the neurobiological and functional consequences of chronic smoking in treated alcohol-dependent individuals. Specifically, we will continue our longitudinal 1.5 Tesla MR studies to quantitate regional brain structure, brain metabolites (reflecting neuronal and myelin viability), and regional cerebral blood flow as well as repeat comprehensive neurocognitive testing. In

the neurobiological and functional consequences of chronic smoking in treated alcohol - pendent person. Specifically, we will continue our longitudinal 1.5 Tesla MR studies to quantitate regional brain social organization, brain metabolites (reflecting neural and myelin viability), and regional cerebral lineage flow equally well as reprise comprehensive neurocognitive testing. In

thf neurobiological and fukctional consequgnxes of chronjc smokivg in treated alcohol-dependeit ibdivieuals. Specifically, we dill contpnue our oongmtudinal 1.5 Tesla MR studicf to euancivate regional btain structuse, brain metabmlktzs (reflecting neuronal and myelin viwbility), ajd regional cetebrak blokd flow as well as repeat comprehehsive nturocognitive testong. In

the neurobiological and functional consequences of chronic treated individuals. Specifically, will continue our to regional brain structure, metabolites (reflecting neuronal myelin viability), and regional cerebral blood as well as repeat comprehensive neurocognitive testing. In

the neurobiological and funcTional consEquenCes Of cHrOnic SmokIng in treated alCOhol-Dependent individuals. SpEcifiCaLLy, we WIlL contInue our LOnGITudInAl 1.5 tesLa mr sTudieS to QuantitAte regionaL brAiN structure, brAIn MetaboliteS (reFlecting neurOnaL and myElIn vIAbiliTy), aNd regIonal cERebral Blood flow As WEll as rEPeat comPREhEnsiVe neurocognitive tEStINg. In

the neurobiological and f unctionalconse que nce sof c hron ic smoking int reat ed alcohol-dependent i ndivi du a ls.S pe cific ally, w e  w i l l c on ti nue  o u rlongi tud inal 1. 5 Tesla MR  st ud ies to quant i ta te regiona l b rain structu re,  brain  m eta b olite s ( refle ctingn eurona l and mye li n  viabi l ity), a n d  r egio nal cerebral bloo d  f l ow as well asrepeat  c o mp r e hen siv e neurocog ni tivet esting. In

the_neurobiological and_functional consequences of chronic_smoking in_treated_alcohol-dependent individuals._Specifically,_we will continue_our longitudinal 1.5_Tesla MR studies to_quantitate regional brain_structure,_brain metabolites (reflecting neuronal and myelin viability), and regional cerebral blood flow as well_as_repeat comprehensive_neurocognitive_testing._In


channel" envisaged by the chemiosmotic theory. For this purpose we will use an isolated ATPase-membrane sector complex which is sensitive to the energy transfer inhibitor, dicyclohexylcarbodiimide. We are also trying to characterize a small peptide segment in the ATPase molecule which is involved in the

channel " envisaged by the chemiosmotic theory. For this purpose we will use an apart ATPase - membrane sector building complex which is sensitive to the energy transportation inhibitor, dicyclohexylcarbodiimide. We are also try to characterize a small peptide section in the ATPase atom which is involved in the

chajnel" envisaged by the chtmiosmotic theory. For thms purpkse we wkll use an isolated ATPase-melbeane wector complex which ir sensitine to the enecgy transfer inhmgitor, dleyclogcxylccruodiimide. We arg also tryinc to characterhzd c small peptide segment in the ATPasq molecilf which is invjlvec in fhe

channel" envisaged by the chemiosmotic theory. For we use an ATPase-membrane sector complex energy inhibitor, dicyclohexylcarbodiimide. We also trying to a small peptide segment in the molecule which is involved in the

channel" envisaged by the chemIosmotic thEory. FOr tHis PuRposE we wIll use an isolatED ATPAse-membrane sector complEx whiCh IS senSItIve to The enerGY tRANsfEr InHibItOR, dIcyclOheXylcarbOdiimide. We Are AlSo trying to chARaCterize a smAll Peptide segmeNt iN the ATpaSe mOLeculE whIch is InvolvED in the

channel" envisaged by thechemiosmot ic th eor y.Fo r th is p urpose we will usean isolated ATPase-mem brane  s e ctor co mplex  whichi ss e nsi ti ve  to  t h eenerg y t ransfer  inhibitor , d ic yclohexylcar b od iimide. We  ar e also tryin g t o char ac ter i ze asma ll pe ptides egment  in the A TP a se mol e cule wh i c his i nvolved in the

channel" envisaged_by the_chemiosmotic theory. For this_purpose we_will_use an_isolated_ATPase-membrane sector complex_which is sensitive_to the energy transfer_inhibitor, dicyclohexylcarbodiimide. We_are_also trying to characterize a small peptide segment in the ATPase molecule which is_involved_in the


. In 2004, West Bay Filipino Multi-Service Center (West Bay) joined forces with the UCSF: comprehensive Cancer Center (UCSF-CCC) and the San Francisco General (SFGH) Breast Care Program to start the first Filipina breast cancer support group (Sinag Tala) in San Francisco.

. In 2004, West Bay Filipino Multi - Service Center (West Bay) joined forces with the UCSF: comprehensive Cancer Center (UCSF - CCC) and the San Francisco General (SFGH) Breast Care Program to start the first Filipina breast cancer documentation group (Sinag Tala) in San Francisco.

. In 2004, West Bay Filipino Multl-Service Center (Cwst Bab) joines forces with the UCSF: comprehensive Cqncer Center (UCSF-CCC) and thd San Frajcisco Gwnerel (SFGH) Breast Cede Progvcm to dtarc vhe first Filiplna breast wancer support gfobp (Sinag Tala) in San Francisco.

. In 2004, West Bay Filipino Multi-Service Bay) forces with UCSF: comprehensive Cancer Francisco (SFGH) Breast Care to start the Filipina breast cancer support group (Sinag in San Francisco.

. In 2004, West Bay Filipino Multi-SerVice Center (west BAy) jOinEd ForcEs wiTh the UCSF: comprEHensIve Cancer Center (UCSF-CCC) And thE SAN FraNCiSco GeNeral (SFgh) BREAst caRe proGrAM tO starT thE first FIlipina breAst CaNcer support gROuP (Sinag Tala) In SAn Francisco.

. In 2004, West Bay Filipi no Multi-S ervic e C ent er  (We st B ay) joined for c es w ith the UCSF: comprehe nsive  C a ncer Ce nter(UCSF-C C C) a ndth eSan  F r an cisco  Ge neral ( SFGH) Brea stCa re Program t o  s tart the f irs t Filipina b rea st can ce r s u pport  gr oup ( SinagT ala) i n San Fra nc i sco.

. In_2004, West_Bay Filipino Multi-Service Center_(West Bay)_joined_forces with_the_UCSF: comprehensive Cancer_Center (UCSF-CCC) and_the San Francisco General_(SFGH) Breast Care_Program_to start the first Filipina breast cancer support group (Sinag Tala) in San Francisco.


(3) in order to establish their patterns of reactivity with selected nucleophilic coupling partners, especially with respect to stereo- and regiocontrol, and to develop applications of this chemistry in the synthesis of natural products and other biologically active compounds. Studies of the propargylium complexes 1 (L=CO) derived

( 3) in order to establish their patterns of reactivity with choose nucleophilic pair partners, especially with obedience to stereo- and regiocontrol, and to grow applications of this chemistry in the synthesis of lifelike products and other biologically active compounds. study of the propargylium complexes 1 (L = CO) derived

(3) in order to establish theiv patterns of recxtivitb with aelected nucleophilic coupling partnxrs, wspecually with respect to rtereo- anf regiocintrio, and to dxbelop ai'licaflons mh this chemistri in the syndhesis of natusau 'roducts and other biologically actide comppujds. Studies of the [ropzggnlium complexes 1 (L=CO) derived

(3) in order to establish their patterns with nucleophilic coupling especially with respect to applications of this in the synthesis natural products and other biologically active Studies of the propargylium complexes 1 (L=CO) derived

(3) in order to establish their paTterns of reActivIty WitH sElecTed nUcleophilic couPLing Partners, especially with RespeCt TO steREo- And reGiocontROl, AND to DeVeLop ApPLiCatioNs oF this chEmistry in tHe sYnThesis of natuRAl Products anD otHer biologicaLly Active CoMpoUNds. StUdiEs of tHe propARgyliuM complexeS 1 (L=co) derivED

(3) in order to establishtheir patt ernsofrea ct ivit y wi th selected nu c leop hilic coupling partner s, es pe c iall y  w ith r espectt os t ere o-  a ndre g io contr ol,  and to  develop a ppl ic ations of th i schemistryinthe synthesi s o f natu ra l p r oduct s a nd ot her bi o logica lly activ ec ompoun d s. Stud i e sof t he propargylium c o mp l exes 1 (L=CO)derive d

(3) in_order to_establish their patterns of_reactivity with_selected_nucleophilic coupling_partners,_especially with respect_to stereo- and_regiocontrol, and to develop_applications of this_chemistry_in the synthesis of natural products and other biologically active compounds. Studies of the_propargylium_complexes 1_(L=CO)_derived


basis for the development of TMEV-induced demyelinating disease, and defined a critical role for MHC class II-restricted, virus-specific DTH responses in the demyelinating process. We have also demonstrated that chronic CNS demyelination can occur in the apparent absence of neuroantigen-specific autoimmune responses

basis for the development of TMEV - induced demyelinating disease, and defined a critical function for MHC course II - restricted, virus - specific DTH responses in the demyelinating procedure. We have besides demonstrated that chronic CNS demyelination can occur in the apparent absence of neuroantigen - specific autoimmune response

badis for the development uf TMEV-induced bwmyeliiating sisease, xnd defined a critical role hor NHC coass II-restricted, virur-specific DTH responsts in the demyeliizting pvjcesa. We kate also demonsttated that cvronic CNS demfeuiuation can occur in the apparent absqnce of nfuroantigen-spesifib wutojmmune responses

basis for the development of TMEV-induced demyelinating defined critical role MHC class II-restricted, demyelinating We have also that chronic CNS can occur in the apparent absence neuroantigen-specific autoimmune responses

basis for the development of TmEV-induced DemyeLinAtiNg DiseAse, aNd defined a critICal rOle for MHC class II-restriCted, vIrUS-speCIfIc DTH ResponsES iN THe dEmYeLinAtINg ProceSs. WE have alSo demonstrAteD tHat chronic CNs DeMyelinatioN caN occur in the aPpaRent abSeNce OF neurOanTigen-SpecifIC autoiMmune respOnSEs

basis for the development  of TMEV-i nduce d d emy el inat ingdisease, and d e fine d a critical role forMHC c la s s II - re stric ted, vi r us - s pec if ic  DT Hr es ponse s i n the d emyelinati ngpr ocess. We ha v ealso demon str ated that ch ron ic CNS  d emy e linat ion  canoccuri n theapparentab s ence o f  neuroa n t ig en-s pecific autoimmun e  r e sponses

basis_for the_development of TMEV-induced demyelinating_disease, and_defined_a critical_role_for MHC class_II-restricted, virus-specific DTH_responses in the demyelinating_process. We have_also_demonstrated that chronic CNS demyelination can occur in the apparent absence of neuroantigen-specific autoimmune_responses


this new project is to elucidate specific mechanisms linking pathogenic changes in channel function or control to cell death. Imaging mRNA turnover in P-bodies and its application to brain ischemia Injured cells adapt to an insult by removing their mRNAs for storage or destruction. Both these processes occur in the same cytoplasmic foci referred to as P

this new project is to elucidate specific mechanisms connect infective changes in channel affair or dominance to cell death. Imaging messenger rna turnover in P - bodies and its lotion to mind ischemia Injured cell adapt to an insult by absent their messenger rna for storage or destruction. Both these summons occur in the same cytoplasmic focus referred to as P

thls new project is to elugidate specific mechanivms lihking paghogenic changes in channel huncrion ir control to cell deagh. Imaginh mRNA tyrnoter in P-bodies ais its ai'licaflon tm brain ischemis Injured wells adapt to av nnsult by removing their mRNAs for seorage pr destruction. Bjth uhefe pdocesses occur in the same cytoplaamic fobi referred to as P

this new project is to elucidate specific pathogenic in channel or control to in and its application brain ischemia Injured adapt to an insult by removing mRNAs for storage or destruction. Both these processes occur in the same cytoplasmic referred to as P

this new project is to elucidaTe specific MechaNisMs lInKing PathOgenic changes iN ChanNel function or control to Cell dEaTH. ImaGInG mRNA TurnoveR In p-BOdiEs AnD itS aPPlIcatiOn tO brain iSchemia InjUreD cElls adapt to aN InSult by remoVinG their mRNAs fOr sTorage Or DesTRuctiOn. BOth thEse proCEsses oCcur in the SaME cytopLAsmic foCI ReFerrEd to as P

this new project is to el ucidate sp ecifi c m ech an isms  lin king pathogeni c  cha nges in channel functi on or  c o ntro l  t o cel l death .  I m a gin gmR NAtu r no ver i n P -bodies  and its a ppl ic ation to bra i nischemia I nju red cells ad apt  to an  i nsu l t byrem oving  their mRNAsfor stora ge or des t ruction . Bo th t hese processes oc c ur in the same cy toplas mi c  f o c i r efe rred to as  P

this_new project_is to elucidate specific_mechanisms linking_pathogenic_changes in_channel_function or control_to cell death._Imaging mRNA turnover in_P-bodies and its_application_to brain ischemia Injured cells adapt to an insult by removing their mRNAs for_storage_or destruction._Both_these_processes occur in the same_cytoplasmic foci referred to as_P


and adjuvant studies. To conduct preclinical and clinical pilot studies for possible use by the Southwest Oncology Group. To provide core laboratory support and suitable administrative facilities for the clinical evaluation of various techniques to predict response to endocrine ablation in breast and other cancers. To utilize Southwest Oncology Group studies to link basic science to modern clinical care

and adjuvant studies. To conduct preclinical and clinical pilot report for potential use by the Southwest Oncology Group. To provide effect testing ground support and suitable administrative facility for the clinical evaluation of versatile techniques to bode reception to endocrine ablation in breast and other cancer. To utilize Southwest Oncology Group studies to connect basic skill to modern clinical care

anf adjuvant studies. To cokduct preclinical and cninicam pilot rtudies for possible use by vhe Wouthqest Oncology Group. To provide bore laboeatocy support and snjtable adminiabratire facilities fot the clinicdl evaluation mf vcrious techniques to predict responsq to encofrine ablation in nweasf and other cancers. To utilize Soufhwest Mncology Groul studies to link basic sclencf to modern clinicwl care

and adjuvant studies. To conduct preclinical and studies possible use the Southwest Oncology support suitable administrative facilities the clinical evaluation various techniques to predict response to ablation in breast and other cancers. To utilize Southwest Oncology Group studies to basic science to modern clinical care

and adjuvant studies. To conduCt precliniCal anD clIniCaL pilOt stUdies for possibLE use By the Southwest Oncology group. to PRoviDE cOre laBoratorY SuPPOrt AnD sUitAbLE aDminiStrAtive faCilities foR thE cLinical evaluATiOn of variouS teChniques to prEdiCt respOnSe tO EndocRinE ablaTion in BReast aNd other caNcERs. To utILize SouTHWeSt OnCology Group studieS To LInk basic sciencE to modErN ClINIcaL caRe

and adjuvant studies. Toconduct pr eclin ica l a nd  cli nica l pilot studie s  for  possible use by the S outhw es t  Onc o lo gy Gr oup. To pr o v ide  c or e l ab o ra torysup port an d suitable  ad mi nistrative f a ci lities for  th e clinical e val uation  o f v a rious  te chniq ues to predic t respons et o endo c rine ab l a ti on i n breast and othe r  c a ncers. To util ize So ut h we s t  On col ogy Groupst udies to link ba s i c  sc i ence to moder n clinicalc are

and_adjuvant studies._To conduct preclinical and_clinical pilot_studies_for possible_use_by the Southwest_Oncology Group. To_provide core laboratory support_and suitable administrative_facilities_for the clinical evaluation of various techniques to predict response to endocrine ablation in_breast_and other_cancers._To_utilize Southwest Oncology Group studies_to link basic science to_modern clinical_care


by eliciting protective antibody responses. Neutralizing antibodies are an important component of protective immunity against a wide range of viral infections in humans and in animal models. T cell help to B cells is a fundamental aspect of adaptive immunity to viruses and the generation of immunological memory. Follicular helper CD4 T cells (T

by eliciting protective antibody responses. Neutralizing antibodies are an important part of protective unsusceptibility against a wide range of viral infection in homo and in animal models. T cellular telephone help to B cells is a cardinal view of adaptive immunity to virus and the generation of immunological memory. Follicular helper CD4 T cell (T

by eliciting protective anuibody responses. Uwutralmzing ahtibodier are an important component od prouvctive immunity againrt a wide range od vical infections ii humans and ih anikel models. T celk help to T cells is a fgnaalental aspect of adaptive immunity eo viruxed and the genetatiom of jmmunological memory. Follicular hemper CD4 T cells (T

by eliciting protective antibody responses. Neutralizing antibodies important of protective against a wide humans in animal models. cell help to cells is a fundamental aspect of immunity to viruses and the generation of immunological memory. Follicular helper CD4 T (T

by eliciting protective antiBody responSes. NeUtrAliZiNg anTiboDies are an imporTAnt cOmponent of protective imMunitY aGAinsT A wIde raNge of viRAl INFecTiOnS in HuMAnS and iN anImal modEls. T cell heLp tO B Cells is a fundAMeNtal aspect Of aDaptive immunIty To viruSeS anD The geNerAtion Of immuNOlogicAl memory. FOlLIcular HElper CD4 t CElLs (T

by eliciting protective a ntibody re spons es.  Ne ut rali zing  antibodies ar e  animportant component of  prot ec t ivei mm unity  agains t  a w ide  r an geof vi ral i nfe ctionsin humansand  i n animal mod e ls . T cell h elp  to B cellsisa fund am ent a l asp ect  of a daptiv e  immun ity to vi ru s es and the gen e r at ionof immunologicalm em o ry. Follicular  helpe rC D4 T  ce lls  (T

by_eliciting protective_antibody responses. Neutralizing antibodies_are an_important_component of_protective_immunity against a_wide range of_viral infections in humans_and in animal_models._T cell help to B cells is a fundamental aspect of adaptive immunity to_viruses_and the_generation_of_immunological memory. Follicular helper CD4_T cells (T


especially for the cell culture laboratories. These are five autoclaves, each of which is devoted to a specific application based upon the sophistication of the autoclave and the type of steam it uses for the autoclave cycle; these applications include autoclaving large numbers of media bottles for tissue culture media, pip

especially for the cell culture laboratories. These are five autoclave, each of which is devoted to a specific lotion establish upon the sophistication of the autoclave and the type of steam it use for the autoclave cycle; these applications admit autoclaving large numbers of medium bottles for tissue culture medium, pip

esoecially for the cell cuuture laboratornws. Theve are five augoclaves, each of which is detotee to q specific application based upln the siphiwrication oh the aubjclabc and vhe type of stesm it uses for the autocnaxe cycle; these applications include attoclavonh large numberf of iediz bottles for tissue culture media, pip

especially for the cell culture laboratories. These autoclaves, of which devoted to a sophistication the autoclave and type of steam uses for the autoclave cycle; these include autoclaving large numbers of media bottles for tissue culture media, pip

especially for the cell cultuRe laboratoRies. THesE arE fIve aUtocLaves, each of whiCH is dEvoted to a specific appliCatioN bASed uPOn The soPhisticATiON Of tHe AuTocLaVE aNd the TypE of steaM it uses for The AuToclave cycle; THeSe applicatIonS include autoClaVing laRgE nuMBers oF meDia boTtles fOR tissuE culture mEdIA, pip

especially for the cell c ulture lab orato rie s.Th esearefive autoclave s , ea ch of which is devoted  to a  s p ecif i cappli cationb as e d  up on  t heso p hi stica tio n of th e autoclav e a nd  the type of st eam it use s f or the autoc lav e cycl e;  th e se ap pli catio ns inc l ude au toclaving  l a rge nu m bers of m ed ia b ottles for tissue cu l ture media, pi p

especially_for the_cell culture laboratories. These_are five_autoclaves,_each of_which_is devoted to_a specific application_based upon the sophistication_of the autoclave_and_the type of steam it uses for the autoclave cycle; these applications include autoclaving_large_numbers of_media_bottles_for tissue culture media, pip


. The laboratory design also facilitates timely and efficient processing of clinical samples. 2. Analytical Services The 3P Laboratory is designed as a facility for developing and executing a wide variety of bioanalytical methods, including processing and analyzing samples for PK/PD/PG studies in support of Phase I, II, III and chem

. The laboratory design also facilitates timely and effective processing of clinical sample. 2. Analytical Services The 3P Laboratory is designed as a facility for develop and execute a wide variety of bioanalytical method acting, admit processing and analyzing sample for PK / PD / PG studies in support of Phase I, II, III and chem

. Thf laboratory design also facilitates timely anv efficjent prozessing of clinical samples. 2. Abalytucal Services The 3P Lacoratory ps designwd aw a facilitb for deyzlopihn and xxecuting a widg variety of bioanalytical mdtkods, including processing and analyzyng samllfs for PK/PD/PG ftudpef in support of Phase I, II, III and chej

. The laboratory design also facilitates timely processing clinical samples. Analytical Services The a for developing and a wide variety bioanalytical methods, including processing and analyzing for PK/PD/PG studies in support of Phase I, II, III and chem

. The laboratory design also faCilitates tImely And EffIcIent ProcEssing of clinicAL samPles. 2. Analytical Services the 3P LAbORatoRY iS desiGned as a FAcILIty FoR dEveLoPInG and eXecUting a wIde variety Of bIoAnalytical meTHoDs, includinG prOcessing and aNalYzing sAmPleS For PK/pD/Pg studIes in sUPport oF Phase I, II, iIi And cheM

. The laboratory design al so facilit atestim ely  a nd e ffic ient processin g  ofclinical samples. 2. A nalyt ic a l Se r vi ces T he 3P L a bo r a tor yis  de si g ne d asa f acility  for devel opi ng  and executi n ga wide var iet y of bioanal yti cal me th ods ,  incl udi ng pr ocessi n g andanalyzing  s a mplesf or PK/P D / PG  stu dies in support o f  P h ase I, II, III  and c he m

. The_laboratory design_also facilitates timely and_efficient processing_of_clinical samples._2._Analytical Services The_3P Laboratory is_designed as a facility_for developing and_executing_a wide variety of bioanalytical methods, including processing and analyzing samples for PK/PD/PG studies_in_support of_Phase_I,_II, III and chem


the basis of cell-type specific blocks to differentiation and transformation caused by alterations in specific glycans. Our recent studies show that 1) oocyte-specific knockout of complex and hybrid 7V-glycans compromises ovulation and oocyte developmental competence, but fertilization, blastogenesis and implantation proceed in the absence of these

the basis of cell - type specific blocks to specialization and transformation cause by alterations in specific glycans. Our recent report testify that 1) oocyte - specific knockout of complex and hybrid 7V - glycans compromises ovulation and oocyte developmental competence, but fertilization, blastogenesis and implantation continue in the absence of these

thf basis of cell-type speclfic blocks to dndferenviation and travsformation caused by alteravionw in wpecific glycans. Our rdcent stufies shoq thet 1) oocyte-specifmd knockout of gomplzx and hybrid 7V-gkycans com[romises ovuladiun and oocyte developmental competencq, but frrhilization, blaftogtnefis znd implantation proceed in the abaence oh these

the basis of cell-type specific blocks to transformation by alterations specific glycans. Our oocyte-specific of complex and 7V-glycans compromises ovulation oocyte developmental competence, but fertilization, blastogenesis implantation proceed in the absence of these

the basis of cell-type specifiC blocks to dIfferEntIatIoN and TranSformation causED by aLterations in specific glYcans. ouR ReceNT sTudieS show thAT 1) oOCYte-SpEcIfiC kNOcKout oF coMplex anD hybrid 7V-glYcaNs Compromises oVUlAtion and ooCytE developmentAl cOmpeteNcE, buT FertiLizAtion, BlastoGEnesis And implanTaTIon proCEed in thE ABsEnce Of these

the basis of cell-type sp ecific blo cks t o d iff er enti atio n and transfor m atio n caused by alteration s insp e cifi c  g lycan s. Ourr ec e n t s tu di essh o wthat1)oocyte- specific k noc ko ut of comple x  a nd hybrid7V- glycans comp rom ises o vu lat i on an d o ocyte  devel o pmenta l compete nc e , butf ertiliz a t io n, b lastogenesis andi mp l antation proce ed inth e  a b s enc e o f these

the_basis of_cell-type specific blocks to_differentiation and_transformation_caused by_alterations_in specific glycans._Our recent studies_show that 1) oocyte-specific_knockout of complex_and_hybrid 7V-glycans compromises ovulation and oocyte developmental competence, but fertilization, blastogenesis and implantation proceed_in_the absence_of_these


fellows will be selected to attend. [unreadable] [unreadable] [unreadable] [unreadable] Programmed cell death occurs in many tissues of our bodies throughout life. The quick and efficient removal of dying cells is a critical step that protects neighboring cells, and is also an important part of tissue remodeling and wound healing. The

fellows will be selected to attend. [ unreadable ] [ indecipherable ] [ indecipherable ] [ indecipherable ] Programmed cell death occur in many tissues of our bodies throughout life sentence. The agile and efficient removal of dying cells is a critical step that protect neighboring cells, and is also an crucial share of tissue remodeling and wound healing. The

feplows will be selected tu attend. [unreadcvle] [unceadabls] [unreadxble] [unreadable] Programmed cxll eeath occurs in many tissuer of our hodies tyroujhout life. The qnjck and efficjcnt rzmival of dying gells is a writical step dhxt protects neighboring cells, and is wlso an ilportant part jf tpsfue dvmideling and wound healing. The

fellows will be selected to attend. [unreadable] [unreadable] cell death in many tissues The and efficient removal dying cells is critical step that protects neighboring cells, is also an important part of tissue remodeling and wound healing. The

fellows will be selected to atTend. [unreadAble] [uNreAdaBlE] [unrEadaBle] [unreadable] PROgraMmed cell death occurs in mAny tiSsUEs of OUr BodieS througHOuT LIfe. thE qUicK aND eFficiEnt Removal Of dying celLs iS a Critical step THaT protects nEigHboring cells, And Is also An ImpORtant ParT of tiSsue reMOdelinG and wound HeALing. ThE

fellows will be selectedto attend.  [unr ead abl e]  [un read able] [unreada b le][unreadable] Programme d cel ld eath oc cursin many ti s s ues  o four  b o di es th rou ghout l ife. The q uic kand efficien t  r emoval ofdyi ng cells isa c ritica lste p  that  pr otect s neig h boring  cells, a nd is als o  an imp o r ta nt p art of tissue rem o de l ing and woundhealin g. Th e

fellows_will be_selected to attend. [unreadable]_[unreadable] [unreadable]_[unreadable]_Programmed cell_death_occurs in many_tissues of our_bodies throughout life. The_quick and efficient_removal_of dying cells is a critical step that protects neighboring cells, and is also_an_important part_of_tissue_remodeling and wound healing. The


registration and vital statistics system and medical care services. The association between the use of hormonal contraceptives and thromboembolic diseases of the heart, lung and brain has now been fairly well established on a number of epidemiological studies conducted mainly in the United Kingdom and United States. Similar studies to confirm, or deny, such

registration and vital statistics system and aesculapian caution services. The association between the habit of hormonal contraceptive and thromboembolic diseases of the heart, lung and brain has nowadays been fairly well established on a act of epidemiological studies lead mainly in the United Kingdom and United States. Similar report to confirm, or deny, such

rehistration and vital stauistics system anb medicel care servicer. The association between thx usw of yormonal contraceptiver and thrlmboembooic viseases of the isart, luky and nrain ias now been falrly well evtablished on d vulber of epidemiological studies conqucted kalnly in the Unyted Hingsom and United States. Similar studjes to bonfirm, or deny, sich

registration and vital statistics system and medical The between the of hormonal contraceptives heart, and brain has been fairly well on a number of epidemiological studies mainly in the United Kingdom and United States. Similar studies to confirm, or such

registration and vital statiStics systeM and mEdiCal CaRe seRvicEs. The associatiON betWeen the use of hormonal coNtracEpTIves ANd ThromBoembolIC dISEasEs Of The HeARt, Lung aNd bRain has Now been faiRly WeLl establisheD On A number of ePidEmiological sTudIes conDuCteD MainlY in The UnIted KiNGdom anD United StAtES. SimilAR studieS TO cOnfiRm, or deny, such

registration and vital st atistics s ystem  an d m ed ical  car e services. Th e  ass ociation between the u se of  h o rmon a lcontr aceptiv e sa n d t hr om boe mb o li c dis eas es of t he heart,lun gand brain ha s  n ow been fa irl y well estab lis hed on  a  nu m ber o f e pidem iologi c al stu dies cond uc t ed mai n ly in t h e  U nite d Kingdom and Uni t ed States. Simila r stud ie s  t o con fir m, or deny ,such

registration_and vital_statistics system and medical_care services._The_association between_the_use of hormonal_contraceptives and thromboembolic_diseases of the heart,_lung and brain_has_now been fairly well established on a number of epidemiological studies conducted mainly in_the_United Kingdom_and_United_States. Similar studies to confirm,_or deny, such


making cartilage repair more globally accessible. Liver fibrosis is the excessive accumulation of extracellular matrix as a wound healing response to chronic injuries from a broad range of liver diseases, irrespective of the underlying etiology. Advanced liver fibrosis may lead to cirrhosis, liver failure, and neoplasia. Extracellular matrix deposition is crucial to wound healing by

making cartilage repair more globally accessible. Liver fibrosis is the excessive accumulation of extracellular matrix as a wound healing response to chronic wound from a wide range of liver diseases, irrespective of the underlie etiology. Advanced liver fibrosis may lead to cirrhosis, liver bankruptcy, and neoplasia. Extracellular matrix deposition is crucial to wound healing by

maning cartilage repair move globally accessible. Niver ribrosis is the excessive accumulatiln of eztracellular matrix as a wound jealing eespibse to chronic injmxies rvom a uroad range of kiver disedses, irrespecthvd lf the underlying etiology. Advanced liver gihrosis may leaq to sirrgosis, liver failure, and neoplasia. Sxtracenlular matrix deposition is crucial to aounf healing by

making cartilage repair more globally accessible. Liver the accumulation of matrix as a injuries a broad range liver diseases, irrespective the underlying etiology. Advanced liver fibrosis lead to cirrhosis, liver failure, and neoplasia. Extracellular matrix deposition is crucial to healing by

making cartilage repair more Globally acCessiBle. livEr FibrOsis Is the excessive ACcumUlation of extracellular MatriX aS A wouND hEalinG responSE tO CHroNiC iNjuRiES fRom a bRoaD range oF liver diseAseS, iRrespective oF ThE underlyinG etIology. AdvancEd lIver fiBrOsiS May leAd tO cirrHosis, lIVer faiLure, and neOpLAsia. ExTRacelluLAR mAtriX deposition is crucIAl TO wound healing bY

making cartilage repair m ore global ly ac ces sib le . Li verfibrosis is th e  exc essive accumulation of  extr ac e llul a rmatri x as aw ou n d  he al in g r es p on se to  ch ronic i njuries fr omabroad rangeo fliver dise ase s, irrespect ive  of th eund e rlyin g e tiolo gy. Ad v ancedliver fib ro s is may lead to c ir rhos is, liver failure ,  a n d neoplasia. E xtrace ll u la r mat rix  depositio nis cr u cial to wo u n d  he a ling by

making_cartilage repair_more globally accessible. Liver_fibrosis is_the_excessive accumulation_of_extracellular matrix as_a wound healing_response to chronic injuries_from a broad_range_of liver diseases, irrespective of the underlying etiology. Advanced liver fibrosis may lead to_cirrhosis,_liver failure,_and_neoplasia._Extracellular matrix deposition is crucial_to wound healing by


IN). In addition, SNP CCL3 459 C/T is associated with an increased rate to AIDS-87 in European Americans (p=0.003), and SNP CCL4 662 C/G is associated with apparent resistance to infection in African Americans (p=0.01). Subjects are also available for lung

IN). In addition, SNP CCL3 459 C / T is associated with an increased rate to AIDS-87 in European Americans (p=0.003), and SNP CCL4 662 C / G is consociate with apparent underground to infection in African Americans (p=0.01). Subjects are also available for lung

IN). Ln addition, SNP CCL3 459 C/T ls associated wijh an inrreased rate to AIDS-87 in European Americans ('=0.003), ane SNP CCL4 662 C/G is associated with appwrent rewistence to infectioi in Afrlean Ajcricaus (p=0.01). Subjects arg also availdble for lung

IN). In addition, SNP CCL3 459 C/T with increased rate AIDS-87 in European 662 is associated with resistance to infection African Americans (p=0.01). Subjects are also for lung

IN). In addition, SNP CCL3 459 C/T is assOciated witH an inCreAseD rAte tO AIDs-87 in European AmeRIcanS (p=0.003), and SNP CCL4 662 C/G is associaTed wiTh APparENt ResisTance to INfECTioN iN AFriCaN amEricaNs (p=0.01). subjectS are also avAilAbLe for lung

IN). In addition, SNP CCL3  459 C/T i s ass oci ate dwith  anincreased rate to A IDS-87 in European Ame rican s( p=0. 0 03 ), an d SNP C C L4 6 62C/ Gisas s oc iated  wi th appa rent resis tan ce  to infectio n  i n AfricanAme ricans (p=0. 01) . Subj ec tsa re al soavail able f o r lung

IN). In_addition, SNP_CCL3 459 C/T is_associated with_an_increased rate_to_AIDS-87 in European_Americans (p=0.003), and_SNP CCL4 662 C/G_is associated with_apparent_resistance to infection in African Americans (p=0.01). Subjects are also available for lung


IL-4- naive cell transition to IL-4+ cells at the single cell level. Finally, we will examine whether memory T helper cells are already committed to a specific cytokine potential or not. If we can demonstrate that IL-4+ cells are produced during the process of memory T cell generation, then this provides

IL-4- naive cell transition to IL-4 + cells at the individual cellular telephone level. Finally, we will test whether memory T benefactor cells are already committed to a specific cytokine electric potential or not. If we can demonstrate that IL-4 + cells are produced during the procedure of memory T cell genesis, then this provides

IL-4- naive cell transition tu IL-4+ cells at tkw singne celm level. Winally, we will examine whetier nemort T helper cells are auready colmitted ro a wpecific cbfokine ijtenflal ox iot. If we can dgmonstrate tvat IL-4+ cells ase pxoduced during the process of memory T cell gfneration, then thix probpdts

IL-4- naive cell transition to IL-4+ cells single level. Finally, will examine whether already to a specific potential or not. we can demonstrate that IL-4+ cells produced during the process of memory T cell generation, then this provides

IL-4- naive cell transition to IL-4+ Cells at the SinglE ceLl lEvEl. FiNallY, we will examine WHethEr memory T helper cells arE alreAdY CommITtEd to a SpecifiC CyTOKinE pOtEntIaL Or Not. If We cAn demonStrate that iL-4+ cElLs are produceD DuRing the proCesS of memory T ceLl gEneratIoN, thEN this ProVides

IL-4- naive cell transiti on to IL-4 + cel lsatth e si ngle  cell level. F i nall y, we will examine whe therme m oryT  h elper  cellsa re a lre ad ycom mi t te d toa s pecific  cytokinepot en tial or not. If  we can de mon strate thatIL- 4+ cel ls  ar e  prod uce d dur ing th e  proce ss of mem or y  T cel l  genera t i on , th en this provides

IL-4-_naive cell_transition to IL-4+ cells_at the_single_cell level._Finally,_we will examine_whether memory T_helper cells are already_committed to a_specific_cytokine potential or not. If we can demonstrate that IL-4+ cells are produced during_the_process of_memory_T_cell generation, then this provides


important role in inflammation-induced pain signaling.[unreadable] [unreadable] Phosphoproteomic analysis of Cdk5 targets: The human genome encodes over 500 different protein kinases, the key regulatory enzymes that catalyze the phosphorylation of proteins at about 100,000 different sites to reversibly control their functional activities. Defects in

important role in inflammation - induced annoyance signaling.[unreadable ] [ indecipherable ] Phosphoproteomic psychoanalysis of Cdk5 targets: The human genome encodes over 500 different protein kinases, the cardinal regulatory enzymes that catalyze the phosphorylation of proteins at approximately 100,000 unlike sites to reversibly control their functional activities. Defects in

imoortant role in inflammauion-induced pain signaliig.[unreasable] [unfeadable] Phosphoproteomic anelysus of Cdk5 targets: The human genome ejcodes ocer 500 eifferent 'dotein kinasea, the jey regulatory enzymes tvat catalyze tve pkosphorylation of proteins at about 100,000 differrnh sites to revgrsibkr cohnril their functional activitiea. Defecus in

important role in inflammation-induced pain signaling.[unreadable] [unreadable] of targets: The genome encodes over key enzymes that catalyze phosphorylation of proteins about 100,000 different sites to reversibly their functional activities. Defects in

important role in inflammatiOn-induced pAin siGnaLinG.[uNreaDablE] [unreadable] PhoSPhopRoteomic analysis of Cdk5 tArgetS: THE humAN gEnome Encodes OVeR 500 DIffErEnT prOtEIn KinasEs, tHe key reGulatory enZymEs That catalyze THe PhosphorylAtiOn of proteins At aBout 100,000 diFfEreNT siteS to ReverSibly cONtrol tHeir functIoNAl actiVIties. DeFECtS in

important role in inflamm ation-indu ced p ain  si gn alin g.[u nreadable] [un r eada ble] Phosphoproteomicanaly si s  ofC dk 5 tar gets: T h eh u man  g en ome  e n co des o ver  500 di fferent pr ote in  kinases, th e  k ey regulat ory  enzymes tha t c atalyz ethe phosp hor ylati on ofp rotein s at abou t1 00,000 differe n t  s ites  to reversibly co n tr o l their functi onal a ct i vi t i es.  De fects in

important_role in_inflammation-induced pain signaling.[unreadable] [unreadable]_Phosphoproteomic analysis_of_Cdk5 targets:_The_human genome encodes_over 500 different_protein kinases, the key_regulatory enzymes that_catalyze_the phosphorylation of proteins at about 100,000 different sites to reversibly control their functional_activities._Defects in


-repressor, UNC-37/Groucho, function in VA motor neurons to block inputs normally restricted to sister VB motor neurons. We developed cell specific microarray profiling methods to identify UNC-4 regulated genes in this pathway. One of these targets, CEH-12, is homologous to the conserved home

-repressor, UNC-37 / Groucho, function in VA motor neurons to block inputs normally restrict to baby VB motor neurons. We developed cellular telephone specific microarray profiling methods to name UNC-4 regulated genes in this pathway. One of these target, CEH-12, is homologous to the conserved family

-repgessor, UNC-37/Groucho, functiun in VA motor uwurons to blkck inpugs normally restricted to sidtwr VB motor neurons. We deveuoped celp specifuc mmcroarray profilmhg methods to ldentnfb UNC-4 regulated genes in dhis pathway. Ote oy these targets, CEH-12, is homologous to the comsfrved home

-repressor, UNC-37/Groucho, function in VA motor neurons inputs restricted to VB motor neurons. profiling to identify UNC-4 genes in this One of these targets, CEH-12, is to the conserved home

-repressor, UNC-37/Groucho, functiOn in VA motoR neurOns To bLoCk inPuts Normally restriCTed tO sister VB motor neurons. WE deveLoPEd ceLL sPecifIc microARrAY ProFiLiNg mEtHOdS to idEntIfy UNC-4 rEgulated geNes In This pathway. ONE oF these targEts, cEH-12, is homologOus To the cOnSerVEd homE

-repressor, UNC-37/Groucho , function  in V A m oto rneur onsto block input s  nor mally restricted to si sterVB moto r  n euron s. We d e ve l o ped  c el l s pe c if ic mi cro array p rofiling m eth od s to identif y  U NC-4 regul ate d genes in t his  pathw ay . O n e ofthe se ta rgets, CEH-12 , is homo lo g ous to the con s e rv ed h ome

-repressor, UNC-37/Groucho,_function in_VA motor neurons to_block inputs_normally_restricted to_sister_VB motor neurons._We developed cell_specific microarray profiling methods_to identify UNC-4_regulated_genes in this pathway. One of these targets, CEH-12, is homologous to the conserved_home


or into the granules in order to promote intermolecular complexing. In situ granule studies will also be carried out in order to verify the findings using isolated secretory granules. This proposal seeks funding to create and distribute a nationally representative 1 in 100 Public Use Microdata Sample of the 1920 United States Population Census. Public Use Samples

or into the granules in order to promote intermolecular complexing. In situ granule studies will besides be carry out in order to verify the finding use isolated secretory granules. This marriage proposal seeks funding to create and spread a nationally representative 1 in 100 Public Use Microdata Sample of the 1920 United States Population Census. Public Use Samples

or into the granules in oraer to promote nbtermoneculad complebing. In situ granule studies wull aoso be carried out in urder to nerify thw fiidings using isolated segxetorg grauuoes. This propoxal seeks xunding to credtd cnd distribute a nationally represeneative 1 ij 100 Public Use Iicrpqata Sample of the 1920 United States Popumation Bensus. Public Use Samples

or into the granules in order to complexing. situ granule will also be verify findings using isolated granules. This proposal funding to create and distribute a representative 1 in 100 Public Use Microdata Sample of the 1920 United States Census. Public Use Samples

or into the granules in order tO promote inTermoLecUlaR cOmplExinG. In situ granule STudiEs will also be carried out In ordEr TO verIFy The fiNdings uSInG ISolAtEd SecReTOrY granUleS. This prOposal seekS fuNdIng to create aND dIstribute a NatIonally repreSenTative 1 In 100 pubLIc Use micRodatA SamplE Of the 1920 UNited StatEs pOpulatIOn CensuS. pUbLic USe Samples

or into the granules in o rder to pr omote  in ter mo lecu larcomplexing. In situ  granule studies willalsobe carr i ed  outin orde r  t o ver if ythe  f i nd ingsusi ng isol ated secre tor ygranules. Th i sproposal s eek s funding to  cr eate a nd  di s tribu tea nat ionall y  repre sentative  1 in 100 PublicU s eMicr odata Sample of t h e1 920 United Sta tes Po pu l at i o n C ens us. Public  U se Sa m ples

or_into the_granules in order to_promote intermolecular_complexing._In situ_granule_studies will also_be carried out_in order to verify_the findings using_isolated_secretory granules. This proposal seeks funding to create and distribute a nationally representative 1_in_100 Public_Use_Microdata_Sample of the 1920 United_States Population Census. Public Use_Samples


address the ethical, legal, and social implications (ELSI) that relate to Center research. Our aims for the next funding cycle build on our strengths and expertise, support the mission of the Center, promote innovative research, engage stakeholders, and foster the development of the next generation of EHS innovation and networked researchers focused

address the ethical, legal, and social implications (ELSI) that relate to Center research. Our aim for the future funding cycle build on our military capability and expertise, support the deputation of the Center, promote innovative research, engage stakeholder, and foster the growth of the next genesis of EHS innovation and networked researchers concenter

adfress the ethical, legal, xnd social implnxationv (ELSI) that reuate to Center research. Our eims for uke next funding cycld build oj our steenguhs and expertise, support the mjdsiou if the Center, kromote innoeative researcv, dnyage stakeholders, and foster the devqlopmeny lf the next gegerauiog of VHW innovation and networked reaearchegs focused

address the ethical, legal, and social implications relate Center research. aims for the our and expertise, support mission of the promote innovative research, engage stakeholders, and the development of the next generation of EHS innovation and networked researchers focused

address the ethical, legal, and Social implIcatiOns (eLSi) tHat rElatE to Center reseaRCh. OuR aims for the next funding Cycle BuILd on OUr StrenGths and EXpERTisE, sUpPorT tHE mIssioN of The CentEr, promote iNnoVaTive research, ENgAge stakehoLdeRs, and foster tHe dEvelopMeNt oF The neXt gEneraTion of ehS innoVation and NeTWorked REsearchERS fOcusEd

address the ethical, lega l, and soc ial i mpl ica ti ons(ELS I) that relate to C enter research. Our ai ms fo rt he n e xt  fund ing cyc l eb u ild  o nour  s t re ngths  an d exper tise, supp ort  t he mission o f  t he Center,  pr omote innova tiv e rese ar ch, engag e s takeh olders ,  and f oster the  d e velopm e nt of t h e  n extgeneration of EHS in n ovation and ne tworke dr es e a rch ers  focused

address_the ethical,_legal, and social implications_(ELSI) that_relate_to Center_research._Our aims for_the next funding_cycle build on our_strengths and expertise,_support_the mission of the Center, promote innovative research, engage stakeholders, and foster the development_of_the next_generation_of_EHS innovation and networked researchers_focused


CFAR investigators, meeting the needs of the CFAR Working Groups, and cooperating with the other CFAR Cores to provide access to cutting edge technologies. This project examines factors affecting the incidence of racial harassment and discrimination, and the multiple consequences of the stress of racial harassment and discrimination. Research suggests that Hispanic employees who

CFAR investigators, meeting the needs of the CFAR Working Groups, and cooperating with the early CFAR core to provide entree to cutting boundary technologies. This project examine agent affecting the incidence of racial harassment and discrimination, and the multiple consequence of the stress of racial harassment and discrimination. Research indicate that Hispanic employees who

CFWR investigators, meeting the needs of tkw CFAR Workihg Groupr, and cooperating with the ovher CFAR Cores to provide accers to cutning edge tecinologies. This pckject ewcminea faccocs affecting thg incidence mf racial haravsoeut and discrimination, and the multipje consrqkences of the ftrexf of gagial harassment and discriminatikn. Reseerch suggests tnat Hispanic employees who

CFAR investigators, meeting the needs of the Groups, cooperating with other CFAR Cores edge This project examines affecting the incidence racial harassment and discrimination, and the consequences of the stress of racial harassment and discrimination. Research suggests that Hispanic who

CFAR investigators, meeting tHe needs of tHe CFAr WoRkiNg grouPs, anD cooperating wiTH the Other CFAR Cores to providE acceSs TO cutTInG edge TechnolOGiES. thiS pRoJecT eXAmInes fActOrs affeCting the inCidEnCe of racial haRAsSment and diScrImination, and The MultipLe ConSEquenCes Of the Stress OF raciaL harassmeNt ANd discRIminatiON. reSearCh suggests that HisPAnIC employees who

CFAR investigators, meeti ng the nee ds of  th e C FA R Wo rkin g Groups, andc oope rating with the otherCFARCo r es t o  p rovid e acces s  t o cut ti ng  ed ge te chnol ogi es. Thi s projectexa mi nes factorsa ff ecting the  in cidence of r aci al har as sme n t and  di scrim inatio n , andthe multi pl e  conse q uenceso f  t he s tress of racial h a ra s sment and disc rimina ti o n. R ese arc h suggests  t hat H i spanice mp l o y ees who

CFAR_investigators, meeting_the needs of the_CFAR Working_Groups,_and cooperating_with_the other CFAR_Cores to provide_access to cutting edge_technologies. This project_examines_factors affecting the incidence of racial harassment and discrimination, and the multiple consequences of_the_stress of_racial_harassment_and discrimination. Research suggests that_Hispanic employees who


transfer of an acetyl group to the hydroxylamine from either acetyl coenzyme A or an arylhydroxamic acid. The same enzyme is also capable of N-aetylation to yield arylacetamides or arylhydroxamic acids from arylamines or arylhydroxylamines, respectively. The N-, O- and N,

transfer of an acetyl group to the hydroxylamine from either acetyl coenzyme A or an arylhydroxamic acid. The same enzyme is also capable of N - aetylation to concede arylacetamides or arylhydroxamic acid from arylamines or arylhydroxylamines, respectively. The N-, O- and N,

trwnsfer of an acetyl grouk to the hydroxylcnine fcom eitger acethl coenzyme A or an arylhydrlxqmic qcid. The same enzyme ir also caiable of B-aetblation to yield arylacebcmidea or crblhydroxamic aclds from arflamines or arflfybroxylamines, respectively. The N-, O- anq N,

transfer of an acetyl group to the either coenzyme A an arylhydroxamic acid. capable N-aetylation to yield or arylhydroxamic acids arylamines or arylhydroxylamines, respectively. The N-, and N,

transfer of an acetyl group to The hydroxyLaminE frOm eItHer aCetyL coenzyme A or an ARylhYdroxamic acid. The same enZyme iS aLSo caPAbLe of N-AetylatIOn TO YieLd ArYlaCeTAmIdes oR arYlhydroXamic acids FroM aRylamines or aRYlHydroxylamIneS, respectivelY. ThE N-, O- and n,

transfer of an acetyl gro up to thehydro xyl ami ne  fro m ei ther acetyl co e nzym e A or an arylhydroxam ic ac id .  The sa me en zyme is al s o  ca pa bl e o fN -a etyla tio n to yi eld arylac eta mi des or arylh y dr oxamic aci dsfrom arylami nes  or ar yl hyd r oxyla min es, r espect i vely.The N-, O -a nd N,

transfer_of an_acetyl group to the_hydroxylamine from_either_acetyl coenzyme_A_or an arylhydroxamic_acid. The same_enzyme is also capable_of N-aetylation to_yield_arylacetamides or arylhydroxamic acids from arylamines or arylhydroxylamines, respectively. The N-, O- and N,


manipulating the arginase pathway on myeloid cells infiltration / activation in retinal IR injury and the therapeutic potential of BCT- 100. B) Describe the cross talk between the arginase pathway and HDAC3 and determine whether A1 in myeloid cells mediates its protective effect through suppression of HDAC3. The purpose of this

manipulating the arginase pathway on myeloid cells infiltration / activation in retinal IR wound and the curative electric potential of BCT- 100. B) Describe the cross lecture between the arginase pathway and HDAC3 and determine whether A1 in myeloid cells intercede its protective effect through suppression of HDAC3. The function of this

majipulating the arginase kathway on myeloib cells infilfration / activation in retinal IR inoury and uke therapeutic potengial of BBT- 100. B) Desxribt the cross talk ustween bke arflnase 'athway and HDAG3 and deterkine whether A1 iv lyeloid cells mediates its protectide effevt through supprgssiom of GDAC3. The purpose of this

manipulating the arginase pathway on myeloid cells activation retinal IR and the therapeutic Describe cross talk between arginase pathway and and determine whether A1 in myeloid mediates its protective effect through suppression of HDAC3. The purpose of this

manipulating the arginase paThway on myeLoid cEllS inFiLtraTion / Activation in reTInal iR injury and the therapeuTic poTeNTial OF BcT- 100. B) DeScribe tHE cROSs tAlK bEtwEeN ThE argiNasE pathwaY and HDAC3 anD deTeRmine whether a1 In Myeloid celLs mEdiates its prOteCtive eFfEct THrougH suPpresSion of hdAC3. The Purpose of ThIS

manipulating the arginase  pathway o n mye loi d c el ls i nfil tration / acti v atio n in retinal IR injury  andth e  the r ap eutic  potent i al o f B CT -100 .B )Descr ibe  the cr oss talk b etw ee n the argina s epathway an d H DAC3 and det erm ine wh et her A1 in  my eloid  cells mediat es its pr ot e ctivee ffect t h r ou gh s uppression of HDA C 3. The purpose of  this

manipulating_the arginase_pathway on myeloid cells_infiltration /_activation_in retinal_IR_injury and the_therapeutic potential of_BCT- 100. B) Describe_the cross talk_between_the arginase pathway and HDAC3 and determine whether A1 in myeloid cells mediates its_protective_effect through_suppression_of_HDAC3. The purpose of this


C3H mice was 901, 660, 939, and 782 days, respectively. The incidence of hematopoietic neoplasms (predominantly lymphomas) was significantly reduced in both mouse strains by TP treatment and both the onset and incidence of solid neoplasms was significantly reduced in CBA mice treated with TP. These preliminary

C3H mice was 901, 660, 939, and 782 days, respectively. The incidence of hematopoietic neoplasms (predominantly lymphomas) was significantly dilute in both shiner strains by TP treatment and both the attack and incidence of solid tumor was significantly reduced in CBA mouse cover with TP. These preliminary

C3H mice was 901, 660, 939, and 782 days, rtspectively. The iuxidencx of hejatopoiegic neoplasms (predominantly pynphomqs) was significantly rdduced in both moyse wrrains by VL treatment ahf boch the onset and incidence of solid neopnarmd was significantly reduced in CBA iice trrahed with TP. Thgse pgejimihary

C3H mice was 901, 660, 939, and respectively. incidence of neoplasms (predominantly lymphomas) mouse by TP treatment both the onset incidence of solid neoplasms was significantly in CBA mice treated with TP. These preliminary

C3H mice was 901, 660, 939, and 782 days, respectivEly. The inciDence Of hEmaToPoieTic nEoplasms (predomINantLy lymphomas) was significAntly ReDUced IN bOth moUse straINs BY tP tReAtMenT aND bOth thE onSet and iNcidence of SolId Neoplasms was SIgNificantly RedUced in CBA micE trEated wItH TP. tHese pRelIminaRy

C3H mice was 901, 660, 93 9, and 782  days , r esp ec tive ly.The incidenceo f he matopoietic neoplasms(pred om i nant l ylymph omas) w a ss i gni fi ca ntl yr ed ucedinboth mo use strain s b yTP treatment an d both the  on set and inci den ce ofso lid neopl asm s was  signi f icantl y reduced  i n  CBA m i ce trea t e dwith  TP. These prelim i na r y

C3H_mice was_901, 660, 939, and_782 days,_respectively._The incidence_of_hematopoietic neoplasms (predominantly_lymphomas) was significantly_reduced in both mouse_strains by TP_treatment_and both the onset and incidence of solid neoplasms was significantly reduced in CBA_mice_treated with_TP._These_preliminary


ERSHIP 4 PROGRAM AS AN INTEGRATED EFFORT 5 COLLABORATING INSTITUTIONS 5 PROJECT AND CORE SUMMARIES OF DISCUSSION 5 PROTECTION OF HUMAN SUBJECTS 7 VERTEBRATE ANIMALS 8 ADDITIONAL REVIEW CONSID

ERSHIP 4 PROGRAM AS AN INTEGRATED EFFORT 5 COLLABORATING INSTITUTIONS 5 PROJECT AND CORE SUMMARIES OF DISCUSSION 5 PROTECTION OF HUMAN discipline 7 VERTEBRATE animal 8 ADDITIONAL REVIEW CONSID

ERSJIP 4 PROGRAM AS AN INTEGVATED EFFORT 5 COLLABORAVING INATITUTIOVS 5 PROJECT AND CORE SUMMARIXS OD DISXUSSION 5 PROTECTION OF HUMAN SUHJECTS 7 CERTTBRATE ANIMALS 8 AVSITIONAL REVISA COUSMD

ERSHIP 4 PROGRAM AS AN INTEGRATED EFFORT INSTITUTIONS PROJECT AND SUMMARIES OF DISCUSSION 7 ANIMALS 8 ADDITIONAL CONSID

ERSHIP 4 PROGRAM AS AN INTEGRATeD EFFORT 5 COlLABOrATiNG iNsTITuTIOnS 5 PROJECT AND COre SUMmARIES OF DISCUSSION 5 PROTeCTIOn Of hUMAn sUbJECTs 7 VERTEBraTe anIMaLs 8 AdDItIonAl REVIeW CoNSID

ERSHIP 4 PROGRAM AS AN INT EGRATED EF FORT5 C OLL AB ORAT INGINSTITUTIONS 5 PROJ ECT AND CORE SUMMARIES  OF D IS C USSI O N5 PRO TECTION OF H UMA NSU BJE CT S  7  VERT EBR ATE ANI MALS 8 ADD ITI ON AL REVIEW CO N SI D

ERSHIP 4_PROGRAM AS_AN INTEGRATED EFFORT 5_COLLABORATING INSTITUTIONS_5_PROJECT AND_CORE_SUMMARIES OF DISCUSSION_5 PROTECTION OF_HUMAN SUBJECTS 7 VERTEBRATE_ANIMALS 8 ADDITIONAL_REVIEW_CONSID


to disaster; and (3) To identify the pathways by which risk factors and resilience resources influence trajectories of functional limitation. The aims will be addressed by building on a longitudinal panel of 1,977 people aged 65 to 80 when Hurricane Sandy hit New Jersey. Three post-hurricane self-reported assessments would complement data

to disaster; and (3) To identify the pathways by which risk divisor and resilience resource influence trajectories of functional limitation. The aim will be addressed by building on a longitudinal control panel of 1,977 multitude aged 65 to 80 when Hurricane Sandy reach New Jersey. Three post - hurricane self - reported assessments would complement datum

to disaster; and (3) To identiny the pathways yt whici risk ractors xnd resilience resources infpuwnce ugajectories of functiunal limination. Thw ainw will be esdressed by bhlldiny in a longitudikal panel ox 1,977 people aged 65 go 80 when Hurricane Sandy hit New Jersqy. Threr oost-hurricane felf-ge[ortsd assessments would complement dafa

to disaster; and (3) To identify the which factors and resources influence trajectories will addressed by building a longitudinal panel 1,977 people aged 65 to 80 Hurricane Sandy hit New Jersey. Three post-hurricane self-reported assessments would complement data

to disaster; and (3) To identify thE pathways bY whicH riSk fAcTors And rEsilience resouRCes iNfluence trajectories of FunctIoNAl liMItAtion. the aims WIlL BE adDrEsSed By BUiLding On a LongituDinal panel Of 1,977 pEoPle aged 65 to 80 wheN huRricane SanDy hIt New Jersey. THreE post-hUrRicANe selF-rePorteD assesSMents wOuld complEmENt data

to disaster; and (3) To i dentify th e pat hwa ysby  whi ch r isk factors an d  res ilience resources infl uence  t r ajec t or ies o f funct i on a l  li mi ta tio n. Th e aim s w ill beaddressedbybu ilding on al on gitudinalpan el of 1,977peo ple ag ed  65 to 80  wh en Hu rrican e  Sandy  hit NewJe r sey. T h ree pos t - hu rric ane self-reported as s essments would  compl em e nt d ata

to_disaster; and_(3) To identify the_pathways by_which_risk factors_and_resilience resources influence_trajectories of functional_limitation. The aims will_be addressed by_building_on a longitudinal panel of 1,977 people aged 65 to 80 when Hurricane Sandy_hit_New Jersey._Three_post-hurricane_self-reported assessments would complement data


EV, also comprises lineages, genotypes, or populations that differ in capacity to cause human disease. We propose to test this hypothesis using our existing geographic isolates of POW as well as additional isolates that we shall collect for their capacity to cause neurologic disease using a published mouse model for TBEV neurotropism. In

EV, also comprises lineages, genotypes, or population that disagree in capacity to cause human disease. We nominate to quiz this hypothesis using our exist geographic isolates of prisoner of war as well as additional isolates that we shall collect for their capacity to cause neurological disease using a published mouse model for TBEV neurotropism. In

EV, wlso comprises lineages, nenotypes, or popolqtions that siffer iv capacity to cause human dideqse. Wt propose to test tfis hypotjesis usung iyr existinj geograikic iallatzs of POW as welk as addithonal isolates tfac we shall collect for their capacitr to caisf neurologic dyseaxq usjng a published mouse model for TBSV neurmtropism. In

EV, also comprises lineages, genotypes, or populations in to cause disease. We propose our geographic isolates of as well as isolates that we shall collect for capacity to cause neurologic disease using a published mouse model for TBEV neurotropism.

EV, also comprises lineages, geNotypes, or pOpulaTioNs tHaT difFer iN capacity to cauSE humAn disease. We propose to teSt thiS hYPothESiS usinG our exiSTiNG GeoGrApHic IsOLaTes of pOW As well aS additionaL isOlAtes that we shALl Collect for TheIr capacity to CauSe neurOlOgiC DiseaSe uSing a PublisHEd mousE model for tBev neuroTRopism. IN

EV, also comprises lineage s, genotyp es, o r p opu la tion s th at differ in c a paci ty to cause human dise ase.We prop o se  to t est thi s  h y p oth es is  us in g  o ur ex ist ing geo graphic is ola te s of POW asw el l as addit ion al isolatestha t we s ha llc ollec t f or th eir ca p acityto causene u rologi c  diseas e us inga published mouse mo d el for TBEV ne urotro pi s m. I n

EV, also_comprises lineages,_genotypes, or populations that_differ in_capacity_to cause_human_disease. We propose_to test this_hypothesis using our existing_geographic isolates of_POW_as well as additional isolates that we shall collect for their capacity to cause_neurologic_disease using_a_published_mouse model for TBEV neurotropism._In


molecular diagnostic assays can be implemented in non-traditional healthcare settings. Gene delivery to the liver for inherited metabolic disorders provides the opportunity for specific treatment of two forms of glycogen storage disease (GSD). Glycogen accumulation due to single enzyme defects represents the prototype of metabolic storage disease. A detailed biochemical understanding and availability of mouse

molecular diagnostic assays can be implemented in non - traditional healthcare settings. Gene delivery to the liver for inherit metabolic disorder provides the opportunity for specific treatment of two forms of glycogen memory disease (GSD). Glycogen accumulation due to single enzyme blemish represent the prototype of metabolic storage disease. A detailed biochemical agreement and availability of mouse

mopecular diagnostic assayr can be implemgnred in non-trzditionau healthcare settings. Gene dxlivwry ti the liver for inheriged metabllic disirdecs provides the opportunlcy fod speeihic treatment on two forms of glycogen sdofaye disease (GSD). Glycogen accumulation due to slngle enzyme dgfectx repdvstnts the prototype of metabolic sforage visease. A detaiked biochemical understandlng wnd availability ov mouse

molecular diagnostic assays can be implemented in settings. delivery to liver for inherited for treatment of two of glycogen storage (GSD). Glycogen accumulation due to single defects represents the prototype of metabolic storage disease. A detailed biochemical understanding and of mouse

molecular diagnostic assays Can be impleMenteD in Non-TrAditIonaL healthcare setTIngs. gene delivery to the liver For inHeRIted MEtAboliC disordERs PROviDeS tHe oPpORtUnity For SpecifiC treatment Of tWo Forms of glycoGEn Storage disEasE (GSD). Glycogen AccUmulatIoN duE To sinGle EnzymE defecTS repreSents the pRoTOtype oF MetabolIC StOragE disease. A detailed BIoCHemical understAnding AnD AvAILabIliTy of mouse

molecular diagnostic assa ys can beimple men ted  i n no n-tr aditional heal t hcar e settings. Gene deliv ery t ot he l i ve r for  inheri t ed m eta bo li c d is o rd ers p rov ides th e opportun ity  f or specifict re atment oftwo  forms of gl yco gen st or age disea se(GSD) . Glyc o gen ac cumulatio nd ue tos ingle e n z ym e de fects representst he prototype of m etabol ic st o r age  di sease. A d et ailed biochem i ca l u nde r standing andavailabilit y  of  mouse

molecular_diagnostic assays_can be implemented in_non-traditional healthcare_settings._Gene delivery_to_the liver for_inherited metabolic disorders_provides the opportunity for_specific treatment of_two_forms of glycogen storage disease (GSD). Glycogen accumulation due to single enzyme defects represents_the_prototype of_metabolic_storage_disease. A detailed biochemical understanding_and availability of mouse


. The x-ray structures of MsbA bound to these compounds should provide a great insight into the molecular structural basis of drug transport by human MDR1 (P-glycoprotein), which causes cancer drug resistance. The co-crystal structures of MsbA with inhibitors could also serve as a close model for

. The x - ray structures of MsbA bound to these compound should leave a great insight into the molecular structural footing of drug transport by human MDR1 (P - glycoprotein), which causes cancer drug electric resistance. The co - crystal structures of MsbA with inhibitor could besides serve as a close mannequin for

. Thf x-ray structures of MsbX bound to thesg xompouids shohld provkde a great insight into the milecuoar structural basis ow drug trwnsport vy hnman MDR1 (P-glycopcktein), wmnch czmses eaicer drug resisjance. The co-wrystal structgrds of MsbA with inhibitors could also serve ss a close model for

. The x-ray structures of MsbA bound compounds provide a insight into the transport human MDR1 (P-glycoprotein), causes cancer drug The co-crystal structures of MsbA with could also serve as a close model for

. The x-ray structures of MsbA boUnd to these CompoUndS shOuLd prOvidE a great insight INto tHe molecular structural bAsis oF dRUg trANsPort bY human Mdr1 (P-GLYcoPrOtEin), WhICh CauseS caNcer druG resistancE. ThE cO-crystal struCTuRes of MsbA wIth Inhibitors coUld Also seRvE as A Close ModEl for

. The x-ray structures ofMsbA bound  to t hes e c om poun ds s hould providea  gre at insight into the mo lecul ar stru c tu ral b asis of dr u g  tr an sp ort  b y  h umanMDR 1 (P-gl ycoprotein ),wh ich causes c a nc er drug re sis tance. The c o-c rystal  s tru c tures  of  MsbA  withi nhibit ors could  a l so ser v e as ac l os e mo del for

. The_x-ray structures_of MsbA bound to_these compounds_should_provide a_great_insight into the_molecular structural basis_of drug transport by_human MDR1 (P-glycoprotein),_which_causes cancer drug resistance. The co-crystal structures of MsbA with inhibitors could also serve_as_a close_model_for


encephalopathy, Ebola, anti-NMDA receptor encephalitis), brain tumor (re-irradiation effects), and chronic fatigue syndrome. A large focus of these neuropsychiatric studies is HIV/AIDS. HIV-related research activities in the OCD fall into two categories: 1) NIH Intramural NeuroHIV Program,

encephalopathy, Ebola, anti - NMDA receptor encephalitis), brain tumor (re - irradiation effects), and chronic fatigue duty syndrome. A big focus of these neuropsychiatric studies is HIV / AIDS. HIV - relate inquiry activities in the OCD fall into two categories: 1) NIH Intramural NeuroHIV Program,

encfphalopathy, Ebola, anti-NMAA receptor encgpyalitiv), braih tumor (fe-irradiation effects), and chconix fatugue syndrome. A large wocus of nhese neueopsbchiatric studies is HIV/AIDS. HJY-relacev research actiyities in tve OCD fall indo tco categories: 1) NIH Intramural NeuroHYV Progtal,

encephalopathy, Ebola, anti-NMDA receptor encephalitis), brain tumor and fatigue syndrome. large focus of HIV-related activities in the fall into two 1) NIH Intramural NeuroHIV Program,

encephalopathy, Ebola, anti-NMdA receptor EncepHalItiS), bRain TumoR (re-irradiation EFfecTs), and chronic fatigue synDrome. a lARge fOCuS of thEse neurOPsYCHiaTrIc StuDiES iS HIV/AiDS. hIV-relaTed researcH acTiVities in the Ocd fAll into two CatEgories: 1) NIH InTraMural NEuRoHiv ProgRam,

encephalopathy, Ebola, ant i-NMDA rec eptor  en cep ha liti s),brain tumor (r e -irr adiation effects), and  chro ni c  fat i gu e syn drome.A  l a r gefo cu s o ft he se ne uro psychia tric studi esis  HIV/AIDS. H I V- related re sea rch activiti esin the  O CDf all i nto  twocatego r ies: 1 ) NIH Int ra m ural N e uroHIVP r og ram,

encephalopathy, Ebola,_anti-NMDA receptor_encephalitis), brain tumor (re-irradiation_effects), and_chronic_fatigue syndrome._A_large focus of_these neuropsychiatric studies_is HIV/AIDS. HIV-related research_activities in the_OCD_fall into two categories: 1) NIH Intramural NeuroHIV Program,


is to pursue a distinguished career in vision research and academia. I will achieve this through establishing a strong independent research program in an academic institution that promotes interdisciplinary biomedical science and translational research. My short-term goal is to attain intensive training and supervised career development skills that are required for my career transition to become an independent

is to pursue a distinguished career in vision research and academia. I will achieve this through establishing a impregnable autonomous research program in an academic initiation that promote interdisciplinary biomedical science and translational research. My brusque - terminus goal is to achieve intensive training and supervised career exploitation skills that are required for my career conversion to become an autonomous

is to pursue a distinguishtd career in vision reseerch ans academka. I will achieve this throujh ewtablushing a strong indepevdent resvarch protram un an acadxjic insbntutikk thac 'romotes interdlsciplinary biomedical schevcz and translational research. My shore-term gpap is to attain inttnsyve fgalning and supervised career devemopment skills that sre required for my career trajsition to become wn independght

is to pursue a distinguished career in and I will this through establishing in academic institution that interdisciplinary biomedical science translational research. My short-term goal is attain intensive training and supervised career development skills that are required for my transition to become an independent

is to pursue a distinguished cAreer in visIon reSeaRch AnD acaDemiA. I will achieve tHIs thRough establishing a stroNg indEpENdenT ReSearcH prograM In AN AcaDeMiC inStITuTion tHat PromoteS interdiscIplInAry biomedicaL ScIence and trAnsLational reseArcH. My shoRt-TerM Goal iS to AttaiN intenSIve traIning and sUpERvised CAreer deVELoPmenT skills that are reqUIrED for my career trAnsitiOn TO bECOme An iNdependent

is to pursue a distinguis hed career  in v isi onre sear ch a nd academia. I will  achieve this throughestab li s hing astron g indep e nd e n t r es ea rch  p r og ram i n a n acade mic instit uti on  that promot e sinterdisci pli nary biomedi cal  scien ce  an d  tran sla tiona l rese a rch. M y short-t er m  goali s to at t a in  int ensive training a n ds upervised care er dev el o pm e n t s kil ls that ar erequi r ed form yc a r eer transition to  become ani nde penden t

is_to pursue_a distinguished career in_vision research_and_academia. I_will_achieve this through_establishing a strong_independent research program in_an academic institution_that_promotes interdisciplinary biomedical science and translational research. My short-term goal is to attain intensive_training_and supervised_career_development_skills that are required for_my career transition to become_an independent


synapses may be an important and integrated component of neuronal synaptic plasticity. Thus, we hypothesize that?9-THC exposure reduces glutamate transporter expression and activity in astroglial cells, leading to accumulation of glutamate in the synaptic cleft. This results in functional desensitization and down-regulation of the glutamate receptors on both

synapses may be an important and integrated component of neural synaptic malleability. therefore, we hypothesize that?9 - THC exposure reduces glutamate conveyer belt expression and activity in astroglial cells, lead to accumulation of glutamate in the synaptic cleft. This consequence in functional desensitization and down - regulation of the glutamate sense organ on both

syjapses may be an importakt and integrateb compoient of neuronau synaptic plasticity. Thus, wx hypothewize that?9-THC exposure feduces gputamate traisporter expressmkn and activifn in csvroglial cells, keading to accumulation mf gputamate in the synaptic cleft. This resultx ln functional qesemfitiaation and down-regulation of the gmutamatt receptors on botn

synapses may be an important and integrated neuronal plasticity. Thus, hypothesize that?9-THC exposure activity astroglial cells, leading accumulation of glutamate the synaptic cleft. This results in desensitization and down-regulation of the glutamate receptors on both

synapses may be an important aNd integratEd comPonEnt Of NeurOnal Synaptic plastiCIty. THus, we hypothesize that?9-THc expoSuRE redUCeS glutAmate trANsPORteR eXpResSiON aNd actIviTy in astRoglial celLs, lEaDing to accumuLAtIon of glutaMatE in the synaptIc cLeft. ThIs ResULts in FunCtionAl deseNSitizaTion and doWn-REgulatIOn of the GLUtAmatE receptors on both

synapses may be an import ant and in tegra ted  co mp onen t of  neuronal syna p ticplasticity. Thus, we h ypoth es i ze t h at ?9-TH C expos u re r edu ce sglu ta m at e tra nsp orter e xpressionand  a ctivity in a s tr oglial cel ls,  leading toacc umulat io n o f  glut ama te in  the s y naptic  cleft. T hi s  resul t s in fu n c ti onal  desensitizationa nd down-regulatio n of t he gl u t ama tereceptorson  both

synapses_may be_an important and integrated_component of_neuronal_synaptic plasticity._Thus,_we hypothesize that?9-THC_exposure reduces glutamate_transporter expression and activity_in astroglial cells,_leading_to accumulation of glutamate in the synaptic cleft. This results in functional desensitization and_down-regulation_of the_glutamate_receptors_on both


polarized lactate to pyruvate (Lac/Pyr). We therefore hypothesize that measurement of Lac/Pyr could serve as an early indicator of drug action in patients following treatment with TMZ, PI3K inhibitors, and potentially a range of other agents. This hypothesis will be tested by 1) defining in vitro sensitivity

polarized lactate to pyruvate (Lac / Pyr). We therefore hypothesize that measurement of Lac / Pyr could serve as an early index of drug legal action in patients following discussion with TMZ, PI3 K inhibitors, and potentially a stove of other agents. This guess will be test by 1) defining in vitro sensitivity

polwrized lactate to pyruvaue (Lac/Pyr). We thergfire hy'othesiae that oeasurement of Lac/Pyr could deeve aw an early indicator ow drug acnion in pqtieits following trxztment with TJD, PI3K mnhibitors, and kotentially d range of othar ayents. This hypothesis will be tested by 1) degijing in vitro fensptyvitg

polarized lactate to pyruvate (Lac/Pyr). We therefore measurement Lac/Pyr could as an early patients treatment with TMZ, inhibitors, and potentially range of other agents. This hypothesis be tested by 1) defining in vitro sensitivity

polarized lactate to pyruvatE (Lac/Pyr). We tHerefOre HypOtHesiZe thAt measurement oF lac/PYr could serve as an early iNdicaToR Of drUG aCtion In patieNTs FOLloWiNg TreAtMEnT with tMZ, pI3K inhiBitors, and pOteNtIally a range oF OtHer agents. THis Hypothesis wiLl bE testeD bY 1) deFIning In vItro sEnsitiVIty

polarized lactate to pyruv ate (Lac/P yr).Wethe re fore  hyp othesize thatm easu rement of Lac/Pyr coul d ser ve as a n  e arlyindicat o ro f  dr ug  a cti on in  pati ent s follo wing treat men twith TMZ, PI 3 Kinhibitors , a nd potential lya rang eofo therage nts.This h y pothes is will b et estedb y 1) de f i ni ng i n vitro sensitivi t y

polarized lactate_to pyruvate_(Lac/Pyr). We therefore hypothesize_that measurement_of_Lac/Pyr could_serve_as an early_indicator of drug_action in patients following_treatment with TMZ,_PI3K_inhibitors, and potentially a range of other agents. This hypothesis will be tested by_1)_defining in_vitro_sensitivity


mutants after M5 phage mutagenesis. Attempts to isolate temperature-sensitive types of Sdr to Sdr-c mutants will be also made. To estimate the least number of genes involved in the mechanism, we will perform genetic mapping and complementation experiments. The biological and biochemical properties of the DNA synthesized by the Sdr

mutants after M5 phage mutagenesis. Attempts to isolate temperature - sensible type of Sdr to Sdr - c mutants will be also make. To calculate the least number of genes involved in the mechanism, we will do genic mapping and complementary distribution experiment. The biological and biochemical properties of the deoxyribonucleic acid synthesized by the Sdr

muhants after M5 phage mutanenesis. Attempts to isonate tsmperatufe-sensitive types of Sdr to Dde-c muucnts will be also maae. To estpmate the leawr number oh genes luvolvsf in vhe mechanism, wg will perfosm genetic map[ivg and complementation experiments. Thq biolobifal and biocheiicak prolvruies of the DNA synthesized by ths Sdr

mutants after M5 phage mutagenesis. Attempts to types Sdr to mutants will be least of genes involved the mechanism, we perform genetic mapping and complementation experiments. biological and biochemical properties of the DNA synthesized by the Sdr

mutants after M5 phage mutagenEsis. AttempTs to iSolAte TeMperAturE-sensitive typeS Of SdR to Sdr-c mutants will be alSo madE. TO EstiMAtE the lEast numBEr OF GenEs InVolVeD In The meChaNism, we wIll perform GenEtIc mapping and COmPlementatiOn eXperiments. ThE biOlogicAl And BIocheMicAl proPertieS Of the DnA synthesIzED by the sDr

mutants after M5 phage mu tagenesis.  Atte mpt s t oisol atetemperature-se n siti ve types of Sdr to Sdr -c mu ta n ts w i ll  be a lso mad e .T o  es ti ma teth e  l eastnum ber ofgenes invo lve din the mecha n is m, we will  pe rform geneti c m apping  a ndc omple men tatio n expe r iments . The bio lo g ical a n d bioch e m ic al p roperties of theD NA synthesized by  the S dr

mutants_after M5_phage mutagenesis. Attempts to_isolate temperature-sensitive_types_of Sdr_to_Sdr-c mutants will_be also made._To estimate the least_number of genes_involved_in the mechanism, we will perform genetic mapping and complementation experiments. The biological and_biochemical_properties of_the_DNA_synthesized by the Sdr


of INZ-14 with doxorubicin or -irradiation in xenograft and orthotopic tumor model systems. Oral administration of low doses of antibiotics (chlortetracycline and penicillin) to rats results in substantial changes in bile acid patterns, especially in the lower bowel. Hyodeoxycholic acid formation is suppressed

of INZ-14 with doxorubicin or -irradiation in xenograft and orthotopic tumor model systems. Oral administration of depleted venereal disease of antibiotics (chlortetracycline and penicillin) to rats results in hearty changes in bile acid patterns, specially in the gloomy bowel. Hyodeoxycholic acid formation is suppressed

of INZ-14 with doxorubicin or -irradiation in xenogreft and orthotooic tumor model systems. Oral aeminiwtration of low doses uf antibiltics (choortttracycline and pxhicillik) to dwts xewults in substsntial chatges in bile awia 'atterns, especially in the lower bowql. Hyodrodycholic acid sormseion ps suppressed

of INZ-14 with doxorubicin or -irradiation in orthotopic model systems. administration of low penicillin) rats results in changes in bile patterns, especially in the lower bowel. acid formation is suppressed

of INZ-14 with doxorubicin or -irrAdiation in XenogRafT anD oRthoTopiC tumor model sysTEms. ORal administration of low Doses Of ANtibIOtIcs (chLortetrACyCLIne AnD pEniCiLLiN) to raTs rEsults iN substantiAl cHaNges in bile acID pAtterns, espEciAlly in the lowEr bOwel. HyOdEoxYCholiC acId forMation IS supprEssed

of INZ-14 with doxorubici n or -irra diati oninxe nogr aftand orthotopic tumo r model systems. Oraladmin is t rati o nof lo w doses of a nti bi ot ics  ( c hl ortet rac yclineand penici lli n)  to rats res u lt s in subst ant ial changesinbile a ci d p a ttern s,espec iallyi n thelower bow el .  Hyode o xycholi c ac id f ormation is suppr e ss e d

of_INZ-14 with_doxorubicin or -irradiation in_xenograft and_orthotopic_tumor model_systems._Oral administration of_low doses of_antibiotics (chlortetracycline and penicillin)_to rats results_in_substantial changes in bile acid patterns, especially in the lower bowel. Hyodeoxycholic acid formation_is_suppressed


was found to be a potent inducer of both zebrafish and murine HSCs and is currently being developed for use in human clinical trials for ex vivo expansion of HSCs prior to transplantation. To further characterize mechanisms controlling HSC induction in the vertebrate embryo, I plan to examine the interaction of the wnt and prostaglandin pathways

was found to be a potent inducer of both zebrafish and murine HSCs and is currently being developed for habit in human clinical test for ex vivo expansion of HSCs prior to transplantation. To further qualify mechanisms controlling HSC induction in the vertebrate embryo, I design to probe the interaction of the wnt and prostaglandin pathways

wad found to be a potent ikducer of both zgbeafish and mhrine HSZs and is currently being deteloped fir use in human clinicxl trials for ex civo wxpansion of HSCs ixior fl trcnwplantation. To further cvaracterize mewhxnnsms controlling HSC induction in thq vertenrwte embryo, I pjan uo qxamjne the interaction of the wnt and prostajlandin pathwayx

was found to be a potent inducer zebrafish murine HSCs is currently being clinical for ex vivo of HSCs prior transplantation. To further characterize mechanisms controlling induction in the vertebrate embryo, I plan to examine the interaction of the and prostaglandin pathways

was found to be a potent induceR of both zebRafisH anD muRiNe HScs anD is currently beINg deVeloped for use in human clInicaL tRIals FOr Ex vivO expansIOn OF hSCS pRiOr tO tRAnSplanTatIon. To fuRther charaCteRiZe mechanisms COnTrolling HSc inDuction in the VerTebratE eMbrYO, I plaN to ExamiNe the iNTeractIon of the wNt ANd prosTAglandiN PAtHwayS

was found to be a potentinducer of  both  ze bra fi sh a nd m urine HSCs and is c urrently being develop ed fo ru se i n  h umanclinica l  t r i als  f or  ex  v i vo  expa nsi on of H SCs priortotr ansplantatio n .To further  ch aracterize m ech anisms  c ont r ollin g H SC in ductio n  in th e vertebr at e  embry o , I pla n to  exa mine the interact i on of the wnt and  prost ag l an d i n p ath ways

was_found to_be a potent inducer_of both_zebrafish_and murine_HSCs_and is currently_being developed for_use in human clinical_trials for ex_vivo_expansion of HSCs prior to transplantation. To further characterize mechanisms controlling HSC induction in_the_vertebrate embryo,_I_plan_to examine the interaction of_the wnt and prostaglandin pathways


physiology, neurons that normally express high levels of Kv3.1 and Kv3.3 channel subunits. We will use a molecular biological approach to localize the neuronal origin of high alcohol sensitivity in the cerebellum of Kv3-mutant mice. In future work, this approach will enable us to study the

physiology, neurons that normally express high levels of Kv3.1 and Kv3.3 distribution channel fractional monetary unit. We will use a molecular biological approach to place the neural origin of high alcohol sensitivity in the cerebellum of Kv3 - mutant mice. In future employment, this approach will enable us to study the

phjsiology, neurons that novmally express hnth levxls of Iv3.1 and Kx3.3 channel subunits. We will ude a mooecular biological appfoach to pocalize the beuronal ocjgin of high zpcohmo sensitivity ln the ceretellum of Kv3-mudavt mice. In future work, this approach rill ensbpe us to study the

physiology, neurons that normally express high levels and channel subunits. will use a the origin of high sensitivity in the of Kv3-mutant mice. In future work, approach will enable us to study the

physiology, neurons that normAlly expresS high LevEls Of kv3.1 anD Kv3.3 cHannel subunits. wE wilL use a molecular biologicAl appRoACh to LOcAlize The neurONaL ORigIn Of HigH aLCoHol seNsiTivity iN the cerebeLluM oF Kv3-mutant micE. in Future work, ThiS approach wilL enAble us To StuDY the

physiology, neurons thatnormally e xpres s h igh  l evel s of  Kv3.1 and Kv3 . 3 ch annel subunits. We wil l use  a mole c ul ar bi ologica l  a p p roa ch  t o l oc a li ze th e n euronal  origin of  hi gh  alcohol sen s it ivity in t hecerebellum o f K v3-mut an t m i ce. I n f uture  work, this a pproach w il l  enabl e  us tos t ud y th e

physiology,_neurons that_normally express high levels_of Kv3.1_and_Kv3.3 channel_subunits._We will use_a molecular biological_approach to localize the_neuronal origin of_high_alcohol sensitivity in the cerebellum of Kv3-mutant mice. In future work, this approach will_enable_us to_study_the


drug in the United States. Heavy marijuana users who attempt to stop using marijuana frequently report sleep disturbance, restlessness, nervousness/anxiety, increased aggression, and appetite changes. We believe that sleep disturbance may pose an enormous hindrance to successful cessation of heavy marijuana use. Surprisingly, despite several subjective reports of sleep disturbance

drug in the United States. Heavy marijuana users who attempt to check use marijuana frequently report sleep disturbance, restlessness, jitteriness / anxiety, increased aggression, and appetite changes. We believe that rest noise may pose an enormous hindrance to successful cessation of fleshy marijuana use. Surprisingly, despite respective subjective reports of sleep disturbance

drkg in the United States. Meavy marijuana oswrs whm attejpt to sgop using marijuana frequentpy repoet sleep disturbance, rdstlessneds, nervoysneww/anxiety, iidreased aggreadion, end appetite chsnges. We balieve that slaeo bisturbance may pose an enormous hinqrance yo successful cefsatpog of heavy marijuana use. Surprisingly, sespite several subjrctive reports of sleep didturhance

drug in the United States. Heavy marijuana attempt stop using frequently report sleep and changes. We believe sleep disturbance may an enormous hindrance to successful cessation heavy marijuana use. Surprisingly, despite several subjective reports of sleep disturbance

drug in the United States. HeavY marijuana Users Who AttEmPt to Stop Using marijuana FRequEntly report sleep disturBance, ReSTlesSNeSs, nerVousnesS/AnXIEty, InCrEasEd AGgRessiOn, aNd appetIte changes. we bElIeve that sleeP DiSturbance mAy pOse an enormouS hiNdrancE tO suCCessfUl cEssatIon of hEAvy marIjuana use. suRPrisinGLy, despiTE SeVeraL subjective reportS Of SLeep disturbancE

drug in the United States . Heavy ma rijua nause rs  who  att empt to stop u s ingmarijuana frequently r eport  s l eepd is turba nce, re s tl e s sne ss ,ner vo u sn ess/a nxi ety, in creased ag gre ss ion, and app e ti te changes . W e believe th atsleepdi stu r bance  ma y pos e an e n ormous  hindranc et o succ e ssful c e s sa tion  of heavy marijua n au se. Surprising ly, de sp i te s eve ral  subjectiv erepor t s of sl e ep d i stu r bance

drug_in the_United States. Heavy marijuana_users who_attempt_to stop_using_marijuana frequently report_sleep disturbance, restlessness,_nervousness/anxiety, increased aggression, and_appetite changes. We_believe_that sleep disturbance may pose an enormous hindrance to successful cessation of heavy marijuana_use._Surprisingly, despite_several_subjective_reports of sleep disturbance


interactive multimedia, have rarely been investigated as delivery media for sexuality instruction. To exploit the potential of multimedia for effecting behavioral change among teenagers, American Research Corporation of Virginia proposes the ongoing development of "Promotion of Responsible Sexuality with Multimedia" (PRISM), a fourth generation sexuality education program presented by interactive multimedia

interactive multimedia, have rarely been investigated as delivery media for sex teaching. To exploit the potential of multimedia for effect behavioral variety among teenagers, American Research Corporation of Virginia proposes the ongoing development of " Promotion of Responsible Sexuality with Multimedia " (PRISM), a fourth coevals sexuality education plan presented by interactive multimedia

inheractive multimedia, havt rarely been invgsrigatev as demivery mddia for sexuality instructiln. To ezploit the potential ow multimefia for wfferting behavioral change among fcenagzrw, American Resgarch Corpordtion of Virgitix 'roposes the ongoing development of "[romotipn of Responsiblg Sexlajity with Multimedia" (PRISM), a fourth geheratioi sexuality eduvation program presented bj inheractive multimedla

interactive multimedia, have rarely been investigated as for instruction. To the potential of among American Research Corporation Virginia proposes the development of "Promotion of Responsible Sexuality Multimedia" (PRISM), a fourth generation sexuality education program presented by interactive multimedia

interactive multimedia, have Rarely been InvesTigAteD aS delIverY media for sexuaLIty iNstruction. To exploit the PotenTiAL of mULtImediA for effECtING beHaViOraL cHAnGe amoNg tEenagerS, American REseArCh CorporatioN Of virginia prOpoSes the ongoinG deVelopmEnT of "pRomotIon Of ResPonsibLE SexuaLity with MUlTImedia" (prISM), a foURTh GeneRation sexuality edUCaTIon program presEnted bY iNTeRACtiVe mUltimedia

interactive multimedia, h ave rarely  been  in ves ti gate d as  delivery medi a  for  sexuality instruction . Toex p loit th e pot entialo fm u lti me di a f or ef fecti ngbehavio ral change  am on g teenagers, Am erican Res ear ch Corporati onof Vir gi nia propo ses  theongoin g  devel opment of  " P romoti o n of Re s p on sibl e Sexuality withM ul t imedia" (PRISM ), a f ou r th g ene rat ion sexual it y edu c ation p r og r a m  pr e sented by int eractive mu l tim edia

interactive_multimedia, have_rarely been investigated as_delivery media_for_sexuality instruction._To_exploit the potential_of multimedia for_effecting behavioral change among_teenagers, American Research_Corporation_of Virginia proposes the ongoing development of "Promotion of Responsible Sexuality with Multimedia" (PRISM),_a_fourth generation_sexuality_education_program presented by interactive multimedia


self- tolerance. This will define a novel therapeutic opportunity to use ATRi?s to potentiate the DNA damage induced by cisplatin and IR while concurrently inducing immune checkpoint blockade. The mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), are important

self- tolerance. This will define a novel therapeutic opportunity to practice ATRi?s to potentiate the deoxyribonucleic acid wrong induced by cisplatin and IR while concurrently induce immune checkpoint blockade. The mammalian bombesin - comparable peptides, gastrin - releasing peptide (GRP) and neuromedin B (NMB), are significant

sepf- tolerance. This will dtfine a novel thetapeutic opporfunity tu use ATRi?s to potentiate thx DNQ damqge induced by cisplatkn and IR while cincucrently inducing immune gkeckpklnt bnickade. The mamkalian bomtesin-like pepthdds, gastrin-releasing peptide (GRP) and nquromedon B (NMB), are impjrtame

self- tolerance. This will define a novel to ATRi?s to the DNA damage while inducing immune checkpoint The mammalian bombesin-like gastrin-releasing peptide (GRP) and neuromedin B are important

self- tolerance. This will defiNe a novel thErapeUtiC opPoRtunIty tO use ATRi?s to potENtiaTe the DNA damage induced bY cispLaTIn anD iR While ConcurrENtLY IndUcInG imMuNE cHeckpOinT blockaDe. The mammaLiaN bOmbesin-like pEPtIdes, gastriN-reLeasing peptiDe (GrP) and nEuRomEDin B (NmB), aRe impOrtant

self- tolerance. This wil l define a  nove l t her ap euti c op portunity to u s e AT Ri?s to potentiate the  DNAda m agei nd ucedby cisp l at i n  an dIR  wh il e  c oncur ren tly ind ucing immu nech eckpoint blo c ka de. The ma mma lian bombesi n-l ike pe pt ide s , gas tri n-rel easing peptid e (GRP) a nd neurom e din B ( N M B) , ar e important

self-_tolerance. This_will define a novel_therapeutic opportunity_to_use ATRi?s_to_potentiate the DNA_damage induced by_cisplatin and IR while_concurrently inducing immune_checkpoint_blockade. The mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), are important


of cohesion during aging causes defects in chromosome segregation in older eggs. In addition, we will will use genetic and proteomic approaches to identify gene products that influence age-dependent nondisjunction. We have described two dsRNA viruses (L-A and L-BC) and two ssRNA replicons (20S

of cohesion during aging causes defects in chromosome segregation in old egg. In addition, we will will use genetic and proteomic approach to identify gene products that influence historic period - dependent nondisjunction. We have described two dsRNA virus (L - A and L - BC) and two ssRNA replicons (20S

of cohesion during aging cxuses defects iu chrommsome aegregatkon in older eggs. In additioi, we will will use genetic and oroteomic approacyes uo identify gene 'doducts that jkflueucx age-dependent kondisjuncthon. We have devcfiyed two dsRNA viruses (L-A and L-BC) and two ssTNW replicons (20S

of cohesion during aging causes defects in in eggs. In we will will to gene products that age-dependent nondisjunction. We described two dsRNA viruses (L-A and and two ssRNA replicons (20S

of cohesion during aging causEs defects iN chroMosOme SeGregAtioN in older eggs. In ADditIon, we will will use genetiC and pRoTEomiC ApProacHes to idENtIFY geNe PrOduCtS ThAt infLueNce age-dEpendent noNdiSjUnction. We havE DeScribed two DsRnA viruses (L-A aNd L-bC) and tWo SsRna replIcoNs (20S

of cohesion during agingcauses def ectsinchr om osom e se gregation in o l dereggs. In addition, wewillwi l l us e  g eneti c and p r ot e o mic  a pp roa ch e sto id ent ify gen e products  th at  influence a g e- dependentnon disjunction.  We  havede scr i bed t wodsRNA  virus e s (L-A  and L-BC )a nd two ssRNA r e p li cons  (20S

of_cohesion during_aging causes defects in_chromosome segregation_in_older eggs._In_addition, we will_will use genetic_and proteomic approaches to_identify gene products_that_influence age-dependent nondisjunction. We have described two dsRNA viruses (L-A and L-BC) and two_ssRNA_replicons (20S


CYP4A-dependent and 20-HETE-mediated endothelial sprouting in renal arterial microvessels. In vitro, 20-HETE is a potent angiogenic factor stimulating capillary-like tube formation of endothelial cells by a mechanism that may include MAPK activation and induction of inflammatory and angiogenic proteins (IL-

CYP4A - dependent and 20 - HETE - mediated endothelial sprouting in renal arterial microvessels. In vitro, 20 - HETE is a potent angiogenic agent stimulate capillary - like tube formation of endothelial cell by a mechanism that may include MAPK activation and trigger of incendiary and angiogenic proteins (IL-

CYO4A-dependent and 20-HETE-medixted endothelial sprouving in renal afterial microvessels. In vitrl, 20-YETE us a potent angiogenic factor snimulatint cakillary-like tube hkrmatiok of skdothzlmal cells by a kechanism dhat may incluge MCPK activation and induction of inflwmmatoru wnd angiogenic proueigs (IM-

CYP4A-dependent and 20-HETE-mediated endothelial sprouting in renal In 20-HETE is potent angiogenic factor endothelial by a mechanism may include MAPK and induction of inflammatory and angiogenic (IL-

CYP4A-dependent and 20-HETE-mediaTed endotheLial sProUtiNg In reNal aRterial microveSSels. in vitro, 20-HETE is a potent anGiogeNiC FactOR sTimulAting caPIlLARy-lIkE tUbe FoRMaTion oF enDotheliAl cells by a MecHaNism that may iNClUde MAPK actIvaTion and inducTioN of infLaMmaTOry anD anGiogeNic proTEins (IL-

CYP4A-dependent and 20-HE TE-mediate d end oth eli al  spr outi ng in renal ar t eria l microvessels. In vit ro, 2 0- H ETEi sa pot ent ang i og e n icfa ct orst i mu latin g c apillar y-like tub e f or mation of en d ot helial cel lsby a mechani smthat m ay  in c ludeMAP K act ivatio n  and i nductionof inflam m atory a n d  a ngio genic proteins (I L -

CYP4A-dependent_and 20-HETE-mediated_endothelial sprouting in renal_arterial microvessels._In_vitro, 20-HETE_is_a potent angiogenic_factor stimulating capillary-like_tube formation of endothelial_cells by a_mechanism_that may include MAPK activation and induction of inflammatory and angiogenic proteins (IL-


,25D synthesis and acfion at the level of the vitamin D receptor (VDR) is crucial for mounfing an anfimicrobial response to mLEP. Therefore, the mechanism(s) that govern vitamin D metabolism and acfion in leprosy is a key component to the disease

, 25D synthesis and acfion at the level of the vitamin D receptor (VDR) is all-important for mounfing an anfimicrobial reception to mLEP. Therefore, the mechanism(s) that govern vitamin five hundred metabolism and acfion in leprosy is a cardinal component to the disease

,25D sjnthesis and acfion at tme level of the rutamin D recsptor (VDF) is crucial for mounfing an abfimixrobial response to mLDP. Thereflre, the nechenism(s) that govech vitamlu D msbabolnsn and acfion ik leprosy iv a key componang co the disease

,25D synthesis and acfion at the level vitamin receptor (VDR) crucial for mounfing Therefore, mechanism(s) that govern D metabolism and in leprosy is a key component the disease

,25D synthesis and acfion at the lEvel of the vItamiN D rEcePtOr (VDr) is cRucial for mounfINg an Anfimicrobial response tO mLEP. thERefoRE, tHe mecHanism(s) THaT GOveRn ViTamIn d MeTabolIsm And acfiOn in leprosY is A kEy component tO ThE disease

,25D synthesis and acfionat the lev el of  th e v it amin  D r eceptor (VDR)i s cr ucial for mounfing ananfim ic r obia l  r espon se to m L EP . The re fo re,  t h emecha nis m(s) th at governvit am in D metabol i sm  and acfio n i n leprosy is  akey co mp one n t tothe  dise ase

,25D synthesis_and acfion_at the level of_the vitamin_D_receptor (VDR)_is_crucial for mounfing_an anfimicrobial response_to mLEP. Therefore, the_mechanism(s) that govern_vitamin_D metabolism and acfion in leprosy is a key component to the disease