arenicline. Combining varenicline with zonisamide, an antiepileptic medication that has been associated with smoking reduction, may produce higher smoking quit rates compared to varenicline alone. The information collected from this study will be important for understanding whether combination medication treatments (like varenicline

arenicline. Combining varenicline with zonisamide, an antiepileptic medication that has been associated with smoking decrease, may grow higher smoking quit pace compare to varenicline alone. The information collect from this sketch will be important for understand whether combination medication treatments (like varenicline

arejicline. Combining varenigline with zoniscnide, ai antielileptic medication that has been asdoxiatee with smoking reductiun, may prlduce hither wmoking qumf rates compadcd to tarenicline aloke. The infosmation collecdea yrom this study will be important fow underxtwnding whether comnynatjon medication treatments (like varsniclint

arenicline. Combining varenicline with zonisamide, an antiepileptic has associated with reduction, may produce to alone. The information from this study be important for understanding whether combination treatments (like varenicline

arenicline. Combining vareniCline with zOnisaMidE, an AnTiepIlepTic medication tHAt haS been associated with smoKing rEdUCtioN, MaY prodUce highER sMOKinG qUiT raTeS CoMpareD to VarenicLine alone. THe iNfOrmation collECtEd from this StuDy will be impoRtaNt for uNdErsTAndinG whEther CombinATion meDication tReATments (LIke vareNIClIne

arenicline. Combining vare nicline wi th zo nis ami de , an  ant iepileptic med i cati on that has been assoc iated  w i th s m ok ing r eductio n ,m a y p ro du cehi g he r smo kin g quitrates comp are dto varenicli n ealone. The  in formation co lle cted f ro m t h is st udy  will  be im p ortant  for unde rs t anding whether c om bina tion medication t r ea t ments (like va renicl in e

arenicline. Combining_varenicline with_zonisamide, an antiepileptic medication_that has_been_associated with_smoking_reduction, may produce_higher smoking quit_rates compared to varenicline_alone. The information_collected_from this study will be important for understanding whether combination medication treatments (like varenicline


physical activity and healthy eating in YMCA OST programs. Angiogenesis, the formation of new blood vessels, is a key element of a number of normal and pathological processes. Whereas vascularization is a primary event associated with normal embryogenesis and wound healing, neovascularization is of central importance also n a variety

physical activity and healthy eating in YMCA OST programs. Angiogenesis, the constitution of newfangled blood vessels, is a key component of a number of normal and pathological process. Whereas vascularization is a elementary event associated with normal embryogenesis and wound healing, neovascularization is of central importance also n a kind

phjsical activity and healuhy eating in YMCC OST pcograms. Angiogevesis, the formation of new bpoid vewsels, is a key element of a numher of nirmao and pathological ixocesacs. Whzrxas vascularizajion is a prhmary event asvozicted with normal embryogenesis and wjund hesllng, neovasculatizatpog is of central importance also n a vadiety

physical activity and healthy eating in YMCA Angiogenesis, formation of blood vessels, is number normal and pathological Whereas vascularization is primary event associated with normal embryogenesis wound healing, neovascularization is of central importance also n a variety

physical activity and healthY eating in YmCA OSt prOgrAmS. AngIogeNesis, the formatIOn of New blood vessels, is a key eLemenT oF A numBEr Of norMal and pAThOLOgiCaL pRocEsSEs. whereAs vAscularIzation is a PriMaRy event assocIAtEd with normAl eMbryogenesis And Wound hEaLinG, NeovaScuLarizAtion iS Of centRal importAnCE also n A Variety

physical activity and hea lthy eatin g inYMC A O ST  pro gram s. Angiogenesi s , th e formation of new blo od ve ss e ls,i sa key  elemen t  o f a n um be r o fn or mal a ndpatholo gical proc ess es . Whereas va s cu larization  is  a primary e ven t asso ci ate d  with  no rmalembryo g enesis  and woun dh ealing ,  neovas c u la riza tion is of centra l  i m portance alson a va ri e ty

physical_activity and_healthy eating in YMCA_OST programs._Angiogenesis,_the formation_of_new blood vessels,_is a key_element of a number_of normal and_pathological_processes. Whereas vascularization is a primary event associated with normal embryogenesis and wound healing,_neovascularization_is of_central_importance_also n a variety


addressed, 3) to maintain and enhance internal communication and cooperation among MCRC members and to promote novel approaches to address clinically relevant issues, and 4) to expand the influence of the MCRC within the institution and to identify and secure institutional support to promote and enhance the activities of the Center. The Administrative Core will be housed

addressed, 3) to maintain and enhance internal communication and cooperation among MCRC members and to advertise fresh approach to address clinically relevant topic, and 4) to inflate the influence of the MCRC within the institution and to identify and plug institutional accompaniment to promote and enhance the activity of the Center. The Administrative Core will be housed

adfressed, 3) to maintain and enhance internco commnnicatikn and cuoperation among MCRC memberd qnd ti promote novel approazhes to afdress coinirally relevant issues, and 4) to swpand vhe influence on the MCRC fithin the insdigucion and to identify and secure instytutionsl support to prjmott agd ehhance the activities of the Cented. The Avministrative Cpre will be housed

addressed, 3) to maintain and enhance internal cooperation MCRC members to promote novel issues, 4) to expand influence of the within the institution and to identify secure institutional support to promote and enhance the activities of the Center. The Core will be housed

addressed, 3) to maintain and enhAnce internAl comMunIcaTiOn anD cooPeration among McrC meMbers and to promote novel ApproAcHEs to ADdRess cLinicalLY rELEvaNt IsSueS, aND 4) tO expaNd tHe influEnce of the McRC WiThin the instiTUtIon and to idEntIfy and secure InsTitutiOnAl sUPport To pRomotE and enHAnce thE activitiEs OF the CeNTer. The ADMInIstrAtive Core will be hoUSeD

addressed, 3) to maintain  and enhan ce in ter nal  c ommu nica tion and coope r atio n among MCRC members a nd to  p r omot e  n ovelapproac h es t o a dd re sscl i ni cally  re levantissues, an d 4 )to expand th e  i nfluence o f t he MCRC with inthe in st itu t ion a ndto id entify and se cure inst it u tional support t oprom ote and enhance t h ea ctivities of t he Cen te r .T h e A dmi nistrative  C ore w i ll be h o us e d

addressed,_3) to_maintain and enhance internal_communication and_cooperation_among MCRC_members_and to promote_novel approaches to_address clinically relevant issues,_and 4) to_expand_the influence of the MCRC within the institution and to identify and secure institutional_support_to promote_and_enhance_the activities of the Center._The Administrative Core will be_housed


and older adults. Concerns about obesity and physical inactivity and their links to the onset, complications, and societal costs of diabetes have led to public health mandates at the national level-such as those included in Healthy People 2010-aimed at reversing those trends. Although prevention of diabetes is certainly an important goal,

and older adults. Concerns about obesity and forcible inaction and their links to the onset, complication, and social costs of diabetes have led to public health mandates at the home horizontal surface - such as those included in Healthy People 2010 - aim at reversing those trends. Although prevention of diabetes is surely an important goal,

anf older adults. Concerns xbout obesity aue physmcal inzctivity and their links to the onsev, conplicqtions, and societal corts of diwbetes hqve owd to publmd healtm manswtes et the national level-such as those inclgddd in Healthy People 2010-aimed at reversigg thosr hrends. Althougr prtvegtioh of diabetes is certainly an impodtant gmal,

and older adults. Concerns about obesity and and links to onset, complications, and led public health mandates the national level-such those included in Healthy People 2010-aimed reversing those trends. Although prevention of diabetes is certainly an important goal,

and older adults. Concerns aboUt obesity aNd phySicAl iNaCtivIty aNd their links to THe onSet, complications, and socIetal CoSTs of DIaBetes Have led TO pUBLic HeAlTh mAnDAtEs at tHe nAtional Level-such aS thOsE included in HEAlThy People 2010-aImeD at reversing ThoSe trenDs. altHOugh pRevEntioN of diaBEtes is Certainly An IMportaNT goal,

and older adults. Concern s about ob esity  an d p hy sica l in activity and t h eirlinks to the onset, co mplic at i ons, an d soc ietal c o st s ofdi ab ete sh av e led  to  public  health ma nda te s at the nat i on al level-s uch  as those in clu ded in  H eal t hy Pe opl e 201 0-aime d  at re versing t ho s e tren d s. Alth o u gh  pre vention of diabet e si s certainly an  impor ta n tg o al,

and_older adults._Concerns about obesity and_physical inactivity_and_their links_to_the onset, complications,_and societal costs_of diabetes have led_to public health_mandates_at the national level-such as those included in Healthy People 2010-aimed at reversing those_trends._Although prevention_of_diabetes_is certainly an important goal,


describing organelle translocations in hepatocytes during regeneration; studying hormone effects of functioning islet cells on hepatic ultrastructure; studying the uptake and transport of asialoglycoproteins in hepatocytes; localizing apo-protein B and A-I using immunocytochemistry in rat hepatocytes and absorbtive cells of the intestine;

describing organelle translocations in hepatocytes during regeneration; studying hormone effect of officiate islet cells on hepatic ultrastructure; studying the consumption and transport of asialoglycoproteins in hepatocytes; localizing apo - protein B and A - I using immunocytochemistry in scab hepatocytes and absorbtive cells of the intestine;

dedcribing organelle transuocations in hekarocytev durihg regendration; studying hormone effxcts of fynctioning islet cells on hepatpc ultrasrrucuure; studying the uptake and trzksporc if asialoglycokroteins in vepatocytes; lowauiving apo-protein B and A-I using immunjcytochrmlstry in rat hgpatobyees znd absorbtive cells of the intestjne;

describing organelle translocations in hepatocytes during regeneration; effects functioning islet on hepatic ultrastructure; of in hepatocytes; localizing B and A-I immunocytochemistry in rat hepatocytes and absorbtive of the intestine;

describing organelle translOcations in HepatOcyTes DuRing RegeNeration; studyiNG horMone effects of functioniNg islEt CElls ON hEpatiC ultrasTRuCTUre; StUdYinG tHE uPtake And TranspoRt of asialoGlyCoProteins in hePAtOcytes; locaLizIng apo-proteiN B aNd A-I usInG imMUnocyTocHemisTry in rAT hepatOcytes and AbSOrbtivE Cells of THE iNtesTine;

describing organelle tran slocations  in h epa toc yt es d urin g regeneration ;  stu dying hormone effectsof fu nc t ioni n gislet  cellso nh e pat ic  u ltr as t ru cture ; s tudying  the uptak e a nd  transport o f  a sialoglyco pro teins in hep ato cytes;  l oca l izing  ap o-pro tein B and A- I using i mm u nocyto c hemistr y in  rat  hepatocytes anda bs o rbtive cells o f thein t es t i ne;

describing_organelle translocations_in hepatocytes during regeneration;_studying hormone_effects_of functioning_islet_cells on hepatic_ultrastructure; studying the_uptake and transport of_asialoglycoproteins in hepatocytes;_localizing_apo-protein B and A-I using immunocytochemistry in rat hepatocytes and absorbtive cells of the_intestine;


WCCC clinical trials. This service is offered to all investigators participating in clinical trials requiring acquisition, processing, storage and shipping of samples for PK/PD/PG studies. Our previous studies have demonstrated the importance of human sis/PDGF-2 gene deregulation in its activation as an oncogene in cells responsive to PD

WCCC clinical trials. This service is offered to all investigators participate in clinical test requiring acquisition, processing, storage and transportation of samples for PK / PD / PG studies. Our previous study have demonstrated the importance of human sis / PDGF-2 gene deregulation in its activation as an oncogene in cell responsive to PD

WCCF clinical trials. This strvice is offered to all invesfigators participating in clinical tcialw reqyiring acquisition, prozessing, snorage ane shmpping of samples for PK/IB/PG sfmdies. Iur previous sjudies have gemonstrated tve ilportance of human sis/PDGF-2 gene derqgulatipn in its activajion sf an oncogene in cells responsive to PS

WCCC clinical trials. This service is offered investigators in clinical requiring acquisition, processing, for studies. Our previous have demonstrated the of human sis/PDGF-2 gene deregulation in activation as an oncogene in cells responsive to PD

WCCC clinical trials. This serVice is offeRed to All InvEsTigaTors Participating iN ClinIcal trials requiring acqUisitIoN, ProcESsIng, stOrage anD ShIPPinG oF sAmpLeS FoR PK/PD/pG sTudies. OUr previous StuDiEs have demonsTRaTed the impoRtaNce of human siS/PDgF-2 gene DeRegULatioN in Its acTivatiON as an oNcogene in CeLLs respONsive to pd

WCCC clinical trials. This  service i s off ere d t oallinve stigators part i cipa ting in clinical trial s req ui r inga cq uisit ion, pr o ce s s ing ,st ora ge an d shi ppi ng of s amples for  PK /P D/PG studies .  O ur previou s s tudies havedem onstra te d t h e imp ort anceof hum a n sis/ PDGF-2 ge ne deregu l ation i n it s ac tivation as an on c og e ne in cells re sponsi ve to P D

WCCC clinical_trials. This_service is offered to_all investigators_participating_in clinical_trials_requiring acquisition, processing,_storage and shipping_of samples for PK/PD/PG_studies. Our previous_studies_have demonstrated the importance of human sis/PDGF-2 gene deregulation in its activation as an_oncogene_in cells_responsive_to_PD


), i.e. during application. MDI is widely used in making flexible and rigid foams, coatings, elastomers and numerous other polyurethane-based products. Exposure to MDI is the best-recognized risk factor for the development of MDI asthma and exposure reduction is the primary strategy of disease prevention.

), i.e. during application. MDI is widely used in making elastic and inflexible foams, coatings, elastomers and numerous early polyurethane - based products. Exposure to MDI is the well - recognized risk component for the development of MDI asthma and exposure decrease is the primary strategy of disease prevention.

), i.e. during application. MDI ls widely used iu makinj flexigle and figid foams, coatings, elastomxrs qnd nymerous other polyuretfane-based productw. Exkosure to MDI is vge best-vzcognjded rnsj factor for tme developmant of MDI astvmx cnd exposure reduction is the primarr stratrgj of disease ptevenuiog.

), i.e. during application. MDI is widely making and rigid coatings, elastomers and to is the best-recognized factor for the of MDI asthma and exposure reduction the primary strategy of disease prevention.

), i.e. during application. MDI is wIdely used iN makiNg fLexIbLe anD rigId foams, coatingS, ElasTomers and numerous other PolyuReTHane-BAsEd proDucts. ExPOsURE to mDi iS thE bESt-RecogNizEd risk fActor for thE deVeLopment of MDI AStHma and expoSurE reduction is The PrimarY sTraTEgy of DisEase pReventIOn.

), i.e. during application . MDI is w idely  us edin  mak ingflexible and r i gidfoams, coatings, elast omers  a n d nu m er ous o ther po l yu r e tha ne -b ase dp ro ducts . E xposure  to MDI is  th ebest-recogni z ed  risk fact orfor the deve lop ment o fMDI asthm a a nd ex posure reduct ion is th ep rimary strateg y of  dis ease prevention.

), i.e._during application._MDI is widely used_in making_flexible_and rigid_foams,_coatings, elastomers and_numerous other polyurethane-based_products. Exposure to MDI_is the best-recognized_risk_factor for the development of MDI asthma and exposure reduction is the primary strategy_of_disease prevention.


), mitochondrial permeability transition (MPT), depolarization and swelling, release of cytochrome c, and activation of both necrosis and caspase-dependent apoptosis in tumor cells. However, PC 4 and a recently synthesized PC 4 derivative PC 181 also localize to endoplasmic reticulum (ER) and lysosomes. We hypothesize that damage to

), mitochondrial permeability transition (MPT), depolarization and swelling, release of cytochrome c, and energizing of both necrosis and caspase - pendent apoptosis in tumor cells. However, PC 4 and a recently synthesize personal computer 4 derivative PC 181 also localize to endoplasmic reticulum (ER) and lysosome. We speculate that damage to

), mihochondrial permeability transition (MPT), depolacizatioh and swdlling, release of cytochrome c, and qctivation of both necfosis and caspase-eepeident apoptosis mh tumor cells. Mowevzr, PC 4 and a recgntly synthevized PC 4 derieagire PC 181 also localize to endoplasmic weticulim (ER) and lysosoies. Eq hylothesize that damage to

), mitochondrial permeability transition (MPT), depolarization and of c, and of both necrosis cells. PC 4 and recently synthesized PC derivative PC 181 also localize to reticulum (ER) and lysosomes. We hypothesize that damage to

), mitochondrial permeability Transition (mPT), dePolAriZaTion And sWelling, release OF cytOchrome c, and activation oF both NeCRosiS AnD caspAse-depeNDeNT ApoPtOsIs iN tUMoR cellS. HoWever, PC 4 And a recentLy sYnThesized PC 4 deRIvAtive PC 181 alsO loCalize to endoPlaSmic reTiCulUM (ER) anD lySosomEs. We hyPOthesiZe that damAgE To

), mitochondrial permeabil ity transi tion(MP T),  d epol ariz ation and swel l ing,  release of cytochrome  c, a nd acti v at ion o f bothn ec r o sis  a nd  ca sp a se -depe nde nt apop tosis in t umo rcells. Howev e r,  PC 4 anda r ecently synt hes ized P C4 d e rivat ive  PC 1 81 als o  local ize to en do p lasmic reticul u m  ( ER)and lysosomes. We hy p othesize thatdamage  t o

), mitochondrial_permeability transition_(MPT), depolarization and swelling,_release of_cytochrome_c, and_activation_of both necrosis_and caspase-dependent apoptosis_in tumor cells. However,_PC 4 and_a_recently synthesized PC 4 derivative PC 181 also localize to endoplasmic reticulum (ER) and_lysosomes._We hypothesize_that_damage_to


plots, we found that less than 2% of the DNA elements which exhibited altered expression were selectively up- or down-regulated in either antisense ODN treated cells or antisense gene overexpressing cells. The microarray analysis of gene profiling is also underway in cells treated with CRE-decoy oligonucleotides. This approach will lead us to

plots, we found that less than 2% of the DNA elements which exhibited adapted formula were selectively up- or down - regulated in either antisense ODN treated cell or antisense gene overexpressing cell. The microarray analysis of gene profiling is also afoot in cells treated with CRE - decoy oligonucleotides. This approach will moderate us to

pllts, we found that less tman 2% of the DNA glwments which exhibitdd altered expression were sxlecrivelt up- or down-regulated kn either antisenwe OVN treated cells or antisense fcne orecexpressing celks. The micsoarray analyshs oy gene profiling is also underway in cells yrfated with CRE-qecoj jligknucleotides. This approach will lezd us tm

plots, we found that less than 2% DNA which exhibited expression were selectively antisense treated cells or gene overexpressing cells. microarray analysis of gene profiling is underway in cells treated with CRE-decoy oligonucleotides. This approach will lead us to

plots, we found that less than 2% oF the DNA eleMents WhiCh eXhIbitEd alTered expressioN Were Selectively up- or down-regUlateD iN EithER aNtiseNse ODN tREaTED ceLlS oR anTiSEnSe genE ovErexpreSsing cells. the MiCroarray analYSiS of gene proFilIng is also undErwAy in ceLlS trEAted wIth cRE-deCoy oliGOnucleOtides. ThiS aPProach WIll lead US To

plots, we found that less  than 2% o f the  DN A e le ment s wh ich exhibiteda lter ed expression were sel ectiv el y  up- or  down -regula t ed i n e it he r a nt i se nse O DNtreated  cells orant is ense gene ov e re xpressingcel ls. The micr oar ray an al ysi s  of g ene  prof ilingi s also  underway  i n  cells treated w it h CR E-decoy oligonucl e ot i des. This appr oach w il l  l e a d u s t o

plots,_we found_that less than 2%_of the_DNA_elements which_exhibited_altered expression were_selectively up- or_down-regulated in either antisense_ODN treated cells_or_antisense gene overexpressing cells. The microarray analysis of gene profiling is also underway in_cells_treated with_CRE-decoy_oligonucleotides._This approach will lead us_to


particularly in cerebral cortex layers I-IV) and thyroid gland and hormone differences that exist in the hyt/hyt hypothyroid mouse fetus and neonate relative to normal mouse offspring; and 2) To choose and isolate, several mouse brain mRNAs which are regulated by thyroid hormone(s) during the intrauterine

particularly in cerebral cortex layers I - IV) and thyroid gland and hormone dispute that exist in the hyt / hyt hypothyroid mouse fetus and neonate relative to normal shiner offspring; and 2) To choose and isolate, respective mouse genius mRNAs which are regulated by thyroid hormone(s) during the intrauterine

parhicularly in cerebral covtex layers I-IV) cbd thycoid glznd and formone differences that exidt in tye hyt/hyt hypothyroid oouse fetls and neinatt relative to normal mousc offairing; end 2) To choose snd isolata, several mousa crcin mRNAs which are regulated by thywoid hotmlne(s) during thg intgatterjne

particularly in cerebral cortex layers I-IV) and and differences that in the hyt/hyt relative normal mouse offspring; 2) To choose isolate, several mouse brain mRNAs which regulated by thyroid hormone(s) during the intrauterine

particularly in cerebral corTex layers I-iV) and ThyRoiD gLand And hOrmone differenCEs thAt exist in the hyt/hyt hypoThyroId MOuse FEtUs and Neonate RElATIve To NoRmaL mOUsE offsPriNg; and 2) To Choose and iSolAtE, several mousE BrAin mRNAs whIch Are regulated By tHyroid HoRmoNE(s) durIng The inTrauteRIne

particularly in cerebral c ortex laye rs I- IV)  an dthyr oidgland and horm o ne d ifferences that existin th eh yt/h y thypot hyroidm ou s e  fe tu sand  n e on ate r ela tive to  normal mo use  o ffspring; an d  2 ) To choos e a nd isolate,sev eral m ou seb rainmRN As wh ich ar e  regul ated by t hy r oid ho r mone(s) d ur ingthe intrauterine

particularly in_cerebral cortex_layers I-IV) and thyroid_gland and_hormone_differences that_exist_in the hyt/hyt_hypothyroid mouse fetus_and neonate relative to_normal mouse offspring;_and_2) To choose and isolate, several mouse brain mRNAs which are regulated by thyroid_hormone(s)_during the_intrauterine


amic acid). Two stages of excitotoxic neuronal damage have been identified: and early phase, occurring in minutes, associated with osmotic imbalance, cellular swelling, and lysis; and a delayed phase, characterized by elevated intracellular calcium. One major homeostatic element which counteracts events underlying both phases of excitotoxicity is the sodium pump

amic acid). Two stages of excitotoxic neuronal damage have been identified: and early phase, occur in moment, associated with osmotic imbalance, cellular swelling, and lysis; and a delay phase, characterized by elevated intracellular calcium. One major homeostatic component which counteracts events underlie both phases of excitotoxicity is the sodium pump

amif acid). Two stages of excltotoxic neuronal damagx have geen idevtified: and early phase, occucrint in ninutes, associated witf osmotic imbalanxe, ctllular swelling, ehd lysis; and z delcyxd phase, characjerized by enevated intracaluupar calcium. One major homeostatic ejement ehlch counteractf evtntf unsvroying both phases of excitotosicity ps the sodium puml

amic acid). Two stages of excitotoxic neuronal been and early occurring in minutes, swelling, lysis; and a phase, characterized by intracellular calcium. One major homeostatic element counteracts events underlying both phases of excitotoxicity is the sodium pump

amic acid). Two stages of excitoToxic neuroNal daMagE haVe Been IdenTified: and early PHase, Occurring in minutes, assoCiateD wITh osMOtIc imbAlance, cELlULAr sWeLlIng, AnD LySis; anD a dElayed pHase, characTerIzEd by elevated INtRacellular CalCium. One major HomEostatIc EleMEnt whIch CountEracts EVents uNderlying BoTH phaseS Of excitOTOxIcitY is the sodium pump

amic acid). Two stages ofexcitotoxi c neu ron alda mage  hav e been identif i ed:and early phase, occur ringin minu t es , ass ociated wi t h  os mo ti c i mb a la nce,cel lular s welling, a ndly sis; and a d e la yed phase,  ch aracterizedbyelevat ed  in t racel lul ar ca lcium. One ma jor homeo st a tic el e ment wh i c hcoun teracts events un d er l ying both phas es ofex c it o t oxi cit y is the s od ium p u mp

amic acid)._Two stages_of excitotoxic neuronal damage_have been_identified:_and early_phase,_occurring in minutes,_associated with osmotic_imbalance, cellular swelling, and_lysis; and a_delayed_phase, characterized by elevated intracellular calcium. One major homeostatic element which counteracts events underlying_both_phases of_excitotoxicity_is_the sodium pump


care arrangements. Thus, the sample is well-suited to study how multiple sources of disadvantage influence child health and development. The data are also unique in containing detailed information on mothers, fathers, and their relationships with each other. The information on unmarried fathers, in particular, allows us to follow a group of men

care arrangements. Thus, the sample is well - befit to analyze how multiple sources of disadvantage influence child health and development. The data are besides unique in containing detailed information on mother, fathers, and their relationships with each early. The data on unmarried fathers, in particular, allow us to follow a group of men

cage arrangements. Thus, the sample is well-suited vo studg how muutiple sources of disadvantaje ibfluebce child health and ddvelopmenn. The datq art also unique in rkntainiky detzlled nnhormation on mojhers, fatherv, and their renagilnships with each other. The informaeion on ujmarried fathets, in [artjbuoar, allows us to follow a grohp of mtn

care arrangements. Thus, the sample is well-suited how sources of influence child health also in containing detailed on mothers, fathers, their relationships with each other. The on unmarried fathers, in particular, allows us to follow a group of men

care arrangements. Thus, the saMple is well-SuiteD to StuDy How mUltiPle sources of diSAdvaNtage influence child heaLth anD dEVeloPMeNt. The Data are ALsO UNiqUe In ConTaINiNg detAilEd inforMation on moTheRs, Fathers, and thEIr RelationshIps With each otheR. ThE inforMaTioN On unmArrIed faThers, iN ParticUlar, allowS uS To follOW a group OF MeN

care arrangements. Thus,the sample  is w ell -su it ed t o st udy how multip l e so urces of disadvantageinflu en c e ch i ld  heal th andd ev e l opm en t.  Th ed at a are  al so uniq ue in cont ain in g detailed i n fo rmation on  mo thers, fathe rs,  and t he irr elati ons hipswith e a ch oth er. The i nf o rmatio n  on unm a r ri ed f athers, in partic u la r , allows us to  follo wa  g r o upofmen

care_arrangements. Thus,_the sample is well-suited_to study_how_multiple sources_of_disadvantage influence child_health and development._The data are also_unique in containing_detailed_information on mothers, fathers, and their relationships with each other. The information on unmarried_fathers,_in particular,_allows_us_to follow a group of_men


CD69 interacts with and down-modulates surface expression and function of S1P1, a G protein coupled receptor, leading to transient lymphocyte sequestration. In addition, engagement of the antigen receptor on T cells leads to transcriptional down-regulation of S1P1 mRNA expression and a prolonged inhibition of lymphocyte egress

CD69 interacts with and down - modulates surface expression and function of S1P1, a deoxyguanosine monophosphate protein pair receptor, leading to transient lymphocyte segregation. In addition, engagement of the antigen receptor on thyroxine cells leads to transcriptional down - rule of S1P1 mRNA formula and a prolonged prohibition of lymphocyte egress

CD69 interacts with and down-oodulates surfaew exprxssion znd funcgion of S1P1, a G protein couplxd rwceptir, leading to transieng lymphocjte sequewtrauion. In addition, xhgagemekc of fme ancijen receptor on T cells laads to transcsiotnonal down-regulation of S1P1 mRNA exprqssion snf a prolonged ynhinytioh of lymphocyte egress

CD69 interacts with and down-modulates surface expression of a G coupled receptor, leading addition, of the antigen on T cells to transcriptional down-regulation of S1P1 mRNA and a prolonged inhibition of lymphocyte egress

CD69 interacts with and down-modUlates surfAce exPreSsiOn And fUnctIon of S1P1, a G proteIN couPled receptor, leading to tRansiEnT LympHOcYte seQuestraTIoN. iN adDiTiOn, eNgAGeMent oF thE antigeN receptor oN T cElLs leads to traNScRiptional dOwn-Regulation of s1P1 mrNA expReSsiON and a ProLongeD inhibITion of LymphocytE eGRess

CD69 interacts with and d own-modula tes s urf ace  e xpre ssio n and function of S 1P1, a G protein coupl ed re ce p tor, le ading  to tra n si e n t l ym ph ocy te se quest rat ion. In  addition,  en ga gement of th e  a ntigen rec ept or on T cell s l eads t otra n scrip tio nal d own-re g ulatio n of S1P1  m R NA exp r essiona n da pr olonged inhibitio n  o f  lymphocyte eg ress

CD69_interacts with_and down-modulates surface expression_and function_of_S1P1, a_G_protein coupled receptor,_leading to transient_lymphocyte sequestration. In addition,_engagement of the_antigen_receptor on T cells leads to transcriptional down-regulation of S1P1 mRNA expression and a_prolonged_inhibition of_lymphocyte_egress


C. burnetii during the host-parasite interaction. We also will examine plasmids and the chromosome for alternative virulence functions; factors that enhance intracellular survival and growth and thus pathogenesis. We will clone genes encoding key metabolic functions as well as those shown to be important for intracellular survival of other organisms. These genes will

C. burnetii during the host - parasite interaction. We also will examine plasmid and the chromosome for alternate virulence function; factors that enhance intracellular survival and growth and therefore pathogenesis. We will clone genes encoding key metabolic function as well as those shown to be significant for intracellular survival of other organisms. These gene will

C. hurnetii during the host-karasite interactnin. We elso wiml examive plasmids and the chromosole for qlternative virulence wunctions; factors thau enhance intracellular smxvivam and jrowth and thus pathogenevis. We will clmnd yenes encoding key metabolic functiogs as wrlp as those shorn tp be jmportant for intracellular survivzl of ouher organisms. Thexe genes will

C. burnetii during the host-parasite interaction. We examine and the for alternative virulence survival growth and thus We will clone encoding key metabolic functions as well those shown to be important for intracellular survival of other organisms. These genes

C. burnetii during the host-parAsite interActioN. We AlsO wIll eXamiNe plasmids and tHE chrOmosome for alternative vIruleNcE FuncTIoNs; facTors thaT EnHANce InTrAceLlULaR survIvaL and groWth and thus PatHoGenesis. We wilL ClOne genes enCodIng key metaboLic FunctiOnS as WEll as ThoSe shoWn to be IMportaNt for intrAcELlular SUrvival OF OtHer oRganisms. These geneS WiLL

C. burnetii during the ho st-parasit e int era cti on . We  als o will examine plas mids and the chromosom e for  a l tern a ti ve vi rulence fu n c tio ns ;fac to r sthatenh ance in tracellula r s ur vival and gr o wt h and thus  pa thogenesis.Wewill c lo neg enesenc oding  key m e taboli c functio ns as wel l  as tho s e  s hown  to be importantf or intracellularsurviv al of o the r o rganisms.Th ese g e nes wil l

C._burnetii during_the host-parasite interaction. We_also will_examine_plasmids and_the_chromosome for alternative_virulence functions; factors_that enhance intracellular survival_and growth and_thus_pathogenesis. We will clone genes encoding key metabolic functions as well as those shown_to_be important_for_intracellular_survival of other organisms. These_genes will


antibody responses to the N-terminal immuno-silent region of MSP1-42, MSP1-33, biologically active antibodies can be produced when combined with low concentrations of anti-MSP1-42 antibodies. This creates an opportunity to devise new vaccine constructs and/or immunization regimens to efficiently induce protective

antibody responses to the N - terminal immuno - silent region of MSP1 - 42, MSP1 - 33, biologically active antibody can be produce when combined with low concentration of anti - MSP1 - 42 antibody. This creates an opportunity to devise new vaccine construct and/or immunization regimens to efficiently induce protective

anhibody responses to the K-terminal immuno-silent cegion kf MSP1-42, MRP1-33, biologically active antibldues cqn be produced when coobined winh low cobcenurations of anti-MSP1-42 antibodies. Fmis cxeetes an opportukity to devhse new vaccina zoustructs and/or immunization regimens to effoclently induce krotebtyve

antibody responses to the N-terminal immuno-silent region MSP1-33, active antibodies be produced when anti-MSP1-42 This creates an to devise new constructs and/or immunization regimens to efficiently protective

antibody responses to the N-teRminal immuNo-silEnt RegIoN of MsP1-42, MSp1-33, biologically aCTive Antibodies can be produceD when CoMBineD WiTh low ConcentRAtIONs oF aNtI-MSp1-42 aNTiBodieS. ThIs creatEs an opportUniTy To devise new vACcIne construCts And/or immunizAtiOn regiMeNs tO EfficIenTly inDuce prOTectivE

antibody responses to the  N-termina l imm uno -si le nt r egio n of MSP1-42,M SP1- 33, biologically activ e ant ib o dies ca n beproduce d  w h e n c om bi ned  w i th  lowcon centrat ions of an ti- MS P1-42 antibo d ie s. This cr eat es an opport uni ty tode vis e  newvac cineconstr u cts an d/or immu ni z ationr egimens t oeffi ciently induce pr o te c tive

antibody_responses to_the N-terminal immuno-silent region_of MSP1-42,_MSP1-33,_biologically active_antibodies_can be produced_when combined with_low concentrations of anti-MSP1-42_antibodies. This creates_an_opportunity to devise new vaccine constructs and/or immunization regimens to efficiently induce protective


idine based heterocycles. The library will consist of 5-10 milligrams each of a total of 384 compounds. SPSC will accomplish this by utilizing it's novel high-loading support and commercially available solvent delivery robot. Specifically, libraries will be made off of this high-loading support to separate the desired products from undes

idine based heterocycles. The library will consist of 5 - 10 milligrams each of a sum of 384 compound. SPSC will accomplish this by utilizing it's novel gamey - loading support and commercially available solvent manner of speaking robot. Specifically, libraries will be make off of this high - loading accompaniment to separate the desired intersection from undes

idije based heterocycles. Tht library will couwist oh 5-10 milljgrams exch of a total of 384 compounds. SPSC wull accomplish this by utilizinh it's nocel iigh-loading support and gjmmedgiallv evailable solvekt delivery robot. Specifiwaulv, libraries will be made off of this high-losdlng support to sepswate nht desired products from undes

idine based heterocycles. The library will consist milligrams of a of 384 compounds. utilizing novel high-loading support commercially available solvent robot. Specifically, libraries will be made of this high-loading support to separate the desired products from undes

idine based heterocycles. The Library wilL consIst Of 5-10 mIlLigrAms eAch of a total of 384 cOMpouNds. SPSC will accomplish tHis by UtILiziNG iT's novEl high-lOAdING suPpOrT anD cOMmErciaLly AvailabLe solvent dEliVeRy robot. SpeciFIcAlly, librarIes Will be made ofF of This hiGh-LoaDIng suPpoRt to sEparatE The desIred produCtS From unDEs

idine based heterocycles.The librar y wil l c ons is t of  5-1 0 milligrams e a ch o f a total of 384 compo unds.  S P SC w i ll  acco mplisht hi s byut il izi ng it 's no vel  high-l oading sup por tand commerci a ll y availabl e s olvent deliv ery  robot .Spe c ifica lly , lib raries will b e made of fo f this high-lo a d in g su pport to separate th e  desired produ cts fr om un d e s

idine based_heterocycles. The_library will consist of_5-10 milligrams_each_of a_total_of 384 compounds._SPSC will accomplish_this by utilizing it's_novel high-loading support_and_commercially available solvent delivery robot. Specifically, libraries will be made off of this high-loading_support_to separate_the_desired_products from undes


to test mechanisms of interest in parallel studies of mice and patients. In the proposed program we plan to study novel human glycosyltransferases. Much emphasis will be made on the identification and characterization of enzymes present in ovarian epithelial linings and fluids. Synthesis of various oligosaccharides which can be effectively employed as acceptor-substr

to test mechanisms of interest in parallel studies of mouse and patient. In the proposed program we plan to learn novel human glycosyltransferases. Much emphasis will be have on the identification and characterization of enzyme present in ovarian epithelial lining and fluids. deduction of various oligosaccharides which can be effectively employed as acceptor - substr

to test mechanisms of intevest in parallel studiev of mjce and oatients. In the proposed projram we poan to study novel humxn glycosjltransfeeasew. Much empheais will be mzfe ou vhe identificatlon and chasacterization mf euzymes present in ovarian epithelial liningx wnd fluids. Synjhesix of barious oligosaccharides which can be efftctively employed ss acceptor-substr

to test mechanisms of interest in parallel mice patients. In proposed program we glycosyltransferases. emphasis will be on the identification characterization of enzymes present in ovarian linings and fluids. Synthesis of various oligosaccharides which can be effectively employed as

to test mechanisms of interesT in paralleL studIes Of mIcE and PatiEnts. In the propoSEd prOgram we plan to study noveL humaN gLYcosYLtRansfErases. MUCh EMPhaSiS wIll Be MAdE on thE idEntificAtion and chAraCtErization of eNZyMes present In oVarian epitheLiaL lininGs And FLuids. synThesiS of varIOus oliGosaccharIdES which CAn be effECTiVely Employed as acceptoR-SuBStr

to test mechanisms of int erest in p arall elstu di es o f mi ce and patient s . In  the proposed programwe pl an to s t ud y nov el huma n  g l y cos yl tr ans fe r as es. M uch  emphas is will be  ma de  on the iden t if ication an d c haracterizat ion  of en zy mes prese ntin ov ariane pithel ial linin gs and fl u ids. Sy n t he sisof various oligos a cc h arides which c an beef f ec t i vel y e mployed as  a ccept o r-subst r

to_test mechanisms_of interest in parallel_studies of_mice_and patients._In_the proposed program_we plan to_study novel human glycosyltransferases._Much emphasis will_be_made on the identification and characterization of enzymes present in ovarian epithelial linings and_fluids._Synthesis of_various_oligosaccharides_which can be effectively employed_as acceptor-substr


effect on PAF. We propose to investigate the PAF signaling pathway and the role of lipoxygenase metabolites in the transcription of collagenase type 1. PAF antagonists and lipoxygenase inhibitors will be evaluated to determine their sites of action and to correlate their biochemical effects with the clinical evolution of corneal ulcers. Another goal

effect on PAF. We propose to investigate the PAF signaling pathway and the function of lipoxygenase metabolite in the transcription of collagenase type 1. PAF antagonist and lipoxygenase inhibitor will be evaluated to determine their sites of military action and to correlate their biochemical effects with the clinical evolution of corneal ulcer. Another finish

efvect on PAF. We propose tu investigate tkw PAF vignaljng pathday and the role of lipoxygeiase metavolites in the transcrkption of collagebase rype 1. PAF ehtagonists ans lipmeygenase inhibijors will be evaluated to gegexmine their sites of action and to cjrrelatr hheir biochemisal tffqcts with the clinical evolution of codneal uncers. Another goal

effect on PAF. We propose to investigate signaling and the of lipoxygenase metabolites type PAF antagonists and inhibitors will be to determine their sites of action to correlate their biochemical effects with the clinical evolution of corneal ulcers. Another

effect on PAF. We propose to invEstigate thE PAF sIgnAliNg PathWay aNd the role of lipOXygeNase metabolites in the trAnscrIpTIon oF CoLlageNase typE 1. pAf ANtaGoNiSts AnD LiPoxygEnaSe inhibItors will bE evAlUated to deterMInE their siteS of Action and to cOrrElate tHeIr bIOchemIcaL effeCts witH The cliNical evolUtIOn of coRNeal ulcERS. ANothEr goal

effect on PAF. We propose  to invest igate  th e P AF  sig nali ng pathway and therole of lipoxygenase m etabo li t es i n  t he tr anscrip t io n ofco ll age na s etype1.PAF ant agonists a ndli poxygenase i n hi bitors wil l b e evaluatedtodeterm in e t h eir s ite s ofaction and to  correlat et heir b i ochemic a l  e ffec ts with the clini c al evolution of c orneal  u l ce r s . A not her goal

effect_on PAF._We propose to investigate_the PAF_signaling_pathway and_the_role of lipoxygenase_metabolites in the_transcription of collagenase type_1. PAF antagonists_and_lipoxygenase inhibitors will be evaluated to determine their sites of action and to correlate_their_biochemical effects_with_the_clinical evolution of corneal ulcers._Another goal


of muscle fibers. For example, (i) Instantaneous elastic response (To T1) and the magnitude of rapid recovery (T2 - T1) after a step length change can be explained well when the rate of attachment is assumed high for positive x. In that case T2 corresponds to the force generated by

of muscle fibers. For example, (i) Instantaneous elastic reception (To T1) and the order of magnitude of rapid recovery (T2 - T1) after a step duration variety can be explained well when the rate of attachment is assume high for positive x. In that event T2 corresponds to the force generated by

of muscle fibers. For exampue, (i) Instantaneous elavtic rssponse (Go T1) and the magnitude of ra'id eecovtgy (T2 - T1) after a step uength chwnge can be txplained well whxh the rate of wttaehnent is assumec high for positive x. In tfac case T2 corresponds to the force gegerated bj

of muscle fibers. For example, (i) Instantaneous (To and the of rapid recovery step change can be well when the of attachment is assumed high for x. In that case T2 corresponds to the force generated by

of muscle fibers. For example, (i) instantaneOus elAstIc rEsPonsE (To T1) And the magnitudE Of raPid recovery (T2 - T1) after a steP lengTh CHangE CaN be exPlained WElL WHen ThE rAte Of ATtAchmeNt iS assumeD high for poSitIvE x. In that case t2 CoRresponds tO thE force generaTed By

of muscle fibers. For exa mple, (i)Insta nta neo us  ela stic  response (ToT 1) a nd the magnitude of ra pid r ec o very (T 2 - T 1) afte r  a s tep  l en gth  c h an ge ca n b e expla ined wellwhe nthe rate ofa tt achment is  as sumed high f orpositi ve  x. In th atcaseT2 cor r espond s to thefo r ce gen e rated b y

of_muscle fibers._For example, (i) Instantaneous_elastic response_(To_T1) and_the_magnitude of rapid_recovery (T2 -_T1) after a step_length change can_be_explained well when the rate of attachment is assumed high for positive x. In_that_case T2_corresponds_to_the force generated by


mechanism(s) of mutant SOD1-mediated toxicity and to define a potential role for the mitochondrial mutant SOD1/Bcl-2 complex in ALS pathogenesis. The specific aims are: 1) (A) To determine whether WT SOD1 pro-survival activity depends on its binding to Bcl-2, and

mechanism(s) of mutant SOD1 - mediated toxicity and to define a potential function for the mitochondrial mutant SOD1 / Bcl-2 building complex in ALS pathogenesis. The specific aims are: 1) (A) To settle whether WT SOD1 pro - survival bodily process depends on its binding to Bcl-2, and

mefhanism(s) of mutant SOD1-meaiated toxicity and to defins a potevtial role for the mitochondcial mutabt SOD1/Bcl-2 complex in AUS pathogvnesis. Thw sptcific aims are: 1) (E) To detcxmine ahetkec WT SOD1 pro-suryival activhty depends on igs binding to Bcl-2, and

mechanism(s) of mutant SOD1-mediated toxicity and to potential for the mutant SOD1/Bcl-2 complex aims 1) (A) To whether WT SOD1 activity depends on its binding to and

mechanism(s) of mutant SOD1-mediAted toxiciTy and To dEfiNe A potEntiAl role for the miTOchoNdrial mutant SOD1/Bcl-2 compLex in aLs PathOGeNesis. the specIFiC AIms ArE: 1) (A) to dEtERmIne whEthEr WT SOD1 Pro-survivaL acTiVity depends oN ItS binding to bcl-2, And

mechanism(s) of mutant SO D1-mediate d tox ici tyan d to  def ine a potentia l  rol e for the mitochondria l mut an t  SOD 1 /B cl-2complex in A LSpa th oge ne s is . The  sp ecificaims are:1)(A ) To determi n ewhether WT  SO D1 pro-survi val  activ it y d e pends  on  itsbindin g  to Bc l-2, and

mechanism(s)_of mutant_SOD1-mediated toxicity and to_define a_potential_role for_the_mitochondrial mutant SOD1/Bcl-2_complex in ALS_pathogenesis. The specific aims_are: 1) (A)_To_determine whether WT SOD1 pro-survival activity depends on its binding to Bcl-2, and


. In carrying out this proposal, we plan to take advantage of our studies involving the characterization of normal epithelial keratin glycosylation and phosphorylation. For example, we recently showed that keratins 8 and 18 are O-linked glycoproteins with glycosylation sites consisting of single N-acetylglucosamine (GlcNAc

. In carrying out this proposal, we plan to take advantage of our report imply the characterization of normal epithelial keratin glycosylation and phosphorylation. For example, we recently showed that keratins 8 and 18 are O - connect glycoproteins with glycosylation sites consist of unmarried N - acetylglucosamine (GlcNAc

. In carrying out this proporal, we plan to jaje adventage kf our sgudies involving the charactxrizqtion of normal epithelial yeratin gpycosylarion qnd phosphorylatiok. For cxampnx, we recently smowed that neratins 8 and 18 afe O-linked glycoproteins with glycosyjation xihes consisting of xyngls N-acetylglucosamine (GlcNAc

. In carrying out this proposal, we take of our involving the characterization and For example, we showed that keratins and 18 are O-linked glycoproteins with sites consisting of single N-acetylglucosamine (GlcNAc

. In carrying out this proposal, We plan to taKe advAntAge Of Our sTudiEs involving the CHaraCterization of normal epiTheliAl KEratIN gLycosYlation ANd PHOspHoRyLatIoN. foR examPle, We recenTly showed tHat KeRatins 8 and 18 are o-LiNked glycopRotEins with glycOsyLation SiTes COnsisTinG of siNgle N-aCEtylglUcosamine (glCnAc

. In carrying out this pro posal, weplantotak eadva ntag e of our studi e s in volving the characteri zatio no f no r ma l epi thelial ke r a tin  g ly cos yl a ti on an d p hosphor ylation. F orex ample, we re c en tly showed  th at keratins8 a nd 18ar e O - linke d g lycop rotein s  withglycosyla ti o n site s  consis t i ng  ofsingle N-acetylgl u co s amine (GlcNAc

. In_carrying out_this proposal, we plan_to take_advantage_of our_studies_involving the characterization_of normal epithelial_keratin glycosylation and phosphorylation._For example, we_recently_showed that keratins 8 and 18 are O-linked glycoproteins with glycosylation sites consisting of_single_N-acetylglucosamine (GlcNAc


the high and low expression levels of IL-15 obtained from Specific Aim 1 will be used to correlate expression levels of IL-15 with tumor regression. We will analyze the local and systemic cellular infiltrate stimulated by plL-15/EP using FACS, immunohistochemistry, Luminex bead array, TUNEL and EL

the high and low expression levels of IL-15 prevail from Specific Aim 1 will be use to correlate expression levels of IL-15 with tumor regression. We will analyze the local and systemic cellular infiltrate induce by plL-15 / EP using FACS, immunohistochemistry, Luminex bead array, TUNEL and EL

thf high and low expressiok levels of IL-15 oyrained from Apecific Aim 1 will be used to correlete wxprewsion levels of IL-15 witf tumor rvgression. We xill analyze the local akb sysfcmic eeolular infiltrste stimuldted by plL-15/EP gskny FACS, immunohistochemistry, Luminex fead artaj, TUNEL and EL

the high and low expression levels of from Aim 1 be used to with regression. We will the local and cellular infiltrate stimulated by plL-15/EP using immunohistochemistry, Luminex bead array, TUNEL and EL

the high and low expression leVels of IL-15 obTaineD frOm SPeCifiC Aim 1 Will be used to coRRelaTe expression levels of IL-15 With tUmOR regREsSion. WE will anALyZE The LoCaL anD sYStEmic cEllUlar infIltrate stiMulAtEd by plL-15/EP usiNG FaCS, immunohIstOchemistry, LuMinEx bead ArRay, tuNEL aNd El

the high and low expressi on levelsof IL -15  ob ta ined  fro m Specific Aim 1 wi ll be used to correlat e exp re s sion le velsof IL-1 5  w i t h t um or  re gr e ss ion.Wewill an alyze theloc al  and systemi c  c ellular in fil trate stimul ate d by p lL -15 / EP us ing  FACS , immu n ohisto chemistry ,L uminex bead ar r a y,  TUN EL and EL

the_high and_low expression levels of_IL-15 obtained_from_Specific Aim_1_will be used_to correlate expression_levels of IL-15 with_tumor regression. We_will_analyze the local and systemic cellular infiltrate stimulated by plL-15/EP using FACS, immunohistochemistry, Luminex_bead_array, TUNEL_and_EL


be studied in chimpanzees. In other studies, we have constructed chimeric genomes from infectious cDNA clones of HCV and bovine viral diarrhea virus. These genomes can replicate in transfected cells but the resultant viral products cannot assemble into infectious virus in the absence of helper virus.We have determined the genetic heterogeneity of HCV isolates that

be studied in chimpanzees. In other studies, we have construct chimeric genome from infectious cDNA clones of HCV and bovine viral diarrhea virus. These genome can replicate in transfected cell but the resultant viral product cannot meet into infectious virus in the absence of helper virus. We have determined the genetic heterogeneity of HCV isolates that

be studied in chimpanzees. Ln other studies, we havx constducted cfimeric genomes from infectiluw cDNQ clones of HCV and boxine virap diarrhwa vmrus. These genomxa can rc'licafc in crensfected cells but the rasultant viral pfobucts cannot assemble into infectiouf virus ij the absence jf htlpqr vjguw.We have determined the genetjc hetegogeneity of HCV osolates that

be studied in chimpanzees. In other studies, constructed genomes from cDNA clones of virus. genomes can replicate transfected cells but resultant viral products cannot assemble into virus in the absence of helper virus.We have determined the genetic heterogeneity of isolates that

be studied in chimpanzees. In oTher studieS, we haVe cOnsTrUcteD chiMeric genomes frOM infEctious cDNA clones of HCV And boViNE virAL dIarrhEa virus. tHeSE GenOmEs Can RePLiCate iN trAnsfectEd cells but The ReSultant viral PRoDucts cannoT asSemble into inFecTious vIrUs iN The abSenCe of hElper vIRus.We hAve determInED the geNEtic hetEROgEneiTy of HCV isolates thAT

be studied in chimpanzees . In other  stud ies , w ehave  con structed chime r ic g enomes from infectious  cDNA  c l ones of  HCVand bov i ne v ira ldi arr he a  v irus.  Th ese gen omes can r epl ic ate in trans f ec ted cellsbut  the resulta ntviralpr odu c ts ca nno t ass emblei nto in fectiousvi r us int he abse n c eof h elper virus.We ha v ed etermined thegeneti ch et e r oge nei ty of HCVis olate s  that

be_studied in_chimpanzees. In other studies,_we have_constructed_chimeric genomes_from_infectious cDNA clones_of HCV and_bovine viral diarrhea virus._These genomes can_replicate_in transfected cells but the resultant viral products cannot assemble into infectious virus in_the_absence of_helper_virus.We_have determined the genetic heterogeneity_of HCV isolates that


cytometry. HLA or non-HLA specificity will be determined by neutralization of antibody with purified HLA antigens. For the second objective, patients with prior allosensitization will be randomized into 2 groups. 1) Group A will receive HLA matched single donor blood products. 2) Group B will receive random single donor blood

cytometry. HLA or non - HLA specificity will be determined by neutralization of antibody with purified HLA antigens. For the second objective, patient with anterior allosensitization will be randomized into 2 groups. 1) Group A will welcome HLA match single donor blood product. 2) Group B will meet random single donor rake

cyhometry. HLA or non-HLA sptcificity will be determmned by neutralkzation of antibody with purmfiee HLA antigens. For the secovd objectpve, patiebts xith prior allosxhsitizabnon wjpl bz candomized into 2 groups. 1) Croup A will racdire HLA matched single donor blood prjducts. 2) Ggoup B will reseivt rwndoj single donor blood

cytometry. HLA or non-HLA specificity will be neutralization antibody with HLA antigens. For prior will be randomized 2 groups. 1) A will receive HLA matched single blood products. 2) Group B will receive random single donor blood

cytometry. HLA or non-HLA speciFicity will Be detErmIneD bY neuTralIzation of antibODy wiTh purified HLA antigens. FOr the SeCOnd oBJeCtive, PatientS WiTH PriOr AlLosEnSItIzatiOn wIll be raNdomized inTo 2 gRoUps. 1) Group A wilL ReCeive HLA maTchEd single donoR blOod proDuCts. 2) gRoup B WilL receIve ranDOm singLe donor blOoD

cytometry. HLA or non-HLA  specifici ty wi llbede term ined  by neutraliza t ionof antibody with purif ied H LA anti g en s. Fo r the s e co n d  ob je ct ive ,p at ients  wi th prio r allosens iti za tion will be ra ndomized i nto  2 groups. 1 ) G roup A  w ill recei veHLA m atched single  donor bl oo d  produ c ts. 2)G r ou p Bwill receive rand o ms ingle donor bl ood

cytometry._HLA or_non-HLA specificity will be_determined by_neutralization_of antibody_with_purified HLA antigens._For the second_objective, patients with prior_allosensitization will be_randomized_into 2 groups. 1) Group A will receive HLA matched single donor blood products._2)_Group B_will_receive_random single donor blood


from vessel walls. The consequences of CAA are associated in part with breakdown of the vessel wall. For this reason, we now propose to use novel methods to define the mechanisms that underlie Ali-induced vascular wall injury, including oxidative stress, activation of matrix metalloproteinases and other proteases and injury to vascular smooth muscle

from vessel walls. The consequences of CAA are associated in part with dislocation of the vessel rampart. For this cause, we now nominate to practice novel methods to define the mechanism that underlie Ali - induced vascular wall injury, include oxidative stress, activation of matrix metalloproteinases and early proteases and injury to vascular smooth muscle

frlm vessel walls. The constquences of CAA ate assocmated ih part wkth breakdown of the vessel xall. For ukis reason, we now prupose to lse novel metiods to define tis mechaknsms fmat uudxrlie Ali-inducec vascular wall injury, itcuubing oxidative stress, activation of iatrix kehalloproteinasgs anc othsg kroteases and injury to vascular amooth kuscle

from vessel walls. The consequences of CAA in with breakdown the vessel wall. propose use novel methods define the mechanisms underlie Ali-induced vascular wall injury, including stress, activation of matrix metalloproteinases and other proteases and injury to vascular smooth

from vessel walls. The consequEnces of CAA Are asSocIatEd In paRt wiTh breakdown of tHE vesSel wall. For this reason, we Now prOpOSe to USe Novel Methods TO dEFIne ThE mEchAnISmS that UndErlie AlI-induced vaScuLaR wall injury, iNClUding oxidaTivE stress, activAtiOn of maTrIx mETalloProTeinaSes and OTher prOteases anD iNJury to VAscular SMOoTh muScle

from vessel walls. The co nsequences  of C AAare  a ssoc iate d in part with brea kdown of the vessel wa ll. F or this re ason,  we now pr o p ose  t ouse  n o ve l met hod s to de fine the m ech an isms that un d er lie Ali-in duc ed vascularwal l inju ry , i n cludi ngoxida tive s t ress,activatio no f matr i x metal l o pr otei nases and other p r ot e ases and injur y to v as c ul a r  sm oot h muscle

from_vessel walls._The consequences of CAA_are associated_in_part with_breakdown_of the vessel_wall. For this_reason, we now propose_to use novel_methods_to define the mechanisms that underlie Ali-induced vascular wall injury, including oxidative stress, activation_of_matrix metalloproteinases_and_other_proteases and injury to vascular_smooth muscle


directly from the application): In the United States, managed care is growing rapidly. The membership of managed care organizations (MCOs) now exceeds 50 million people and may grow by an additional 50 million by the year 2,000. The most rapidly growing type of MCO is that based on the Individual Practice Association (

directly from the application ): In the United States, managed care is grow quickly. The membership of managed care administration (MCOs) immediately exceeds 50 million people and may develop by an extra 50 million by the year 2,000. The most rapidly growing type of MCO is that free-base on the Individual Practice Association (

digectly from the applicatlon): In the Uniteb Statev, manafed care is growing rapidly. The membxrshup of managed care organizagions (MCOd) now exxeedw 50 million 'sople akb may nrow yy an additional 50 million ty the year 2,000. Tve mlst rapidly growing type of MCO is ehat baxef on the Indivyduak Pradnige Association (

directly from the application): In the United care growing rapidly. membership of managed 50 people and may by an additional million by the year 2,000. The rapidly growing type of MCO is that based on the Individual Practice Association

directly from the applicatioN): In the UnitEd StaTes, ManAgEd caRe is Growing rapidly. tHe meMbership of managed care oRganiZaTIons (mcOS) now eXceeds 50 mILlION peOpLe And MaY GrOw by aN adDitionaL 50 million by The YeAr 2,000. The most rapIDlY growing tyPe oF MCO is that baSed On the INdIviDUal PrActIce AsSociatIOn (

directly from the applica tion): Inthe U nit edSt ates , ma naged care isg rowi ng rapidly. The member shipof mana g ed  care  organi z at i o ns(M CO s)no w  e xceed s 5 0 milli on peopleand  m ay grow by a n  a dditional50million by t heyear 2 ,0 00. The m ost  rapi dly gr o wing t ype of MC Oi s that based o n th e In dividual Practice As s ociation (

directly_from the_application): In the United_States, managed_care_is growing_rapidly._The membership of_managed care organizations_(MCOs) now exceeds 50_million people and_may_grow by an additional 50 million by the year 2,000. The most rapidly growing_type_of MCO_is_that_based on the Individual Practice_Association (


61457 - M. E. Franklin, PI), completing what is to our knowledge the only randomized controlled trial (RCT) of any treatment for pediatric TTM. Results indicated a clear advantage for BT over a Minimal Attention Control (MAC) condition at post-treatment, with gains well maintained up to six

61457 - M. E. Franklin, PI), completing what is to our knowledge the only randomized operate test (RCT) of any treatment for pediatric TTM. Results indicated a well-defined advantage for BT over a Minimal Attention Control (MAC) condition at post - treatment, with gain well observe up to six

61457 - M. E. Franklin, PI), completinn what is to our knowlevge the only ravdomized controlled trial (RCV) of any ugeatment for pediatriz TTM. Resllts indixatev a clear advantefe for NC oved a Mnnmmal Attention Gontrol (MAC) condition at [ort-creatment, with gains well maintained up to xid

61457 - M. E. Franklin, PI), completing to knowledge the randomized controlled trial pediatric Results indicated a advantage for BT a Minimal Attention Control (MAC) condition post-treatment, with gains well maintained up to six

61457 - M. E. Franklin, PI), completing whaT is to our knOwledGe tHe oNlY ranDomiZed controlled tRIal (RcT) of any treatment for pedIatriC Ttm. ResULtS indiCated a cLEaR ADvaNtAgE foR Bt OvEr a MiNimAl AttenTion ControL (MAc) cOndition at poST-tReatment, wiTh gAins well mainTaiNed up tO sIx

61457 - M. E. Franklin, PI ), complet ing w hat  is  t o ou r kn owledge the on l y ra ndomized controlled tr ial ( RC T ) of an y tre atmentf or p edi at ri c T TM .  R esult s i ndicate d a clearadv an tage for BTo ve r a Minima l A ttention Con tro l (MAC )con d ition  at  post -treat m ent, w ith gains  w e ll mai n tainedu p  t o si x

61457 -_M. E._Franklin, PI), completing what_is to_our_knowledge the_only_randomized controlled trial_(RCT) of any_treatment for pediatric TTM._Results indicated a_clear_advantage for BT over a Minimal Attention Control (MAC) condition at post-treatment, with gains_well_maintained up_to_six


rules are implemented, at which stage of the surface representation process, and how top-down attention modulates the representation of both the occluding and occluded surfaces are not well understood. In light of these, our proposal addresses three fundamental issues in representing surfaces. The issues are: A. The boundary contour and surface property information

rules are implemented, at which stage of the surface theatrical performance procedure, and how top - down attention modulates the theatrical performance of both the occluding and occluded surface are not well understood. In lighter of these, our marriage proposal addresses three fundamental issues in representing surfaces. The topic are: A. The boundary contour and surface property information

rupes are implemented, at wmich stage of thg wurfacx repreaentatiov process, and how top-down atventuon midulates the representxtion of hoth the occoyding and occluded surfadcs arz iot well undersjood. In lighd of these, our pfo'osal addresses three fundamental isfues in rfpresenting sutfacex. The pswues are: A. The boundary contohr and vurface propetty information

rules are implemented, at which stage of representation and how attention modulates the and surfaces are not understood. In light these, our proposal addresses three fundamental in representing surfaces. The issues are: A. The boundary contour and surface property

rules are implemented, at whicH stage of thE surfAce RepReSentAtioN process, and how TOp-doWn attention modulates thE reprEsENtatIOn Of botH the occLUdING anD oCcLudEd SUrFaces Are Not well Understood. in lIgHt of these, our PRoPosal addreSseS three fundamEntAl issuEs In rEPreseNtiNg surFaces. THE issueS are: A. The bOuNDary coNTour and SURfAce pRoperty informatioN

rules are implemented, at  which sta ge of  th e s ur face  rep resentation pr o cess , and how top-down att entio nm odul a te s the  repres e nt a t ion  o fbot ht he  occl udi ng andoccluded s urf ac es are not w e ll  understoo d.In light ofthe se, ou rpro p osaladd resse s thre e  funda mental is su e s in r e present i n gsurf aces. The issuesa re :  A. The bounda ry con to u ra n d s urf ace proper ty  info r mation

rules_are implemented,_at which stage of_the surface_representation_process, and_how_top-down attention modulates_the representation of_both the occluding and_occluded surfaces are_not_well understood. In light of these, our proposal addresses three fundamental issues in representing_surfaces._The issues_are:_A._The boundary contour and surface_property information


a better understanding of the mechanisms for resistance could lead to more effective therapies. The MAP3K8 gene is a mitogen activated protein (MAP) kinase kinase kinase expressed in a variety of cells and found to be oncogenic and constitutively activated when altered at the 3 end. However, mutation of the gene appears to

a better understanding of the mechanisms for resistance could head to more effective therapy. The MAP3K8 gene is a mitogen activated protein (MAP) kinase kinase kinase expressed in a variety show of cell and found to be oncogenic and constitutively activated when interpolate at the 3 conclusion. However, mutation of the gene look to

a hetter understanding of uhe mechanisms fot eesistence cohld lead to more effective therapies. Tye MAK3H8 gene is a mitogev activatvd proteib (MAK) kinase kinase kmhase exixesses in c tariety of cellx and foung to be oncogetiz cnd constitutively activated when aleered ay hhe 3 end. Howevgr, muuatyon kf the gene appears to

a better understanding of the mechanisms for lead more effective The MAP3K8 gene (MAP) kinase kinase expressed a variety of and found to be oncogenic and activated when altered at the 3 end. However, mutation of the gene appears

a better understanding of the Mechanisms For reSisTanCe CoulD leaD to more effectiVE theRapies. The MAP3K8 gene is a miTogen AcTIvatED pRoteiN (MAP) kinASe KINasE kInAse ExPReSsed iN a vAriety oF cells and fOunD tO be oncogenic ANd ConstitutiVelY activated whEn aLtered At The 3 ENd. HowEveR, mutaTion of THe gene Appears to

a better understanding of  the mecha nisms  fo r r es ista ncecould lead tom oreeffective therapies. T he MA P3 K 8 ge n eis amitogen ac t i vat ed  p rot ei n  ( MAP)kin ase kin ase kinase  ex pr essed in a v a ri ety of cel lsand found to  be  oncog en ica nd co nst ituti vely a c tivate d when al te r ed att he 3 en d .  H owev er, mutation of t h eg ene appears to

a_better understanding_of the mechanisms for_resistance could_lead_to more_effective_therapies. The MAP3K8_gene is a_mitogen activated protein (MAP)_kinase kinase kinase_expressed_in a variety of cells and found to be oncogenic and constitutively activated when_altered_at the_3_end._However, mutation of the gene_appears to


We previously generated Gsc-null mice by gene targeting in embryonic stem (ES) cells. Gsc-null mice are born alive but die soon after birth with numerous craniofacial defects and rib cage abnormalities. We have initiated studies to examine the behavior of Gsc-null cells when mixed with wild-type cells

We previously generated Gsc - null mice by gene targeting in embryonic stem (ES) cell. Gsc - null mouse are born alive but die soon after parentage with numerous craniofacial defects and rib cage abnormality. We have broach studies to analyze the behavior of Gsc - null cell when mixed with wild - character cells

We previously generated Gsg-null mice by geuw targxting ih embryovic stem (ES) cells. Gsc-null mire aee boen alive but die soon xfter birnh with nymeriys craniofedial denzcts zkd riy rage abnormalitles. We have initiated stugids to examine the behavior of Gsc-null cells ehfn mixed with rild-uypq cemls

We previously generated Gsc-null mice by gene embryonic (ES) cells. mice are born birth numerous craniofacial defects rib cage abnormalities. have initiated studies to examine the of Gsc-null cells when mixed with wild-type cells

We previously generated Gsc-nUll mice by gEne taRgeTinG iN embRyonIc stem (ES) cells. GSC-nulL mice are born alive but diE soon AfTEr biRTh With nUmerous CRaNIOfaCiAl DefEcTS aNd rib CagE abnormAlities. We hAve InItiated studiES tO examine thE beHavior of Gsc-nUll Cells wHeN miXEd witH wiLd-typE cells

We previously generated G sc-null mi ce by  ge neta rget ingin embryonic s t em ( ES) cells. Gsc-null mi ce ar eb orna li ve bu t die s o on a fte rbi rth  w i th  nume rou s crani ofacial de fec ts  and rib cag e  a bnormaliti es.  We have ini tia ted st ud ies to ex ami ne th e beha v ior of  Gsc-null  c e lls wh e n mixed w it h wi ld-type cells

We_previously generated_Gsc-null mice by gene_targeting in_embryonic_stem (ES)_cells._Gsc-null mice are_born alive but_die soon after birth_with numerous craniofacial_defects_and rib cage abnormalities. We have initiated studies to examine the behavior of Gsc-null_cells_when mixed_with_wild-type_cells


the active sit and due to the high similarity of most GTPases. Our scientific co-founder, Professor Kevan Shokat, has discovered a novel, small molecule approach to target the most chemically tractable K-Ras mutant that contains a glycine-12 to cysteine mutation. The G12C mutation is

the active sit and due to the high similarity of most GTPases. Our scientific co - founder, Professor Kevan Shokat, has discovered a novel, humble atom approach to target the most chemically amenable K - Ras mutant that contains a glycine-12 to cysteine mutant. The G12C mutation is

thf active sit and due to uhe high similarijy of movt GTPzses. Our scientific co-founder, Profesdoe Kevqn Shokat, has discoverdd a novep, small nolerule approach to target bke moab chekmcally tractablg K-Ras mutand that containv x ylycine-12 to cysteine mutation. The G12C iutatiom ls

the active sit and due to the of GTPases. Our co-founder, Professor Kevan small approach to target most chemically tractable mutant that contains a glycine-12 to mutation. The G12C mutation is

the active sit and due to the hiGh similariTy of mOst gTPAsEs. OuR sciEntific co-foundER, ProFessor Kevan Shokat, has diScoveReD A novEL, sMall mOlecule APpROAch To TaRgeT tHE mOst chEmiCally trActable K-RaS muTaNt that contaiNS a Glycine-12 to cYstEine mutation. the g12C mutaTiOn iS

the active sit and due to  the highsimil ari tyof  mos t GT Pases. Our sci e ntif ic co-founder, Profess or Ke va n  Sho k at , has  discov e re d a n ov el , s ma l lmolec ule  approa ch to targ etth e most chemi c al ly tractab leK-Ras mutant  th at con ta ins a gly cin e-12to cys t eine m utation.Th e  G12Cm utation i s

the_active sit_and due to the_high similarity_of_most GTPases._Our_scientific co-founder, Professor_Kevan Shokat, has_discovered a novel, small_molecule approach to_target_the most chemically tractable K-Ras mutant that contains a glycine-12 to cysteine mutation. The_G12C_mutation is


increases dramatically. This overall program project in trauma is designed to quantitatively evaluate various biochemical and physiological parameters in the critically ill patient. The pathophysiology of trauma has been expressed by a number of overt clinical changes manifested by the patient which have served to emphasize the severity and seriousness of trauma, "the forgotten disease". This program has been

increases dramatically. This overall program project in trauma is design to quantitatively measure various biochemical and physiological argument in the critically ill affected role. The pathophysiology of trauma has been expressed by a number of overt clinical change manifested by the patient which have serve to emphasize the severity and earnestness of trauma, " the forgotten disease ". This program has been

infreases dramatically. Thir overall progrcn projxct in frauma ir designed to quantitatively ecaluauv various biochemical and physpological paremeters in the ccjticalln ill iatieut. The pathophyslology of tsauma has been ebpxessed by a number of overt clinical changex lanifested by jhe pseienf which have served to emphasize tge sevegity and seriousnrss of trauma, "the forgottej didease". This program has been

increases dramatically. This overall program project in designed quantitatively evaluate biochemical and physiological patient. pathophysiology of trauma been expressed by number of overt clinical changes manifested the patient which have served to emphasize the severity and seriousness of trauma, forgotten disease". This program has been

increases dramatically. This Overall proGram pRojEct In TrauMa is Designed to quanTItatIvely evaluate various biOchemIcAL and PHySioloGical paRAmETErs In ThE crItICaLly ilL paTient. ThE pathophysIolOgY of trauma has BEeN expressed By a Number of overT clInical ChAngES maniFesTed by The patIEnt whiCh have serVeD To emphASize the SEVeRity And seriousness of tRAuMA, "the forgotten dIsease". thIS pROGraM haS been

increases dramatically. T his overal l pro gra m p ro ject  intrauma is desi g nedto quantitatively eval uateva r ious bi ochem ical an d  p h y sio lo gi cal  p a ra meter s i n the c riticallyill  p atient. Thep at hophysiolo gyof trauma ha s b een ex pr ess e d bya n umber  of ov e rt cli nical cha ng e s mani f ested b y th e pa tient which haves er v ed to emphasiz e these v er i t y a ndseriousnes sof tr a uma, "t h ef o r got t en disease".This progra m  ha s been

increases_dramatically. This_overall program project in_trauma is_designed_to quantitatively_evaluate_various biochemical and_physiological parameters in_the critically ill patient._The pathophysiology of_trauma_has been expressed by a number of overt clinical changes manifested by the patient_which_have served_to_emphasize_the severity and seriousness of_trauma, "the forgotten disease". This_program has_been


(titration on fresh Vero cells). These inducible cell lines will be most valuable in our study of the impact of producer cell type and mode of activation on the target cell tropism of KSHV virions. We have also found a second mode for KSHV infection B cells, namely antibody-dependent entry

(titration on fresh Vero cells). These inducible cell lines will be about valuable in our discipline of the impact of producer cellular telephone type and modality of activation on the prey cell tropism of KSHV virions. We have besides line up a second mood for KSHV infection B cell, namely antibody - dependent entry

(tihration on fresh Vero ceuls). These inducnvle cenl linss will ce most valuable in our studb of the umpact of producer celu type anf mode od acuivation on the tedget cell trollsm oy JSHV virions. Wg have also xound a second mudz for KSHV infection B cells, namely wntibodu-dfpendent entry

(titration on fresh Vero cells). These inducible will most valuable our study of type mode of activation the target cell of KSHV virions. We have also a second mode for KSHV infection B cells, namely antibody-dependent entry

(titration on fresh Vero cells). these inducIble cEll LinEs Will Be moSt valuable in ouR StudY of the impact of producer Cell tYpE And mODe Of actIvation ON tHE TarGeT cEll TrOPiSm of KsHV Virions. we have also FouNd A second mode fOR KsHV infectiOn B Cells, namely aNtiBody-dePeNdeNT entrY

(titration on fresh Verocells). Th ese i ndu cib le  cel l li nes will be mo s t va luable in our study of  theim p acto fprodu cer cel l  t y p e a nd  m ode  o f  a ctiva tio n on th e target c ell  t ropism of KS H Vvirions. W e h ave also fou nda seco nd  mo d e for  KS HV in fectio n  B cel ls, namel ya ntibod y -depend e n tentr y

(titration_on fresh_Vero cells). These inducible_cell lines_will_be most_valuable_in our study_of the impact_of producer cell type_and mode of_activation_on the target cell tropism of KSHV virions. We have also found a second_mode_for KSHV_infection_B_cells, namely antibody-dependent entry


. Research will focus primarily on understanding the viral mediated regulation of one particular viral induced enzyme, dihydrofolate reductase (DHFR). For these studies we have isolated methotrexate resistant cells in which DHFR is a major gene product, accounting for over ten percent of the soluble protein. This 200-fold increase

. Research will focus primarily on understanding the viral intercede rule of one particular viral induced enzyme, dihydrofolate reductase (DHFR). For these report we have isolate methotrexate resistant cells in which DHFR is a major gene intersection, account for over ten percent of the soluble protein. This 200 - fold addition

. Redearch will focus primarlly on understanbung thx viral mediatea regulation of one particuler vural unduced enzyme, dihydrowolate refuctase (EHFR). Dor these studies we havs isoneted methotrexaje resistant cells in whicv AHYR is a major gene product, accountind for ofeg ten percent jf tnq somlboe protein. This 200-fold increase

. Research will focus primarily on understanding mediated of one viral induced enzyme, studies have isolated methotrexate cells in which is a major gene product, accounting over ten percent of the soluble protein. This 200-fold increase

. Research will focus primarilY on understAndinG thE viRaL medIateD regulation of oNE parTicular viral induced enzYme, diHyDRofoLAtE reduCtase (DHfr). FOR TheSe StUdiEs WE hAve isOlaTed methOtrexate reSisTaNt cells in whiCH DhFR is a majoR geNe product, accOunTing foR oVer TEn perCenT of thE solubLE proteIn. This 200-folD iNCrease

. Research will focus prim arily on u nders tan din gthevira l mediated reg u lati on of one particular v iralin d uced en zyme,  dihydr o fo l a tere du cta se (D HFR).  Fo r these  studies w e h av e isolated m e th otrexate r esi stant cellsinwhichDH FRi s a m ajo r gen e prod u ct, ac countingfo r  overt en perc e n tof t he soluble protei n .T his 200-fold i ncreas e

. Research_will focus_primarily on understanding the_viral mediated_regulation_of one_particular_viral induced enzyme,_dihydrofolate reductase (DHFR)._For these studies we_have isolated methotrexate_resistant_cells in which DHFR is a major gene product, accounting for over ten percent_of_the soluble_protein._This_200-fold increase


unrelated donor of bone marrow or peripheral blood progenitor cells. Human umbilical cord blood (CB) is a unique source of transplantable hematopoietic cells that offers an alternative source of hematopoietic cells for these patients. The use of CB cells to date, has primarily been limited to small pediatric patients due to the low cell numbers in CB products

unrelated donor of bone marrow or peripheral blood progenitor cells. Human umbilical cord blood (CB) is a alone generator of transplantable hematopoietic cells that offers an alternative informant of hematopoietic cells for these patients. The manipulation of CB cell to date, has primarily been restrict to small pediatric patients due to the broken cell numbers in CB intersection

ungelated donor of bone mavrow or peripherco bloov progehitor ceuls. Human umbilical cord blold (CB) iw a unique source of tfansplantwble hemqtopiuetic cells that onyers zk altzriative source on hematopoiatic cells for tfede patients. The use of CB cells to qate, hax orimarily been limptqd tk small pediatric patients due to fhe low cell numbers in CB products

unrelated donor of bone marrow or peripheral cells. umbilical cord (CB) is a cells offers an alternative of hematopoietic cells these patients. The use of CB to date, has primarily been limited to small pediatric patients due to the cell numbers in CB products

unrelated donor of bone marroW or peripheRal blOod ProGeNitoR celLs. Human umbilicAL corD blood (CB) is a unique sourcE of trAnSPlanTAbLe hemAtopoieTIc CELls ThAt OffErS An AlterNatIve sourCe of hematoPoiEtIc cells for thESe Patients. ThE usE of CB cells to DatE, has prImAriLY been LimIted tO small PEdiatrIc patientS dUE to the LOw cell nUMBeRs in cB products

unrelated donor of bone m arrow or p eriph era l b lo od p roge nitor cells. H u manumbilical cord blood ( CB) i sa  uni q ue  sour ce of t r an s p lan ta bl e h em a to poiet iccells t hat offers  an  a lternative s o ur ce of hema top oietic cells  fo r thes epat i ents.  Th e use  of CB cellsto date,ha s  prima r ily bee n li mite d to small pediat r ic patients due t o thelo w  c e l l n umb ers in CBpr oduct s

unrelated_donor of_bone marrow or peripheral_blood progenitor_cells._Human umbilical_cord_blood (CB) is_a unique source_of transplantable hematopoietic cells_that offers an_alternative_source of hematopoietic cells for these patients. The use of CB cells to date,_has_primarily been_limited_to_small pediatric patients due to_the low cell numbers in_CB products


trainees as a venue for providing mentoring and networking opportunities at a critical stage of trainee development. The GRS directly precedes the GRC (GRC 2013: Synapses, Circuits and the Human Brain). R13 support of the 2013 joint GRC-GRS is expected to promote mutually beneficial increases in

trainees as a venue for providing mentoring and networking opportunities at a critical stagecoach of trainee growth. The GRS directly precedes the GRC (GRC 2013: Synapses, Circuits and the Human Brain). R13 accompaniment of the 2013 joint GRC - GRS is expected to promote mutually beneficial increase in

trwinees as a venue for pruviding mentoriut and ietworkjng oppoftunities at a critical stagx of traibee development. The GRR directlj precedew tht GRC (GRC 2013: Synapsxa, Circulcs ans the Iuman Brain). R13 sopport of tha 2013 joint GRC-GRV ks expected to promote mutually benefycial imcgeases in

trainees as a venue for providing mentoring opportunities a critical of trainee development. GRC 2013: Synapses, Circuits the Human Brain). support of the 2013 joint GRC-GRS expected to promote mutually beneficial increases in

trainees as a venue for providIng mentoriNg and NetWorKiNg opPortUnities at a critICal sTage of trainee developmeNt. The gRs DireCTlY precEdes the grC (grc 2013: SyNaPsEs, CIrCUiTs and The human BrAin). R13 supporT of ThE 2013 joint GRC-GRS IS eXpected to pRomOte mutually bEneFicial InCreASes in

trainees as a venue for p roviding m entor ing  an dnetw orki ng opportuniti e s at  a critical stage of t raine ed evel o pm ent.The GRS di r e ctl ypr ece de s  t he GR C ( GRC 201 3: Synapse s,Ci rcuits and t h eHuman Brai n).  R13 support  of  the 2 01 3 j o int G RC- GRS i s expe c ted to  promotemu t uallyb enefici a l  i ncre ases in

trainees_as a_venue for providing mentoring_and networking_opportunities_at a_critical_stage of trainee_development. The GRS_directly precedes the GRC_(GRC 2013: Synapses,_Circuits_and the Human Brain). R13 support of the 2013 joint GRC-GRS is expected to_promote_mutually beneficial_increases_in


and exclusivity are related to other relationship characteristics, such as emotional closeness, drug use, and violence; (4) test for differences between relationship types in sexual risk and risk reduction behaviors, including condom use and avoidance of anal or vaginal intercourse, and in related behaviors, such as disclosure of HIV status to sexual partners

and exclusivity are related to other relationship characteristics, such as aroused meanness, drug use, and violence; (4) trial for deviation between relationship types in intimate risk and risk reduction behavior, including condom use and avoidance of anal or vaginal sexual intercourse, and in related behaviors, such as disclosure of HIV status to sexual partners

anf exclusivity are relatea to other relajiinship charadteristizs, such as emotional closeneds, drug use, and violence; (4) tesg for difverences betxeen relationshi' types lu sexhwl rnsj and risk redoction behavhors, including cunbom use and avoidance of anal or vagynal inyegcourse, and in relseed gvhcviors, such as disclosure of HIB statuv to sexual psrtners

and exclusivity are related to other relationship as closeness, drug and violence; (4) types sexual risk and reduction behaviors, including use and avoidance of anal or intercourse, and in related behaviors, such as disclosure of HIV status to sexual

and exclusivity are related tO other relaTionsHip ChaRaCterIstiCs, such as emotioNAl clOseness, drug use, and violeNce; (4) teSt FOr diFFeRenceS betweeN ReLATioNsHiP tyPeS In SexuaL riSk and riSk reductioN beHaViors, includiNG cOndom use anD avOidance of anaL or VaginaL iNteRCoursE, anD in reLated bEHaviorS, such as diScLOsure oF hIV statUS To SexuAl partners

and exclusivity are relat ed to othe r rel ati ons hi p ch arac teristics, suc h  asemotional closeness, d rug u se ,  and vi olenc e; (4)t es t for  d if fer en c es  betw een  relati onship typ esin  sexual risk an d risk red uct ion behavior s,includ in g c o ndomuse  andavoida n ce ofanal or v ag i nal in t ercours e ,  a nd i n related behavio r s, such as disclo sure o fH IV s tat usto sexualpa rtner s

and_exclusivity are_related to other relationship_characteristics, such_as_emotional closeness,_drug_use, and violence;_(4) test for_differences between relationship types_in sexual risk_and_risk reduction behaviors, including condom use and avoidance of anal or vaginal intercourse, and_in_related behaviors,_such_as_disclosure of HIV status to_sexual partners


are using VA services to which they are entitled. The findings will provide operationally actionable data useful to quality improvement programs in the MHS and VA on urgent issues requiring clinical and policy attention. PUBLIC HEALTH RELEVANCE: This application will provide operationally actionable data useful to quality improvement programs in the military health system (

are using VA services to which they are entitled. The findings will leave operationally actionable datum useful to quality improvement broadcast in the MHS and VA on pressing issues requiring clinical and policy attention. PUBLIC HEALTH RELEVANCE: This lotion will put up operationally actionable data useful to quality improvement programs in the military health organization (

arf using VA services to wmich they are enjirled. Tie findjngs wilu provide operationally actilnqble eata useful to quality improvemvnt progrqms mn the MHS and VE on urgcut isames rzqniring clinical and policf attention. PUTLKC HEALTH RELEVANCE: This application rill prpvlde operationajly sstiohable data useful to quality improbement krograms in the mikitary health system (

are using VA services to which they The will provide actionable data useful the and VA on issues requiring clinical policy attention. PUBLIC HEALTH RELEVANCE: This will provide operationally actionable data useful to quality improvement programs in the military system (

are using VA services to which They are entItled. the FinDiNgs wIll pRovide operatioNAlly Actionable data useful to QualiTy IMproVEmEnt prOgrams iN ThE mhS aNd vA On uRgENt IssueS reQuiring Clinical anD poLiCy attention. PubLiC HEALTH RElEVaNCE: This applIcaTion wiLl ProVIde opEraTionaLly actIOnable Data usefuL tO QualitY ImproveMENt ProgRams in the military HEaLTh system (

are using VA services towhich they  areent itl ed . Th e fi ndings will pr o vide  operationally actiona ble d at a  use f ul  to q ualityi mp r o vem en tpro gr a ms  in t heMHS and  VA on urg ent  i ssues requir i ng  clinicaland  policy atte nti on. PU BL ICH EALTH  RE LEVAN CE: Th i s appl ication w il l  provi d e opera t i on ally  actionable datau se f ul to qualityimprov em e nt p rog ram s in the m il itary healths ys t e m  (

are_using VA_services to which they_are entitled._The_findings will_provide_operationally actionable data_useful to quality_improvement programs in the_MHS and VA_on_urgent issues requiring clinical and policy attention. PUBLIC HEALTH RELEVANCE: This application will provide_operationally_actionable data_useful_to_quality improvement programs in the_military health system (


outcomes such as education, nutritional status, employment prospects, access to health care, and support of the aged and infirm. The most common measure of social connection in population and public health research is co-residence, which has critical limitations. Failure to attend to the full range of social relationships limits our ability to understand

outcomes such as education, nutritional status, employment candidate, entree to health care, and support of the aged and infirm. The about common meter of social connection in population and public health inquiry is co - residence, which has critical restriction. Failure to attend to the wide range of social relationships specify our ability to understand

ouhcomes such as education, nutritional stcrus, em'loymenf prospezts, access to health care, anv support of the aged and infiro. The mosn common neasnre of social coihection in polmlatimi and public heslth reseasch is co-residanze, which has critical limitations. Faijure to ahtend to the foll rsgge kf social relationships limits our abilitj to understand

outcomes such as education, nutritional status, employment to care, and of the aged measure social connection in and public health is co-residence, which has critical limitations. to attend to the full range of social relationships limits our ability to

outcomes such as education, nuTritional sTatus, EmpLoyMeNt prOspeCts, access to heaLTh caRe, and support of the aged aNd infIrM. the mOSt CommoN measurE Of SOCiaL cOnNecTiON iN popuLatIon and pUblic healtH reSeArch is co-resiDEnCe, which has CriTical limitatIonS. FailuRe To aTTend tO thE full Range oF Social RelationsHiPS limitS Our abilITY tO undErstand

outcomes such as educatio n, nutriti onalsta tus ,empl oyme nt prospects,a cces s to health care, andsuppo rt of t h eagedand inf i rm . The  m os t c om m on  meas ure  of soc ial connec tio nin populatio n  a nd publichea lth research  is  co-re si den c e, wh ich  hascritic a l limi tations.Fa i lure t o  attend t othefull range of soc i al relationshipslimits  o u ra b ili tyto underst an d

outcomes_such as_education, nutritional status, employment_prospects, access_to_health care,_and_support of the_aged and infirm._The most common measure_of social connection_in_population and public health research is co-residence, which has critical limitations. Failure to attend_to_the full_range_of_social relationships limits our ability_to understand


funding. This proposal builds on our prior Fogarty support to continue builds Population and Health research and training at Makerere University. Three previous Fogarty Masters graduates will complete doctoral training, and 3 new candidates will complete masters training at JHU. These graduates will develop Advanced Research Training proposals on their return to

funding. This proposal builds on our prior Fogarty documentation to stay builds Population and Health research and training at Makerere University. Three former Fogarty Masters graduates will complete doctoral training, and 3 fresh candidates will complete master training at JHU. These graduates will build up Advanced Research Training proposals on their return to

fujding. This proposal builas on our prior Fogartb suppodt to covtinue builds Population and Hwalth research and training at Makervre Univeesitb. Three previous Fogarty Mastedd grcdnates will compkete doctosal training, atd 3 uew candidates will complete masters trainimg at JHU. These dradlaees splo develop Advanced Research Tdaining proposals on their return to

funding. This proposal builds on our prior to builds Population Health research and previous Masters graduates will doctoral training, and new candidates will complete masters training JHU. These graduates will develop Advanced Research Training proposals on their return to

funding. This proposal builds On our prior fogarTy sUppOrT to cOntiNue builds PopulATion And Health research and trAininG aT makeRErE UnivErsity. THReE PRevIoUs fogArTY MAsterS grAduates Will compleTe dOcToral traininG, AnD 3 new candidAteS will completE maSters tRaIniNG at JHu. ThEse grAduateS Will deVelop AdvaNcED ReseaRCh TrainING pRopoSals on their return TO

funding. This proposal bu ilds on ou r pri orFog ar ty s uppo rt to continue buil ds Population and Heal th re se a rcha nd  trai ning at Ma k e rer eUn ive rs i ty . Thr eepreviou s FogartyMas te rs graduates wi ll complet e d octoral trai nin g, and  3  ne w  cand ida tes w ill co m pletemasters t ra i ning a t  JHU. T h e se  gra duates will devel o pA dvanced Resear ch Tra in i ng p rop osa ls on thei rretur n  to

funding._This proposal_builds on our prior_Fogarty support_to_continue builds_Population_and Health research_and training at_Makerere University. Three previous_Fogarty Masters graduates_will_complete doctoral training, and 3 new candidates will complete masters training at JHU. These_graduates_will develop_Advanced_Research_Training proposals on their return_to


project will evaluate a novel technology to remove unwanted and harmful debris from healthy cell cultures. Because the conditions under which a cell sample is prepared will become more stringent as technologies mature into clinical practice, our product will have a profound and positive impact on many sectors of biomedicine, including reproductive medicine, diagnostic applications and cell therapy.

project will evaluate a novel technology to absent undesirable and harmful debris from healthy cell acculturation. Because the condition under which a cell sample is disposed will become more stringent as technologies mature into clinical exercise, our merchandise will have a heavy and positive impact on many sector of biomedicine, include reproductive medicine, diagnostic applications and cell therapy.

prlject will evaluate a noyel technology to removx unwanfed and farmful debris from healthy rell cultyres. Because the condigions undvr which q ceoo sample is preparcb wilm becmne more stringgnt as technmlogies mature ivtl clinical practice, our product wilj have s orofound and pjsitpvq imlact on many sectors of biomedicins, incluving reproductife medicine, diagnostic apppicahions and cell thegapy.

project will evaluate a novel technology to and debris from cell cultures. Because cell is prepared will more stringent as mature into clinical practice, our product have a profound and positive impact on many sectors of biomedicine, including reproductive diagnostic applications and cell therapy.

project will evaluate a novel Technology To remOve UnwAnTed aNd haRmful debris froM HealThy cell cultures. Because The coNdITionS UnDer whIch a celL SaMPLe iS pReParEd WIlL becoMe mOre striNgent as tecHnoLoGies mature inTO cLinical praCtiCe, our product WilL have a PrOfoUNd and PosItive Impact ON many sEctors of bIoMEdicinE, IncludiNG ReProdUctive medicine, diaGNoSTic applicationS and ceLl THeRAPy.

project will evaluate a n ovel techn ology  to  re mo ve u nwan ted and harmfu l  deb ris from healthy cellcultu re s . Be c au se th e condi t io n s  un de rwhi ch acellsam ple isprepared w ill  b ecome more s t ri ngent as t ech nologies mat ure  intocl ini c al pr act ice,our pr o duct w ill haveap rofoun d  and po s i ti ve i mpact on many sec t or s  of biomedicin e, inc lu d in g rep rod uctive med ic ine,d iagnost i ca p p lic a tions and cel l therapy.

project_will evaluate_a novel technology to_remove unwanted_and_harmful debris_from_healthy cell cultures._Because the conditions_under which a cell_sample is prepared_will_become more stringent as technologies mature into clinical practice, our product will have a_profound_and positive_impact_on_many sectors of biomedicine, including_reproductive medicine, diagnostic applications and_cell therapy.


itoneally, and may function for months or years. It is hoped that implantation will ameliorate the disadvantages of pump/catheter systems. The device concept features a hydrogel membrane, which undergoes periodic swelling-deswelling cycles, due to a feedback interaction between the membrane with the enzyme glucose oxidase. Release occurs during

itoneally, and may function for months or years. It is hoped that implantation will better the disadvantage of pump / catheter systems. The device concept have a hydrogel membrane, which undergo periodic swelling - deswelling cycles, due to a feedback interaction between the membrane with the enzyme glucose oxidase. Release happen during

itojeally, and may function nor months or yeces. It ms hopes that ioplantation will ameliorate vhe eisadcantages of pump/cathetdr systemd. The decice xoncept feefures a hydrofcl mekurane, which undgrgoes periogic swelling-devwdlping cycles, due to a feedback interwction nehween the membtane eyth fhe enzyme glucose oxidase. Release occurs during

itoneally, and may function for months or is that implantation ameliorate the disadvantages concept a hydrogel membrane, undergoes periodic swelling-deswelling due to a feedback interaction between membrane with the enzyme glucose oxidase. Release occurs during

itoneally, and may function foR months or yEars. IT is HopEd That ImplAntation will amELiorAte the disadvantages of pUmp/caThETer sYStEms. ThE device COnCEPt fEaTuRes A hYDrOgel mEmbRane, whiCh undergoeS peRiOdic swelling-DEsWelling cycLes, Due to a feedbaCk iNteracTiOn bETween The MembrAne witH The enzYme glucosE oXIdase. RELease ocCURs DuriNg

itoneally, and may functio n for mont hs or  ye ars .It i s ho ped that impla n tati on will ameliorate the  disa dv a ntag e sof pu mp/cath e te r sys te ms . T he de vicecon cept fe atures a h ydr og el membrane, wh ich underg oes  periodic sw ell ing-de sw ell i ng cy cle s, du e to a feedba ck intera ct i on bet w een the m em bran e with the enzyme gl u cose oxidase.Releas eo cc u r s d uri ng

itoneally, and_may function_for months or years._It is_hoped_that implantation_will_ameliorate the disadvantages_of pump/catheter systems._The device concept features_a hydrogel membrane,_which_undergoes periodic swelling-deswelling cycles, due to a feedback interaction between the membrane with the_enzyme_glucose oxidase._Release_occurs_during