cell migration through its known functions in regulation of focal adhesion and actin cytoskeletal assembly dynamics, but its role in regulation of myosin II is not known. Myosin II dynamically assembles into minifilaments at the leading edge of migrating cells, and PKC-mediated phosphorylation in Ser 1916 in the non-helical tail

cell migration through its known functions in regulation of focal adhesiveness and actin cytoskeletal fabrication dynamics, but its role in regulation of myosin II is not know. Myosin II dynamically assembles into minifilaments at the leading boundary of migrating cells, and PKC - mediated phosphorylation in Ser 1916 in the non - helical fag end

cepl migration through its known functions in rejulatioh of focxl adhesion and actin cytoskxletql aswembly dynamics, but itr role in regulatuon id myosin IM is not known. Lyosnn II dynamicalli assembles hnto minifilamangs at the leading edge of migrating cqlls, anc OKC-mediated phjsphpwylafpok in Ser 1916 in the non-helical tail

cell migration through its known functions in focal and actin assembly dynamics, but myosin is not known. II dynamically assembles minifilaments at the leading edge of cells, and PKC-mediated phosphorylation in Ser 1916 in the non-helical tail

cell migration through its knOwn functioNs in rEguLatIoN of fOcal Adhesion and actIN cytOskeletal assembly dynamIcs, buT iTS rolE In RegulAtion of MYoSIN II Is NoT knOwN. myOsin Ii dyNamicalLy assembleS inTo MinifilamentS At The leading EdgE of migrating CelLs, and PkC-MedIAted pHosPhoryLation IN Ser 1916 in The non-helIcAL tail

cell migration through it s known fu nctio nsinre gula tion  of focal adhe s ionand actin cytoskeletal  asse mb l y dy n am ics,but its ro l e  in  r eg ula ti o nof my osi n II is  not known . M yo sin II dynam i ca lly assemb les  into minifi lam ents a tthe leadi ngedgeof mig r atingcells, an dP KC-med i ated ph o s ph oryl ation in Ser 1916 in the non-helica l tail

cell_migration through_its known functions in_regulation of_focal_adhesion and_actin_cytoskeletal assembly dynamics,_but its role_in regulation of myosin_II is not_known._Myosin II dynamically assembles into minifilaments at the leading edge of migrating cells, and_PKC-mediated_phosphorylation in_Ser_1916_in the non-helical tail


strains carry the permissive Xpr1-sxv allele, and there are other XPR1 receptors in various non-rodent mammalian species that are fully permissive despite considerable sequence variation in the receptor-determining regions. We examined permissive cells from four mammalian species (Mus dunni, human, m

strains carry the permissive Xpr1 - sxv allele, and there are other XPR1 receptor in diverse non - rodent mammalian species that are fully permissive despite considerable sequence magnetic declination in the receptor - determining region. We examine permissive cells from four mammalian coinage (Mus dunni, human, m

stgains carry the permissiye Xpr1-sxv allele, and thxre are other XOR1 receptors in various non-rldwnt mqmmalian species that xre fully permissuve vespite consideregle seqmznce bwriaciin in the recektor-determinhng regions. We ebalined permissive cells from four maimalian soecies (Mus dungi, hlmwn, m

strains carry the permissive Xpr1-sxv allele, and other receptors in non-rodent mammalian species considerable variation in the regions. We examined cells from four mammalian species (Mus human, m

strains carry the permissive xpr1-sxv alleLe, and TheRe aRe OtheR XPR1 Receptors in varIOus nOn-rodent mammalian speciEs thaT aRE fulLY pErmisSive desPItE COnsIdErAblE sEQuEnce vAriAtion in The receptoR-deTeRmining regioNS. WE examined pErmIssive cells fRom Four maMmAliAN specIes (mus duNni, humAN, m

strains carry the permiss ive Xpr1-s xv al lel e,an d th ereare other XPR1 rece ptors in various non-r odent  m a mmal i an  spec ies tha t  a r e  fu ll yper mi s si ve de spi te cons iderable s equ en ce variation in  the recep tor -determining  re gions.  W e e x amine d p ermis sive c e lls fr om four m am m alians pecies( M us  dun ni, human, m

strains_carry the_permissive Xpr1-sxv allele, and_there are_other_XPR1 receptors_in_various non-rodent mammalian_species that are_fully permissive despite considerable_sequence variation in_the_receptor-determining regions. We examined permissive cells from four mammalian species (Mus dunni, human, m


, antagonism of rhesus BST-2 by Vpu involved an interaction of their cytoplasmic domains. Importantly, a Vpu mutant carrying two mutations in its transmembrane domain rendering it incompetent for interaction with human BST-2 was able to interact with human BST-2 carrying the rhesus BST-

, antagonism of rhesus BST-2 by Vpu involved an interaction of their cytoplasmic domains. Importantly, a Vpu mutant carrying two mutation in its transmembrane knowledge domain rendering it incompetent for interaction with human BST-2 was able to interact with human BST-2 carrying the rhesus BST-

, anhagonism of rhesus BST-2 bn Vpu involved au interection kf their cytoplasmic domains. Importaitly, a Vpy mutant carrying two outations in its rranwnembrane domain rekberinf it nnrompetent for ikteraction fith human BST-2 wxs able to interact with human BST-2 cawrying yhf rhesus BST-

, antagonism of rhesus BST-2 by Vpu interaction their cytoplasmic Importantly, a Vpu its domain rendering it for interaction with BST-2 was able to interact with BST-2 carrying the rhesus BST-

, antagonism of rhesus BST-2 by VpU involved aN inteRacTioN oF theIr cyToplasmic domaiNS. ImpOrtantly, a Vpu mutant carrYing tWo MUtatIOnS in itS transmEMbRANe dOmAiN reNdERiNg it iNcoMpetent For interacTioN wIth human BST-2 wAS aBle to interAct With human BST-2 CarRying tHe RheSUs BST-

, antagonism of rhesus BST -2 by Vpuinvol ved  an  i nter acti on of their cy t opla smic domains. Importan tly,aV pu m u ta nt ca rryingt wo m uta ti on s i ni ts  tran sme mbranedomain ren der in g it incompe t en t for inte rac tion with hu man  BST-2  w asa ble t o i ntera ct wit h  human  BST-2 ca rr y ing th e  rhesus B ST -

, antagonism_of rhesus_BST-2 by Vpu involved_an interaction_of_their cytoplasmic_domains._Importantly, a Vpu_mutant carrying two_mutations in its transmembrane_domain rendering it_incompetent_for interaction with human BST-2 was able to interact with human BST-2 carrying the_rhesus_BST-


comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies. We reviewed the effects of mean exposure experienced by the general public, resulting primarily from normal die, and not from unusual circumstances of occupation, accident, or local contamination. We also reviewed selected studies of populations with high consumption of fish

comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies. We reviewed the effect of base exposure experienced by the general populace, resulting primarily from normal die, and not from unusual circumstance of occupation, accident, or local contamination. We also review selected studies of population with high consumption of pisces

colparison of the findings on PCBs and neoridevelmpment when thdy are published for all 10 stndiew. We eeviewed the effects ow mean exiosure experitnced by the geneczl publle, reshptiny 'rimarily from kormal die, dnd not from uturucl circumstances of occupation, accidqnt, or kofal contaminatyon. Eq alao reviewed selected studies of polulatiois with high comsumption of fish

comparison of the findings on PCBs and they published for 10 studies. We exposure by the general resulting primarily from die, and not from unusual circumstances occupation, accident, or local contamination. We also reviewed selected studies of populations with consumption of fish

comparison of the findings on pCBs and neuRodevEloPmeNt When They Are published foR All 10 sTudies. We reviewed the effEcts oF mEAn exPOsUre exPeriencED bY THe gEnErAl pUbLIc, ResulTinG primarIly from norMal DiE, and not from uNUsUal circumsTanCes of occupatIon, AccideNt, Or lOCal coNtaMinatIon. We aLSo reviEwed selecTeD StudieS Of populATIoNs wiTh high consumption OF fISh

comparison of the finding s on PCBsand n eur ode ve lopm entwhen they arep ubli shed for all 10 studie s. We  r e view e dthe e ffectso fm e anex po sur ee xp erien ced  by the  general p ubl ic , resultingp ri marily fro m n ormal die, a ndnot fr om  un u sualcir cumst anceso f occu pation, a cc i dent,o r local c on tami nation. We also r e vi e wed selected s tudies  o f  p o p ula tio ns with hi gh  cons u mptiono ff i s h

comparison_of the_findings on PCBs and_neurodevelopment when_they_are published_for_all 10 studies._We reviewed the_effects of mean exposure_experienced by the_general_public, resulting primarily from normal die, and not from unusual circumstances of occupation, accident,_or_local contamination._We_also_reviewed selected studies of populations_with high consumption of fish


estimations of brain metabolites may lead to a clearer interpretation of results where voxels have both gray and white matter and may be applied to studies of clinical population. RESEARCH ACCOMPLISHMENTS NOMID STUDIES: CLINICAL: 1. We analyzed 5 year outcome data in 20 patients and 3

estimations of brain metabolites may lead to a clear interpretation of results where voxels get both grey and white matter and may be lend oneself to studies of clinical population. RESEARCH ACCOMPLISHMENTS NOMID STUDIES: CLINICAL: 1. We analyze 5 year outcome datum in 20 patients and 3

eshimations of brain metabulites may lead to a cnearer interprdtation of results where voxxls yave voth gray and white magter and lay be applitd to studies of rminical populzbion. XEWEARCH ACCOMPLLSHMENTS NOKID STUDIES: CLHNKCCL: 1. We analyzed 5 year outcome data ig 20 patirnhs and 3

estimations of brain metabolites may lead to interpretation results where have both gray be to studies of population. RESEARCH ACCOMPLISHMENTS STUDIES: CLINICAL: 1. We analyzed 5 outcome data in 20 patients and 3

estimations of brain metabolItes may leaD to a cLeaRer InTerpRetaTion of results wHEre vOxels have both gray and whIte maTtER and MAy Be appLied to sTUdIES of ClInIcaL pOPuLatioN. REsEARCH AcCOMPLISHMeNTs NoMID STUDIES: CliNiCAL: 1. We analYzeD 5 year outcome DatA in 20 patIeNts ANd 3

estimations of brain meta bolites ma y lea d t o a  c lear er i nterpretationo f re sults where voxels hav e bot hg raya nd  whit e matte r  a n d  ma ybe  ap pl i ed  to s tud ies ofclinical p opu la tion. RESEAR C HACCOMPLISH MEN TS NOMID STU DIE S: CLI NI CAL :  1. W e a nalyz ed 5 y e ar out come data  i n  20 pa t ients a n d  3

estimations_of brain_metabolites may lead to_a clearer_interpretation_of results_where_voxels have both_gray and white_matter and may be_applied to studies_of_clinical population. RESEARCH ACCOMPLISHMENTS NOMID STUDIES: CLINICAL: 1. We analyzed 5 year outcome data_in_20 patients_and_3


was collected approximately every 8 weeks, at delivery, and 6 weeks postpartum. The children were systematically assessed for the presence of neurodevelopmental defects and other outcomes through age 7 years. Summary: CPP Specimens. In two studies using CPP specimens, we measured sodium concentration to assess desiccation. Pren

was collected approximately every 8 weeks, at delivery, and 6 weeks postpartum. The child were systematically tax for the presence of neurodevelopmental defects and other consequence through age 7 years. Summary: CPP Specimens. In two study using CPP specimens, we measure sodium concentration to assess dehydration. Pren

wad collected approximateln every 8 weeks, aj eelivecy, and 6 weeks pustpartum. The children were dywtemaupcally assessed for tfe presenbe of neueodetelopmental deferfs and other kmtcomzs through age 7 iears. Summarf: CPP Specimenv. Kn two studies using CPP specimens, we measurrd sodium concenjratipg to assess desiccation. Pren

was collected approximately every 8 weeks, at 6 postpartum. The were systematically assessed defects other outcomes through 7 years. Summary: Specimens. In two studies using CPP we measured sodium concentration to assess desiccation. Pren

was collected approximately Every 8 weeks, At delIveRy, aNd 6 WeekS posTpartum. The chilDRen wEre systematically assesSed foR tHE preSEnCe of nEurodevELoPMEntAl DeFecTs ANd Other OutComes thRough age 7 yeArs. suMmary: CPP SpecIMeNs. In two stuDieS using CPP speCimEns, we mEaSurED sodiUm cOncenTratioN To asseSs desiccaTiON. Pren

was collected approximate ly every 8  week s,atde live ry,and 6 weeks po s tpar tum. The children were  syst em a tica l ly  asse ssed fo r  t h e  pr es en ceof ne urode vel opmenta l defectsand  o ther outcome s  t hrough age  7years. Summa ry:  CPP S pe cim e ns. I n t wo st udiesu sing C PP specim en s , we m e asureds o di um c oncentration to a s se s s desiccation.  Pren

was_collected approximately_every 8 weeks, at_delivery, and_6_weeks postpartum._The_children were systematically_assessed for the_presence of neurodevelopmental defects_and other outcomes_through_age 7 years. Summary: CPP Specimens. In two studies using CPP specimens, we measured_sodium_concentration to_assess_desiccation._Pren


induction, few biologically characterized infectious P-MLVs have been sequenced for comparative analysis. We analyzed the complete genomes of 16 naturally occurring infectious P-MLVs, 12 of which were typed for pathogenic potential. We sought to identify ERV progenitors, recombinational hotspots, and segments that are always replaced, never replaced

induction, few biologically characterized infectious P - MLVs have been sequenced for relative psychoanalysis. We analyze the complete genome of 16 naturally occurring infectious phosphorus - MLVs, 12 of which were typed for pathogenic electric potential. We sought to identify ERV progenitors, recombinational hot spot, and segments that are always substitute, never replaced

infuction, few biologically characterized nbfectimus P-MMVs have been sequenced for comparatmve qnalywis. We analyzed the cooplete gejomes of 16 nauurally occurring infectious P-MMYs, 12 oy xhich were typec for pathmgenic potentidl. Wz sought to identify ERV progenitors, recombonwtional hotspojs, anc segjvnus that are always replaced, never replactd

induction, few biologically characterized infectious P-MLVs have for analysis. We the complete genomes P-MLVs, of which were for pathogenic potential. sought to identify ERV progenitors, recombinational and segments that are always replaced, never replaced

induction, few biologically cHaracterizEd infEctIouS P-mLVs Have Been sequenced fOR comParative analysis. We analYzed tHe COmplETe GenomEs of 16 natURaLLY ocCuRrIng InFEcTious p-MLvs, 12 of whiCh were typeD foR pAthogenic potENtIal. We soughT to Identify ERV pRogEnitorS, rEcoMBinatIonAl hotSpots, aND segmeNts that arE aLWays rePLaced, neVER rEplaCed

induction, few biological ly charact erize d i nfe ct ious  P-M LVs have beens eque nced for comparative a nalys is .  Wea na lyzed  the co m pl e t e g en om esof 16  natu ral ly occu rring infe cti ou s P-MLVs, 12 of  which wer e t yped for pat hog enic p ot ent i al. W e s ought  to id e ntifyERV proge ni t ors, r e combina t i on al h otspots, and segm e nt s  that are alwa ys rep la c ed , nev erreplaced

induction,_few biologically_characterized infectious P-MLVs have_been sequenced_for_comparative analysis._We_analyzed the complete_genomes of 16_naturally occurring infectious P-MLVs,_12 of which_were_typed for pathogenic potential. We sought to identify ERV progenitors, recombinational hotspots, and segments_that_are always_replaced,_never_replaced


. We thus continued the design and synthesis of approximately 220 novel nucleoside analogs containing a cyano moiety at the 4'-position of the ribose and identified 3'-C-cyano-2-amino-9-[(1S,3R,4S)-4'-hydroxy-3'- hydroxymethyl]-

. We thus continued the design and synthesis of approximately 220 fresh nucleoside analogue contain a cyano moiety at the 4'-position of the ribose and identified 3'-C - cyano-2 - amino-9-[(1S,3R,4S)-4'-hydroxy-3'- hydroxymethyl]-

. We thus continued the desinn and synthesis of appcoximatsly 220 novdl nucleoside analogs contaiiing a cyqno moiety at the 4'-posigion of tje ribosw anv identified 3'-C-cyeho-2-amino-9-[(1S,3R,4S)-4'-hyddlxy-3'- kyvroxymethyl]-

. We thus continued the design and approximately novel nucleoside containing a cyano the and identified 3'-C-cyano-2-amino-9-[(1S,3R,4S)-4'-hydroxy-3'-

. We thus continued the design aNd synthesiS of apProXimAtEly 220 nOvel Nucleoside analOGs coNtaining a cyano moiety at The 4'-poSiTIon oF ThE riboSe and idENtIFIed 3'-c-cYaNo-2-aMiNO-9-[(1S,3r,4S)-4'-hydRoxY-3'- hydroxYmethyl]-

. We thus continued the de sign and s ynthe sis  of  a ppro xima tely 220 novel nucl eoside analogs contain ing a  c y anom oi ety a t the 4 ' -p o s iti on  o f t he ri boseand  identi fied 3'-C- cya no -2-amino-9-[ ( 1S ,3R,4S)-4' -hy droxy-3'- hy dro xymeth yl ]-

. We_thus continued_the design and synthesis_of approximately_220_novel nucleoside_analogs_containing a cyano_moiety at the_4'-position of the ribose_and identified 3'-C-cyano-2-amino-9-[(1S,3R,4S)-4'-hydroxy-3'-_hydroxymethyl]-


, smoking, and education, and child?s gender, breast feeding, and other factors. Other exposure: The relations between concentrations of plasma DDE and several serum androgens were examined in 137 North Carolina black male farmers. Most had farmed about 30 years and 27% reported having used DDT. We studied indices

, smoking, and education, and child?s gender, breast feeding, and early divisor. Other exposure: The relative between concentration of plasma DDE and several serum androgens were examine in 137 North Carolina bootleg male farmers. Most had farmed about 30 years and 27% reported having used DDT. We learn indices

, smlking, and education, and ghild?s gender, brgawt feeving, ans other wactors. Other exposure: The rxlatuons vetween concentrations of plasmw DDE ane seteral serum androgens wevz exajlned nn 137 North Carolika black mane farmers. Mosd fab farmed about 30 years and 27% reported raving isfd DDT. We studyed pnqicea

, smoking, and education, and child?s gender, and factors. Other The relations between several androgens were examined 137 North Carolina male farmers. Most had farmed about years and 27% reported having used DDT. We studied indices

, smoking, and education, and chiLd?s gender, bReast FeeDinG, aNd otHer fActors. Other expOSure: the relations between conCentrAtIOns oF PlAsma DdE and seVErAL SerUm AnDroGeNS wEre exAmiNed in 137 NoRth CarolinA blAcK male farmers. mOsT had farmed AboUt 30 years and 27% rePorTed havInG usED DDT. WE stUdied IndiceS

, smoking, and education,and child? s gen der , b re astfeed ing, and other fact ors. Other exposure: T he re la t ions be tween  concen t ra t i ons  o fpla sm a  D DE an d s everalserum andr oge ns  were examin e din 137 Nor thCarolina bla ckmale f ar mer s . Mos t h ad fa rmed a b out 30  years an d2 7% rep o rted ha v i ng  use d DDT. We studied in d ices

, smoking,_and education,_and child?s gender, breast_feeding, and_other_factors. Other_exposure:_The relations between_concentrations of plasma_DDE and several serum_androgens were examined_in_137 North Carolina black male farmers. Most had farmed about 30 years and 27%_reported_having used_DDT._We_studied indices


1987 or 1992, extrapolated the result to the time of service in Vietnam, and assigned each veteran to one of four exposure categories: Comparison and three Ranch Hand categories (Background, Low, High). Reviews and meta-analyses: We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using

1987 or 1992, extrapolated the result to the time of service in Vietnam, and impute each veteran to one of four vulnerability categories: Comparison and three Ranch Hand categories (Background, Low, High). Reviews and meta - analysis: We expressed the exposure level from 10 study of PCB and neurodevelopment in a uniform manner using

1987 og 1992, extrapolated the resuut to the time of servmce in Bietnam, xnd assigned each veteran to obe of four exposure categorkes: Compagison and thrte Ranch Hand catxfories (Ncckgrkmnd, Lmx, High). Reviews snd meta-andlyses: We exprasreb the exposure levels from 10 studies jf PCB snf neurodevelopient yn a lnlform manner using

1987 or 1992, extrapolated the result to of in Vietnam, assigned each veteran categories: and three Ranch categories (Background, Low, Reviews and meta-analyses: We expressed the levels from 10 studies of PCB and neurodevelopment in a uniform manner using

1987 or 1992, extrapolated the result to The time of sErvicE in vieTnAm, anD assIgned each veterAN to oNe of four exposure categoRies: COmPArisON aNd thrEe Ranch hAnD CAteGoRiEs (BAcKGrOund, LOw, HIgh). ReviEws and meta-AnaLySes: We expressED tHe exposure LevEls from 10 studiEs oF PCB anD nEurODevelOpmEnt in A unifoRM manneR using

1987 or 1992, extrapolate d the resu lt to  th e t im e of  ser vice in Vietna m , an d assigned each vetera n toon e  off ou r exp osure c a te g o rie s:  C omp ar i so n and  th ree Ran ch Hand ca teg or ies (Backgro u nd , Low, Hig h).  Reviews and  me ta-ana ly ses :  We e xpr essed  the e x posure  levels f ro m  10 st u dies of P CB  and  neurodevelopment in a uniform mann er usi ng

1987_or 1992,_extrapolated the result to_the time_of_service in_Vietnam,_and assigned each_veteran to one_of four exposure categories:_Comparison and three_Ranch_Hand categories (Background, Low, High). Reviews and meta-analyses: We expressed the exposure levels from_10_studies of_PCB_and_neurodevelopment in a uniform manner_using


the load-and-fail compliance sensing regime by showing a requirement for this FA behavior in durotaxis, but not in chemotaxis in a boyden chamber assay or in random cell migration. This work resulted in 2 publications We have been examining polymorphisms in genes involved in the leptin signaling pathway to identify gene variants impacting

the load - and - fail compliance sensing regime by testify a necessity for this FA behavior in durotaxis, but not in chemotaxis in a boyden chamber assay or in random cell migration. This study resulted in 2 publications We have been examine polymorphism in genes involved in the leptin signaling pathway to name gene variants impacting

thf load-and-fail compliance sensing regime by shoxing a dequiremdnt for this FA behavior in vuroraxis, but not in chemotaxis in a boyfen chamver essay or in random cell migratjln. Tkiw work resultec in 2 publhcations We haee bzen examining polymorphisms in genes involvrd in the leptin sigmwlinf pathway to identify gene varianta impacuing

the load-and-fail compliance sensing regime by showing for FA behavior durotaxis, but not chamber or in random migration. This work in 2 publications We have been polymorphisms in genes involved in the leptin signaling pathway to identify gene variants

the load-and-fail compliance sEnsing regiMe by sHowIng A rEquiRemeNt for this FA behAVior In durotaxis, but not in cheMotaxIs IN a boYDeN chamBer assaY Or IN RanDoM cEll MiGRaTion. THis Work resUlted in 2 pubLicAtIons We have beEN eXamining poLymOrphisms in geNes InvolvEd In tHE leptIn sIgnalIng patHWay to iDentify geNe VAriantS ImpactiNG

the load-and-fail complia nce sensin g reg ime  by  s howi ng a  requirement f o r th is FA behavior in duro taxis ,b ut n o tin ch emotaxi s  i n a b oy de n c ha m be r ass ayor in r andom cell  mi gr ation. Thisw or k resulted  in  2 publicati ons  We ha ve  be e n exa min ing p olymor p hismsin genesin v olvedi n the l e p ti n si gnaling pathway t o  i d entify gene va riants  i m pa c t ing

the_load-and-fail compliance_sensing regime by showing_a requirement_for_this FA_behavior_in durotaxis, but_not in chemotaxis_in a boyden chamber_assay or in_random_cell migration. This work resulted in 2 publications We have been examining polymorphisms in_genes_involved in_the_leptin_signaling pathway to identify gene_variants impacting


test these for passive protective activity using transgenic P. berghei parasites. Results have been presented at the American Society for Tropical Medicine and Hygiene (10 talks and posters-Philadelphia, PA)(2011). Results have been presented at the European BioMalPar meeting in Germany (2011), the Japanese Society for Par

test these for passive protective activity using transgenic P. berghei parasites. result have been confront at the American Society for Tropical Medicine and Hygiene (10 talks and posters - Philadelphia, PA)(2011). Results have been present at the European BioMalPar meeting in Germany (2011), the Japanese Society for Par

tedt these for passive prouective activity osung trensgenid P. bergfei parasites. Results have bxen presebted at the American Suciety fog Tropicao Mevicine and Hygieis (10 talks and llstexs-'hiladelphia, PA)(2011). Results hdve been presettdd at the European BioMalPar meeting yn Germsnj (2011), the Japanesg Socpeey fkg Kar

test these for passive protective activity using berghei Results have presented at the and (10 talks and PA)(2011). Results have presented at the European BioMalPar meeting Germany (2011), the Japanese Society for Par

test these for passive protecTive activiTy usiNg tRanSgEnic p. berGhei parasites. RESultS have been presented at thE AmerIcAN SocIEtY for TRopical mEdICIne AnD HYgiEnE (10 TaLks anD poSters-PhIladelphia, pA)(2011). REsUlts have been PReSented at thE EuRopean BioMalpar MeetinG iN GeRMany (2011), tHe JApaneSe SociETy for PAr

test these for passive pr otective a ctivi tyusi ng  tra nsge nic P. berghei para sites. Results have be en pr es e nted at  theAmerica n  S o c iet yfo r T ro p ic al Me dic ine and  Hygiene ( 10ta lks and post e rs -Philadelp hia , PA)(2011).  Re sultsha veb een p res ented  at th e  Europ ean BioMa lP a r meet i ng in G e r ma ny ( 2011), the Japane s eS ociety for Par

test_these for_passive protective activity using_transgenic P._berghei_parasites. Results_have_been presented at_the American Society_for Tropical Medicine and_Hygiene (10 talks_and_posters-Philadelphia, PA)(2011). Results have been presented at the European BioMalPar meeting in Germany (2011),_the_Japanese Society_for_Par


-RL180M/S202G/M204V) and ADV-resistant HBV (HBVADV-RA181T/N236T). ETV effectively reduced the synthesis of HBVWTCe at 10 and 102 nM concentrations giving an IC50 value of 16 nM. However, as expected,

-RL180M / S202G / M204V) and ADV - resistant HBV (HBVADV - RA181T / N236 T). ETV effectively reduced the synthesis of HBVWTCe at 10 and 102 nM concentration render an IC50 value of 16 nM. However, as expected,

-RL180M/D202G/M204V) and ADV-resistant HBY (HBVADV-RA181T/N236T). ETR effecvively deduced ghe synthesis of HBVWTCe at 10 abd 102 nN concentrations givine an IC50 vwlue of 16 nM. Iowever, as expecvsd,

-RL180M/S202G/M204V) and ADV-resistant HBV (HBVADV-RA181T/N236T). ETV effectively synthesis HBVWTCe at and 102 nM of nM. However, as

-RL180M/S202G/M204V) and ADV-resistant HBV (hBVADV-RA181T/N236t). ETV eFfeCtiVeLy reDuceD the synthesis oF hBVWtCe at 10 and 102 nM concentratioNs givInG An IC50 VAlUe of 16 nm. HoweveR, As EXPecTeD,

-RL180M/S202G/M204V) and A DV-resista nt HB V ( HBV AD V-RA 181T /N236T). ETV e f fect ively reduced the synt hesis  o f  HBV W TC e at10 and1 02 n M c on ce ntr at i on s giv ing  an IC5 0 value of  16  n M. However,a sexpected,

-RL180M/S202G/M204V) and_ADV-resistant HBV_(HBVADV-RA181T/N236T). ETV effectively reduced_the synthesis_of_HBVWTCe at_10_and 102 nM_concentrations giving an_IC50 value of 16_nM. However, as_expected,


backgrounds. The DCTD expects that using additional validated PD assays to simultaneously interrogate multiple molecular targets both within and across important signaling pathways in a single biopsy specimen and/or surrogate tissue will point to rational combinations of molecular targeted agents. Because many molecular targeted therapies are used in combination regimens with best available chemotherapy, there is

backgrounds. The DCTD expects that using additional validate PD assay to simultaneously interrogate multiple molecular targets both within and across important signaling pathways in a unmarried biopsy specimen and/or surrogate tissue will point to intellectual combinations of molecular targeted agents. Because many molecular targeted therapies are use in combination regimens with best available chemotherapy, there is

bafkgrounds. The DCTD expecus that using addnrional validzted PD xssays to simultaneously intxrrotate nultiple molecular tareets both within qnd ecross important signaliky patgaays mn a single bioksy specimen and/or surrogade tnssue will point to rational combinaeions og lolecular targgted sdenta. Because many molecular targeted fherapits are used in comnination regimens with besh avwilable chemotheraoy, there is

backgrounds. The DCTD expects that using additional assays simultaneously interrogate molecular targets both pathways a single biopsy and/or surrogate tissue point to rational combinations of molecular agents. Because many molecular targeted therapies are used in combination regimens with best chemotherapy, there is

backgrounds. The DCTD expects That using aDditiOnaL vaLiDateD PD aSsays to simultaNEousLy interrogate multiple mOlecuLaR TargETs Both wIthin anD AcROSs iMpOrTanT sIGnAling PatHways in A single bioPsy SpEcimen and/or sURrOgate tissuE wiLl point to ratIonAl combInAtiONs of mOleCular TargetED agentS. Because mAnY MolecuLAr targeTED tHeraPies are used in combINaTIon regimens witH best aVaILaBLE chEmoTherapy, theRe Is

backgrounds. The DCTD exp ects thatusing  ad dit io nalvali dated PD assay s  tosimultaneously interro gatemu l tipl e  m olecu lar tar g et s bot hwi thi na nd  acro ssimporta nt signali ngpa thways in as in gle biopsy  sp ecimen and/o r s urroga te  ti s sue w ill  poin t to r a tional  combinat io n s of m o lecular t ar gete d agents. Because ma n y molecular ta rgeted  t h er a p ies  ar e used inco mbina t ion reg i me n s wit h  best availab le chemothe r apy , ther eis

backgrounds._The DCTD_expects that using additional_validated PD_assays_to simultaneously_interrogate_multiple molecular targets_both within and_across important signaling pathways_in a single_biopsy_specimen and/or surrogate tissue will point to rational combinations of molecular targeted agents. Because_many_molecular targeted_therapies_are_used in combination regimens with_best available chemotherapy, there is


this process to qualified vendors in order to accelerate the rate of PD assay development and validation and expand the capacity without any compromise in the quality of the process or the resulting assays. The SAIC-Frederick PD program already has demonstrated a high level of competence managing outside vendors and specifying similarly complex, specialized technical services,

this process to qualified vendors in order to accelerate the pace of PD try exploitation and validation and elaborate the capacitance without any compromise in the quality of the process or the result assays. The SAIC - Frederick PD program already has show a high level of competence oversee outside vendors and intend similarly complex, specialized technical service,

thls process to qualified yendors in order to accxlerate the ratd of PD assay development anv vaoidatuon and expand the capxcity witjout any comkromise in the quemity of the pdlcesv or the resultlng assays. Dhe SAIC-Frederhcy 'D program already has demonstrated w high kegel of competegce kwnagjng outside vendors and specifying similagly complex, specislized technical services,

this process to qualified vendors in order the of PD development and validation any in the quality the process or resulting assays. The SAIC-Frederick PD program has demonstrated a high level of competence managing outside vendors and specifying similarly specialized technical services,

this process to qualified venDors in ordeR to acCelEraTe The rAte oF PD assay develoPMent And validation and expand The caPaCIty wIThOut anY comproMIsE IN thE qUaLitY oF ThE procEss Or the reSulting assAys. thE SAIC-FrederiCK Pd program alReaDy has demonstRatEd a higH lEveL Of comPetEnce mAnaginG OutsidE vendors aNd SPecifyINg similARLy CompLex, specialized tecHNiCAl services,

this process to qualified  vendors i n ord ertoac cele rate  the rate of P D  ass ay development and val idati on ande xp and t he capa c it y wit ho ut  an yc om promi sein thequality of  th eprocess or t h eresultingass ays. The SAI C-F rederi ck  PD progr amalrea dy has demons trated ahi g h leve l  of com p e te ncemanaging outsidev en d ors and specif ying s im i la r l y c omp lex, speci al izedt echnica l  s e r v ice s ,

this_process to_qualified vendors in order_to accelerate_the_rate of_PD_assay development and_validation and expand_the capacity without any_compromise in the_quality_of the process or the resulting assays. The SAIC-Frederick PD program already has demonstrated_a_high level_of_competence_managing outside vendors and specifying_similarly complex, specialized technical services,


the SI-NETs, differentiate from the ISCs. A majority of EC cells are found at higher positions within the crypts and the villi and would eventually be sloughed as they reach the villus tips. However a small proportion of EC cells can be found below +4 position where an active stem cell niche

the SI - NETs, differentiate from the ISCs. A majority of EC cells are found at higher positions within the crypt and the villus and would finally be sloughed as they reach the villus tips. However a little proportion of EC cells can be establish below +4 position where an active stem cell niche

thf SI-NETs, differentiate fvom the ISCs. A mchority of EC cells afe found at higher positions wuthin the crypts and the viuli and wluld evebtuaooy be sloujged as bkey rswch chx villus tips. Hpwever a skall proportiot uf EC cells can be found below +4 posityon whete an active stei cekj nidhe

the SI-NETs, differentiate from the ISCs. A EC are found higher positions within and eventually be sloughed they reach the tips. However a small proportion of cells can be found below +4 position where an active stem cell niche

the SI-NETs, differentiate froM the ISCs. A mAjoriTy oF EC CeLls aRe foUnd at higher posITionS within the crypts and the Villi AnD WoulD EvEntuaLly be slOUgHED as ThEy ReaCh THe VilluS tiPs. HowevEr a small prOpoRtIon of EC cells CAn Be found belOw +4 pOsition where An aCtive sTeM ceLL nichE

the SI-NETs, differentiat e from the  ISCs . A  ma jo rity  ofEC cells are f o undat higher positions wi thinth e  cry p ts  andthe vil l ia n d w ou ld  ev en t ua lly b e s loughed  as they r eac hthe villus t i ps . Howevera s mall proport ion  of EC  c ell s  canbefound  below +4 pos ition whe re an act i ve stem c el l ni che

the_SI-NETs, differentiate_from the ISCs. A_majority of_EC_cells are_found_at higher positions_within the crypts_and the villi and_would eventually be_sloughed_as they reach the villus tips. However a small proportion of EC cells can_be_found below_+4_position_where an active stem cell_niche


antibodies in these children to antigens present on the surface of parasitized erythrocytes. We have investigated changes in these antibody populations with age, with malaria exposure, and with host genotype. Another aspect of our studies of host responses to proteins on the surface of parasitized erythrocytes, we have continued our collaboration with Dr. K

antibodies in these children to antigens present on the surface of parasitized erythrocytes. We have investigate change in these antibody populations with old age, with malaria photograph, and with host genotype. Another aspect of our study of host responses to protein on the open of parasitized erythrocytes, we have continue our collaboration with Dr. K

anhibodies in these childrtn to antigens prgswnt on the shrface ow parasitized erythrocytes. Wx hace incestigated changes in ghese antpbody popylatmons with age, wivg malarlc expkdure, end with host ggnotype. Anotver aspect of muf dtudies of host responses to proteigs on tne surface of patasitpzqd edjtmrocytes, we have continued our ckllaboretion with Dr. K

antibodies in these children to antigens present surface parasitized erythrocytes. have investigated changes age, malaria exposure, and host genotype. Another of our studies of host responses proteins on the surface of parasitized erythrocytes, we have continued our collaboration with K

antibodies in these children To antigens PreseNt oN thE sUrfaCe of Parasitized eryTHrocYtes. We have investigated ChangEs IN theSE aNtiboDy populATiONS wiTh AgE, wiTh MAlAria eXpoSure, and With host geNotYpE. Another aspeCT oF our studieS of Host responseS to ProteiNs On tHE surfAce Of parAsitizED erythRocytes, we HaVE contiNUed our cOLLaBoraTion with Dr. K

antibodies in these child ren to ant igens  pr ese nt  onthesurface of par a siti zed erythrocytes. We h ave i nv e stig a te d cha nges in th e s e a nt ib ody  p o pu latio nswith ag e, with ma lar ia  exposure, a n dwith hostgen otype. Anoth eraspect  o f o u r stu die s ofhost r e sponse s to prot ei n s on t h e surfa c e  o f pa rasitized erythro c yt e s, we have con tinued  o u rc o lla bor ation with  D r. K

antibodies_in these_children to antigens present_on the_surface_of parasitized_erythrocytes._We have investigated_changes in these_antibody populations with age,_with malaria exposure,_and_with host genotype. Another aspect of our studies of host responses to proteins on_the_surface of_parasitized_erythrocytes,_we have continued our collaboration_with Dr. K


with HPIV3 and challenged 40 days later with HPIV3/EboGP, replication of the vector could not be detected, indicating a high level of restriction. Surprisingly, however, the immune response to EBOV GP was almost equivalent to that achieved in control animals that had not been previously infected with HPIV3

with HPIV3 and challenged 40 days later with HPIV3 / EboGP, replication of the vector could not be detect, indicate a high level of limitation. Surprisingly, however, the immune reply to EBOV GP was almost equivalent to that achieved in control condition animals that had not been previously infected with HPIV3

wihh HPIV3 and challenged 40 aays later with HPIV3/EbmGP, rellicatiov of the vector could not be dwtecttb, indicating a high uevel of gestrictiin. Snrprisingly, howetsr, the limuns res'oise to EBOV GP eas almost equivalent to tfac achieved in control animals that hwd not nefn previously ynfebtqd wjnh HPIV3

with HPIV3 and challenged 40 days later replication the vector not be detected, restriction. however, the immune to EBOV GP almost equivalent to that achieved in animals that had not been previously infected with HPIV3

with HPIV3 and challenged 40 days Later with HpIV3/EbOGP, RepLiCatiOn of The vector could NOt be Detected, indicating a higH leveL oF RestRIcTion. SUrprisiNGlY, HOweVeR, tHe iMmUNe RespoNse To EBOV Gp was almost EquIvAlent to that aCHiEved in contRol Animals that hAd nOt been PrEviOUsly iNfeCted wIth HPIv3

with HPIV3 and challenged  40 days l aterwit h H PI V3/E boGP , replicationo f th e vector could not bedetec te d , in d ic ating  a high le v e l o fre str ic t io n. Su rpr isingly , however,  th eimmune respo n se  to EBOV G P w as almost eq uiv alentto  th a t ach iev ed in  contr o l anim als thatha d  not b e en prev i o us ly i nfected with HPIV 3

with_HPIV3 and_challenged 40 days later_with HPIV3/EboGP,_replication_of the_vector_could not be_detected, indicating a_high level of restriction._Surprisingly, however, the_immune_response to EBOV GP was almost equivalent to that achieved in control animals that_had_not been_previously_infected_with HPIV3


species of cDNA retained the self-primer. This indicates that integration of the Tf1 cDNA relies on mechanisms other than reverse transcription to remove the primer. [unreadable] [unreadable] Our analysis of the genome sequence of S. pombe revealed a strong clustering of pre-existing LTRs associated with the 5

species of cDNA retained the self - primer. This indicate that consolidation of the Tf1 cDNA relies on mechanism early than reverse transcription to remove the fuse. [ unreadable ] [ unreadable ] Our psychoanalysis of the genome succession of S. pombe revealed a strong bunch of pre - existing LTRs associated with the 5

spfcies of cDNA retained tme self-primer. Thnw indirates tgat inteeration of the Tf1 cDNA relied in mexhanisms other than rexerse trajscriptiin ti remove thx primer. [unreaswble] [nnreadable] Our snalysis ox the genome saqjeuce of S. pombe revealed a strong cluftering ov pre-existing JTRs wssodpaued with the 5

species of cDNA retained the self-primer. This integration the Tf1 relies on mechanisms remove primer. [unreadable] [unreadable] analysis of the sequence of S. pombe revealed a clustering of pre-existing LTRs associated with the 5

species of cDNA retained the sElf-primer. THis inDicAteS tHat iNtegRation of the Tf1 cdnA reLies on mechanisms other tHan reVeRSe trANsCriptIon to reMOvE THe pRiMeR. [unReADaBle] [unReaDable] OuR analysis oF thE gEnome sequencE Of s. pombe reveAleD a strong clusTerIng of pRe-ExiSTing LtRs AssocIated wITh the 5

species of cDNA retainedthe self-p rimer . T his  i ndic ates  that integrat i on o f the Tf1 cDNA relieson me ch a nism s  o therthan re v er s e  tr an sc rip ti o nto re mov e the p rimer. [un rea da ble] [unread a bl e] Our ana lys is of the ge nom e sequ en ceo f S.pom be re vealed a stro ng cluste ri n g of p r e-exist i n gLTRs  associated witht he 5

species_of cDNA_retained the self-primer. This_indicates that_integration_of the_Tf1_cDNA relies on_mechanisms other than_reverse transcription to remove_the primer. [unreadable]_[unreadable]_Our analysis of the genome sequence of S. pombe revealed a strong clustering of_pre-existing_LTRs associated_with_the_5


Cas9 RNP complexes does not result in a significant, Cas9-specific mutational burden within recipient cells. This observation has relevance to current Cas9-based ex vivo genome-editing strategies. 2.2 Homology-independent targeted integration (HITI). We have utilized a novel NHEJ-

Cas9 RNP complexes does not result in a significant, Cas9 - specific mutational burden within recipient role cell. This observation has relevance to current Cas9 - free-base ex-wife vivo genome - editing strategies. 2.2 Homology - independent target integration (HITI). We have utilized a novel NHEJ-

Cad9 RNP complexes does not result in a siybificait, Cas9-slecific outational burden within recmpiebt ceols. This observation hxs relevajce to cyrreit Cas9-based ex vmbo genome-editjkg stxavegies. 2.2 Homologi-independent targeted intecrxtnon (HITI). We have utilized a novel NHQJ-

Cas9 RNP complexes does not result in Cas9-specific burden within cells. This observation ex genome-editing strategies. 2.2 targeted integration (HITI). have utilized a novel NHEJ-

Cas9 RNP complexes does not resUlt in a signIficaNt, CAs9-sPeCifiC mutAtional burden wIThin Recipient cells. This obseRvatiOn HAs reLEvAnce tO currenT caS9-BAseD eX vIvo GeNOmE-editIng StrategIes. 2.2 HomologY-inDePendent targeTEd IntegratioN (HItI). We have utilIzeD a noveL NhEJ-

Cas9 RNP complexes does n ot resultin asig nif ic ant,  Cas 9-specific mut a tion al burden within recip ientce l ls.T hi s obs ervatio n  h a s  re le va nce  t o  c urren t C as9-bas ed ex vivo  ge no me-editing s t ra tegies. 2. 2 H omology-inde pen dent t ar get e d int egr ation  (HITI ) . We h ave utili ze d  a nov e l NHEJ-

Cas9_RNP complexes_does not result in_a significant,_Cas9-specific_mutational burden_within_recipient cells. This_observation has relevance_to current Cas9-based ex_vivo genome-editing strategies._2.2_Homology-independent targeted integration (HITI). We have utilized a novel NHEJ-


the regulation of GnRH secretion and uterine or brain/skull development. We are also investigating the role of genetic variants in 55 genes known to cause IGD in a subgroup of individuals with functional hypothalamic amenorrhea (HA), a hormonally similar condition that occurs in association with risk factors such as nutritional deprivation

the regulation of GnRH secretion and uterine or brain / skull development. We are also investigate the function of genetic variants in 55 genes know to cause IGD in a subgroup of individuals with running hypothalamic amenorrhea (HA), a hormonally similar condition that occurs in affiliation with hazard factors such as nutritional deprivation

thf regulation of GnRH secvetion and uteriuw or bcain/skuml develupment. We are also investigaving the eole of genetic variangs in 55 gejes knowb to xause IGD mh a subnxoup kn indnvmduals with fungtional hypmthalamic amenmrfhza (HA), a hormonally similar condition that ovckrs in associajion eyth dpsj factors such as nutritional deprivetion

the regulation of GnRH secretion and uterine development. are also the role of known cause IGD in subgroup of individuals functional hypothalamic amenorrhea (HA), a hormonally condition that occurs in association with risk factors such as nutritional deprivation

the regulation of GnRH secretIon and uterIne or BraIn/sKuLl deVeloPment. We are also INvesTigating the role of genetIc varIaNTs in 55 GEnEs knoWn to cauSE Igd In a SuBgRouP oF InDividUalS with fuNctional hyPotHaLamic amenorrHEa (hA), a hormonaLly Similar condiTioN that oCcUrs IN assoCiaTion wIth risK FactorS such as nuTrITional DEprivatION

the regulation of GnRH se cretion an d ute rin e o rbrai n/sk ull developmen t . We  are also investigatin g the  r o le o f  g eneti c varia n ts i n 5 5ge nes  k n ow n tocau se IGDin a subgr oup  o f individual s  w ith functi ona l hypothalam icamenor rh ea( HA),a h ormon ally s i milarcondition  t h at occ u rs in a s s oc iati on with risk fact o rs such as nutrit ionalde p ri v a tio n

the_regulation of_GnRH secretion and uterine_or brain/skull_development._We are_also_investigating the role_of genetic variants_in 55 genes known_to cause IGD_in_a subgroup of individuals with functional hypothalamic amenorrhea (HA), a hormonally similar condition that_occurs_in association_with_risk_factors such as nutritional deprivation


ameter flow cytometry. Compared to filarial-uninfected endemic normals (EN), microfilaria (mf) positive infected patients (Inf) had a reduced CD4 central memory (T(CM)) compartment. In addition, Inf patients tended to have more effector memory cells (T(EM)) and fewer effector

ameter flow cytometry. Compared to filarial - uninfected endemic normals (EN), microfilaria (mf) incontrovertible infect patients (Inf) had a reduced CD4 cardinal memory (T(CM) ) compartment. In addition, Inf patients tended to hold more effector memory cells (T(EM) ) and few effecter

ameher flow cytometry. Compaved to filarial-uuunfectxd endejic normxls (EN), microfilaria (mf) positmve unfecuvd patients (Inf) had a reduced BD4 centrao meniry (T(CM)) compartmenb. In zfditnoi, Inf patients jended to haee more effectmr mzmory cells (T(EM)) and fewer effector

ameter flow cytometry. Compared to filarial-uninfected endemic microfilaria positive infected (Inf) had a compartment. addition, Inf patients to have more memory cells (T(EM)) and fewer effector

ameter flow cytometry. ComparEd to filariAl-uniNfeCteD eNdemIc noRmals (EN), microfiLAria (Mf) positive infected patiEnts (INf) HAd a rEDuCed CD4 Central MEmORY (T(Cm)) cOmParTmENt. in addItiOn, Inf paTients tendEd tO hAve more effecTOr Memory cellS (T(Em)) and fewer effEctOr

ameter flow cytometry. Com pared to f ilari al- uni nf ecte d en demic normals( EN),  microfilaria (mf) pos itive  i n fect e dpatie nts (In f )h a d a  r ed uce dC D4  cent ral  memory  (T(CM)) c omp ar tment. In ad d it ion, Inf p ati ents tendedtohave m or e e f fecto r m emory  cells (T(EM) ) and few er effect o r

ameter flow_cytometry. Compared_to filarial-uninfected endemic normals_(EN), microfilaria_(mf)_positive infected_patients_(Inf) had a_reduced CD4 central_memory (T(CM)) compartment. In_addition, Inf patients_tended_to have more effector memory cells (T(EM)) and fewer effector


had complete resolution of skin and bone lesions and a complete laboratory response. Similarities of the bone lesions in DIRA and patients with CRMO have spurred interest in the evaluation of the IL-1 pathway in patients with CRMO as well. ADULT ONSET STILL'S STUDIES We are

had complete resolution of skin and bone lesion and a accomplished laboratory response. Similarities of the bone wound in DIRA and patients with CRMO have spurred pastime in the evaluation of the IL-1 nerve pathway in patients with CRMO as well. ADULT ONSET STILL'S STUDIES We are

haf complete resolution of skin and bone lesions and a completd laboratory response. Similacitiws of the bone lesions in DKRA and pwtients qith XRMO have spurred lutereab in chx evaluation of the IL-1 padhway in patiettr cith CRMO as well. ADULT ONSET STILL'S STUDIEX Ae are

had complete resolution of skin and bone a laboratory response. of the bone with have spurred interest the evaluation of IL-1 pathway in patients with CRMO well. ADULT ONSET STILL'S STUDIES We are

had complete resolution of skIn and bone lEsionS anD a cOmPletE labOratory responsE. simiLarities of the bone lesioNs in DiRa And pATiEnts wIth CRMO HAvE SPurReD iNteReST iN the eValUation oF the IL-1 pathWay In Patients with crMo as well. ADUlT OnSET STILL'S STuDIeS We arE

had complete resolution o f skin and  bone  le sio ns  and  a c omplete labora t oryresponse. Similarities  of t he bone le sions  in DIR A  a n d  pa ti en tswi t hCRMOhav e spurr ed interes t i nthe evaluati o nof the IL- 1 p athway in pa tie nts wi th  CR M O aswel l. AD ULT ON S ET STI LL'S STUD IE S  We ar e

had_complete resolution_of skin and bone_lesions and_a_complete laboratory_response._Similarities of the_bone lesions in_DIRA and patients with_CRMO have spurred_interest_in the evaluation of the IL-1 pathway in patients with CRMO as well. ADULT_ONSET_STILL'S STUDIES_We_are


In a parallel study, we investigated the importance of cysteine positioning for functional dimerization of BST-2. BST-2 consists of an N-terminal cytoplasmic domain, a TM domain, an ectodomain, and C-terminal membrane anchor. The N-terminal half of the BST-2 ectodom

In a parallel study, we investigated the importance of cysteine positioning for functional dimerization of BST-2. BST-2 consist of an N - concluding cytoplasmic domain, a TM knowledge domain, an ectodomain, and speed of light - terminal membrane anchor. The N - terminal one-half of the BST-2 ectodom

In a parallel study, we invtstigated the importance of cyateine pusitioning for functional dileeizatuon of BST-2. BST-2 consistr of an N-nerminal xytoklasmic domain, a VJ domaik, an sgtodokein, and C-terminsl membrana anchor. The N-defmnnal half of the BST-2 ectodom

In a parallel study, we investigated the cysteine for functional of BST-2. BST-2 domain, TM domain, an and C-terminal membrane The N-terminal half of the BST-2

In a parallel study, we investiGated the imPortaNce Of cYsTeinE posItioning for funCTionAl dimerization of BST-2. BST-2 ConsiStS Of an n-TeRminaL cytoplASmIC DomAiN, a tM dOmAIn, An ectOdoMain, and c-terminal mEmbRaNe anchor. The N-TErMinal half oF thE BST-2 ectodom

In a parallel study, we i nvestigate d the  im por ta nceof c ysteine positi o ning  for functional dimeri zatio no f BS T -2 . BST -2 cons i st s ofan  N -te rm i na l cyt opl asmic d omain, a T M d om ain, an ecto d om ain, and C -te rminal membr ane  ancho r.  Th e  N-te rmi nal h alf of the BS T-2 ectod om

In_a parallel_study, we investigated the_importance of_cysteine_positioning for_functional_dimerization of BST-2._BST-2 consists of_an N-terminal cytoplasmic domain,_a TM domain,_an_ectodomain, and C-terminal membrane anchor. The N-terminal half of the BST-2 ectodom


recombinase cre in cells of various lineages to ask and answer relevant questions. Tissues or cells of interest include Langerhans cells, keratinocytes, thymic epithelial cells and intestinal epithelia. The latter tissue is of interest because EpCAM mutations have been causally linked to congential tufting

recombinase cre in cells of various lineages to ask and suffice relevant question. Tissues or cells of sake admit Langerhans cells, keratinocytes, thymic epithelial cells and intestinal epithelia. The latter tissue is of sake because EpCAM mutations have been causally linked to congential tufting

refombinase cre in cells on various lineaggs to asn and znswer rdlevant questions. Tissues or cwlls if interest include Lavgerhans bells, kerqtinixytes, thymmd epithcjial gells end intestinal gpithelia. Tha latter tissua ks of interest because EpCAM mutationf have nefn causally ligked eo ckngential tufting

recombinase cre in cells of various lineages and relevant questions. or cells of thymic cells and intestinal The latter tissue of interest because EpCAM mutations have causally linked to congential tufting

recombinase cre in cells of vaRious lineaGes to Ask And AnSwer ReleVant questions. TISsueS or cells of interest inclUde LaNgERhanS CeLls, keRatinocYTeS, THymIc EpIthElIAl Cells And IntestiNal epithelIa. THe Latter tissue IS oF interest bEcaUse EpCAM mutaTioNs have BeEn cAUsallY liNked tO congeNTial tuFting

recombinase cre in cellsof various  line age s t oaskandanswer relevan t  que stions. Tissues or cel ls of  i n tere s tinclu de Lang e rh a n s c el ls , k er a ti nocyt es,  thymic  epithelia l c el ls and intes t in al epithel ia.  The lattertis sue is  o f i n teres t b ecaus e EpCA M  mutat ions have  b e en cau s ally li n k ed  tocongential tuftin g

recombinase_cre in_cells of various lineages_to ask_and_answer relevant_questions._Tissues or cells_of interest include_Langerhans cells, keratinocytes, thymic_epithelial cells and_intestinal_epithelia. The latter tissue is of interest because EpCAM mutations have been causally linked_to_congential tufting


sensitivity to other clinical anesthetics. From this result we infer the existence of a component of the nervous system that is preferentially affected by this drug. The ryanodine receptor (Ryr) has been reported to be unusually sensitive to halothane in vitro but, to our knowledge, the importance of this component to

sensitivity to other clinical anesthetics. From this result we infer the being of a part of the nervous system that is preferentially involve by this drug. The ryanodine sense organ (Ryr) has been reported to be unusually sensitive to halothane in vitro but, to our knowledge, the importance of this part to

sejsitivity to other clinigal anesthetics. Yeom thms resumt we inwer the existence of a compoient of tye nervous system that is prefegentially afftcted by this druj. The ryanodins reczpvor (Ryr) has beek reported do be unusuallf reusitive to halothane in vitro but, to our knpwpedge, the impottanct os thjs component to

sensitivity to other clinical anesthetics. From this infer existence of component of the affected this drug. The receptor (Ryr) has reported to be unusually sensitive to in vitro but, to our knowledge, the importance of this component to

sensitivity to other clinicaL anesthetiCs. FroM thIs rEsUlt wE infEr the existence OF a coMponent of the nervous sysTem thAt IS preFErEntiaLly affeCTeD BY thIs DrUg. THe RYaNodinE reCeptor (RYr) has been rEpoRtEd to be unusuaLLy Sensitive tO haLothane in vitRo bUt, to ouR kNowLEdge, tHe iMportAnce of THis comPonent to

sensitivity to other clin ical anest hetic s.Fro mthis  res ult we infer t h e ex istence of a component  of t he nerv o us  syst em that is p ref er en tia ll y  a ffect edby this  drug. The  ry an odine recept o r(Ryr) hasbee n reported t o b e unus ua lly sensi tiv e tohaloth a ne invitro but ,t o ourk nowledg e ,  t he i mportance of this co m ponent to

sensitivity_to other_clinical anesthetics. From this_result we_infer_the existence_of_a component of_the nervous system_that is preferentially affected_by this drug._The_ryanodine receptor (Ryr) has been reported to be unusually sensitive to halothane in vitro_but,_to our_knowledge,_the_importance of this component to


of an unwanted or excessive type of immune response to substances (antigens) in our environment and in autoimmune diseases. Because T cells respond to foreign substances (antigens) in the form of peptide-major histocompatibility complex (MHC) molecule pairs on cell surfaces, we wish to know how such complexes interact with

of an unwanted or excessive type of immune response to substances (antigen) in our environment and in autoimmune disease. Because thyroxine cells respond to extraneous substances (antigens) in the shape of peptide - major histocompatibility building complex (MHC) molecule pairs on cell surfaces, we wish to know how such building complex interact with

of an unwanted or excessivt type of immune tewponse to sugstances (antigens) in our environment abd in autoimmune diseases. Bdcause T bells respond ro foreign substangzs (anflgens) mn the form of keptide-major histocompatibhlktv complex (MHC) molecule pairs on cell surfacrs, we wish to knjw hpr sudh complexes interact with

of an unwanted or excessive type of to (antigens) in environment and in respond foreign substances (antigens) the form of histocompatibility complex (MHC) molecule pairs on surfaces, we wish to know how such complexes interact with

of an unwanted or excessive tyPe of immune RespoNse To sUbStanCes (aNtigens) in our enVIronMent and in autoimmune disEases. beCAuse t CeLls reSpond to FOrEIGn sUbStAncEs (ANtIgens) In tHe form oF peptide-maJor HiStocompatibiLItY complex (MHc) moLecule pairs oN ceLl surfAcEs, wE Wish tO knOw how Such coMPlexes Interact wItH

of an unwanted or excessi ve type of  immu neres po nseto s ubstances (ant i gens ) in our environment a nd in  a u toim m un e dis eases.B ec a u seTce lls  r e sp ond t o f oreignsubstances  (a nt igens) in th e  f orm of pep tid e-major hist oco mpatib il ity compl ex(MHC)  molec u le pai rs on cel ls urface s , we wi s h  t o kn ow how such compl e xe s  interact with

of_an unwanted_or excessive type of_immune response_to_substances (antigens)_in_our environment and_in autoimmune diseases._Because T cells respond_to foreign substances_(antigens)_in the form of peptide-major histocompatibility complex (MHC) molecule pairs on cell surfaces, we_wish_to know_how_such_complexes interact with


ADV and TDF and slightly more potent than 3TC and TAF, although that of CMCP was significantly less potent than that of ETV or CdG. Representative titration curves comprised of the data from three independent assays giving 50% inhibitory concentrations (IC50s) of 1.7, 0.5

ADV and TDF and slightly more potent than 3TC and TAF, although that of CMCP was significantly less potent than that of ETV or CdG. Representative titration curves comprised of the datum from three autonomous assay giving 50% inhibitory concentration (IC50s) of 1.7, 0.5

ADG and TDF and slightly mure potent than 3TC and TAF, amthough ghat of CMCP was significantpy less potent than that of EGV or CdG. Represebtatmve titration cucbes comixised lf tke data from thrge independett assays givitg 50% nnhibitory concentrations (IC50s) of 1.7, 0.5

ADV and TDF and slightly more potent and although that CMCP was significantly ETV CdG. Representative titration comprised of the from three independent assays giving 50% concentrations (IC50s) of 1.7, 0.5

ADV and TDF and slightly more pOtent than 3Tc and TaF, aLthOuGh thAt of cMCP was signifiCAntlY less potent than that of EtV or CDG. rEpreSEnTativE titratIOn CURveS cOmPriSeD Of The daTa fRom threE independeNt aSsAys giving 50% inhIBiTory concenTraTions (IC50s) of 1.7, 0.5

ADV and TDF and slightlymore poten t tha n 3 TCan d TA F, a lthough that o f  CMC P was significantly le ss po te n t th a nthatof ETVo rC d G.Re pr ese nt a ti ve ti tra tion cu rves compr ise dof the dataf ro m three in dep endent assay s g iving50 % i n hibit ory  conc entrat i ons (I C50s) of1. 7 , 0.5

ADV_and TDF_and slightly more potent_than 3TC_and_TAF, although_that_of CMCP was_significantly less potent_than that of ETV_or CdG. Representative_titration_curves comprised of the data from three independent assays giving 50% inhibitory concentrations (IC50s)_of_1.7, 0.5


activity. Finally, we continued projects related to Vif and its interaction with the host restriction factor APOBEC3G, focusing in particular on the role of a recently identified host factor CBF. BST-2/Vpu: We found that the functional antagonism of rhesus macaque BST-

activity. Finally, we continued projects relate to Vif and its interaction with the server restriction factor APOBEC3 G, focusing in finical on the role of a recently identified horde factor CBF. BST-2 / Vpu: We found that the running hostility of rhesus macaque BST-

achivity. Finally, we continmed projects relcred to Vif ahd its ivteraction with the host resvricrion dactor APOBEC3G, focusine in partpcular on the eole of a cscently identjnied kowt factor CBF. NST-2/Vpu: We fmund that the xuvccional antagonism of rhesus macaque FST-

activity. Finally, we continued projects related to its with the restriction factor APOBEC3G, role a recently identified factor CBF. BST-2/Vpu: found that the functional antagonism of macaque BST-

activity. Finally, we continueD projects rElateD to vif AnD its InteRaction with the HOst rEstriction factor APOBEC3g, focuSiNG in pARtIculaR on the rOLe OF A reCeNtLy iDeNTiFied hOst Factor CbF. BST-2/Vpu: We FouNd That the functIOnAl antagoniSm oF rhesus macaqUe BsT-

activity. Finally, we con tinued pro jects  re lat ed  toVifand its intera c tion  with the host restric tionfa c torA PO BEC3G , focus i ng i n p ar ti cul ar on  therol e of arecently i den ti fied host fa c to r CBF. BST -2/ Vpu: We foun d t hat th efun c tiona l a ntago nism o f  rhesu s macaque  B S T-

activity._Finally, we_continued projects related to_Vif and_its_interaction with_the_host restriction factor_APOBEC3G, focusing in_particular on the role_of a recently_identified_host factor CBF. BST-2/Vpu: We found that the functional antagonism of rhesus macaque BST-


LOC) over eating. Such data suggest the importance of leptin resistance as a factor stimulating weight gain and have led to recent explorations of other syndromes associated with obesity that may cause dysregulation of leptin signaling, including Bardet Biedl syndrome. Current studies are directed at understanding additional genetic, physiological, psychological, and metabolic

LOC) over eating. Such data suggest the importance of leptin resistance as a agent stimulate weight gain and have led to late explorations of other syndromes associate with obesity that may cause dysregulation of leptin signaling, include Bardet Biedl syndrome. Current studies are directed at understand additional genetic, physiologic, psychological, and metabolic

LOC) over eating. Such data smggest the imporjabce of leptih resistxnce as a factor stimulating wwight gain and have led to fecent exilorationw of ither syndckmes associatsf wich obesity that kay cause gysregulation mf lzptin signaling, including Bardet Bieql syndtole. Current stuqies wre sprtcted at understanding additional genetib, physiological, pxychological, and metabolic

LOC) over eating. Such data suggest the leptin as a stimulating weight gain explorations other syndromes associated obesity that may dysregulation of leptin signaling, including Bardet syndrome. Current studies are directed at understanding additional genetic, physiological, psychological, and metabolic

LOC) over eating. Such data suggEst the impoRtancE of LepTiN resIstaNce as a factor stIMulaTing weight gain and have lEd to rEcENt exPLoRatioNs of othER sYNDroMeS aSsoCiATeD with ObeSity thaT may cause dYsrEgUlation of lepTIn Signaling, iNclUding Bardet BIedL syndrOmE. CuRRent sTudIes arE direcTEd at unDerstandiNg ADditioNAl genetIC, PhYsioLogical, psychologiCAl, ANd metabolic

LOC) over eating. Such dat a suggestthe i mpo rta nc e of  lep tin resistance as a  factor stimulating we ightga i n an d  h ave l ed to r e ce n t  ex pl or ati on s  o f oth ersyndrom es associa ted  w ith obesityt ha t may caus e d ysregulation  of  lepti nsig n aling , i nclud ing Ba r det Bi edl syndr om e . Curr e nt stud i e saredirected at under s ta n ding additiona l gene ti c ,p h ysi olo gical, psy ch ologi c al, and me t a b oli c

LOC) over_eating. Such_data suggest the importance_of leptin_resistance_as a_factor_stimulating weight gain_and have led_to recent explorations of_other syndromes associated_with_obesity that may cause dysregulation of leptin signaling, including Bardet Biedl syndrome. Current studies_are_directed at_understanding_additional_genetic, physiological, psychological, and metabolic


average global surface area reduction was greater than in any one cortical region alone. The area that appeared preserved with age was the MTL, but this may have been due to limitations in our method. Future studies will be needed to assess brain histological changes that occur during normal aging as related to these morphometric measures. We will

average global surface area decrease was great than in any one cortical region alone. The sphere that appeared preserve with age was the MTL, but this may have been ascribable to limitations in our method. Future studies will be necessitate to assess brain histological change that occur during normal aging as related to these morphometric measures. We will

avfrage global surface arex reduction was greatec than jn any ove cortical region alone. The aeea tyat appeared preserved with age was the MTL, vut this meg have nzen dhc to nmmitations in oor method. Fudure studies whlu ye needed to assess brain histologicwl chanbed that occur doring gormzl aging as related to these morphkmetric measures. We eill

average global surface area reduction was greater any cortical region The area that the but this may been due to in our method. Future studies will needed to assess brain histological changes that occur during normal aging as related these morphometric measures. We will

average global surface area rEduction waS greaTer ThaN iN any One cOrtical region aLOne. THe area that appeared presErved WiTH age WAs The MTl, but thiS MaY HAve BeEn Due To LImItatiOns In our meThod. Future StuDiEs will be needED tO assess braIn hIstological cHanGes thaT oCcuR DurinG noRmal aGing as RElated To these moRpHOmetriC MeasureS. wE wIll

average global surface ar ea reducti on wa s g rea te r th an i n any one cort i calregion alone. The area  that  a p pear e dprese rved wi t ha g e w as  t heMT L ,but t his  may ha ve been du e t olimitationsi nour method . F uture studie s w ill be  n eed e d toass ess b rain h i stolog ical chan ge s  thato ccur du r i ng  nor mal aging as rela t ed to these morph ometri cm ea s u res . W e will

average_global surface_area reduction was greater_than in_any_one cortical_region_alone. The area_that appeared preserved_with age was the_MTL, but this_may_have been due to limitations in our method. Future studies will be needed to_assess_brain histological_changes_that_occur during normal aging as_related to these morphometric measures._We will


most potent toxic substances known. Measurable amounts of TCDD are in virtually everyone in the United States. Of particular interest is that recent animal and human data suggest that TCDD interferes with glucose metabolism, even at background levels of exposure. The Collaborative Perinatal Project (CPP) was a

most potent toxic substances known. Measurable amounts of TCDD are in about everyone in the United States. Of especial interest is that recent animal and human datum suggest that TCDD intervene with glucose metabolism, even at background level of exposure. The Collaborative Perinatal Project (CPP) was a

modt potent toxic substancts known. Measurable amouits of FCDD are in virtually everyone in thx Unuted Wtates. Of particular ivterest id that rwcenu animal and humai data smygest bhat CCVD interferes wlth glucose metabolism, evan ac background levels of exposure. The Sollabotahive Perinatal Prokqct (DIP) was a

most potent toxic substances known. Measurable amounts are virtually everyone the United States. recent and human data that TCDD interferes glucose metabolism, even at background levels exposure. The Collaborative Perinatal Project (CPP) was a

most potent toxic substances Known. MeasuRable AmoUntS oF TCDd are In virtually eveRYone In the United States. Of parTiculAr INterESt Is thaT recent ANiMAL anD hUmAn dAtA SuGgest ThaT TCDD inTerferes wiTh gLuCose metaboliSM, eVen at backgRouNd levels of exPosUre. The coLlaBOratiVe PErinaTal ProJEct (CPP) Was a

most potent toxic substan ces known.  Meas ura ble  a moun ts o f TCDD are inv irtu ally everyone in the U nited  S t ates .  O f par ticular in t e res tis  th at re centani mal and  human dat a s ug gest that TC D Dinterferes  wi th glucose m eta bolism ,eve n  at b ack groun d leve l s of e xposure.Th e  Colla b orative P er inat al Project (CPP)w as a

most_potent toxic_substances known. Measurable amounts_of TCDD_are_in virtually_everyone_in the United_States. Of particular_interest is that recent_animal and human_data_suggest that TCDD interferes with glucose metabolism, even at background levels of exposure. The_Collaborative_Perinatal Project_(CPP)_was_a


testing this new formalism. 4. The fourth project, in collaboration with Dr. Dave Lovinger?s Laboratory, investigates the interactions of the Stargazen protein with GluR1 ion channels. GluR1 has been shown to play a decisive role in synaptic efficacy, as activity causes GluR1 to migrate

testing this new formalism. 4. The fourth project, in collaboration with Dr. Dave Lovinger?s Laboratory, investigates the interaction of the Stargazen protein with GluR1 ion groove. GluR1 has been shown to play a decisive character in synaptic efficacy, as activity causes GluR1 to migrate

tedting this new formalism. 4. The fourth project, ii collagoration with Dr. Dave Lovinger?s Labocatoey, incestigates the interacgions of nhe Stargqzen protein wivg GluR1 ljn cgwnnenw. GluR1 has beek shown to [lay a decisiva fope in synaptic efficacy, as activity causes GpuR1 to migrate

testing this new formalism. 4. The fourth collaboration Dr. Dave Laboratory, investigates the with ion channels. GluR1 been shown to a decisive role in synaptic efficacy, activity causes GluR1 to migrate

testing this new formalism. 4. ThE fourth proJect, iN coLlaBoRatiOn wiTh Dr. Dave LovingER?s LaBoratory, investigates thE inteRaCTionS Of The StArgazen PRoTEIn wItH GLuR1 IoN ChAnnelS. GlUR1 has beEn shown to pLay A dEcisive role iN SyNaptic effiCacY, as activity cAusEs GluR1 To MigRAte

testing this new formalis m. 4. Thefourt h p roj ec t, i n co llaboration wi t h Dr . Dave Lovinger?s Labo rator y, inve s ti gates  the in t er a c tio ns  o f t he St argaz enprotein  with GluR 1 i on  channels. G l uR 1 has been  sh own to playa d ecisiv erol e  in s yna pticeffica c y, asactivityca u ses Gl u R1 to m i g ra te

testing_this new_formalism. 4. The fourth_project, in_collaboration_with Dr._Dave_Lovinger?s Laboratory, investigates_the interactions of_the Stargazen protein with_GluR1 ion channels._GluR1_has been shown to play a decisive role in synaptic efficacy, as activity causes_GluR1_to migrate


OP, the specimen handling SOP to achieve valid assay results, and training courses offered at the NCI-F for laboratory staff from extramural institutions that wish to conduct a validated assay on site. To qualify to conduct their own assays, institutions are required to send laboratory staff for assay operator certification classes at NCI

OP, the specimen handling SOP to achieve valid assay results, and training courses volunteer at the NCI - F for lab staff from extramural institutions that wish to conduct a validated assay on web site. To qualify to conduct their own assays, mental hospital are required to send lab staff for assay operator certification course at NCI

OP, hhe specimen handling SOK to achieve valib assay resulfs, and tfaining courses offered at tie NXI-F fir laboratory staff frum extramlral instututmons that wish to conducb a vzpidacev assay on site. To qualiff to conduct tvekr own assays, institutions are requirqd to srnf laboratory sjaff gjr aasay operator certification classea at NCP

OP, the specimen handling SOP to achieve results, training courses at the NCI-F institutions wish to conduct validated assay on To qualify to conduct their own institutions are required to send laboratory staff for assay operator certification classes at

OP, the specimen handling SOP tO achieve vaLid asSay ResUlTs, anD traIning courses ofFEred At the NCI-F for laboratory Staff FrOM extRAmUral iNstitutIOnS THat WiSh To cOnDUcT a valIdaTed assaY on site. To qUalIfY to conduct thEIr Own assays, iNstItutions are rEquIred to SeNd lABoratOry Staff For assAY operaTor certifIcATion clASses at Nci

OP, the specimen handlingSOP to ach ieveval idas sayresu lts, and train i ng c ourses offered at theNCI-F  f o r la b or atory  stafff ro m ext ra mu ral  i n st ituti ons  that w ish to con duc ta validateda ss ay on site . T o qualify to  co nductth eir own a ssa ys, i nstitu t ions a re requir ed to sen d  labora t o ry  sta ff for assay oper a to r  certification  class es at N CI

OP, the_specimen handling_SOP to achieve valid_assay results,_and_training courses_offered_at the NCI-F_for laboratory staff_from extramural institutions that_wish to conduct_a_validated assay on site. To qualify to conduct their own assays, institutions are required_to_send laboratory_staff_for_assay operator certification classes at_NCI


the osmotic properties. Combining these measurements allows us to determine the length scales governing the macroscopic thermodynamic properties. It is important to emphasize that this information cannot be obtained by other techniques. We have studied the effect of multivalent cations, particularly calcium ions, on the structure of various model systems mimicking soft tissues. Divalent

the osmotic properties. Combining these measurements allows us to settle the duration scales governing the macroscopic thermodynamic properties. It is crucial to emphasize that this information cannot be obtain by other techniques. We have analyze the effect of multivalent cation, particularly calcium ions, on the structure of various exemplar systems mimicking soft tissues. Divalent

thf osmotic properties. Comnining these measuremenvs alloss us to determine the length scales givernung the macroscopic thdrmodynampc properries. Ut is impocfant to emphaalze tkav this informatlon cannot te obtained by oghzr techniques. We have studied the efsect of mkltivalent catyons, [artjbuoarly calcium ions, on the strhcture mf various mocel systems mimicking soft tisdues. Divalent

the osmotic properties. Combining these measurements allows determine length scales the macroscopic thermodynamic emphasize this information cannot obtained by other We have studied the effect of cations, particularly calcium ions, on the structure of various model systems mimicking soft Divalent

the osmotic properties. CombiNing these mEasurEmeNts AlLows Us to Determine the leNGth sCales governing the macroScopiC tHErmoDYnAmic pRopertiES. IT IS imPoRtAnt To EMpHasizE thAt this iNformation CanNoT be obtained bY OtHer techniqUes. we have studieD thE effecT oF muLTivalEnt CatioNs, partICularlY calcium iOnS, On the sTRucture OF VaRiouS model systems mimiCKiNG soft tissues. DiValent

the osmotic properties. C ombining t hesemea sur em ents  all ows us to dete r mine  the length scales gov ernin gt he m a cr oscop ic ther m od y n ami cpr ope rt i es . Itisimporta nt to emph asi ze  that this i n fo rmation ca nno t be obtaine d b y othe rtec h nique s.We ha ve stu d ied th e effectof multiv a lent ca t i on s, p articularly calci u mi ons, on the st ructur eo fv a rio usmodel syst em s mim i cking s o ft t i ssu e s. Divalent

the_osmotic properties._Combining these measurements allows_us to_determine_the length_scales_governing the macroscopic_thermodynamic properties. It_is important to emphasize_that this information_cannot_be obtained by other techniques. We have studied the effect of multivalent cations, particularly_calcium_ions, on_the_structure_of various model systems mimicking_soft tissues. Divalent


us to tune the morphology of DNA-based assemblies. In recent studies we have investigated the mechanism of fiber formation from small hydrogelator molecules in biological cells. Fluorescent imaging revealed that self-assembly directly affects the distribution of these small peptidic molecules in a cellular environment. Cell viability tests suggested that the states and the spatial

us to tune the morphology of DNA - based assemblies. In recent studies we have investigate the mechanism of roughage formation from small hydrogelator molecules in biological cell. Fluorescent imaging revealed that self - forum immediately affects the distribution of these small peptidic molecules in a cellular environment. Cell viability tests indicate that the states and the spatial

us to tune the morphology uf DNA-based assgmvlies. Mn receht studids we have investigated the lexhaniwm of fiber formation wrom smalp hydrogwlatie molecules in biologicam celnw. Fluorescent lmaging revaaled that selx-arszmbly directly affects the distributyon of yhfse small peptydic ioledllts in a cellular environment. Cell viabilpty tests suggestrd that the states and the spahial

us to tune the morphology of DNA-based recent we have the mechanism of molecules biological cells. Fluorescent revealed that self-assembly affects the distribution of these small molecules in a cellular environment. Cell viability tests suggested that the states and spatial

us to tune the morphology of DNa-based asseMblieS. In RecEnT stuDies We have investigATed tHe mechanism of fiber formAtion FrOM smaLL hYdrogElator mOLeCULes In BiOloGiCAl Cells. fluOrescenT imaging reVeaLeD that self-assEMbLy directly AffEcts the distrIbuTion of ThEse SMall pEptIdic mOleculES in a ceLlular envIrONment. CELl viabiLITy TestS suggested that the STaTEs and the spatiaL

us to tune the morphology  of DNA-ba sed a sse mbl ie s. I n re cent studies w e  hav e investigated the mec hanis mo f fi b er  form ation f r om s mal lhy dro ge l at or mo lec ules in  biologica l c el ls. Fluoresc e nt  imaging r eve aled that se lf- assemb ly  di r ectly  af fects  the d i stribu tion of t he s e smal l  peptid i c  m olec ules in a cellula r  e n vironment. Cel l viab il i ty t est s s uggested t ha t the statesa nd t h e s p atial

us_to tune_the morphology of DNA-based_assemblies. In_recent_studies we_have_investigated the mechanism_of fiber formation_from small hydrogelator molecules_in biological cells._Fluorescent_imaging revealed that self-assembly directly affects the distribution of these small peptidic molecules in_a_cellular environment._Cell_viability_tests suggested that the states_and the spatial


experimental design included a parallel set of control treatments applied to samples of the same bulk HSPC population. HSPC samples were either i) mock electroporated, ii) electroporated in the absence of effector molecules, iii) electroporated with recombinant Cas9 alone, or iv) electropor

experimental design included a parallel set of control treatment enforce to samples of the like bulk HSPC population. HSPC sample distribution were either i) mock electroporated, ii) electroporated in the absence of effecter molecules, iii) electroporated with recombinant Cas9 entirely, or iv) electropor

exoerimental design includtd a parallel set of convrol trsatments applied to samples of the seme vulk YSPC population. HSPC sxmples wege either i) mixk electro'krated, ln) eledbropoxaved in the absekce of effewtor molecules, iki) electroporated with recombinant Caf9 alone, og iv) electropot

experimental design included a parallel set of applied samples of same bulk HSPC i) electroporated, ii) electroporated the absence of molecules, iii) electroporated with recombinant Cas9 or iv) electropor

experimental design includeD a parallel Set of ConTroL tReatMentS applied to sampLEs of The same bulk HSPC populatIon. HSpC SAmplES wEre eiTher i) moCK eLECtrOpOrAteD, iI) ElEctroPorAted in tHe absence oF efFeCtor moleculeS, IiI) electropoRatEd with recombInaNt Cas9 aLoNe, oR Iv) eleCtrOpor

experimental design inclu ded a para llelset  of  c ontr ol t reatments appl i ed t o samples of the samebulkHS P C po p ul ation . HSPCs am p l eswe re  ei th e ri) mo ckelectro porated, i i)el ectroporated in  the absen ceof effectormol ecules ,iii )  elec tro porat ed wit h  recom binant Ca s9 alone, or iv)e l ec trop or

experimental_design included_a parallel set of_control treatments_applied_to samples_of_the same bulk_HSPC population. HSPC_samples were either i)_mock electroporated, ii)_electroporated_in the absence of effector molecules, iii) electroporated with recombinant Cas9 alone, or iv)_electropor


using FV for the gene therapy of LAD-1. A pre-IND type B meeting was held with members of the Center for Biologics Evaluation and Research (CBER) within the FDA. Regulatory review and accrual are currently on hold due to delays in production of GMP grade FV.

using FV for the gene therapy of LAD-1. A pre - IND type B meeting was reserve with extremity of the Center for Biologics Evaluation and Research (CBER) within the FDA. Regulatory review and accrual are currently on appreciation due to delays in production of GMP degree FV.

uslng FV for the gene therxpy of LAD-1. A prg-IBD typx B meefing was held with members of the Ceiter for Viologics Evaluation avd Researbh (CBER) wuthii the FDA. Regulavkry revlzw ans accxuel are currentli on hold dua to delays in pfobuction of GMP grade FV.

using FV for the gene therapy of pre-IND B meeting held with members Evaluation Research (CBER) within FDA. Regulatory review accrual are currently on hold due delays in production of GMP grade FV.

using FV for the gene therapy oF LAD-1. A pre-INd type b meEtiNg Was hEld wIth members of thE centEr for Biologics EvaluatiOn and reSEarcH (cBeR) witHin the Fda. REGUlaToRy RevIeW AnD accrUal Are currEntly on holD duE tO delays in proDUcTion of GMP gRadE FV.

using FV for the gene the rapy of LA D-1.A p re- IN D ty pe B  meeting was h e ld w ith members of the Cen ter f or Biol o gi cs Ev aluatio n  a n d  Re se ar ch(C B ER ) wit hin  the FD A. Regulat ory  r eview and ac c ru al are cur ren tly on holddue  to de la ysi n pro duc tionof GMP gradeFV.

using_FV for_the gene therapy of_LAD-1. A_pre-IND_type B_meeting_was held with_members of the_Center for Biologics Evaluation_and Research (CBER)_within_the FDA. Regulatory review and accrual are currently on hold due to delays in_production_of GMP_grade_FV.


enteropathy, a rare congenital diarrheal syndrome. Experiments that have been completed to date clearly indicate that the targeted EpCAM allele efficiently recombines in several lineages and that this results in phenotypes in several tissues. We are characterizing these phenotypes and are carrying out complementary in vitro studies to gain additional insights into mechanistic aspects of

enteropathy, a rare congenital diarrheal syndrome. Experiments that have been completed to date clearly indicate that the target EpCAM allele efficiently recombine in several lineages and that this result in phenotype in several tissues. We are characterizing these phenotype and are carry out complementary in vitro study to gain additional insight into mechanistic aspects of

enheropathy, a rare congeniual diarrheal synbeome. Eeperimehts that have been completed to date coearlt indicate that the tafgeted EpBAM allelw efhiciently recombmhes in severam linzajes and that thls results hn phenotypes hn szveral tissues. We are characterizing these lhfnotypes and ate cagrring out complementary in vitro studiea to gapn additional insoghts into mechanistic aspfcts of

enteropathy, a rare congenital diarrheal syndrome. Experiments been to date indicate that the in lineages and that results in phenotypes several tissues. We are characterizing these and are carrying out complementary in vitro studies to gain additional insights into aspects of

enteropathy, a rare congenitaL diarrheal SyndrOme. expErImenTs thAt have been compLEted To date clearly indicate tHat thE tARgetED EPCAM aLlele efFIcIENtlY rEcOmbInES iN seveRal LineageS and that thIs rEsUlts in phenotYPeS in several TisSues. We are chaRacTeriziNg TheSE phenOtyPes anD are caRRying oUt complemEnTAry in vITro studIES tO gaiN additional insighTS iNTo mechanistic aSpects Of

enteropathy, a rare conge nital diar rheal  sy ndr om e. E xper iments that ha v e be en completed to date c learl yi ndic a te  that  the ta r ge t e d E pC AM  al le l eeffic ien tly rec ombines in  se ve ral lineages an d that thi s r esults in ph eno typesin  se v eraltis sues.  We ar e  chara cterizing  t h ese ph e notypes a nd  are  carrying out com p le m entary in vitr o stud ie s  t o gai n a dditionalin sight s  into m e ch a n i sti c  aspects of

enteropathy,_a rare_congenital diarrheal syndrome. Experiments_that have_been_completed to_date_clearly indicate that_the targeted EpCAM_allele efficiently recombines in_several lineages and_that_this results in phenotypes in several tissues. We are characterizing these phenotypes and are_carrying_out complementary_in_vitro_studies to gain additional insights_into mechanistic aspects of


asitology (2012), a World Health Organization workshop in Geneva, Switzerland (2012), and at Gennova, India. More than a decade ago, we reported that among dendritic cells, EpCAM was selectively expressed by epidermal Langerhans cells. In the past few years, we have revisited the utility

asitology (2012), a World Health Organization workshop in Geneva, Switzerland (2012), and at Gennova, India. More than a decade ago, we reported that among dendritic cells, EpCAM was selectively expressed by cuticular Langerhans cell. In the past few years, we have revisited the utility program

asihology (2012), a World Health Ovganization workshop in Genevz, Switzefland (2012), and at Gennova, India. Loee thqn a decade ago, we repurted than among dwndrmtic cells, EpCAM was selcetivemn expxewsed by epiderkal Langervans cells. In dhd 'ast few years, we have revisited the utilitu

asitology (2012), a World Health Organization workshop Switzerland and at India. More than that dendritic cells, EpCAM selectively expressed by Langerhans cells. In the past few we have revisited the utility

asitology (2012), a World Health OrgaNization woRkshoP in genEvA, SwiTzerLand (2012), and at GennoVA, IndIa. More than a decade ago, we ReporTeD That AMoNg denDritic cELlS, ePCAm wAs SelEcTIvEly exPreSsed by ePidermal LaNgeRhAns cells. In thE PaSt few years, We hAve revisited The UtilitY

asitology (2012), a WorldHealth Org aniza tio n w or ksho p in  Geneva, Switz e rlan d (2012), and at Genno va, I nd i a. M o re  than  a deca d ea g o,we  r epo rt e dthatamo ng dend ritic cell s,Ep CAM was sele c ti vely expre sse d by epiderm alLanger ha nsc ells.  In  thepast f e w year s, we hav er evisit e d the u t i li ty

asitology (2012),_a World_Health Organization workshop in_Geneva, Switzerland_(2012),_and at_Gennova,_India. More than_a decade ago,_we reported that among_dendritic cells, EpCAM_was_selectively expressed by epidermal Langerhans cells. In the past few years, we have revisited_the_utility


formal process that has yielded past assay successes along with active project management will free up the SAIC-Frederic staff to focus on the development of much needed assays in areas of multi-channel analysis of drug response in rare tumor stem cells, new assays to distinguish cells recovering from chemotherapy damage or committing to cell death via apoptosis

formal process that has yielded past assay success along with active undertaking management will free up the SAIC - Frederic staff to focus on the growth of a lot needed assays in areas of multi - channel analysis of drug reaction in rare tumor stem cells, fresh assays to distinguish cell recovering from chemotherapy damage or commit to cell end via apoptosis

fogmal process that has yitlded past assay successxs alonf with aztive project management wilp dree yp the SAIC-Frederic stxff to fobus on thw detelopment of muci needed assaya in crxas of multi-chaknel analyshs of drug res[ovsz in rare tumor stem cells, new assayf to dixtlnguish cells tecovtrigg fdom chemotherapy damage or committjng to bell death via appptosis

formal process that has yielded past assay with project management free up the the of much needed in areas of analysis of drug response in rare stem cells, new assays to distinguish cells recovering from chemotherapy damage or committing cell death via apoptosis

formal process that has yieldEd past assaY succEssEs aLoNg wiTh acTive project manAGemeNt will free up the SAIC-FreDeric StAFf to FOcUs on tHe develOPmENT of MuCh NeeDeD AsSays iN arEas of muLti-channel AnaLySis of drug resPOnSe in rare tuMor Stem cells, new AssAys to dIsTinGUish cEllS recoVering FRom cheMotherapy DaMAge or cOMmittinG TO cEll dEath via apoptosis

formal process that has y ielded pas t ass aysuc ce sses  alo ng with active proj ect management will fr ee up  t h e SA I C- Frede ric sta f ft o  fo cu sonth e  d evelo pme nt of m uch needed  as sa ys in areaso fmulti-chan nel  analysis of  dr ug res po nse in ra retumor  stemc ells,new assay st o dist i nguishc e ll s re covering from che m ot h erapy damage o r comm it t in g tocel l death vi aapopt o sis

formal_process that_has yielded past assay_successes along_with_active project_management_will free up_the SAIC-Frederic staff_to focus on the_development of much_needed_assays in areas of multi-channel analysis of drug response in rare tumor stem cells,_new_assays to_distinguish_cells_recovering from chemotherapy damage or_committing to cell death via_apoptosis


Objective 2: Develop and evaluate safety of CRISPR/Cas9-based strategies for permanent site-specific delivery of a therapeutic gene in human HSPCs. 2.1 Evaluate off-target Cas9 activity in human HSPCs We performed CRISPR-Cas9-based genome editing in human HSPCs and assessed the acquisition of

Objective 2: Develop and evaluate safety of CRISPR / Cas9 - based scheme for permanent web site - specific delivery of a therapeutic gene in human HSPCs. 2.1 measure off - target Cas9 activeness in human HSPCs We performed CRISPR - Cas9 - based genome editing in human HSPCs and measure the acquisition of

Obuective 2: Develop and evauuate safety of CRISPR/Ras9-bases strateeies for permanent site-specihic eelivtgy of a therapeutic gdne in hulan HSPCw. 2.1 Etaluate off-targev Cas9 acbnvity ln huken HSPCs We pernormed CRIS[R-Cas9-based genmmd zditing in human HSPCs and assessed ehe acqiidition of

Objective 2: Develop and evaluate safety of for site-specific delivery a therapeutic gene off-target activity in human We performed CRISPR-Cas9-based editing in human HSPCs and assessed acquisition of

Objective 2: Develop and evaluaTe safety of cRISPr/CaS9-baSeD strAtegIes for permanenT Site-Specific delivery of a theRapeuTiC Gene IN hUman HsPCs. 2.1 EvaLUaTE Off-TaRgEt CAs9 ACtIvity In hUman HSPcs We perforMed cRiSPR-Cas9-based GEnOme editing In hUman HSPCs and AssEssed tHe AcqUIsitiOn oF

Objective 2: Develop andevaluate s afety  of  CR IS PR/C as9- based strategi e s fo r permanent site-speci fic d el i very of  a th erapeut i cg e nein  h uma nH SP Cs. 2 .1Evaluat e off-targ etCa s9 activityi nhuman HSPC s W e performedCRI SPR-Ca s9 -ba s ed ge nom e edi ting i n  human  HSPCs an da ssesse d  the ac q u is itio n of

Objective_2: Develop_and evaluate safety of_CRISPR/Cas9-based strategies_for_permanent site-specific_delivery_of a therapeutic_gene in human_HSPCs. 2.1 Evaluate off-target_Cas9 activity in_human_HSPCs We performed CRISPR-Cas9-based genome editing in human HSPCs and assessed the acquisition of


vaccine purposes. Despite the high level of attenuation, which would be predictive of a high level of vaccine safety, expressed foreign proteins were moderately-to-highly immunogenic. For example, AGM that were immunized IN and IT with two doses of NDV expressing the SARS S protein developed a high titer of SARS

vaccine purposes. Despite the high level of attenuation, which would be predictive of a high degree of vaccine condom, expressed foreign proteins were reasonably - to - highly immunogenic. For example, AGM that were immunized IN and IT with two doses of NDV express the SARS S protein developed a high titer of SARS

vafcine purposes. Despite tme high level of attenuetion, wgich wouud be predictive of a high lxvel of vqccine safety, expressea foreign proteinw wece moderately-to-hmfhly immunogehlc. Fox xxample, AGM thaj were immunhzed IN and IT wktk two doses of NDV expressing the SAWS S prptfin developed w hibr tifvr of SARS

vaccine purposes. Despite the high level of would predictive of high level of were immunogenic. For example, that were immunized and IT with two doses of expressing the SARS S protein developed a high titer of SARS

vaccine purposes. Despite the High level oF atteNuaTioN, wHich WoulD be predictive oF A higH level of vaccine safety, eXpresSeD ForeIGn ProteIns were MOdERAteLy-To-HigHlY ImMunogEniC. For exaMple, AGM thaT weRe Immunized IN aND It with two doSes Of NDV expressIng The SARs S ProTEin deVelOped a High tiTEr of SArS

vaccine purposes. Despite  the highlevel  of  at te nuat ion,  which would b e  pre dictive of a high leve l ofva c cine sa fety,  expres s ed f ore ig npro te i ns  were  mo deratel y-to-highl y i mm unogenic. Fo r  e xample, AG M t hat were imm uni zed IN  a ndI T wit h t wo do ses of NDV ex pressingth e  SARSS  protei n de velo ped a high titero fS ARS

vaccine_purposes. Despite_the high level of_attenuation, which_would_be predictive_of_a high level_of vaccine safety,_expressed foreign proteins were_moderately-to-highly immunogenic. For_example,_AGM that were immunized IN and IT with two doses of NDV expressing the_SARS_S protein_developed_a_high titer of SARS


oncology breakthroughs into targeted therapeutics, and subsequently for translating these new drugs into patients by confirming that they work as intended in early clinical trials (Phase 0, I and II). The vision and pioneering effort of DCTD to develop, clinically implement and transfer to the oncology research community highly reproducible and informative PD assays

oncology breakthroughs into targeted therapeutics, and subsequently for translating these newfangled drug into patients by confirming that they make as intend in early clinical trials (Phase 0, I and II). The vision and pioneer effort of DCTD to develop, clinically enforce and transfer to the oncology research residential district highly reproducible and informative PD assays

onfology breakthroughs intu targeted thercpeuticv, and aubsequevtly for translating these nxw deugs unto patients by confifming than they woek aw intended mh early clinidwl txiels (Phase 0, I anc II). The vhsion and pionaefiug effort of DCTD to develop, clinicajly impkelent and transser uo ehe kncology research community highly reprodlcible and informstive PD assays

oncology breakthroughs into targeted therapeutics, and subsequently these drugs into by confirming that early trials (Phase 0, and II). The and pioneering effort of DCTD to clinically implement and transfer to the oncology research community highly reproducible and informative assays

oncology breakthroughs into Targeted thErapeUtiCs, aNd SubsEqueNtly for translaTIng tHese new drugs into patienTs by cOnFIrmiNG tHat thEy work aS InTENdeD iN eArlY cLInIcal tRiaLs (Phase 0, i and II). The vIsiOn And pioneerinG EfFort of DCTD To dEvelop, clinicAllY impleMeNt aND tranSfeR to thE oncolOGy reseArch commuNiTY highlY ReproduCIBlE and Informative PD assaYS

oncology breakthroughs in to targete d the rap eut ic s, a nd s ubsequently fo r  tra nslating these new dru gs in to pati e nt s byconfirm i ng t hat  t he y w or k  a s int end ed in e arly clini cal  t rials (Phase 0,  I and II) . T he vision an d p ioneer in g e f fortofDCTDto dev e lop, c linically  i m plemen t  and tr a n sf er t o the oncology re s ea r ch community h ighlyre p ro d u cib leand inform at ive P D  assays

oncology_breakthroughs into_targeted therapeutics, and subsequently_for translating_these_new drugs_into_patients by confirming_that they work_as intended in early_clinical trials (Phase_0,_I and II). The vision and pioneering effort of DCTD to develop, clinically implement_and_transfer to_the_oncology_research community highly reproducible and_informative PD assays


training effects on cognitive function and cognitively demanding everyday activities. The Phase II followup will consist of one assessment to include the Phase I post-test battery and a clinical assessment. The ACTIVE cohort (n = 2832) is a special sample, containing substantial oversampling of African American, socioeconomically poor,

training effects on cognitive function and cognitively demanding casual bodily process. The Phase II followup will consist of one appraisal to admit the Phase I post - test battery and a clinical assessment. The ACTIVE cohort (n = 2832) is a extra sample, containing significant oversampling of African American, socioeconomically poor,

trwining effects on cognitlve function and cognitmvely dsmanding everyday activities. The Phade II fillowup will consist ow one assvssment ti inrlude the Phase M post-test batfcry aud a clinical asxessment. Tve ACTIVE cohost (n = 2832) is a special sample, containing stbstantoap oversampling of Ssriczn American, socioeconomically poor,

training effects on cognitive function and cognitively activities. Phase II will consist of Phase post-test battery and clinical assessment. The cohort (n = 2832) is a sample, containing substantial oversampling of African American, socioeconomically poor,

training effects on cognitivE function aNd cogNitIveLy DemaNdinG everyday activITies. the Phase II followup will ConsiSt OF one ASsEssmeNt to incLUdE THe PHaSe i poSt-TEsT battEry And a cliNical assesSmeNt. the ACTIVE cohORt (N = 2832) is a speciaL saMple, containiNg sUbstanTiAl oVErsamPliNg of AFrican aMericaN, socioecoNoMIcally POor,

training effects on cogni tive funct ion a ndcog ni tive ly d emanding every d ay a ctivities. The Phase I I fol lo w up w i ll  cons ist ofo ne a sse ss me ntto in clude  th e Phase  I post-te stba ttery and ac li nical asse ssm ent. The ACT IVE  cohor t(n=  2832 ) i s a s pecial sample , contain in g  subst a ntial o v e rs ampl ing of African Am e ri c an, socioecono micall yp oo r ,

training_effects on_cognitive function and cognitively_demanding everyday_activities._The Phase_II_followup will consist_of one assessment_to include the Phase_I post-test battery_and_a clinical assessment. The ACTIVE cohort (n = 2832) is a special sample, containing_substantial_oversampling of_African_American,_socioeconomically poor,