environment, which can have profound effects on its physiology and morphology. Such susceptibility of the developing brain to environmental influence by sensory manipulation or to environmental toxicants is particularly pronounced during defined critical periods of postnatal life. On the one hand, this susceptibility makes the developing brain particularly vulnerable to toxic insults. On the other hand, the

environment, which can have profound effects on its physiology and morphology. Such susceptibility of the developing mind to environmental influence by centripetal manipulation or to environmental toxicants is particularly pronounce during defined critical periods of postnatal life sentence. On the one handwriting, this susceptibility makes the developing brain particularly vulnerable to toxic insult. On the other hand, the

engironment, which can have profound effecjs on itv physjology avd morphology. Such susceptibmlitt of uke developing brain go envirojmental unflnence by sensory manipulation kv to zntironmental toxlcants is pdrticularly prmnuuuced during defined critical periods of posynwtal life. On tre omq hahd, this susceptibility makes the dsvelopiig brain particilarly vulnerable to toxic insklts. On the other jand, the

environment, which can have profound effects on and Such susceptibility the developing brain manipulation to environmental toxicants particularly pronounced during critical periods of postnatal life. On one hand, this susceptibility makes the developing brain particularly vulnerable to toxic insults. the other hand, the

environment, which can have prOfound effeCts on Its PhySiOlogY and Morphology. Such SUscePtibility of the developiNg braIn TO envIRoNmentAl influENcE BY seNsOrY maNiPUlAtion Or tO enviroNmental toxIcaNtS is particulaRLy Pronounced DurIng defined crItiCal perIoDs oF PostnAtaL life. on the oNE hand, tHis suscepTiBIlity mAKes the dEVElOpinG brain particularlY VuLNerable to toxic InsultS. ON ThE OTheR haNd, the

environment, which can ha ve profoun d eff ect s o nitsphys iology and mor p holo gy. Such susceptibilit y ofth e  dev e lo pingbrain t o  e n v iro nm en tal  i n fl uence  by  sensor y manipula tio nor to enviro n me ntal toxic ant s is particu lar ly pro no unc e d dur ing  defi ned cr i ticalperiods o fp ostnat a l life. O ntheone hand, this su s ce p tibility makes  the d ev e lo p i ngbra in particu la rly v u lnerabl e  t o t oxi c  insults. Onthe other h a nd,  the

environment,_which can_have profound effects on_its physiology_and_morphology. Such_susceptibility_of the developing_brain to environmental_influence by sensory manipulation_or to environmental_toxicants_is particularly pronounced during defined critical periods of postnatal life. On the one hand,_this_susceptibility makes_the_developing_brain particularly vulnerable to toxic_insults. On the other hand,_the


, IL-6 receptor-alpha (IL-6R), and the type II IL-1 decoy receptor (IL-1RII) can all be inhibited by hydroxamic acid based zinc metalloprotease inhibitors, we hypothesized that ARTS-1 might also regulate IL-6R and IL-1R

, IL-6 receptor - alpha (IL-6R), and the type II IL-1 decoy receptor (IL-1RII) can all be inhibited by hydroxamic acid free-base zinc metalloprotease inhibitor, we hypothesized that ARTS-1 might also determine IL-6R and IL-1R

, IL-6 receptor-alpha (IL-6R), and tme type II IL-1 deeiy recxptor (IM-1RII) can all be inhibited by hydroxalix acie based zinc metalloprutease injibitors, we iypothesized thav ARTS-1 mlyht amdo rzgnlate IL-6R and IK-1R

, IL-6 receptor-alpha (IL-6R), and the type decoy (IL-1RII) can be inhibited by inhibitors, hypothesized that ARTS-1 also regulate IL-6R IL-1R

, IL-6 receptor-alpha (IL-6R), and the tYpe II IL-1 decOy recEptOr (Il-1RiI) caN all Be inhibited by hYDroxAmic acid based zinc metalLoproTeASe inHIbItors, We hypotHEsIZEd tHaT ArTS-1 MiGHt Also rEguLate IL-6R And IL-1R

, IL-6 receptor-alpha (IL- 6R), and t he ty peIIIL -1 d ecoy  receptor (IL- 1 RII)  can all be inhibitedby hy dr o xami c  a cid b ased zi n cm e tal lo pr ote as e  i nhibi tor s, we h ypothesize d t ha t ARTS-1 mig h talso regul ate  IL-6R and I L-1 R

, IL-6_receptor-alpha (IL-6R),_and the type II_IL-1 decoy_receptor_(IL-1RII) can_all_be inhibited by_hydroxamic acid based_zinc metalloprotease inhibitors, we_hypothesized that ARTS-1_might_also regulate IL-6R and IL-1R


to provide risk feedback to participants from Mexican American households in the Houston, TX area. We successfully recruited 497 participants for baseline assessments (162 households), 481 participants completed the 1-month follow-up assessment and 461 participants completed the 6-month follow-up assessment. Recent efforts have focused on analyzing these data to identify how

to provide risk feedback to participants from Mexican American households in the Houston, TX sphere. We successfully recruit 497 participants for baseline assessment (162 family), 481 participants completed the 1 - month trace - up assessment and 461 participants complete the 6 - month follow - up judgment. Recent efforts have concenter on analyzing these data to identify how

to provide risk feedback tu participants yeom Meeican Ajerican fouseholds in the Houston, TX aeea. Wt successfully recrjited 497 pagticipantw foc baseline assessments (162 mjusegllds), 481 participants gompleted tve 1-month follof-uo cssessment and 461 participants completqd the 6-kojth follow-up afsesxient. Gegent efforts have focused on anamyzing uhese data to idenyify how

to provide risk feedback to participants from households the Houston, area. We successfully assessments households), 481 participants the 1-month follow-up and 461 participants completed the 6-month assessment. Recent efforts have focused on analyzing these data to identify how

to provide risk feedback to paRticipants From MExiCan amEricAn hoUseholds in the HOUstoN, TX area. We successfully rEcruiTeD 497 PartICiPants For baseLInE ASseSsMeNts (162 HoUSeHolds), 481 ParTicipanTs completeD thE 1-mOnth follow-up ASsEssment and 461 ParTicipants comPleTed the 6-MoNth FOllow-Up aSsessMent. ReCEnt effOrts have fOcUSed on aNAlyzing THEsE datA to identify how

to provide risk feedbackto partici pants  fr omMe xica n Am erican househo l ds i n the Houston, TX area . Wesu c cess f ul ly re cruited 49 7 par ti ci pan ts fo r bas eli ne asse ssments (1 62ho useholds), 4 8 1participan tscompleted th e 1 -month  f oll o w-upass essme nt and 461 pa rticipant sc omplet e d the 6 - m on th f ollow-up assessme n t. Recent efforts  havefo c us e d  on  an alyzing th es e dat a  to ide n ti f y how

to_provide risk_feedback to participants from_Mexican American_households_in the_Houston,_TX area. We_successfully recruited 497_participants for baseline assessments_(162 households), 481_participants_completed the 1-month follow-up assessment and 461 participants completed the 6-month follow-up assessment. Recent_efforts_have focused_on_analyzing_these data to identify how


SI-NETs. Recent results identified multifocal aberrant crypt-containing endocrine cell clusters (ACECs) that contain crypt EC cell microtumors in patients with familial SI-NETs. RNA in situ hybridization revealed expression of the EC cell and reserve stem cell genes TPH1, BMI1, HOPX,

SI - NETs. Recent results identified multifocal aberrant crypt - containing hormone cellular telephone clusters (ACECs) that contain crypt EC cellular telephone microtumors in patients with familial SI - NETs. RNA in situ hybridization unwrap expression of the EC cellular telephone and reserve bow cell gene TPH1, BMI1, HOPX,

SI-JETs. Recent results idenuified multifocal aberrait crypf-containkng endocrine cell clusters (ECECw) thau contain crypt EC zell micrltumors un petients with fammmial SI-KZTs. RHW in witu hybridizajion revealeg expression ox ghz EC cell and reserve stem cell genef TPH1, BKI1, HOPX,

SI-NETs. Recent results identified multifocal aberrant crypt-containing clusters that contain EC cell microtumors RNA situ hybridization revealed of the EC and reserve stem cell genes TPH1, HOPX,

SI-NETs. Recent results identiFied multifOcal aBerRanT cRypt-ContAining endocrinE Cell Clusters (ACECs) that contaIn cryPt ec celL MiCrotuMors in pATiENTs wItH fAmiLiAL Si-NETs. rNA In situ hYbridizatiOn rEvEaled expressIOn Of the EC celL anD reserve stem CelL genes tPh1, BMi1, hOPX,

SI-NETs. Recent results i dentifiedmulti foc alab erra nt c rypt-containin g  end ocrine cell clusters ( ACECs )t hatc on taincrypt E C  c e l l m ic ro tum or s  i n pat ien ts with  familialSI- NE Ts. RNA in s i tu  hybridiza tio n revealed e xpr ession  o f t h e ECcel l and  reser v e stem  cell gen es TPH1,B MI1, HO P X ,

SI-NETs._Recent results_identified multifocal aberrant crypt-containing_endocrine cell_clusters_(ACECs) that_contain_crypt EC cell_microtumors in patients_with familial SI-NETs. RNA_in situ hybridization_revealed_expression of the EC cell and reserve stem cell genes TPH1, BMI1, HOPX,


. This suggests these MLV variants evolved to adapt to host receptor polymorphisms, to circumvent blocks by competing viruses or to avoid host-encoded envelope glycoproteins acquired for defense. In another series of experiments we characterized pathogenic and nonpathogenic MLVs of polytropic host range. Ecotropic, xenotropic and polytropic

. This suggests these MLV variants evolved to adapt to server sense organ polymorphisms, to circumvent block by compete viruses or to avoid host - encode envelope glycoprotein acquired for defense. In another series of experiments we characterized infective and nonpathogenic MLVs of polytropic host range. Ecotropic, xenotropic and polytropic

. Thls suggests these MLV vaviants evolved to adapt to hoat recepgor polymorphisms, to circumvxnt vlockw by competing viruses or to avlid host-wncoved envelope glyrkproteikf acsmired hor defense. In snother sesies of experikevtd we characterized pathogenic and njnpathobejic MLVs of pojytrp[ic gost range. Ecotropic, xenotropic ans polytgopic

. This suggests these MLV variants evolved to receptor polymorphisms, circumvent blocks by host-encoded glycoproteins acquired for In another series experiments we characterized pathogenic and nonpathogenic of polytropic host range. Ecotropic, xenotropic and polytropic

. This suggests these MLV variaNts evolved To adaPt tO hoSt RecePtor Polymorphisms, tO CircUmvent blocks by competinG viruSeS Or to AVoId hosT-encodeD EnVELopE gLyCopRoTEiNs acqUirEd for deFense. In anoTheR sEries of experIMeNts we charaCteRized pathogeNic And nonPaThoGEnic MlVs Of polYtropiC Host raNge. EcotroPiC, XenotrOPic and pOLYtRopiC

. This suggests these MLVvariants e volve d t o a da pt t o ho st receptor po l ymor phisms, to circumventblock sb y co m pe tingviruses or t o a vo id  ho st - en coded  en velopeglycoprote ins  a cquired ford ef ense. In a not her series o f e xperim en tsw e cha rac teriz ed pat h ogenic  and nonp at h ogenic MLVs of p ol ytro pic host range. E c ot r opic, xenotrop ic and  p o ly t r opi c

. This_suggests these_MLV variants evolved to_adapt to_host_receptor polymorphisms,_to_circumvent blocks by_competing viruses or_to avoid host-encoded envelope_glycoproteins acquired for_defense._In another series of experiments we characterized pathogenic and nonpathogenic MLVs of polytropic host_range._Ecotropic, xenotropic_and_polytropic


1 susceptibility variants in wild mice and described the geographic and species distribution of these Mus Xpr1 variants. Five of these receptors restrict entry by two or more of the virus host range variants that rely on XPR1, and all of these receptors evolved in populations exposed to X-MLVs. Virtually all mammalian species

1 susceptibility variants in wild mice and described the geographic and species distribution of these Mus Xpr1 random variable. Five of these receptor restrict entry by two or more of the virus host image variants that rely on XPR1, and all of these sense organ evolve in populations exposed to X - MLVs. Virtually all mammalian coinage

1 sudceptibility variants in wild mice and bwscribxd the feographkc and species distribution lf thest Mus Xpr1 variants. Wive of tjese recwptocs restrict entrb by two or modc of chx virus host rakge variantv that rely on XOR1, and all of these receptors evolved in popilwtions exposed to Q-MJVs. Bpruually all mammalian species

1 susceptibility variants in wild mice and geographic species distribution these Mus Xpr1 restrict by two or of the virus range variants that rely on XPR1, all of these receptors evolved in populations exposed to X-MLVs. Virtually all mammalian

1 susceptibility variants in wIld mice and DescrIbeD thE gEogrAphiC and species disTRibuTion of these Mus Xpr1 variaNts. FiVe OF theSE rEceptOrs restRIcT ENtrY bY tWo oR mORe Of the VirUs host rAnge varianTs tHaT rely on XPR1, anD AlL of these reCepTors evolved iN poPulatiOnS exPOsed tO X-MlVs. ViRtuallY All mamMalian speCiES

1 susceptibility variantsin wild mi ce an d d esc ri bedthegeographic and spec ies distribution of th ese M us Xpr1 va riant s. Five of t hes ere cep to r srestr ict  entryby two ormor eof the virus ho st range v ari ants that re lyon XPR 1,  an d  allofthese  recep t ors ev olved inpo p ulatio n s expos e d  t o X- MLVs. Virtually a l lm ammalian speci es

1 susceptibility_variants in_wild mice and described_the geographic_and_species distribution_of_these Mus Xpr1_variants. Five of_these receptors restrict entry_by two or_more_of the virus host range variants that rely on XPR1, and all of these_receptors_evolved in_populations_exposed_to X-MLVs. Virtually all mammalian_species


transcription was not important for target site activity. We next considered whether transcription factors themselves were directing the integration of Tf1. To identify positions where factors bind in the promoter of Ade6, we used micrococcal nuclease mapping. We observed a strong correlation between micrococcal sensitive sites and the position of the prominent

transcription was not important for target site natural process. We next view whether transcription divisor themselves were target the integration of Tf1. To identify position where agent bind in the showman of Ade6, we use micrococcal nuclease mapping. We note a strong correlation between micrococcal sensitive sites and the position of the prominent

trwnscription was not impovtant for target site artivity. We next considered whether transcri'tiob facujrs themselves werd directijg the ibtegcation of Tf1. To msentify positjlns chxre factors binc in the psomoter of Ade6, wd bsed micrococcal nuclease mapping. We observrd a strong corrglatipg befween micrococcal sensitive sites znd the position of yhe prominent

transcription was not important for target site next whether transcription themselves were directing identify where factors bind the promoter of we used micrococcal nuclease mapping. We a strong correlation between micrococcal sensitive sites and the position of the prominent

transcription was not importAnt for targEt sitE acTivItY. We nExt cOnsidered whethER traNscription factors themsElves WeRE dirECtIng thE integrATiON Of TF1. TO iDenTiFY pOsitiOns Where faCtors bind iN thE pRomoter of Ade6, WE uSed microcoCcaL nuclease mapPinG. We obsErVed A StronG coRrelaTion beTWeen miCrococcal SeNSitive SItes and THE pOsitIon of the prominent

transcription was not imp ortant for  targ etsit eacti vity . We next cons i dere d whether transcriptio n fac to r s th e ms elves  were d i re c t ing  t he  in te g ra tionofTf1. To  identifypos it ions where f a ct ors bind i n t he promoterofAde6,we  us e d mic roc occal  nucle a se map ping. Weob s erveda  strong c or rela tion between micr o co c cal sensitivesitesan d  t h e  po sit ion of the  p romin e nt

transcription_was not_important for target site_activity. We_next_considered whether_transcription_factors themselves were_directing the integration_of Tf1. To identify_positions where factors_bind_in the promoter of Ade6, we used micrococcal nuclease mapping. We observed a strong_correlation_between micrococcal_sensitive_sites_and the position of the_prominent


cells, how variations in these recognition and signaling events leads to desirable versus undesirable forms of immunity, and how we can manipulate these events to augment useful immune responses and inhibit damaging ones. Our studies currently focus on biochemical regulatory pathways that help T cells discriminate between self- and foreign peptide:MHC molecule complexes, on the explicit

cells, how variations in these recognition and signaling event go to desirable versus undesirable forms of immunity, and how we can manipulate these event to augment useful immune responses and suppress damaging ones. Our studies currently concentrate on biochemical regulatory pathways that avail T cells discriminate between self- and alien peptide: MHC molecule complexes, on the explicit

cepls, how variations in thtse recognition aue signeling ebents lexds to desirable versus undedieable forms of immunity, and how we cwn manipylatt these events to augment usefum immbnx responses and inhibit ddmaging ones. Ogr scudies currently focus on biochemicaj regulstlry pathways trat nqlp F cells discriminate between self- znd fortign peptide:MHC mokecule complexes, on the exoliclt

cells, how variations in these recognition and leads desirable versus forms of immunity, these to augment useful responses and inhibit ones. Our studies currently focus on regulatory pathways that help T cells discriminate between self- and foreign peptide:MHC molecule on the explicit

cells, how variations in these RecognitioN and sIgnAliNg EvenTs leAds to desirable VErsuS undesirable forms of immUnity, AnD How wE CaN maniPulate tHEsE EVenTs To AugMeNT uSeful ImmUne respOnses and inHibIt Damaging ones. oUr Studies curRenTly focus on biOchEmical ReGulATory pAthWays tHat helP t cells DiscriminAtE BetweeN Self- and FOReIgn pEptide:MHC molecule COmPLexes, on the explIcit

cells, how variations inthese reco gniti onand  s igna ling  events leadst o de sirable versus undesir ablefo r ms o f  i mmuni ty, and ho w weca nman ip u la te th ese  events  to augmen t u se ful immune r e sp onses andinh ibit damagin g o nes. O ur  st u diescur rentl y focu s  on bi ochemical  r e gulato r y pathw a y sthat  help T cells dis c ri m inate betweenself-an d  f o r eig n p eptide:MHC  m olecu l e compl e xe s , ont he explicit

cells,_how variations_in these recognition and_signaling events_leads_to desirable_versus_undesirable forms of_immunity, and how_we can manipulate these_events to augment_useful_immune responses and inhibit damaging ones. Our studies currently focus on biochemical regulatory pathways_that_help T_cells_discriminate_between self- and foreign peptide:MHC_molecule complexes, on the explicit


in MOLT-4 cells and the same was seen at 100 microM in Daudi cells. There was also a sharp reudction in the amount of mtDNA at 10 and 100 microM in MOLT-4 and Daudi cells, respectively. By contrast, there was no sharp reduction when the cells were cultivated

in MOLT-4 cells and the same was seen at 100 microM in Daudi cells. There be besides a sharp reudction in the amount of mtDNA at 10 and 100 microM in MOLT-4 and Daudi cell, respectively. By line, there was no sharp reduction when the cellular telephone were cultivated

in MOLT-4 cells and the same was seen at 100 mnxroM ii Daudi cells. Tfere was also a sharp reudctmon un tht amount of mtDNA ag 10 and 100 mpcroM in NOLT-4 qnd Daudi rslls, respectibcly. Bv rontrast, there eas no shasp reduction wvev che cells were cultivated

in MOLT-4 cells and the same was 100 in Daudi There was also amount mtDNA at 10 100 microM in and Daudi cells, respectively. By contrast, was no sharp reduction when the cells were cultivated

in MOLT-4 cells and the same was sEen at 100 microm in DaUdi CelLs. therE was Also a sharp reudCTion In the amount of mtDNA at 10 anD 100 micrOM IN MOLt-4 AnD DaudI cells, rESpECTivElY. BY coNtRAsT, therE waS no sharP reduction WheN tHe cells were cULtIvated

in MOLT-4 cells and the s ame was se en at  10 0 m ic roMin D audi cells. Th e re w as also a sharp reudct ion i nt he a m ou nt of  mtDNAa t1 0  an d10 0 m ic r oM  in M OLT -4 andDaudi cell s,re spectively.B ycontrast,the re was no sh arp  reduc ti onw hen t hecells  werec ultiva ted

in_MOLT-4 cells_and the same was_seen at_100_microM in_Daudi_cells. There was_also a sharp_reudction in the amount_of mtDNA at_10_and 100 microM in MOLT-4 and Daudi cells, respectively. By contrast, there was no_sharp_reduction when_the_cells_were cultivated


established a challenge model using AGM and showed that two doses of NDV-HA conferred essentially complete protection against challenge with a high dose (7.2 log10 PFU) of HPAIV. The high level of restriction of HPAIV challenge virus was established by assay of nasal swabs and tracheal lav

established a challenge model using AGM and showed that two venereal disease of NDV - HA confer essentially complete protection against challenge with a gamey dose (7.2 log10 PFU) of HPAIV. The high horizontal surface of limitation of HPAIV challenge virus was established by assay of nasal swabs and tracheal lav

eshablished a challenge moael using AGM aue showxd that two dosds of NDV-HA conferred essentmallt comkjete protection agxinst chaplenge wuth e high dose (7.2 log10 PFU) of M'AIV. Fme hiyh level of resttiction of H[AIV challenge vkrbs was established by assay of nasal swabs snf tracheal lav

established a challenge model using AGM and two of NDV-HA essentially complete protection dose log10 PFU) of The high level restriction of HPAIV challenge virus was by assay of nasal swabs and tracheal lav

established a challenge modeL using AGM aNd shoWed ThaT tWo doSes oF NDV-HA conferreD EsseNtially complete protectIon agAiNSt chALlEnge wIth a higH DoSE (7.2 Log10 pFu) oF HPaIv. thE high LevEl of resTriction of hPAiV Challenge virUS wAs establisHed By assay of nasAl sWabs anD tRacHEal laV

established a challenge m odel using  AGMand  sh ow ed t hattwo doses of N D V-HA  conferred essentially  comp le t e pr o te ction  agains t  c h a lle ng ewit ha  h igh d ose  (7.2 l og10 PFU)ofHP AIV. The hig h  l evel of re str iction of HP AIV  chall en gev iruswas  esta blishe d  by as say of na sa l  swabs and tra c h ea l la v

established_a challenge_model using AGM and_showed that_two_doses of_NDV-HA_conferred essentially complete_protection against challenge_with a high dose_(7.2 log10 PFU)_of_HPAIV. The high level of restriction of HPAIV challenge virus was established by assay_of_nasal swabs_and_tracheal_lav


suppressed the replication of wild-type HBV strains (HBVWT) as examined in HepG2.2.2.15.7 cells, HBVWT-plasmid-transfected Huh7 cells, and in HBVWT-exposed human-liver-chimeric-uPA+/+/SCID+/+

suppressed the replication of wild - type HBV tune (HBVWT) as probe in HepG2.2.2.15.7 cells, HBVWT - plasmid - transfected Huh7 cells, and in HBVWT - exposed human - liver - chimeric - uPA+/+/SCID+/+

suopressed the replication of wild-type HBR straiis (HBVWF) as exaoined in HepG2.2.2.15.7 cells, HBVWT-pladmud-trabsfected Huh7 cells, and in HBVWT-vxposed hyman-ouver-chimermd-uPA+/+/SCID+/+

suppressed the replication of wild-type HBV strains examined HepG2.2.2.15.7 cells, Huh7 cells, and

suppressed the replication oF wild-type HbV strAinS (HBvWt) as eXamiNed in HepG2.2.2.15.7 cells, hbVWT-Plasmid-transfected Huh7 cElls, aNd IN HBVwt-eXposeD human-lIVeR-CHimErIc-UPA+/+/sCid+/+

suppressed the replicatio n of wild- typeHBV  st ra ins(HBV WT) as examine d  inHepG2.2.2.15.7 cells,HBVWT -p l asmi d -t ransf ected H u h7 c ell s,  a ndin HB VWT-e xpo sed hum an-liver-c him er ic-uPA+/+/SC I D+ /+

suppressed_the replication_of wild-type HBV strains_(HBVWT) as_examined_in HepG2.2.2.15.7_cells,_HBVWT-plasmid-transfected Huh7 cells,_and in HBVWT-exposed_human-liver-chimeric-uPA+/+/SCID+/+


biopolymer molecules and assemblies in their natural environment and to correlate the changes in the environmental conditions (e.g., ion concentration, ion valance, pH, temperature) with physical properties such as molecular conformation and osmotic pressure. These techniques simultaneously provide information about the size of different structural elements and their respective contribution to

biopolymer molecules and assemblies in their natural environment and to correlate the changes in the environmental condition (for example, ion concentration, ion valance, pH, temperature) with forcible properties such as molecular conformity and osmotic pressure. These techniques simultaneously supply information about the size of different geomorphologic elements and their respective contribution to

bilpolymer molecules and arsemblies in thgie natucal envjronment and to correlate the changed un tht environmental conaitions (e.h., ion cobcenuration, ion valanrs, pH, temperathve) wich physical propgrties such ds molecular cmnwoxmation and osmotic pressure. These tqchniqurs simultaneousli proniqe ihformation about the size of diffedent stguctural elements and their respective contgibuhion to

biopolymer molecules and assemblies in their natural to the changes the environmental conditions pH, with physical properties as molecular conformation osmotic pressure. These techniques simultaneously provide about the size of different structural elements and their respective contribution to

biopolymer molecules and assEmblies in tHeir nAtuRal EnViroNmenT and to correlatE The cHanges in the environmentAl conDiTIons (E.G., iOn conCentratIOn, ION vaLaNcE, pH, TeMPeRaturE) wiTh physiCal propertIes SuCh as moleculaR CoNformation And Osmotic pressUre. these tEcHniQUes siMulTaneoUsly prOVide inFormation AbOUt the sIZe of difFEReNt stRuctural elements aND tHEir respective cOntribUtIOn TO

biopolymer molecules andassemblies  in t hei r n at ural  env ironment and t o  cor relate the changes inthe e nv i ronm e nt al co ndition s  ( e . g.,  i on  co nc e nt ratio n,ion val ance, pH,tem pe rature) with ph ysical pro per ties such as  mo lecula rcon f ormat ion  andosmoti c  press ure. Thes et echniq u es simu l t an eous ly provide inform a ti o n about the si ze ofdi f fe r e ntstr uctural el em entsa nd thei r  r e s p ect i ve contributi on to

biopolymer_molecules and_assemblies in their natural_environment and_to_correlate the_changes_in the environmental_conditions (e.g., ion_concentration, ion valance, pH,_temperature) with physical_properties_such as molecular conformation and osmotic pressure. These techniques simultaneously provide information about the_size_of different_structural_elements_and their respective contribution to


N-terminus of the surface subunit, and the cytoplasmic tail R peptide. Viral gag gene replacements are influenced by host restriction genes Fv1 and Apobec3. Pathogenic potential maps to the env transmembrane subunit segment encoding the N-heptad repeat (HR1). Molecular dynamics simulations identified three novel inter

N - terminus of the surface subunit, and the cytoplasmic tail radius peptide. Viral joke gene replacements are influenced by server limitation genes Fv1 and Apobec3. Pathogenic potential map to the env transmembrane subunit segment encode the N - seven repeat (HR1). Molecular dynamics simulations identify three novel inter

N-tfrminus of the surface smbunit, and the citiplasmmc tail R peptiae. Viral gag gene replacemenvs aee indluenced by host restrkction gejes Fv1 abd Akobec3. Pathogenic 'ktential maps bo thz xnv transmembrake subunit vegment encoditg tke N-heptad repeat (HR1). Molecular dynamycs similwtions identifyed uhrqe nkneo inter

N-terminus of the surface subunit, and the R Viral gag replacements are influenced and Pathogenic potential maps the env transmembrane segment encoding the N-heptad repeat (HR1). dynamics simulations identified three novel inter

N-terminus of the surface subuNit, and the cYtoplAsmIc tAiL R pePtidE. Viral gag gene rEPlacEments are influenced by hOst reStRIctiON gEnes FV1 and ApoBEc3. pAThoGeNiC poTeNTiAl mapS to The env tRansmembraNe sUbUnit segment eNCoDing the N-hePtaD repeat (HR1). MolEcuLar dynAmIcs SImulaTioNs ideNtifieD Three nOvel inter

N-terminus of the surface  subunit,and t hecyt op lasm ic t ail R peptide. Vira l gag gene replacement s are  i n flue n ce d byhost re s tr i c tio nge nes  F v 1and A pob ec3. Pa thogenic p ote nt ial maps tot he  env trans mem brane subuni t s egment  e nco d ing t heN-hep tad re p eat (H R1). Mole cu l ar dyn a mics si m u la tion s identified thre e  n o vel inter

N-terminus_of the_surface subunit, and the_cytoplasmic tail_R_peptide. Viral_gag_gene replacements are_influenced by host_restriction genes Fv1 and_Apobec3. Pathogenic potential_maps_to the env transmembrane subunit segment encoding the N-heptad repeat (HR1). Molecular dynamics simulations_identified_three novel_inter


effect of Vif on APOBEC3G is modulated by CBF. We have cloned CBF from human cells. Also, since CBF is ubiquitously expressed in most cell types, we created stable CBF knock-down cell lines to be able to perform experiments on a CBF negative background. Several studies

effect of Vif on APOBEC3 G is modulated by CBF. We have cloned CBF from human cells. besides, since CBF is ubiquitously carry in most cell types, we create static CBF knock - down cell lines to be able to perform experiment on a CBF negative background. respective study

efvect of Vif on APOBEC3G ir modulated by EVF. We iave clkned CBF from human cells. Also, since CVF is ubiquitously expressea in most cell types, xe created stablx CBF knock-dowh celn lines to be anle to perfmrm experimentv un a CBF negative background. Several ftudies

effect of Vif on APOBEC3G is modulated We cloned CBF human cells. Also, in cell types, we stable CBF knock-down lines to be able to perform on a CBF negative background. Several studies

effect of Vif on APOBEC3G is modUlated by CBf. We haVe cLonEd cBF fRom hUman cells. Also, sINce CbF is ubiquitously expresSed in MoST celL TyPes, we Created STaBLE CBf kNoCk-dOwN CeLl linEs tO be able To perform eXpeRiMents on a CBF nEGaTive backgrOunD. Several studIes

effect of Vif on APOBEC3G  is modula ted b y C BF.  W e ha ve c loned CBF from huma n cells. Also, since C BF is  u b iqui t ou sly e xpresse d  i n mos tce llty p es , wecre ated st able CBF k noc k- down cell li n es  to be abl e t o perform ex per iments  o n a CBF n ega tivebackgr o und. S everal st ud i es

effect_of Vif_on APOBEC3G is modulated_by CBF._We_have cloned_CBF_from human cells._Also, since CBF_is ubiquitously expressed in_most cell types,_we_created stable CBF knock-down cell lines to be able to perform experiments on a_CBF_negative background._Several_studies


V6-copGFP at either 48 hr or 36 hr pre- or 0.5 hr post-RNP electroporation. Gene edited cells were cultured for up to 28 days post-electroporation and periodically sampled for flow cytometry and genomic DNA (gDNA) extraction. Transduction of HSPCs prior to

V6 - copGFP at either 48 hr or 36 hr pre- or 0.5 hr post - RNP electroporation. Gene edited cell were culture for up to 28 days post - electroporation and sporadically sampled for stream cytometry and genomic DNA (gDNA) extraction. Transduction of HSPCs prior to

V6-cooGFP at either 48 hr or 36 hv pre- or 0.5 hr posj-RBP elertroporztion. Geve edited cells were culturev foe up uj 28 days post-electruporation and peruodirally sampled foc flow cncometdn and jenomic DNA (gDNS) extractimn. Transductiot uf HSPCs prior to

V6-copGFP at either 48 hr or 36 or hr post-RNP Gene edited cells 28 post-electroporation and periodically for flow cytometry genomic DNA (gDNA) extraction. Transduction of prior to

V6-copGFP at either 48 hr or 36 hr pre- oR 0.5 hr post-RNP ElectRopOraTiOn. GeNe edIted cells were cULturEd for up to 28 days post-electRoporAtIOn anD PeRiodiCally saMPlED For FlOw CytOmETrY and gEnoMic DNA (gdNA) extractIon. trAnsduction of hsPcs prior to

V6-copGFP at either 48 hror 36 hr p re- o r 0 .5hr  pos t-RN P electroporat i on.Gene edited cells were  cult ur e d fo r  u p to28 days po s t -el ec tr opo ra t io n and  pe riodica lly sample d f or  flow cytome t ry  and genom icDNA (gDNA) e xtr action .Tra n sduct ion  of H SPCs p r ior to

V6-copGFP at_either 48_hr or 36 hr_pre- or_0.5_hr post-RNP_electroporation._Gene edited cells_were cultured for_up to 28 days_post-electroporation and periodically_sampled_for flow cytometry and genomic DNA (gDNA) extraction. Transduction of HSPCs prior to


will be used in interpreting anisotropy decay experiments. This relatively new method has the potential for monitoring how proteins form multimers, and their stoichiometry in living cells. The generation of fluorescent protein anisotropy standards required the generation of a mutant variant of GFP that has the same fundamental structure as GFP but is not capable of participating in

will be used in interpreting anisotropy decay experiments. This relatively new method acting have the potential for monitoring how protein form multimers, and their stoichiometry in animation cells. The coevals of fluorescent protein anisotropy standards required the coevals of a mutant variant of GFP that has the like fundamental structure as GFP but is not capable of participating in

wipl be used in interpretikg anisotropy deeqy expxrimenta. This rdlatively new method has the pitentual for monitoring how proteins form muotimtrs, and their stomdhiometvv in mlving rells. The generstion of fnuorescent prodekn anisotropy standards required the deneratooj of a mutant darisgt or GFP that has the same fundamentam strucuure as GFP but is not capable of participatlng ln

will be used in interpreting anisotropy decay relatively method has potential for monitoring their in living cells. generation of fluorescent anisotropy standards required the generation of mutant variant of GFP that has the same fundamental structure as GFP but not capable of participating in

will be used in interpreting aNisotropy dEcay eXpeRimEnTs. ThIs reLatively new metHOd haS the potential for monitoRing hOw PRoteINs Form mUltimerS, AnD THeiR sToIchIoMEtRy in lIviNg cells. the generatIon Of Fluorescent pROtEin anisotrOpy Standards reqUirEd the gEnEraTIon of A muTant vAriant OF GFP thAt has the sAmE FundamENtal strUCTuRe as gFP but is not capablE Of PArticipating in

will be used in interpret ing anisot ropydec ayex peri ment s. This relati v elynew method has the pot entia lf or m o ni torin g how p r ot e i nsfo rm  mu lt i me rs, a ndtheir s toichiomet ryin  living cell s .The genera tio n of fluores cen t prot ei n a n isotr opy  stan dardsr equire d the gen er a tion o f  a muta n t  v aria nt of GFP that ha s  t h e same fundame ntal s tr u ct u r e a s G FP but isno t cap a ble ofp ar t i c ipa t ing in

will_be used_in interpreting anisotropy decay_experiments. This_relatively_new method_has_the potential for_monitoring how proteins_form multimers, and their_stoichiometry in living_cells._The generation of fluorescent protein anisotropy standards required the generation of a mutant variant_of_GFP that_has_the_same fundamental structure as GFP_but is not capable of_participating in


marginal band of microtubules that extends down from the axon and loops throughout the synaptic terminal. This microtubule loop is structurally similar to those found in red blood cells. Using 3D confocal fluorescence, block-face serial scanning electron microscopy, and transmission electron microscopy we fully characterized this structure. We found that this microtubule structure associates with

marginal band of microtubules that extends down from the axon and iteration throughout the synaptic end. This microtubule loop is structurally similar to those establish in crimson blood cells. use 3D confocal fluorescence, auction block - face consecutive scan electron microscopy, and transmission electron microscopy we in full characterized this structure. We find oneself that this microtubule structure associates with

magginal band of microtubuues that extends down hrom ths axon avd loops throughout the syna'tic termunal. This microtubule uoop is snructuraloy smmilar to those hkund in red bmlod eeols. Using 3D cokfocal fluosescence, block-xaze serial scanning electron microscopr, and ttajsmission elecjron kycroaboky we fully characterized this stducture. We found thay this microtubule structuge adsociates with

marginal band of microtubules that extends down axon loops throughout synaptic terminal. This to found in red cells. Using 3D fluorescence, block-face serial scanning electron microscopy, transmission electron microscopy we fully characterized this structure. We found that this microtubule associates with

marginal band of microtubuleS that extenDs dowN frOm tHe Axon And lOops throughout THe syNaptic terminal. This micrOtubuLe LOop iS StRuctuRally siMIlAR To tHoSe FouNd IN rEd bloOd cElls. UsiNg 3D confocaL flUoRescence, blocK-FaCe serial scAnnIng electron mIcrOscopy, AnD trANsmisSioN elecTron miCRoscopY we fully cHaRActeriZEd this sTRUcTure. we found that this miCRoTUbule structure AssociAtES wITH

marginal band of microtub ules thatexten dsdow nfrom  the  axon and loop s  thr oughout the synaptic t ermin al .  Thi s  m icrot ubule l o op i s s tr uc tur al l ysimil arto thos e found in  re dblood cells. Us ing 3D con foc al fluoresce nce , bloc k- fac e  seri alscann ing el e ctronmicroscop y, and tr a nsmissi o n  e lect ron microscopy we fu l ly characteriz ed thi ss tr u c tur e.We found t ha t thi s  microt u bu l e str u cture associa tes with

marginal_band of_microtubules that extends down_from the_axon_and loops_throughout_the synaptic terminal._This microtubule loop_is structurally similar to_those found in_red_blood cells. Using 3D confocal fluorescence, block-face serial scanning electron microscopy, and transmission electron_microscopy_we fully_characterized_this_structure. We found that this_microtubule structure associates with


This study has been accepted for publication in the Biophysical Journal (due out in October 2005) and will be highlighted on the journals cover. A second manuscript, evaluating how quantitative spectral imaging is for discriminating proteins labeled with either blue (CFP) or yellow (YFP) variants of green fluorescent protein (GFP)

This study has been accepted for publication in the Biophysical Journal (due out in October 2005) and will be foreground on the daybook cover. A second manuscript, evaluating how quantitative spectral imagination is for discriminating proteins labeled with either gloomy (CFP) or yellow (YFP) variants of fleeceable fluorescent protein (GFP )

Thls study has been accepttd for publicatiou in thx Biophgsical Juurnal (due out in October 2005) aid wull bt highlighted on thd journald cover. Q serond manuscript, xbaluatiky how euancivative spectral imaging iv for discrimitagiug proteins labeled with either blue (CFP) or yfllow (YFP) variwnts jf gdvek fluorescent protein (GFP)

This study has been accepted for publication Biophysical (due out October 2005) and journals A second manuscript, how quantitative spectral is for discriminating proteins labeled with blue (CFP) or yellow (YFP) variants of green fluorescent protein (GFP)

This study has been accepted fOr publicatIon in The bioPhYsicAl JoUrnal (due out in OCTobeR 2005) and will be highlighted oN the jOuRNals COvEr. A seCond manUScRIPt, eVaLuAtiNg HOw QuantItaTive speCtral imagiNg iS fOr discriminaTInG proteins lAbeLed with eitheR blUe (CFP) oR yEllOW (YFP) vAriAnts oF green FLuoresCent proteIn (gfP)

This study has been accep ted for pu blica tio n i ntheBiop hysical Journa l  (du e out in October 2005)  andwi l l be hi ghlig hted on th e jou rn al s c ov e r.  A se con d manus cript, eva lua ti ng how quant i ta tive spect ral  imaging isfor  discr im ina t ing p rot einslabele d  witheither bl ue (CFP)o r yello w (Y FP)variants of green fl u orescent prote in (GF P)

This_study has_been accepted for publication_in the_Biophysical_Journal (due_out_in October 2005)_and will be_highlighted on the journals_cover. A second_manuscript,_evaluating how quantitative spectral imaging is for discriminating proteins labeled with either blue (CFP)_or_yellow (YFP)_variants_of_green fluorescent protein (GFP)


strength of the clutch determines range of ECM stiffness cells are able to sense to mediate durotaxis. Using high-resolution traction force microscopy on polyacrylamide ECMs of varying stiffnesses, we found that the mechanical behavior of the integrin-actin interface at FA exhibited ECM stiffness-dependent switching between a load-and-

strength of the clutch determines range of ECM stiffness cells are able to feel to intercede durotaxis. Using high - settlement grip force microscopy on polyacrylamide ECMs of varying severity, we found that the mechanical behavior of the integrin - actin interface at FA exhibit ECM stiffness - dependent switching between a warhead - and-

stgength of the clutch dettrmines range of GCN stifhness cslls are able to sense to mediate ducotazis. Uwing high-resolution trxction fogce microwcopb on polyacrylammse ECMs of vadning vviffnesses, we fpund that dhe mechanical bdhcvior of the integrin-actin interface at FA rxjibited ECM styffntss-qepehdent switching between a load-and-

strength of the clutch determines range of cells able to to mediate durotaxis. on ECMs of varying we found that mechanical behavior of the integrin-actin interface FA exhibited ECM stiffness-dependent switching between a load-and-

strength of the clutch determInes range oF ECM sTifFneSs CellS are Able to sense to mEDiatE durotaxis. Using high-resOlutiOn TRactIOn Force MicroscOPy ON PolYaCrYlaMiDE EcMs of VarYing stiFfnesses, we FouNd That the mechaNIcAl behavior Of tHe integrin-acTin InterfAcE at fa exhiBitEd ECM StiffnESs-depeNdent switChINg betwEEn a load-AND-

strength of the clutch de termines r angeofECM  s tiff ness  cells are abl e  tosense to mediate durot axis.  U s ingh ig h-res olution tr a c tio nfo rce  m i cr oscop y o n polya crylamideECM sof varying s t if fnesses, w e f ound that th e m echani ca l b e havio r o f the  integ r in-act in interf ac e  at FA exhibit e d  E CM s tiffness-dependen t  s w itching betwee n a lo ad - an d -

strength_of the_clutch determines range of_ECM stiffness_cells_are able_to_sense to mediate_durotaxis. Using high-resolution_traction force microscopy on_polyacrylamide ECMs of_varying_stiffnesses, we found that the mechanical behavior of the integrin-actin interface at FA exhibited_ECM_stiffness-dependent switching_between_a_load-and-


clinical and laboratory manifestations of the diseases are being assessed. A treatment protocol to assess the role of a novel long acting IL-1 inhibitor XOMA 052 has been approved by the IRB and is expected to start recruitment soon. UNDIFFERENTIATED DISEASE We have accumulated a number of patients who have

clinical and laboratory manifestations of the diseases are being assessed. A discussion protocol to measure the role of a novel retentive act IL-1 inhibitor XOMA 052 has been approved by the IRB and is expected to begin recruitment soon. UNDIFFERENTIATED DISEASE We have accumulate a number of patient who have

cllnical and laboratory makifestations of jhw diseeses ars being xssessed. A treatment protocop ro aswess the role of a novdl long abting IL-1 unhiuitor XOMA 052 has usen appvjved ny thz MRB and is expegted to stast recruitment suou. UNDIFFERENTIATED DISEASE We have ascumulayef a number of katiemes wgo have

clinical and laboratory manifestations of the diseases assessed. treatment protocol assess the role IL-1 XOMA 052 has approved by the and is expected to start recruitment UNDIFFERENTIATED DISEASE We have accumulated a number of patients who have

clinical and laboratory maniFestations Of the DisEasEs Are bEing Assessed. A treatMEnt pRotocol to assess the role Of a noVeL Long ACtIng IL-1 InhibitOR Xoma 052 haS bEeN apPrOVeD by thE IRb and is eXpected to sTarT rEcruitment soON. UnDIFFERENTiATeD DISEASE We hAve AccumuLaTed A NumbeR of PatieNts who HAve

clinical and laboratory m anifestati ons o f t hedi seas es a re being asses s ed.A treatment protocol t o ass es s  the ro le of  a nove l  l o n g a ct in g I L- 1  i nhibi tor  XOMA 0 52 has bee n a pp roved by the IR B and is e xpe cted to star t r ecruit me nts oon.UND IFFER ENTIAT E D DISE ASE We ha ve accumu l ated an u mb er o f patients who ha v e

clinical_and laboratory_manifestations of the diseases_are being_assessed._A treatment_protocol_to assess the_role of a_novel long acting IL-1_inhibitor XOMA 052_has_been approved by the IRB and is expected to start recruitment soon. UNDIFFERENTIATED DISEASE_We_have accumulated_a_number_of patients who have


) fused with the diphtheria toxin fragment 390 (DT390) is underway. This recombinant toxin fragment is safer because it lacks the native toxin-binding domain, therefore, preventing internalization of toxin in off-target cells. The resulting scFv-DT390 (69.55 kDa) and svF

) fused with the diphtheria toxin fragment 390 (DT390) is underway. This recombinant toxin fragment is safe because it miss the native toxin - binding domain, consequently, preventing internalization of toxin in off - aim cells. The resulting scFv - DT390 (69.55 kDa) and svF

) fuded with the diphtheria uoxin fragment 390 (DJ390) us undxrway. Tgis recoobinant toxin fragment is saher vecauwe it lacks the native toxin-binfing domqin, uherefore, preventmhg intevualizzbion mh toxin in off-tsrget cellv. The resultinc rcYv-DT390 (69.55 kDa) and svF

) fused with the diphtheria toxin fragment is This recombinant fragment is safer toxin-binding therefore, preventing internalization toxin in off-target The resulting scFv-DT390 (69.55 kDa) and

) fused with the diphtheria toxIn fragment 390 (dT390) is uNdeRwaY. THis rEcomBinant toxin fraGMent Is safer because it lacks tHe natIvE ToxiN-BiNding Domain, tHErEFOre, PrEvEntInG InTernaLizAtion of Toxin in off-TarGeT cells. The resULtIng scFv-DT390 (69.55 kda) aNd svF

) fused with the diphtheri a toxin fr agmen t 3 90(D T390 ) is  underway. Thi s  rec ombinant toxin fragmen t issa f er b e ca use i t lacks th e nat iv etox in - bi nding  do main, t herefore,pre ve nting intern a li zation oftox in in off-ta rge t cell s.  Th e  resu lti ng sc Fv-DT3 9 0 (69. 55 kDa) a nd svF

) fused_with the_diphtheria toxin fragment 390_(DT390) is_underway._This recombinant_toxin_fragment is safer_because it lacks_the native toxin-binding domain,_therefore, preventing internalization_of_toxin in off-target cells. The resulting scFv-DT390 (69.55 kDa) and svF


7 years. Third trimester serum was analyzed for PCBs in 1997-1999 for 730 women selected at random and for an additional 153 women whose children had either a low or high IQ score. The PCB-IQ association was examined while adjusting for study center, maternal age, race, serum lipids, parity, socioeconomic status

7 years. Third trimester serum was analyzed for PCBs in 1997 - 1999 for 730 women selected at random and for an extra 153 charwoman whose children had either a depleted or gamey IQ score. The PCB - IQ affiliation was examined while adjusting for study center field, maternal age, raceway, serum lipids, parity, socioeconomic condition

7 yfars. Third trimester sermm was analyzed yir PCBv in 1997-1999 ror 730 womdn selected at random and foc an addiuponal 153 women whose chkldren haf either a liq or high MS score. The PDN-IQ avwociation was gxamined whine adjusting fmr scudy center, maternal age, race, serum jipids, lagity, socioeconjmic ftaths

7 years. Third trimester serum was analyzed in for 730 selected at random women children had either low or high score. The PCB-IQ association was examined adjusting for study center, maternal age, race, serum lipids, parity, socioeconomic status

7 years. Third trimester serum wAs analyzed For PCbs iN 1997-1999 foR 730 wOmen SeleCted at random anD For aN additional 153 women whose cHildrEn HAd eiTHeR a low Or high Iq ScORE. ThE PcB-iQ aSsOCiAtion Was ExamineD while adjuStiNg For study centER, mAternal age, RacE, serum lipids, ParIty, socIoEcoNOmic sTatUs

7 years. Third trimesterserum wasanaly zed  fo rPCBs  in1997-1999 for7 30 w omen selected at rando m and  f o r an ad ditio nal 153 wo m e n w ho se  ch il d re n had  ei ther alow or hig h I Qscore. The P C B- IQ associa tio n was examin edwhilead jus t ing f orstudy  cente r , mate rnal age,  r a ce, se r um lipi d s ,pari ty, socioeconomic st a tus

7_years. Third_trimester serum was analyzed_for PCBs_in_1997-1999 for_730_women selected at_random and for_an additional 153 women_whose children had_either_a low or high IQ score. The PCB-IQ association was examined while adjusting for_study_center, maternal_age,_race,_serum lipids, parity, socioeconomic status


family history based risk feedback motivates family communications about common, complex diseases and the development of cooperative strategies, such as encouragement to screen, to address this risk. Within the current reporting period, we have published three manuscripts from this project, two are under review, and two are in preparation. Based on results from Project RAM

family history based risk feedback motivates syndicate communication about common, complex diseases and the development of accommodative strategies, such as encouragement to shield, to cover this risk. Within the current reporting period, we have published three manuscripts from this undertaking, two are under review, and two are in preparation. Based on results from Project RAM

falily history based risk needback motivatgs familb commuhicationr about common, complex diseadew and the development of couperative strategues, wych as encouragemekc to agreen, vo address this risk. Withhn the current rdplrting period, we have published thrqe manuxcgipts from thif prptect, nwi are under review, and two ars in prtparation. Based on results from Project RAM

family history based risk feedback motivates family common, diseases and development of cooperative screen, address this risk. the current reporting we have published three manuscripts from project, two are under review, and two are in preparation. Based on results Project RAM

family history based risk feeDback motivAtes fAmiLy cOmMuniCatiOns about common, COmplEx diseases and the develoPment Of COopeRAtIve stRategieS, SuCH As eNcOuRagEmENt To scrEen, To addreSs this risk. witHiN the current rEPoRting perioD, we Have publisheD thRee manUsCriPTs froM thIs proJect, twO Are undEr review, aNd TWo are iN PreparaTIOn. baseD on results from ProJEcT rAM

family history based risk  feedbackmotiv ate s f am ilycomm unications abo u t co mmon, complex diseases  andth e  dev e lo pment  of coo p er a t ive  s tr ate gi e s,  such  as  encour agement to  sc re en, to addre s sthis risk.  Wi thin the cur ren t repo rt ing perio d,we ha ve pub l ishedthree man us c riptsf rom thi s pr ojec t, two are underr ev i ew, and two ar e in p re p ar a t ion . B ased on re su lts f r om Proj e ct R A M

family_history based_risk feedback motivates family_communications about_common,_complex diseases_and_the development of_cooperative strategies, such_as encouragement to screen,_to address this_risk._Within the current reporting period, we have published three manuscripts from this project, two_are_under review,_and_two_are in preparation. Based on_results from Project RAM


existing chronic helminth infection on susceptibility to mycobacteria, on modulating the response to aeroallergens, and potentially to HIV and malaria. Specifically, we have recently demonstrated that coincident filarial infections profoundly alter the pro-inflammatory and Th1/Th17 responses to malarial antigens (in filarial/

existing chronic helminth infection on susceptibility to mycobacteria, on modulating the response to aeroallergens, and potentially to HIV and malaria. Specifically, we have recently attest that coincident filarial infection profoundly alter the pro - inflammatory and Th1 / Th17 responses to malarial antigen (in filarial/

exidting chronic helminth ikfection on suscgpribilivy to mgcobactefia, on modulating the responde to atgoallergens, and potengially to HIV and maleria. Specificallb, we havc recsktly benonstrated thaj coincident filarial infewtkous profoundly alter the pro-inflammatjry and Tj1/Th17 responses jo makwriam antigens (in filarial/

existing chronic helminth infection on susceptibility to modulating response to and potentially to have demonstrated that coincident infections profoundly alter pro-inflammatory and Th1/Th17 responses to malarial (in filarial/

existing chronic helminth inFection on sUscepTibIliTy To myCobaCteria, on modulaTIng tHe response to aeroallergEns, anD pOTentIAlLy to HiV and maLArIA. speCiFiCalLy, WE hAve reCenTly demoNstrated thAt cOiNcident filarIAl Infections ProFoundly alter The Pro-infLaMmaTOry anD Th1/th17 resPonses TO malarIal antigeNs (IN filarIAl/

existing chronic helminthinfectionon su sce pti bi lity  tomycobacteria,o n mo dulating the responseto ae ro a ller g en s, an d poten t ia l l y t oHI V a nd ma laria . S pecific ally, we h ave  r ecently demo n st rated that  co incident fil ari al inf ec tio n s pro fou ndlyaltert he pro -inflamma to r y andT h1/Th17 r es pons es to malarial an t ig e ns (in filaria l/

existing chronic_helminth infection_on susceptibility to mycobacteria,_on modulating_the_response to_aeroallergens,_and potentially to_HIV and malaria._Specifically, we have recently_demonstrated that coincident_filarial_infections profoundly alter the pro-inflammatory and Th1/Th17 responses to malarial antigens (in filarial/


could give important insights into the mechanisms of SAMHD1 function and/or regulation. APOBEC3G/Vif: In FY12 we initiated a project studying the role of a newly identified host factor, CBF, in the control of APOBEC3G by Vif. Recent studies indicate that the

could give important insights into the mechanisms of SAMHD1 affair and/or rule. APOBEC3G / Vif: In FY12 we initiated a project study the character of a newly identified host gene, CBF, in the command of APOBEC3 G by Vif. Recent study indicate that the

cokld give important insigmts into the meckqnisms of SAJHD1 funcgion and/or regulation. APOBEC3J/Vif: In FT12 we initiated a projezt studyijg the rile id a newly msentificb hosf faccoc, CBF, in the coktrol of APMBEC3G by Vif. Racdnc studies indicate that the

could give important insights into the mechanisms function regulation. APOBEC3G/Vif: FY12 we initiated of newly identified host CBF, in the of APOBEC3G by Vif. Recent studies that the

could give important insightS into the meChaniSms Of SaMhD1 fuNctiOn and/or regulatIOn. APoBEC3G/Vif: In FY12 we initiateD a proJeCT stuDYiNg the Role of a NEwLY IdeNtIfIed HoST fActor, cBF, In the coNtrol of APObEC3g bY Vif. Recent stUDiEs indicate ThaT the

could give important insi ghts intothe m ech ani sm s of  SAM HD1 function a n d/or  regulation. APOBEC3G/ Vif:In FY12 we  init iated a pr o j ect  s tu dyi ng th e rol e o f a new ly identif ied  h ost factor,C BF , in the c ont rol of APOBE C3G  by Vi f.  Re c ent s tud ies i ndicat e  thatthe

could_give important_insights into the mechanisms_of SAMHD1_function_and/or regulation._APOBEC3G/Vif:_In FY12 we_initiated a project_studying the role of_a newly identified_host_factor, CBF, in the control of APOBEC3G by Vif. Recent studies indicate that the


age-matched controls. We believe that the lower titers in the HbAS children may result from their lower incidence of infection and we are analyzing a study of asymptomatic parasitemia in these children. During the past year we have followed these children into a new transmission season and shown that, surprisingly, their IgG levels to specific

age - matched controls. We believe that the low titer in the HbAS children may result from their low incidence of contagion and we are analyzing a study of asymptomatic parasitemia in these children. During the past class we have trace these children into a fresh transmission season and shown that, amazingly, their IgG levels to specific

agf-matched controls. We belleve that the locwr titxrs in fhe HbAS children may result from thxir oower incidence of infectiov and we wre analtzinj a study of asymptomatig parzditekma in these chikdren. Duritg the past yedr wz have followed these children into w new ttajsmission seasjn amq shkwn that, surprisingly, their IgG lebels to specific

age-matched controls. We believe that the lower the children may from their lower are a study of parasitemia in these During the past year we have these children into a new transmission season and shown that, surprisingly, their IgG to specific

age-matched controls. We belieVe that the lOwer tIteRs iN tHe HbaS chIldren may resulT From Their lower incidence of iNfectIoN And wE ArE analYzing a sTUdY OF asYmPtOmaTiC PaRasitEmiA in thesE children. DUriNg The past year wE HaVe followed TheSe children inTo a New traNsMisSIon seAsoN and sHown thAT, surprIsingly, thEiR igG levELs to speCIFiC

age-matched controls. Webelieve th at th e l owe rtite rs i n the HbAS chi l dren  may result from their  lowe ri ncid e nc e ofinfecti o na n d w ear e a na l yz ing a  st udy ofasymptomat icpa rasitemia in th ese childr en.  During thepas t year  w e h a ve fo llo wed t hese c h ildren  into a n ew transm i ssion s e a so n an d shown that, sur p ri s ingly, their I gG lev el s  t o spe cif ic

age-matched_controls. We_believe that the lower_titers in_the_HbAS children_may_result from their_lower incidence of_infection and we are_analyzing a study_of_asymptomatic parasitemia in these children. During the past year we have followed these children_into_a new_transmission_season_and shown that, surprisingly, their_IgG levels to specific


is one of the main regulators. We hypothesized that Rac1 may regulate myosin II minifilament assembly dynamics during cell migration via downstream regulation of PKC and Ser 1916 phosphorylation. To test this, we analyzed the effects of Rac1 activation on the phosphorylation and dynamics of myosin IIA in U2OS cells. We found

is one of the main regulators. We hypothesized that Rac1 may regulate myosin II minifilament fabrication moral force during cell migration via downstream regulation of PKC and Ser 1916 phosphorylation. To screen this, we analyze the effects of Rac1 activation on the phosphorylation and moral force of myosin IIA in U2OS cells. We found

is one of the main regulaturs. We hypothesnzed thet Rac1 jay reguuate myosin II minifilament essenbly eynamics during cell mkgration nia downsrrean regulatioi of PKC and Ssv 1916 phmwphorylation. Tp test thiv, we analyzed dhd zffects of Rac1 activation on the phofphorylstlon and dynamiss og myoapn IIA in U2OS cells. We found

is one of the main regulators. We Rac1 regulate myosin minifilament assembly dynamics regulation PKC and Ser phosphorylation. To test we analyzed the effects of Rac1 on the phosphorylation and dynamics of myosin IIA in U2OS cells. We found

is one of the main regulators. WE hypothesiZed thAt RAc1 mAy ReguLate Myosin II minifiLAmenT assembly dynamics durinG cell MiGRatiON vIa dowNstream REgULAtiOn Of pKC AnD seR 1916 phosPhoRylatioN. To test thiS, we AnAlyzed the effECtS of Rac1 actiVatIon on the phosPhoRylatiOn And DYnamiCs oF myosIn IIA iN u2OS celLs. We found

is one of the main regula tors. We h ypoth esi zed  t hatRac1  may regulatem yosi n II minifilament asse mblydy n amic s  d uring  cell m i gr a t ion  v ia  do wn s tr eam r egu lationof PKC and  Se r1916 phospho r yl ation. Totes t this, we a nal yzed t he  ef f ectsofRac1activa t ion on  the phos ph o rylati o n and d y n am icsof myosin IIA inU 2O S  cells. We fou nd

is_one of_the main regulators. We_hypothesized that_Rac1_may regulate_myosin_II minifilament assembly_dynamics during cell_migration via downstream regulation_of PKC and_Ser_1916 phosphorylation. To test this, we analyzed the effects of Rac1 activation on the_phosphorylation_and dynamics_of_myosin_IIA in U2OS cells. We_found


These studies may help lead to community studies examining if interrupting sedentary behavior is a promising prevention strategy for reducing cardiometabolic risk in children. Investigations concentrating on binge eating behaviors in children suggest that such behaviors are also associated with adiposity in children and predict future weight gain in children at-risk for overweight. The

These studies may help lead to community report probe if interrupting sedentary behavior is a promising prevention scheme for reducing cardiometabolic risk in children. probe concentrating on binge eat behaviors in children indicate that such behaviors are also consociate with adiposity in children and predict future weight gain in children at - hazard for overweight. The

Thfse studies may help leaa to community studies examihing if knterrupting sedentary behavmor us a kgomising prevention sgrategy flr reducung rardiometabolic cjsk in gkildrsk. Invzsvigations concektrating on binge eating tefariors in children suggest that such fehaviots are also assosiattd rith adiposity in children and predict future weight gain on children at-risk for ovegweihht. The

These studies may help lead to community if sedentary behavior a promising prevention in Investigations concentrating on eating behaviors in suggest that such behaviors are also with adiposity in children and predict future weight gain in children at-risk for The

These studies may help lead to Community sTudieS exAmiNiNg if InteRrupting sedentARy beHavior is a promising prevEntioN sTRateGY fOr redUcing caRDiOMEtaBoLiC riSk IN cHildrEn. INvestigAtions concEntRaTing on binge eATiNg behaviorS in Children suggEst That suCh BehAViors Are Also aSsociaTEd with Adiposity In CHildreN And predICT fUturE weight gain in chilDReN At-risk for overwEight. THe

These studies may help le ad to comm unity  st udi es  exa mini ng if interrup t ingsedentary behavior isa pro mi s ingp re venti on stra t eg y for  r ed uci ng ca rdiom eta bolic r isk in chi ldr en . Investigat i on s concentr ati ng on bingeeat ing be ha vio r s inchi ldren  sugge s t that  such beh av i ors ar e  also a s s oc iate d with adiposityi nc hildren and pr edictfu t ur e wei ght  gain in c hi ldren at-risk fo r o ver w eight. The

These_studies may_help lead to community_studies examining_if_interrupting sedentary_behavior_is a promising_prevention strategy for_reducing cardiometabolic risk in_children. Investigations concentrating_on_binge eating behaviors in children suggest that such behaviors are also associated with adiposity_in_children and_predict_future_weight gain in children at-risk_for overweight. The


we demonstrated that a time related TGF-beta gene expression signature established in mouse primary hepatocytes successfully discriminated distinct subgroups of HCC. The TGF-beta positive cluster included two novel homogeneous groups of HCC associated with early and late TGF-beta signatures. Kaplan-Meier plots and logrank statistics indicated that patients with the late TGF-beta

we demonstrated that a time related TGF - beta gene expression touch prove in mouse primary hepatocytes successfully discriminated distinct subgroups of HCC. The TGF - beta plus cluster included two fresh homogeneous groups of HCC associated with early and late TGF - beta signature. Kaplan - Meier plots and logrank statistics argue that patients with the late TGF - beta

we demonstrated that a timt related TGF-beta gene eepressikn signagure established in mouse prmmart hepqtocytes successfully aiscriminwted disrincu subgroups of HCR. The TGN-yeta llsitnvx cluster incluced two noeel homogeneouv erlups of HCC associated with early agd late THF-beta signatutes. Ks[lan-Jvitr plots and logrank statistics ihdicatev that patients with the late TGF-beta

we demonstrated that a time related TGF-beta signature in mouse hepatocytes successfully discriminated TGF-beta cluster included two homogeneous groups of associated with early and late TGF-beta Kaplan-Meier plots and logrank statistics indicated that patients with the late TGF-beta

we demonstrated that a time reLated TGF-beTa genE exPreSsIon sIgnaTure establisheD In moUse primary hepatocytes sUccesSfULly dIScRiminAted disTInCT SubGrOuPs oF Hcc. THe TGF-BetA positiVe cluster iNclUdEd two novel hoMOgEneous grouPs oF HCC associatEd wIth earLy And LAte TGf-beTa sigNatureS. kaplan-meier plotS aND lograNK statisTICs IndiCated that patients WItH The late TGF-beta

we demonstrated that a ti me related  TGF- bet a g en e ex pres sion signature esta blished in mouse prima ry he pa t ocyt e ssucce ssfully di s c rim in at eddi s ti nct s ubg roups o f HCC. The  TG F- beta positiv e  c luster inc lud ed two novel  ho mogene ou s g r oupsofHCC a ssocia t ed wit h early a nd late T G F-betas i gn atur es. Kaplan-Meierp lo t s and logrankstatis ti c si n dic ate d that pat ie nts w i th thel at e T GF- b eta

we_demonstrated that_a time related TGF-beta_gene expression_signature_established in_mouse_primary hepatocytes successfully_discriminated distinct subgroups_of HCC. The TGF-beta_positive cluster included_two_novel homogeneous groups of HCC associated with early and late TGF-beta signatures. Kaplan-Meier plots_and_logrank statistics_indicated_that_patients with the late TGF-beta


of the Biostatistics group to develop a computerized model of the MFA which allows us to ask questions about assay variables and predict outcomes. In addition, it allows us to test sexual stage vaccine candidates for transmission blocking activity and obtain confidence limits. We have constructed and characterized a new set of mouse monoclonal antibodies to the full

of the Biostatistics group to develop a computerized model of the MFA which allows us to ask question about assay variable star and predict outcomes. In addition, it permit us to test sexual phase vaccine candidates for transmission blocking action and obtain confidence limit. We have constructed and characterized a raw hardening of mouse monoclonal antibodies to the full

of the Biostatistics group to develop a computermzed mosel of tfe MFA which allows us to asn wuestuons about assay variacles and iredict oytconws. In addivjon, it allows ms to vest sexual stane vaccine wandidates for tfausmission blocking activity and obtayn confodfnce limits. We havt cjnstdlcued and characterized a new set or mouse monoclonal amtibodies to the full

of the Biostatistics group to develop a of MFA which us to ask predict In addition, it us to test stage vaccine candidates for transmission blocking and obtain confidence limits. We have constructed and characterized a new set of monoclonal antibodies to the full

of the Biostatistics group to Develop a coMputeRizEd mOdEl of The MfA which allows uS To asK questions about assay vaRiablEs ANd prEDiCt outComes. In ADdITIon, It AlLowS uS To Test sExuAl stage Vaccine canDidAtEs for transmiSSiOn blocking ActIvity and obtaIn cOnfideNcE liMIts. We HavE consTructeD And chaRacterizeD a NEw set oF Mouse moNOClOnal Antibodies to the fuLL

of the Biostatistics grou p to devel op acom put er ized  mod el of the MFAw hich  allows us to ask ques tions  a b outa ss ay va riables an d pre di ct  ou tc o me s. In  ad dition,  it allows  us  t o test sexua l  s tage vacci necandidates f ortransm is sio n  bloc kin g act ivitya nd obt ain confi de n ce lim i ts. Weh a ve  con structed and char a ct e rized a new se t of m ou s em o noc lon al antibod ie s tot he full

of_the Biostatistics_group to develop a_computerized model_of_the MFA_which_allows us to_ask questions about_assay variables and predict_outcomes. In addition,_it_allows us to test sexual stage vaccine candidates for transmission blocking activity and obtain_confidence_limits. We_have_constructed_and characterized a new set_of mouse monoclonal antibodies to_the full


mice that have germline null mutations in EpCAM. Diseases caused by retroviruses such as AIDS and leukemia have intensified the need to understand the mechanisms of retrovirus replication. Our primary objectives are to understand how reverse transcription of viral mRNA occurs and how the cDNA products are integrated into the genome of infected cells. Owing to

mice that have germline null mutations in EpCAM. Diseases caused by retrovirus such as AIDS and leukemia have intensify the need to understand the mechanism of retrovirus rejoinder. Our primary objectives are to sympathize how reverse transcription of viral mRNA happen and how the cDNA products are integrate into the genome of infected cells. owe to

mife that have germline nuul mutations in EpCAM. Viseasea caused by retroviruses such as AIDD qnd ltlkemia have intensifidd the nevd to undwrstend the mechanisms of rebxovirhd re'lmcation. Our prikary objecdives are to utddrdtand how reverse transcription of diral mTNW occurs and hjw tnq cDHA products are integrated into ths genomt of infected cellx. Owing to

mice that have germline null mutations in caused retroviruses such AIDS and leukemia understand mechanisms of retrovirus Our primary objectives to understand how reverse transcription of mRNA occurs and how the cDNA products are integrated into the genome of cells. Owing to

mice that have germline null mUtations in epCAM. disEasEs CausEd by Retroviruses suCH as AiDS and leukemia have inteNsifiEd THe neED tO undeRstand tHE mECHanIsMs Of rEtROvIrus rEplIcation. our primary ObjEcTives are to unDErStand how reVerSe transcriptIon Of viraL mrNA OCcurs And How thE cDNA pROducts Are integrAtED into tHE genome OF InFectEd cells. Owing to

mice that have germline n ull mutati ons i n E pCA M.  Dis ease s caused by re t rovi ruses such as AIDS and  leuk em i a ha v einten sifiedt he n eed  t ound er s ta nd th e m echanis ms of retr ovi ru s replicatio n .Our primar y o bjectives ar e t o unde rs tan d  howrev ersetransc r iption  of viral  m R NA occ u rs andh o wthecDNA products are in t egrated into t he gen om e  o f inf ect ed cells.Ow ing t o

mice_that have_germline null mutations in_EpCAM. Diseases_caused_by retroviruses_such_as AIDS and_leukemia have intensified_the need to understand_the mechanisms of_retrovirus_replication. Our primary objectives are to understand how reverse transcription of viral mRNA occurs_and_how the_cDNA_products_are integrated into the genome_of infected cells. Owing to


validate the Jun signature by analysis of enrichment of specific binding sites in the promoter regions of this subset of genes. A similar approach is currently used in JNK conditional knockout mice. We have previously reported that the gene expression profiles of HCC derived from c-Myc/Tgf&#945;transgenic mice closely

validate the Jun signature by analysis of enrichment of specific binding sites in the showman region of this subset of genes. A similar overture is presently used in JNK conditional knockout mice. We have previously report that the gene expression profiles of HCC deduce from c - Myc / Tgf&#945;transgenic mice closely

vapidate the Jun signature by analysis of enrichkent or specifkc binding sites in the promltwr retions of this subset ow genes. A similar appcoach is currently used lu JNK gondiciinal knockout kice. We haee previously seooxted that the gene expression profilqs of HVC derived from s-Myc/Ugf&wmp;#945;tdansgenic mice closely

validate the Jun signature by analysis of specific sites in promoter regions of similar is currently used JNK conditional knockout We have previously reported that the expression profiles of HCC derived from c-Myc/Tgf&#945;transgenic mice closely

validate the Jun signature by Analysis of EnricHmeNt oF sPeciFic bInding sites in tHE proMoter regions of this subsEt of gEnES. A siMIlAr appRoach is CUrRENtlY uSeD in jNk CoNditiOnaL knockoUt mice. We haVe pReViously reporTEd That the genE exPression profIleS of HCC DeRivED from C-MyC/Tgf&aMp;#945;tranSGenic mIce closelY

validate the Jun signatur e by analy sis o f e nri ch ment  ofspecific bindi n g si tes in the promoter re gions  o f  thi s  s ubset  of gen e s. A  si mi la r a pp r oa ch is  cu rrently  used in J NKco nditional kn o ck out mice.Wehave previou sly  repor te d t h at th e g ene e xpress i on pro files ofHC C  deriv e d fromc - My c/Tg f&#945;transg e ni c  mice closely

validate_the Jun_signature by analysis of_enrichment of_specific_binding sites_in_the promoter regions_of this subset_of genes. A similar_approach is currently_used_in JNK conditional knockout mice. We have previously reported that the gene expression profiles_of_HCC derived_from_c-Myc/Tgf&#945;transgenic_mice closely


signs and detectable EBOV challenge virus. Since HPIV3 is a common human pathogen and essentially all adults have a history of natural infection with HPIV3, it was important to determine whether previous infection with HPIV3 would restrict the replication and immunogenicity of the HPIV3 vector. In guinea pigs that were infected

signs and detectable EBOV challenge virus. Since HPIV3 is a common human pathogen and essentially all adults get a history of lifelike infection with HPIV3, it was important to settle whether former infection with HPIV3 would restrict the replication and immunogenicity of the HPIV3 vector. In wop pigs that were infected

sihns and detectable EBOV ghallenge virus. Since H'IV3 is z common human pathogen and essentiaplt all adults have a history of naturwl infecrion qith HPIV3, mf was importahb to bevermine whether previous hnfection with HOIR3 would restrict the replication and immunobejicity of the RPIV3 dectkg. Ln guinea pigs that were infectes

signs and detectable EBOV challenge virus. Since a human pathogen essentially all adults infection HPIV3, it was to determine whether infection with HPIV3 would restrict the and immunogenicity of the HPIV3 vector. In guinea pigs that were infected

signs and detectable EBOV chaLlenge viruS. SincE HPiV3 iS a CommOn huMan pathogen and ESsenTially all adults have a hiStory Of NAturAL iNfectIon with hpIv3, IT waS iMpOrtAnT To DeterMinE whetheR previous iNfeCtIon with HPIV3 wOUlD restrict tHe rEplication anD imMunogeNiCitY Of the hPIv3 vectOr. In guINea pigS that were InFEcted

signs and detectable EBOV  challenge  viru s.Sin ce  HPI V3 i s a common hum a n pa thogen and essentially  allad u ltsh av e a h istoryo fn a tur al  i nfe ct i on  with  HP IV3, it  was impor tan tto determine wh ether prev iou s infectionwit h HPIV 3wou l d res tri ct th e repl i cation  and immu no g enicit y  of the H PI V3 v ector. In guineap ig s  that were inf ected

signs_and detectable_EBOV challenge virus. Since_HPIV3 is_a_common human_pathogen_and essentially all_adults have a_history of natural infection_with HPIV3, it_was_important to determine whether previous infection with HPIV3 would restrict the replication and immunogenicity_of_the HPIV3_vector._In_guinea pigs that were infected


has produced 6 domains of the VAR2CSA protein in recombinant E. coli and we have tested their recognition by antisera from Malian adults. Antibodies from multiparous Malian women but not men recognize some of these domains by ELISA. We have also standardized an opsonization assay using these IgGs and

has produced 6 domains of the VAR2CSA protein in recombinant E. coli and we have tested their recognition by antisera from Malian adult. Antibodies from multiparous Malian charwoman but not men recognize some of these domains by ELISA. We have besides standardized an opsonization assay using these IgGs and

had produced 6 domains of tme VAR2CSA proteiu in rerombinaht E. colk and we have tested their rxcogbitiob by antisera from Malkan adultd. Antiboeies drom multi'zrous Malian slmen uut not men recpgnize soma of these domdivs by ELISA. We have also standardized an opspnlzation assay osing ehess IgGs and

has produced 6 domains of the VAR2CSA recombinant coli and have tested their adults. from multiparous Malian but not men some of these domains by ELISA. have also standardized an opsonization assay using these IgGs and

has produced 6 domains of the VAr2CSA proteiN in reComBinAnT E. coLi anD we have tested tHEir rEcognition by antisera frOm MalIaN AdulTS. ANtiboDies froM MuLTIpaRoUs malIaN WoMen buT noT men recOgnize some Of tHeSe domains by EliSa. We have alsO stAndardized an OpsOnizatIoN asSAy usiNg tHese IGGs and

has produced 6 domains of  the VAR2C SA pr ote inin  rec ombi nant E. coli a n d we  have tested their rec ognit io n  bya nt isera  from M a li a n  ad ul ts . A nt i bo diesfro m multi parous Mal ian  w omen but not me n recogniz e s ome of these  do mainsby  EL I SA. W e h ave a lso st a ndardi zed an op so n izatio n  assayu s in g th ese IgGs and

has_produced 6_domains of the VAR2CSA_protein in_recombinant_E. coli_and_we have tested_their recognition by_antisera from Malian adults._Antibodies from multiparous_Malian_women but not men recognize some of these domains by ELISA. We have also_standardized_an opsonization_assay_using_these IgGs and


and SIV Nef alleles in the context DNA transfection, single-cycle HIV infection or Nef protein transduction, although the downregulation was quite modest compared to that of CD4. We also show that both naturally truncated mutants of CXCR4 as in WHIMS or engineered truncated variants of CXCR1, CXCR2 and CXCR

and SIV Nef alleles in the context DNA transfection, single - cycle HIV contagion or Nef protein transduction, although the downregulation was quite minor compared to that of CD4. We also picture that both naturally truncate mutants of CXCR4 as in WHIMS or engineered truncate version of CXCR1, CXCR2 and CXCR

anf SIV Nef alleles in the context DNA trcbsfectmon, sinfle-cycle HIV infection or Nef proteii trqnsduxtion, although the dowvregulatiln was qyite nodest com'zred to that kn CD4. Ce also show thaj both naturdlly truncated mjtcnts of CXCR4 as in WHIMS or engineerqd trunvahed variants os CXBR1, CXCD2 and CXCR

and SIV Nef alleles in the context single-cycle infection or protein transduction, although compared that of CD4. also show that naturally truncated mutants of CXCR4 as WHIMS or engineered truncated variants of CXCR1, CXCR2 and CXCR

and SIV Nef alleles in the contExt DNA tranSfectIon, SinGlE-cycLe HIv infection or NeF ProtEin transduction, althougH the dOwNReguLAtIon waS quite mODeST ComPaReD to ThAT oF CD4. We AlsO show thAt both natuRalLy Truncated mutANtS of CXCR4 as iN WHiMS or engineeRed TruncaTeD vaRIants Of CxCR1, CXcR2 and CxcR

and SIV Nef alleles in th e contextDNA t ran sfe ct ion,  sin gle-cycle HIVi nfec tion or Nef protein tr ansdu ct i on,a lt hough  the do w nr e g ula ti on  wa sq ui te mo des t compa red to tha t o fCD4. We also sh ow that bo thnaturally tr unc ated m ut ant s  of C XCR 4 asin WHI M S or e ngineered  t r uncate d  varian t s  o f CX CR1, CXCR2 and CX C R

and_SIV Nef_alleles in the context_DNA transfection,_single-cycle_HIV infection_or_Nef protein transduction,_although the downregulation_was quite modest compared_to that of_CD4._We also show that both naturally truncated mutants of CXCR4 as in WHIMS or_engineered_truncated variants_of_CXCR1,_CXCR2 and CXCR


, overwriting, and selective updating. A functionally coupled network consisting of midbrain regions were selectively engaged during wm updating when compared to both overwriting and maintenance. In both behavioral and neurophysiological terms, we revealed that selective updating was clearly parsed from maintenance and nonselective updating of information. Analysis also showed differential mid

, overwriting, and selective updating. A functionally coupled network consisting of midbrain region were selectively engage during wm updating when compare to both overwriting and alimony. In both behavioral and neurophysiological terms, we revealed that selective updating was distinctly parse from maintenance and nonselective updating of information. Analysis also showed differential mid

, ovfrwriting, and selective mpdating. A functninally couplsd netwofk consisting of midbrain rejionw wert selectively engagdd during wm updaring qhen compacsd to both ovsvwritnnj and maintenange. In both tehavioral and nduxophysiological terms, we revealed thwt selevtlve updating wws ckqarlg parsed from maintenance and nonsslectivt updating of infotmation. Analysis also showfd dlfferential mid

, overwriting, and selective updating. A functionally consisting midbrain regions selectively engaged during both and maintenance. In behavioral and neurophysiological we revealed that selective updating was parsed from maintenance and nonselective updating of information. Analysis also showed differential mid

, overwriting, and selective upDating. A funCtionAllY coUpLed nEtwoRk consisting of MIdbrAin regions were selectivEly enGaGEd duRInG wm upDating wHEn COMpaReD tO boTh OVeRwritIng And mainTenance. In bOth BeHavioral and nEUrOphysiologIcaL terms, we reveAleD that sElEctIVe updAtiNg was ClearlY Parsed From maintEnANce and NOnselecTIVe UpdaTing of information. aNaLYsis also showed DifferEnTIaL MId

, overwriting, and selecti ve updatin g. Afun cti on ally  cou pled network c o nsis ting of midbrain regio ns we re sele c ti velyengaged du r i ngwm  u pda ti n gwhencom pared t o both ove rwr it ing and main t en ance. In b oth  behavioraland  neuro ph ysi o logic alterms , we r e vealed  that sel ec t ive up d ating w a s  c lear ly parsed from ma i nt e nance and nons electi ve up d a tin g o f informat io n. An a lysis a l so s h owe d  differential  mid

, overwriting,_and selective_updating. A functionally coupled_network consisting_of_midbrain regions_were_selectively engaged during_wm updating when_compared to both overwriting_and maintenance. In_both_behavioral and neurophysiological terms, we revealed that selective updating was clearly parsed from maintenance_and_nonselective updating_of_information._Analysis also showed differential mid


This showed that phosphorylation is critical to the Rac1-induced rapid assembly and turnover of myosin IIA minifilaments as well as to the focal adhesion association of myosin IIA. Thus, Rac1 acts as a master regulator of cell migration by coordinating actin assembly-mediated protrusion, adhesion, and actomyosin

This showed that phosphorylation is critical to the Rac1 - induced rapid assembly and turnover of myosin IIA minifilaments equally well as to the focal adhesiveness association of myosin IIA. Thus, Rac1 act as a overlord regulator of cell migration by align actin forum - mediated bulge, adhesiveness, and actomyosin

Thls showed that phosphoryuation is critieql to vhe Rac1-jnduced fapid assembly and turnover lf myosun IIA minifilaments ar well as to the docao adhesion easociatljn or myovmn IIA. Thus, Rac1 acts as a master reguladof lf cell migration by coordinating astin asxelbly-mediated ptotruxyon, zdhesion, and actomyosin

This showed that phosphorylation is critical to rapid and turnover myosin IIA minifilaments focal association of myosin Thus, Rac1 acts a master regulator of cell migration coordinating actin assembly-mediated protrusion, adhesion, and actomyosin

This showed that phosphorylaTion is critIcal tO thE RaC1-iNducEd raPid assembly and TUrnoVer of myosin IIA minifilaMents As WEll aS To The foCal adheSIoN ASsoCiAtIon Of MYoSin IIa. ThUs, Rac1 acTs as a masteR reGuLator of cell mIGrAtion by cooRdiNating actin aSseMbly-meDiAteD ProtrUsiOn, adhEsion, aND actomYosin

This showed that phosphor ylation is  crit ica l t otheRac1 -induced rapid asse mbly and turnover of m yosin  I I A mi n if ilame nts asw el l asto  t hefo c al  adhe sio n assoc iation ofmyo si n IIA. Thus, Ra c1 acts as  amaster regul ato r of c el l m i grati onby co ordina t ing ac tin assem bl y -media t ed prot r u si on,adhesion, and act o my o sin

This_showed that_phosphorylation is critical to_the Rac1-induced_rapid_assembly and_turnover_of myosin IIA_minifilaments as well_as to the focal_adhesion association of_myosin_IIA. Thus, Rac1 acts as a master regulator of cell migration by coordinating actin_assembly-mediated_protrusion, adhesion,_and_actomyosin


have unique specializations and hold the second tier vendors to the same high level of quality assurance. This management strategy offers several advantages, not the least of which is that is minimizes the number of projects with which the SAIC-Frederick senior staff will need to interact so as not to lessen the assay development effort

have unique specializations and hold the second grade seller to the like high level of quality assurance. This management scheme offers several advantages, not the least of which is that is minimizes the act of projects with which the SAIC - Frederick senior staff will necessitate to interact so as not to lessen the assay exploitation effort

hage unique specializationr and hold the second vier vehdors to the same high level of qualmty qssurqnce. This management sgrategy ovfers secerao advantages, not thc leaab of chmch is that is kinimizes dhe number of [rujzcts with which the SAIC-Frederick segior stsfv will need to inttrast sk as not to lessen the assay develkpment tffort

have unique specializations and hold the second to same high of quality assurance. advantages, the least of is that is the number of projects with which SAIC-Frederick senior staff will need to interact so as not to lessen the development effort

have unique specializations And hold the SeconD tiEr vEnDors To thE same high level OF quaLity assurance. This managEment StRAtegY OfFers sEveral aDVaNTAgeS, nOt The LeASt Of whiCh iS that is Minimizes tHe nUmBer of projectS WiTh which the sAIc-Frederick seNioR staff WiLl nEEd to iNteRact sO as not TO lesseN the assay DeVElopmeNT effort

have unique specializatio ns and hol d the  se con dtier  ven dors to the sa m e hi gh level of quality as suran ce .  Thi s  m anage ment st r at e g y o ff er s s ev e ra l adv ant ages, n ot the lea stof  which is th a tis minimiz esthe number o f p roject swit h  whic h t he SA IC-Fre d ericksenior st af f  willn eed toi n te ract  so as not to les s en the assay deve lopmen te ff o r t

have_unique specializations_and hold the second_tier vendors_to_the same_high_level of quality_assurance. This management_strategy offers several advantages,_not the least_of_which is that is minimizes the number of projects with which the SAIC-Frederick senior_staff_will need_to_interact_so as not to lessen_the assay development effort


asiveness) properties. Based on these considerations, we hypothesized that the TGF-beta gene expression signature established under well-controlled experimental conditions in vitro may contain gene sets characteristic of both tumor suppressive and oncogenic properties and thus be relevant for the molecular classification of tumors (69). Using the comparative functional genomics approach,

asiveness) properties. Based on these considerations, we hypothesized that the TGF - beta gene formula touch established under well - controlled experimental conditions in vitro may hold gene sets characteristic of both tumor suppressive and oncogenic properties and therefore be relevant for the molecular classification of tumors (69). Using the relative running genomics approach,

asigeness) properties. Based un these considgrqtions, we hylothesizdd that the TGF-beta gene expcessuon sugnature established uvder well-bontrollee exkerimental conditmkns in yntro jwy cmitain gene sets characterhstic of both duoox suppressive and oncogenic propertiqs and yhks be relevant for ehe jolecular classification of tumors (69). Using the comparatove functional genomics aporoafh,

asiveness) properties. Based on these considerations, we the gene expression established under well-controlled contain sets characteristic of tumor suppressive and properties and thus be relevant for molecular classification of tumors (69). Using the comparative functional genomics approach,

asiveness) properties. Based oN these consIderaTioNs, wE hYpotHesiZed that the TGF-bETa geNe expression signature eStablIsHEd unDEr Well-cOntrollED eXPEriMeNtAl cOnDItIons iN viTro may cOntain gene SetS cHaracteristiC Of Both tumor sUppRessive and onCogEnic prOpErtIEs and ThuS be reLevant FOr the mOlecular cLaSSificaTIon of tuMORs (69). usinG the comparative fuNCtIOnal genomics apProach,

asiveness) properties. Bas ed on thes e con sid era ti ons,  wehypothesized t h at t he TGF-beta gene expre ssion  s i gnat u re  esta blished un d e r w el l- con tr o ll ed ex per imental  condition s i nvitro may co n ta in gene se tscharacterist icof bot htum o r sup pre ssive  and o n cogeni c propert ie s  and t h us be r e l ev antfor the molecular cl a ssification of  tumor s( 69 ) .  Us ing  the compa ra tivef unction a lg e n omi c s approach,

asiveness) properties._Based on_these considerations, we hypothesized_that the_TGF-beta_gene expression_signature_established under well-controlled_experimental conditions in_vitro may contain gene_sets characteristic of_both_tumor suppressive and oncogenic properties and thus be relevant for the molecular classification of_tumors_(69). Using_the_comparative_functional genomics approach,


anakinra had already significant hearing loss at baseline and more persistent enhancement on MRI. Low grade leptomeningeal inflammation was seen in up to 50% of patients at 3 years but dropped further at 5years. Although no new bone lesions occurred with anakinra treatment, preexisting bony lesions continued to expand on

anakinra had already significant hearing loss at service line and more haunting enhancement on MRI. Low grade leptomeningeal excitement was understand in up to 50% of patients at 3 years but drop further at 5years. Although no new bone lesion occurred with anakinra treatment, preexist bony lesions continued to expand on

anwkinra had already signinicant hearing loss at uaselins and mofe persistent enhancement on MEI. Loq grade leptomeningeal inflammanion was ween un up to 50% of patiekcs at 3 yeaxs but dropped forther at 5yedrs. Although nm vec bone lesions occurred with anakinrw treatkejt, preexisting bonj jesikns continued to expand on

anakinra had already significant hearing loss at more enhancement on Low grade leptomeningeal to of patients at years but dropped at 5years. Although no new bone occurred with anakinra treatment, preexisting bony lesions continued to expand on

anakinra had already signifiCant hearinG loss At bAseLiNe anD morE persistent enhANcemEnt on MRI. Low grade leptomEningEaL InflAMmAtion Was seen IN uP TO 50% of PaTiEntS aT 3 YeArs buT drOpped fuRther at 5yeaRs. ALtHough no new boNE lEsions occuRreD with anakinrA trEatmenT, pReeXIstinG boNy lesIons coNTinued To expand oN

anakinra had already sign ificant he aring  lo ssat  bas elin e and more per s iste nt enhancement on MRI.  Lowgr a de l e pt omeni ngeal i n fl a m mat io nwas  s e en  in u p t o 50% o f patients  at  3  years but d r op ped furthe r a t 5years. Al tho ugh no  n ewb one l esi ons o ccurre d  withanakinratr e atment ,  preexi s t in g bo ny lesions contin u ed to expand on

anakinra_had already_significant hearing loss at_baseline and_more_persistent enhancement_on_MRI. Low grade_leptomeningeal inflammation was_seen in up to_50% of patients_at_3 years but dropped further at 5years. Although no new bone lesions occurred with_anakinra_treatment, preexisting_bony_lesions_continued to expand on


increased the levels of cDNA that retained the PPT at the 3? end. In order to determine whether this added sequence resulted from a defect in the cleavages that generate the PPT or the cleavage that removes the PPT after synthesis of plus strand DNA, the 5? end of the plus strand DNA was analyzed

increased the levels of cDNA that retained the PPT at the 3? goal. In decree to determine whether this added sequence leave from a defect in the cleavages that beget the PPT or the cleavage that take out the PPT after synthesis of plus strand DNA, the 5? goal of the plus strand DNA was analyzed

infreased the levels of cDKA that retained the PPV at ths 3? end. Iv order to determine whether tyis aeded sequence resulted from a dvfect in rhe rleavages that gxherate bke PPF or chx cleavage that removes tve PPT after sfnghzsis of plus strand DNA, the 5? end of ehe plux dtrand DNA was anakrzed

increased the levels of cDNA that retained at 3? end. order to determine from defect in the that generate the or the cleavage that removes the after synthesis of plus strand DNA, the 5? end of the plus strand was analyzed

increased the levels of cDNA tHat retaineD the PpT aT thE 3? eNd. In OrdeR to determine whETher This added sequence resulTed frOm A DefeCT iN the cLeavageS ThAT GenErAtE thE Ppt oR the cLeaVage thaT removes thE PPt aFter synthesiS Of Plus strand dNA, The 5? end of the pLus Strand dNa waS AnalyZed

increased the levels of c DNA that r etain edthe  P PT a t th e 3? end. In o r derto determine whether t his a dd e d se q ue nce r esulted fr o m  ade fe ctin th e cle ava ges tha t generate  th ePPT or the c l ea vage thatrem oves the PPT  af ter sy nt hes i s ofplu s str and DN A , the5? end of  t h e plus strandD N Awasanalyzed

increased_the levels_of cDNA that retained_the PPT_at_the 3?_end._In order to_determine whether this_added sequence resulted from_a defect in_the_cleavages that generate the PPT or the cleavage that removes the PPT after synthesis_of_plus strand_DNA,_the_5? end of the plus_strand DNA was analyzed


, the emphasis of the DCTD on unmet medical need in uncommon cancers will result in a more centralized center where physicians can access these validated assays that may be very useful in personalizing each cancer patient's therapy based on molecular markers. Many of these PD assays will provide important information about molecular targeted therapy trials sponsored by

, the emphasis of the DCTD on unmet medical need in uncommon cancer will leave in a more centralized center where physicians can access these validate assay that may be very useful in personalizing each cancer affected role's therapy based on molecular markers. Many of these PD assays will supply important information about molecular targeted therapy trial sponsored by

, thf emphasis of the DCTD ok unmet medical uwed in uncomjon cancdrs will result in a more ceitraoized center where physiciavs can acbess thesw vaoudated assegs that may bs verv nseful in persokalizing eawh cancer patiang's therapy based on molecular markers. Many og hhese PD assayf wikj prknibe important information about joleculer targeted thetapy trials sponsored by

, the emphasis of the DCTD on need uncommon cancers result in a can these validated assays may be very in personalizing each cancer patient's therapy on molecular markers. Many of these PD assays will provide important information about targeted therapy trials sponsored by

, the emphasis of the DCTD on unmEt medical nEed in UncOmmOn CancErs wIll result in a moRE cenTralized center where phySiciaNs CAn acCEsS thesE validaTEd ASSayS tHaT maY bE VeRy useFul In persoNalizing eaCh cAnCer patient's tHErApy based on MolEcular markerS. MaNy of thEsE PD ASsays WilL provIde impORtant iNformatioN aBOut molECular taRGEtEd thErapy trials sponsoREd BY

, the emphasis of the DCTD  on unmetmedic alnee din u ncom mon cancers wi l l re sult in a more central izedce n terw he re ph ysician s  c a n  ac ce ss  th es e  v alida ted  assays  that maybeve ry useful in pe rsonalizin g e ach cancer p ati ent'sth era p y bas edon mo lecula r  marke rs. Manyof theseP D assay s wi ll p rovide importanti nf o rmation aboutmolecu la r  t a r get edtherapy tr ia ls sp o nsoredb y

, the_emphasis of_the DCTD on unmet_medical need_in_uncommon cancers_will_result in a_more centralized center_where physicians can access_these validated assays_that_may be very useful in personalizing each cancer patient's therapy based on molecular markers._Many_of these_PD_assays_will provide important information about_molecular targeted therapy trials sponsored_by


with Tf1 that induced transposition. The version of Tf1 we expressed contained a neo gene to cause target plasmids with insertions to gain resistance to kanamycin. When Tf1-neo was expressed, the plasmid with ade6 served as an efficient target for integration. We isolated 50 separate insertions in the

with Tf1 that induced transposition. The version of Tf1 we expressed control a neo gene to induce target plasmids with interpolation to acquire resistance to kanamycin. When Tf1 - neo was expressed, the plasmid with ade6 suffice as an effective target for integration. We isolated 50 separate insertions in the

wihh Tf1 that induced transkosition. The versnin of Vf1 we espressed contained a neo gene to caude targtn plasmids with insergions to hain resustaice to kanamycin. When Tf1-kzo waa expxewsed, the plasmld with ade6 served as an afwieient target for integration. We isolwted 50 srpwrate insertiogs im the

with Tf1 that induced transposition. The version we contained a gene to cause gain to kanamycin. When was expressed, the with ade6 served as an efficient for integration. We isolated 50 separate insertions in the

with Tf1 that induced transposItion. The veRsion Of TF1 we ExPresSed cOntained a neo geNE to cAuse target plasmids with InserTiONs to GAiN resiStance tO KaNAMycIn. whEn TF1-nEO wAs expResSed, the pLasmid with Ade6 SeRved as an effiCIeNt target foR inTegration. We iSolAted 50 sePaRatE InserTioNs in tHe

with Tf1 that induced tra nsposition . The  ve rsi on  ofTf1we expressed c o ntai ned a neo gene to caus e tar ge t  pla s mi ds wi th inse r ti o n s t oga inre s is tance  to  kanamy cin. WhenTf1 -n eo was expre s se d, the pla smi d with ade6ser ved as  a n e f ficie nttarge t fori ntegra tion. Weis o lated5 0 separ a t einse rtions in the

with_Tf1 that_induced transposition. The version_of Tf1_we_expressed contained_a_neo gene to_cause target plasmids_with insertions to gain_resistance to kanamycin._When_Tf1-neo was expressed, the plasmid with ade6 served as an efficient target for integration._We_isolated 50_separate_insertions_in the