoxic even at levels establish in background - exposed humans. Epidemiologic data on health effects lead advisories regarding pisces pulmonary tuberculosis and are

thf manufacture of PCBs har been banned worldwidx, they lersist kn measurable amounts in neacly wveryine in developed countfies. Animwl and hyman eata suggest that IEBs ihberfexe with thyroid mormone metdbolism and ara vebrotoxic even at levels found in bachground-rxoosed humans. Ekidempojogid data on health effects guide advjsories regarding fixh consumption and are

the manufacture of PCBs has been banned persist measurable amounts nearly everyone in data that PCBs interfere thyroid hormone metabolism are neurotoxic even at levels found background-exposed humans. Epidemiologic data on health effects guide advisories regarding fish consumption and

the manufacture of PCBs has beEn banned woRldwiDe, tHey PeRsisT in mEasurable amounTS in nEarly everyone in developEd couNtRIes. ANImAl and Human daTA sUGGesT tHaT PCbs INtErferE wiTh thyroId hormone mEtaBoLism and are neURoToxic even aT leVels found in bAckGround-ExPosED humaNs. EPidemIologiC Data on Health effEcTS guide ADvisoriES ReGardIng fish consumptioN AnD Are

the manufacture of PCBs h as been ba nnedwor ldw id e, t heypersist in mea s urab le amounts in nearly e veryo ne in d e ve loped  countr i es . Ani ma land  h u ma n dat a s uggestthat PCBsint er fere with th y ro id hormone  me tabolism and  ar e neur ot oxi c  even  at  leve ls fou n d in b ackground -e x posedh umans.E p id emio logic data on hea l th effects guideadviso ri e sr e gar din g fish con su mptio n  and ar e

the_manufacture of_PCBs has been banned_worldwide, they_persist_in measurable_amounts_in nearly everyone_in developed countries._Animal and human data_suggest that PCBs_interfere_with thyroid hormone metabolism and are neurotoxic even at levels found in background-exposed humans._Epidemiologic_data on_health_effects_guide advisories regarding fish consumption_and are


. The results of primer extension provided strong evidence that the mutations in RNase H specifically inhibited the removal of the PPT RNA from the 5? end of the plus strand. As a result, our data identified a cluster of conserved amino acids in RNase H that have the specific function of removing the PPT. [unreadable]

. The results of primer extension provided impregnable evidence that the mutation in RNase H specifically inhibited the removal of the PPT RNA from the 5? end of the plus strand. As a solution, our data identified a bunch of conserved amino acids in RNase H that have the specific affair of removing the PPT. [ unreadable ]

. Thf results of primer exteksion provided sjring evmdence fhat the mutations in RNase H specifmcaloy inyibited the removal of the PPT GNA from rhe 5? wnd of the plus stvcnd. Aa a rzsnlt, our data idgntified a cnuster of consarxeb amino acids in RNase H that have tre specoflc function of rempding nht PPT. [unreadable]

. The results of primer extension provided that mutations in H specifically inhibited RNA the 5? end the plus strand. a result, our data identified a of conserved amino acids in RNase H that have the specific function of the PPT. [unreadable]

. The results of primer extensiOn provided StronG evIdeNcE thaT the Mutations in RNaSE H spEcifically inhibited the RemovAl OF the ppT rNA frOm the 5? enD Of THE plUs StRanD. AS A rEsult, Our Data ideNtified a clUstEr Of conserved aMInO acids in RNAse h that have the SpeCific fUnCtiON of reMovIng thE PPT. [unREadablE]

. The results of primer ex tension pr ovide d s tro ng  evi denc e that the mut a tion s in RNase H specifica lly i nh i bite d  t he re moval o f  t h e  PP TRN A f ro m  t he 5?  en d of th e plus str and .As a result, ou r data ide nti fied a clust erof con se rve d  amin o a cidsin RNa s e H th at have t he specif i c funct i o nof r emoving the PPT.[ un r eadable]

. The_results of_primer extension provided strong_evidence that_the_mutations in_RNase_H specifically inhibited_the removal of_the PPT RNA from_the 5? end_of_the plus strand. As a result, our data identified a cluster of conserved amino_acids_in RNase_H_that_have the specific function of_removing the PPT. [unreadable]


proteins, such as receptors, channels, and their regulatory partners, are typically synthesized by ribosome?s associated with the endoplasmic reticulum, but ultimately function at the cell surface. Thus, the logistics of their production, assembly, transport, and exocytotic insertion into the cell surface is key to understanding both normal physiological

proteins, such as receptors, channels, and their regulatory partner, are typically synthesize by ribosome?s associated with the endoplasmic reticulum, but ultimately function at the cell airfoil. Thus, the logistics of their production, forum, tape drive, and exocytotic insertion into the cellular telephone open is key to understand both normal physiological

prlteins, such as receptors, channels, and tkwir rejulatorg partnefs, are typically synthesized bt ribisome?s associated with the endoilasmic rwticnlum, but ultimatxmy funcbnon af the rell surface. Thos, the logisdics of their [rudbction, assembly, transport, and exocytjtic inxegtion into the celk surrace is key to understanding both hormal khysiological

proteins, such as receptors, channels, and their are synthesized by associated with the at cell surface. Thus, logistics of their assembly, transport, and exocytotic insertion into cell surface is key to understanding both normal physiological

proteins, such as receptors, chAnnels, and tHeir rEguLatOrY parTnerS, are typically sYNtheSized by ribosome?s associAted wItH The eNDoPlasmIc reticULuM, BUt uLtImAteLy FUnCtion At tHe cell sUrface. Thus, The LoGistics of theIR pRoduction, aSseMbly, transporT, anD exocyToTic INsertIon Into tHe cell SUrface Is key to unDeRStandiNG both noRMAl PhysIological

proteins, such as recepto rs, channe ls, a ndthe ir  reg ulat ory partners,a re t ypically synthesized b y rib os o me?s as socia ted wit h  t h e  en do pl asm ic re ticul um,  but ul timately f unc ti on at the ce l lsurface. T hus , the logist ics  of th ei r p r oduct ion , ass embly, transp ort, andex o cytoti c  insert i o ninto  the cell surface is key to underst anding  b o th n orm alphysiologi ca l

proteins,_such as_receptors, channels, and their_regulatory partners,_are_typically synthesized_by_ribosome?s associated with_the endoplasmic reticulum,_but ultimately function at_the cell surface._Thus,_the logistics of their production, assembly, transport, and exocytotic insertion into the cell surface_is_key to_understanding_both_normal physiological


-mentioned factors in disease pathogenesis by comparing the plasma levels of the various markers in four groups of individuals: chronic pathology individuals with or without active filarial infection; asymptomatic, filaria-infected individuals; and uninfected, endemic normal individuals. We show that altered ratios of the metalloproteinases and their inhibitorsas well as

-mentioned factors in disease pathogenesis by comparing the plasma levels of the various marker in four group of individuals: chronic pathology individuals with or without active filarial infection; asymptomatic, filaria - infect individuals; and uninfected, endemic normal individual. We express that altered ratio of the metalloproteinases and their inhibitorsas well as

-menhioned factors in diseast pathogenesis by comparmng the plasma uevels of the various markerd un foyr groups of individuaus: chronib patholoty iidividuals with or withomc actjye finerial infection; asymptomadic, filaria-infacgeb individuals; and uninfected, endemic normal ijdividuals. We fhow ehat altered ratios of the metalloprotsinases and their innibitorsas well as

-mentioned factors in disease pathogenesis by comparing levels the various in four groups with without active filarial asymptomatic, filaria-infected individuals; uninfected, endemic normal individuals. We show altered ratios of the metalloproteinases and their inhibitorsas well as

-mentioned factors in disease PathogenesIs by cOmpAriNg The pLasmA levels of the vaRIous Markers in four groups of iNdiviDuALs: chROnIc patHology iNDiVIDuaLs WiTh oR wIThOut acTivE filariAl infectioN; asYmPtomatic, filaRIa-Infected inDivIduals; and uniNfeCted, enDeMic NOrmal IndIviduAls. We sHOw that Altered raTiOS of the MEtallopROTeInasEs and their inhibitORsAS well as

-mentioned factors in dise ase pathog enesi s b y c om pari ng t he plasma leve l s of  the various markers i n fou rg roup s  o f ind ividual s :c h ron ic  p ath ol o gy  indi vid uals wi th or with out  a ctive filari a linfection;  as ymptomatic,fil aria-i nf ect e d ind ivi duals ; andu ninfec ted, ende mi c  norma l  indivi d u al s. W e show that alter e dr atios of the m etallo pr o te i n ase s a nd their i nh ibito r sas wel l  a s

-mentioned factors_in disease_pathogenesis by comparing the_plasma levels_of_the various_markers_in four groups_of individuals: chronic_pathology individuals with or_without active filarial_infection;_asymptomatic, filaria-infected individuals; and uninfected, endemic normal individuals. We show that altered ratios of_the_metalloproteinases and_their_inhibitorsas_well as