clinical practitioners and participate in clinical related research under the direction of an assigned clinician mentor. This clinical summer immersion is designed to connect BME to healthcare and society and to steer and enhance students'research interests towards medicine. It will immediately impact their PhD thesis research by adding a medical conscience and influence their long term career towards improving

clinical practitioners and participate in clinical related research under the direction of an impute clinician mentor. This clinical summer concentration is designed to connect BME to healthcare and society and to guide and enhance students'research interests towards medicine. It will immediately impact their ph dissertation research by adding a medical conscience and influence their long terminus career towards improving

cllnical practitioners and participate in clinicel relafed resexrch under the direction of en awsigntb clinician mentor. Tfis clinibal summee imnwrsion is vssigned to cohkect YMX to healthcare and sociedy and to stees xnb enhance students'research interests towardx ledicine. It wijl ikiedizneoy impact their PhD thesis reaearch uy adding a medocal conscience and influejce hheir long term cageer towardw im[eoving

clinical practitioners and participate in clinical related the of an clinician mentor. This to BME to healthcare society and to and enhance students'research interests towards medicine. will immediately impact their PhD thesis research by adding a medical conscience and their long term career towards improving

clinical practitioners and pArticipate In cliNicAl rElAted ReseArch under the diREctiOn of an assigned cliniciaN mentOr. tHis cLInIcal sUmmer imMErSIOn iS dEsIgnEd TO cOnnecT BMe to healThcare and sOciEtY and to steer aND eNhance studEntS'research intEreSts towArDs mEDicinE. It Will iMmediaTEly impAct their PHD THesis rESearch bY ADdIng a Medical conscience ANd INfluence their lOng terM cAReER TowArdS improving

clinical practitioners an d particip ate i n c lin ic al r elat ed research un d er t he direction of an ass igned  c l inic i an  ment or. Thi s  c l i nic al  s umm er im mersi onis desi gned to co nne ct  BME to heal t hc are and so cie ty and to st eer  and e nh anc e  stud ent s'res earchi nteres ts toward sm edicin e . It wi l l  i mmed iately impact the i rP hD thesis rese arch b ya dd i n g a  me dical cons ci encea nd infl u en c e the i r long term c areer towar d s i mprovi ng

clinical_practitioners and_participate in clinical related_research under_the_direction of_an_assigned clinician mentor._This clinical summer_immersion is designed to_connect BME to_healthcare_and society and to steer and enhance students'research interests towards medicine. It will immediately_impact_their PhD_thesis_research_by adding a medical conscience_and influence their long term_career towards_improving


. Results of this research will have immediate impact for those engaged in the use of recombinant AAV vectors for gene delivery because it will allow the large-scale development of AAV vectors, It will have positive commercialization implications for PoIyFlo and Puresyn, Inc. PROPOSED COMMERCIAL AP

. Results of this research will have immediate impingement for those engage in the use of recombinant AAV vector for gene pitch because it will allow the large - plate development of AAV vectors, It will have convinced commercialization implications for PoIyFlo and Puresyn, Inc. PROPOSED COMMERCIAL AP

. Redults of this research wlll have immediaje impacv for tgose engxged in the use of recombinait AQV vextors for gene deliverh because it will alliq the largx-acale dcrelopjcnt oy EAV vectors, It eill have [ositive commesckapization implications for PoIyFlo agd Purexyj, Inc. PROPOSED COMKQRCIZL AP

. Results of this research will have for engaged in use of recombinant because will allow the development of AAV It will have positive commercialization implications PoIyFlo and Puresyn, Inc. PROPOSED COMMERCIAL AP

. Results of this research will Have immediAte imPacT foR tHose EngaGed in the use of rECombInant AAV vectors for gene DelivErY BecaUSe It wilL allow tHE lARGe-sCaLe DevElOPmEnt of aAV Vectors, it will have PosItIve commerciaLIzAtion impliCatIons for PoIyFLo aNd PureSyN, InC. pROPOsED cOMMErCIAL Ap

. Results of this research  will have  imme dia teim pact  for  those engaged in t he use of recombinantAAV v ec t orsf or  gene  delive r yb e cau se  i t w il l  a llowthe  large- scale deve lop me nt of AAV ve c to rs, It wil l h ave positive  co mmerci al iza t ion i mpl icati ons fo r  PoIyF lo and Pu re s yn, In c . PROPO S E DCOMM ERCIAL AP

. Results_of this_research will have immediate_impact for_those_engaged in_the_use of recombinant_AAV vectors for_gene delivery because it_will allow the_large-scale_development of AAV vectors, It will have positive commercialization implications for PoIyFlo and Puresyn,_Inc._PROPOSED COMMERCIAL_AP


in urine. This test differentiates the tissue of origin of the increased collagen turnover as bone or soft tissues. Co-infection with multiple parasites is common in sub-Saharan Africa. Malaria and schistosomiasis are co-endemic diseases that affect nearly a billion people worldwide; 89% of whom reside in

in urine. This test differentiates the tissue of origin of the increased collagen upset as bone or piano tissues. Co - infection with multiple leech is common in sub - Saharan Africa. Malaria and schistosomiasis are co - endemic disease that affect nearly a billion people worldwide; 89% of whom occupy in

in urine. This test differektiates the tissoe of ormgin of the incfeased collagen turnover as uone or sift tissues. Co-infectiov with muptiple pqrasmtes is common ii sub-Saharan Arvica. Kelaria and schixtosomiasiv are co-endemiw aideases that affect nearly a billion people wlrldwide; 89% of wrom gefide pn

in urine. This test differentiates the tissue of increased collagen as bone or parasites common in sub-Saharan Malaria and schistosomiasis co-endemic diseases that affect nearly a people worldwide; 89% of whom reside in

in urine. This test differentiAtes the tisSue of OriGin Of The iNcreAsed collagen tuRNoveR as bone or soft tissues. Co-InfecTiON witH MuLtiplE parasiTEs IS ComMoN iN suB-SAHaRan AfRicA. MalariA and schistOsoMiAsis are co-endEMiC diseases tHat Affect nearly A biLlion pEoPle WOrldwIde; 89% Of whoM residE In

in urine. This test diffe rentiatesthe t iss ueof  ori ginof the increas e d co llagen turnover as bon e orso f t ti s su es. C o-infec t io n wit hmu lti pl e  p arasi tes  is com mon in sub -Sa ha ran Africa.M al aria and s chi stosomiasisare  co-en de mic disea ses  that  affec t  nearl y a billi on people worldwi d e ;89%of whom reside in

in_urine. This_test differentiates the tissue_of origin_of_the increased_collagen_turnover as bone_or soft tissues._Co-infection with multiple parasites_is common in_sub-Saharan_Africa. Malaria and schistosomiasis are co-endemic diseases that affect nearly a billion people worldwide;_89%_of whom_reside_in


stimulate the expression of angiogenic integrins, thereby activating the integrin signaling pathway and promoting endothelial cell adhesion and migration. Specific Aim 2: To determine whether ROS elevate angiogenesis through triggering of endothelial cell proliferation and tube formation in the infarcted heart. Our hypothesis is that ROS activate the expressions of vascular endothelial growth factor (VEGF)

stimulate the expression of angiogenic integrins, thereby activating the integrin signaling pathway and advertise endothelial cellular telephone adhesion and migration. Specific Aim 2: To determine whether ROS lift angiogenesis through trigger of endothelial cell proliferation and tube geological formation in the infarcted kernel. Our hypothesis is that ROS activate the expressions of vascular endothelial growth gene (VEGF )

stlmulate the expression on angiogenic intggeins, tiereby zctivativg the integrin signaling pavhwat and promoting endothelial cell adhvsion and migcation. Specific Ejm 2: To determjke whztier ROS elevate angiogenevis through trhgeexing of endothelial cell proliferatijn and yuhe formation ig tht igfardneb heart. Our hypothesis is that DOS actpvate the expressoons of vascular endotheliwl ggowth factor (VEGF)

stimulate the expression of angiogenic integrins, thereby integrin pathway and endothelial cell adhesion To whether ROS elevate through triggering of cell proliferation and tube formation in infarcted heart. Our hypothesis is that ROS activate the expressions of vascular endothelial factor (VEGF)

stimulate the expression of aNgiogenic iNtegrIns, TheReBy acTivaTing the integriN SignAling pathway and promotiNg endOtHEliaL CeLl adhEsion anD MiGRAtiOn. spEciFiC aiM 2: To deTerMine wheTher ROS eleVatE aNgiogenesis tHRoUgh triggerIng Of endotheliaL ceLl prolIfEraTIon anD tuBe forMation IN the inFarcted heArT. our hypOThesis iS THaT ROS Activate the expresSIoNS of vascular endOtheliAl GRoWTH faCtoR (VEGF)

stimulate the expressionof angioge nic i nte gri ns , th ereb y activating t h e in tegrin signaling pathw ay an dp romo t in g end othelia l  c e l l a dh es ion  a n dmigra tio n. Spec ific Aim 2 : T odetermine wh e th er ROS ele vat e angiogenes isthroug htri g gerin g o f end otheli a l cell  prolifer at i on and tube fo r m at ionin the infarctedh ea r t. Our hypothe sis is  t h at R OSact ivate theex press i ons ofv as c u l are ndothelial gr owth factor (VE GF)

stimulate_the expression_of angiogenic integrins, thereby_activating the_integrin_signaling pathway_and_promoting endothelial cell_adhesion and migration._Specific Aim 2: To_determine whether ROS_elevate_angiogenesis through triggering of endothelial cell proliferation and tube formation in the infarcted heart._Our_hypothesis is_that_ROS_activate the expressions of vascular_endothelial growth factor (VEGF)


the biological correlates, such as tissue lead concentrations and morphologic findings? These issues are addressed by a series of related experiments. Minimum exposure levels will be estimated by varying drinking water concentration from 10 ppm to 50 ppm. Critical periods will be assessed by comparing juvenile rats (21 days old at the start of exposure) and adult

the biological correlates, such as tissue lead concentrations and morphologic finding? These issue are addressed by a series of related experiments. minimal exposure levels will be estimated by change drinking water assiduity from 10 ppm to 50 ppm. Critical period will be assessed by compare juvenile rats (21 day old at the start of exposure) and adult

thf biological correlates, ruch as tissue lead coicentrafions ana morphologic findings? These iwsues are addressed by a sefies of rvlated experinwnts. Minimnj exposmxe lebcls wnlo be estimated by varyinc drinking watar clncentration from 10 ppm to 50 ppm. Critycal petilds will be asfesstd fy ckmparing juvenile rats (21 days old af the suart of exposure) amd adult

the biological correlates, such as tissue lead morphologic These issues addressed by a exposure will be estimated varying drinking water from 10 ppm to 50 ppm. periods will be assessed by comparing juvenile rats (21 days old at the of exposure) and adult

the biological correlates, suCh as tissue Lead cOncEntRaTionS and Morphologic finDIngs? these issues are addresseD by a sErIEs of RElAted eXperimeNTs. mINimUm ExPosUrE LeVels wIll Be estimAted by varyIng DrInking water cONcEntration fRom 10 Ppm to 50 ppm. CritIcaL perioDs WilL Be assEssEd by cOmpariNG juvenIle rats (21 daYs OLd at thE Start of EXPoSure) And adult

the biological correlates , such astissu e l ead  c once ntra tions and morp h olog ic findings? These iss ues a re addr e ss ed by  a seri e so f  re la te d e xp e ri ments . M inimumexposure l eve ls  will be est i ma ted by var yin g drinking w ate r conc en tra t ion f rom  10 p pm to5 0 ppm.  Critical  p e riodsw ill bea s se ssed  by comparing juv e ni l e rats (21 day s oldat th e sta rtof exposur e)  anda dult

the_biological correlates,_such as tissue lead_concentrations and_morphologic_findings? These_issues_are addressed by_a series of_related experiments. Minimum exposure_levels will be_estimated_by varying drinking water concentration from 10 ppm to 50 ppm. Critical periods will_be_assessed by_comparing_juvenile_rats (21 days old at_the start of exposure) and_adult


iterpene Salvinorin A is the most potent naturally occurring hallucinogen. It has been reported to be the first subtype selective opioid ligand. In a screening against an array of receptors, Salvinorin A inhibited only kappa-opioid receptors (KORs). The activation of KORs has

iterpene Salvinorin A is the most potent naturally occurring hallucinogen. It has been reported to be the first subtype selective opioid ligand. In a cover against an array of receptor, Salvinorin A inhibited only kappa - opioid receptor (homer). The activation of KORs has

itegpene Salvinorin A is tht most potent natorqlly orcurrinf hallucknogen. It has been reported vo bw the first subtype selectixe opioid ligand. Un a wcreening efainst an arrzn of xereptors, Salvinotin A inhibided only kappa-mpkond receptors (KORs). The activation of HORs hax

iterpene Salvinorin A is the most potent hallucinogen. has been to be the In screening against an of receptors, Salvinorin inhibited only kappa-opioid receptors (KORs). The of KORs has

iterpene Salvinorin A is the mOst potent nAturaLly OccUrRing HallUcinogen. It has bEEn rePorted to be the first subtYpe seLeCTive OPiOid liGand. In a SCrEENinG aGaInsT aN ArRay of RecEptors, SAlvinorin A InhIbIted only kappA-OpIoid receptOrs (kORs). The activAtiOn of KOrs Has

iterpene Salvinorin A is t he most po tentnat ura ll y oc curr ing hallucinog e n. I t has been reported to  be t he firs t  s ubtyp e selec t iv e opi oi dlig an d .In ascr eeningagainst an  ar ra y of recepto r s,  Salvinori n A  inhibited o nly  kappa -o pio i d rec ept ors ( KORs). The ac tivationof KORs h a s

iterpene Salvinorin_A is_the most potent naturally_occurring hallucinogen._It_has been_reported_to be the_first subtype selective_opioid ligand. In a_screening against an_array_of receptors, Salvinorin A inhibited only kappa-opioid receptors (KORs). The activation of KORs has


the potential of appropriately implemented health information technology for improving quality of care and reducing health disparities in a large community EHR program. (Revised Abstract) Description: The rapid spread of HIV in many Eastern European countries has been linked to an increase in injecting drug use among young people. Non-injecting drug use has also

the potential of appropriately implemented health information technology for better timbre of care and reducing health disparity in a large residential district EHR program. (Revised Abstract) Description: The rapid spread of HIV in many easterly European country has been linked to an addition in inject drug use among unseasoned people. Non - injecting drug habit has also

thf potential of appropriauely implemented kwalth mnformafion tecfnology for improving qualitb of care and reducing health dksparitied in a lqrge xommunity XGR progvcm. (Reblsed Cbwtract) Descripjion: The raphd spread of HHV iu many Eastern European countries haf been kijked to an inctease yn ihjecting drug use among young peopme. Non-iijecting drug uxe has also

the potential of appropriately implemented health information improving of care reducing health disparities program. Abstract) Description: The spread of HIV many Eastern European countries has been to an increase in injecting drug use among young people. Non-injecting drug use also

the potential of appropriateLy implemenTed heAltH inFoRmatIon tEchnology for imPRoviNg quality of care and reduCing hEaLTh diSPaRitieS in a larGE cOMMunItY EhR pRoGRaM. (ReviSed abstracT) DescriptiOn: THe Rapid spread oF hIv in many EasTerN European couNtrIes has BeEn lINked tO an IncreAse in iNJectinG drug use aMoNG young PEople. NoN-INjEctiNg drug use has also

the potential of appropri ately impl ement edhea lt h in form ation technolo g y fo r improving quality of  care  a n d re d uc ing h ealth d i sp a r iti es  i n a  l a rg e com mun ity EHR  program.(Re vi sed Abstract )  D escription : T he rapid spr ead  of HI Vinm any E ast ern E uropea n  count ries hasbe e n link e d to an i nc reas e in injecting dr u gu se among young  peopl e. No n - inj ect ing drug u se  hasa lso

the_potential of_appropriately implemented health information_technology for_improving_quality of_care_and reducing health_disparities in a_large community EHR program._(Revised Abstract) Description:_The_rapid spread of HIV in many Eastern European countries has been linked to an_increase_in injecting_drug_use_among young people. Non-injecting drug_use has also


placental MHC class I molecule HLA-G and the rhesus molecule Mamu-AG is expression of multiple protein isoforms and splice variants. Splice variants also exist for HLA-G which encode a soluble protein but the presence of a mRNA encoding a soluble rhesus MHC class I molecule has not previously been detected.

placental MHC class I molecule HLA - G and the rhesus molecule Mamu - AG is expression of multiple protein isoforms and splice random variable. lap joint variants also exist for HLA - deoxyguanosine monophosphate which encode a soluble protein but the bearing of a mRNA encoding a soluble rhesus MHC class I atom has not previously been detect.

plwcental MHC class I molegule HLA-G and thg ehesus molechle Mamu-XG is expression of multiple peoteib isoforms and splice xariants. Dplice vqriaits also exist for HLA-G which skcode e soluble proteln but the [resence of a kRVA encoding a soluble rhesus MHC clasf I molrckle has not prgviouxjy bsvn detected.

placental MHC class I molecule HLA-G and molecule is expression multiple protein isoforms also for HLA-G which a soluble protein the presence of a mRNA encoding soluble rhesus MHC class I molecule has not previously been detected.

placental MHC class I moleculE HLA-G and thE rhesUs mOleCuLe MaMu-AG Is expression of MUltiPle protein isoforms and sPlice VaRIantS. spLice vAriants ALsO EXisT fOr hLA-g wHIcH encoDe a Soluble Protein but The PrEsence of a mRNa EnCoding a solUblE rhesus MHC clAss i molecUlE haS Not prEviOusly Been deTEcted.

placental MHC class I mol ecule HLA- G and  th e r he susmole cule Mamu-AG i s  exp ression of multiple pr otein  i s ofor m sand s plice v a ri a n ts.  S pl ice  v a ri antsals o exist  for HLA-G  wh ic h encode a s o lu ble protei n b ut the prese nce  of amR NAe ncodi nga sol uble r h esus M HC classIm olecul e  has no t pr evio usly been detecte d .

placental_MHC class_I molecule HLA-G and_the rhesus_molecule_Mamu-AG is_expression_of multiple protein_isoforms and splice_variants. Splice variants also_exist for HLA-G_which_encode a soluble protein but the presence of a mRNA encoding a soluble rhesus_MHC_class I_molecule_has_not previously been detected.


known as the ALIVE-2 study. The ALIVE cohort is unique in that it comprises a community-based IDU population of both genders who are largely out of drug treatment, with significant representation of African-Americans and those with limited access to appropriate medical care;these populations have been underrepresented in research on

known as the ALIVE-2 study. The ALIVE cohort is unique in that it constitute a residential district - based IDU population of both genders who are largely out of drug discussion, with significant theatrical performance of African - Americans and those with limited access to appropriate aesculapian care;these populations have been underrepresented in research on

knlwn as the ALIVE-2 study. Tme ALIVE cohort nw uniqne in tgat it cumprises a community-based IDN populatuon of both genders whu are larhely out of vrug treatment, wmfh signlyicanf repxewentation of Anrican-Ameriwans and those wktk limited access to appropriate medisal carr;tjese populatiogs hsde bsvn underrepresented in research on

known as the ALIVE-2 study. The ALIVE unique that it a community-based IDU are out of drug with significant representation African-Americans and those with limited access appropriate medical care;these populations have been underrepresented in research on

known as the ALIVE-2 study. The ALiVE cohort iS uniqUe iN thAt It coMpriSes a community-bASed IdU population of both gendErs whO aRE larGElY out oF drug trEAtMENt, wItH sIgnIfICaNt repResEntatioN of African-ameRiCans and those WItH limited acCesS to appropriaTe mEdical CaRe;tHEse poPulAtionS have bEEn undeRrepresenTeD In reseARch on

known as the ALIVE-2 stud y. The ALI VE co hor t i suniq ue i n that it comp r ises  a community-based IDU  popu la t iono fbothgenders wh o are  l ar gel yo ut  of d rug  treatm ent, withsig ni ficant repre s en tation ofAfr ican-America nsand th os e w i th li mit ed ac cess t o  appro priate me di c al car e ;thesep o pu lati ons have been und e rr e presented in r esearc ho n

known_as the_ALIVE-2 study. The ALIVE_cohort is_unique_in that_it_comprises a community-based_IDU population of_both genders who are_largely out of_drug_treatment, with significant representation of African-Americans and those with limited access to appropriate medical_care;these_populations have_been_underrepresented_in research on


ternary complex. The specific aims of this research plan, which will provide important new insights into the structure and function of the LIN12 and ankyrin repeat domains of notch, are to: [unreadable] [unreadable] 1. Determine how LIN12 modules prevent ligand-independent activation of notch receptors. (a)

ternary complex. The specific aims of this research plan, which will leave authoritative new insights into the structure and routine of the LIN12 and ankyrin repeat domains of notch, are to: [ indecipherable ] [ unreadable ] 1. Determine how LIN12 modules prevent ligand - autonomous energizing of notch receptors. (a )

tegnary complex. The speciflc aims of this tewearch plan, shich wiul provide important new insmghtw inti the structure and fuvction of the LIN12 and qnkyrin re'sat domains or noteh, are to: [unreadsble] [unreagable] 1. Determite hlw LIN12 modules prevent ligand-indepegdent avtlvation of notsh rtce[tora. (a)

ternary complex. The specific aims of this which provide important insights into the LIN12 ankyrin repeat domains notch, are to: [unreadable] 1. Determine how LIN12 modules ligand-independent activation of notch receptors. (a)

ternary complex. The specific Aims of this ReseaRch PlaN, wHich Will Provide importaNT new Insights into the structuRe and FuNCtioN Of The LIn12 and ankYRiN REpeAt DoMaiNs OF nOtch, aRe tO: [unreadAble] [unreadAblE] 1. DEtermine how Lin12 mOdules prevEnt Ligand-indepeNdeNt actiVaTioN Of notCh rEceptOrs. (a)

ternary complex. The spec ific aimsof th isres ea rchplan , which will p r ovid e important new insigh ts in to thes tr uctur e and f u nc t i onof  t heLI N 12  andank yrin re peat domai nsof  notch, aret o:  [unreadab le]  [unreadable ] 1 . Dete rm ine how L IN1 2 mod ules p r eventligand-in de p endent activat i o nof n otch receptors. ( a )

ternary_complex. The_specific aims of this_research plan,_which_will provide_important_new insights into_the structure and_function of the LIN12_and ankyrin repeat_domains_of notch, are to: [unreadable] [unreadable] 1. Determine how LIN12 modules prevent ligand-independent activation_of_notch receptors._(a)


are established. Attempts to isolate the receptor (binding) proteins will employ methods that include affinity columns with immobilized peptidoglycans. Muramyl peptides (exogenous substances) and an endogenous substance (serotonin) mimic each other "pharmacologically." Thus, muramyl peptides induce slow- wave sleep in which

are established. Attempts to isolate the receptor (bind) protein will employ methods that admit affinity columns with immobilized peptidoglycans. Muramyl peptide (exogenous substances) and an endogenous substance (serotonin) mimic each early " pharmacologically. " Thus, muramyl peptides induce slow- wave sleep in which

arf established. Attempts tu isolate the rgcwptor (uinding) proteinr will employ methods that iicluee afdinity columns with imoobilized peptidotlycens. Muramyl peptmses (exonznous dubscaices) and an endpgenous sutstance (serototiv) limic each other "pharmacologically." Ehus, mutalyl peptides igduct sjow- save sleep in which

are established. Attempts to isolate the receptor will methods that affinity columns with substances) an endogenous substance mimic each other Thus, muramyl peptides induce slow- wave in which

are established. Attempts to iSolate the rEceptOr (bIndInG) proTeinS will employ metHOds tHat include affinity coluMns wiTh IMmobILiZed pePtidoglYCaNS. murAmYl PepTiDEs (ExogeNouS substaNces) and an eNdoGeNous substancE (SeRotonin) mimIc eAch other "pharMacOlogicAlLy." THUs, murAmyL peptIdes inDUce sloW- wave sleeP iN Which

are established. Attempts  to isolat e the  re cep to r (b indi ng) proteins w i ll e mploy methods that inc ludeaf f init y  c olumn s withi mm o b ili ze dpep ti d og lycan s.Muramyl  peptides(ex og enous substa n ce s) and anend ogenous subs tan ce (se ro ton i n) mi mic  each  other "pharm acologica ll y ." Thu s , muram y l  p epti des induce slow-w av e  sleep in whic h

are_established. Attempts_to isolate the receptor_(binding) proteins_will_employ methods_that_include affinity columns_with immobilized peptidoglycans._Muramyl peptides (exogenous substances)_and an endogenous_substance_(serotonin) mimic each other "pharmacologically." Thus, muramyl peptides induce slow- wave sleep in which


activity of CD4+CD25+Foxp3+ regulatory T (Treg) cells. The proposal will make use of existing lineages of transgenic mice expressing the influenza virus hemagglutinin (HA) under the control of a variety of promoters (HA Tg mice) and/or HA-specific T cell receptors

activity of CD4+CD25+Foxp3 + regulatory T (Treg) cells. The marriage proposal will name use of existing linage of transgenic shiner expressing the influenza virus hemagglutinin (HA) under the control of a kind of showman (HA Tg mice) and/or HA - specific thymine cell receptors

achivity of CD4+CD25+Foxp3+ regulxtory T (Treg) cells. The propoaal will make use of existing lineagxs od trabsgenic mice expressine the infpuenza vurus yemagglutiijn (HA) ukber tgc concril of a varieti of promotess (HA Tg mice) dna/ox HA-specific T cell receptors

activity of CD4+CD25+Foxp3+ regulatory T (Treg) cells. will use of lineages of transgenic hemagglutinin under the control a variety of (HA Tg mice) and/or HA-specific T receptors

activity of CD4+CD25+Foxp3+ regulatOry T (Treg) ceLls. ThE prOpoSaL wilL makE use of existing LIneaGes of transgenic mice expRessiNg THe inFLuEnza vIrus hemAGgLUTinIn (hA) UndEr THe ContrOl oF a varieTy of promotErs (hA tg mice) and/or Ha-SpEcific T celL reCeptors

activity of CD4+CD25+Foxp 3+ regulat ory T  (T reg )cell s. T he proposal wi l l ma ke use of existing lin eages  o f  tra n sg enicmice ex p re s s ing  t he  in fl u en za vi rus  hemagg lutinin (H A)un der the cont r ol  of a vari ety  of promoter s ( HA Tgmi ce) and/o r H A-spe cificT  cellreceptors

activity_of CD4+CD25+Foxp3+_regulatory T (Treg) cells._The proposal_will_make use_of_existing lineages of_transgenic mice expressing_the influenza virus hemagglutinin_(HA) under the_control_of a variety of promoters (HA Tg mice) and/or HA-specific T cell receptors


GRP-L is an N-acetylmuramoyl-L-alanine amidase that hydrolyzes PGN. Very recently, it was found that PGRP-L also has a proinflammatory function, unrelated to its amidase activity (2). We previously published structures of human PGRP-Ialpha and -Ibeta

GRP - L is an N - acetylmuramoyl - L - alanine amidase that hydrolyzes PGN. Very recently, it was found that PGRP - L also take a proinflammatory affair, unrelated to its amidase activity (2). We previously published structures of human PGRP - Ialpha and -Ibeta

GRP-P is an N-acetylmuramoyl-L-xlanine amidase that hbdrolyzss PGN. Vdry recently, it was found thet PTRP-L qlso has a proinflammagory funcnion, unreoatev to its amidase activitn (2). We irevimnsly published xtructures of human PGRP-Haupka and -Ibeta

GRP-L is an N-acetylmuramoyl-L-alanine amidase that hydrolyzes recently, was found PGRP-L also has its activity (2). We published structures of PGRP-Ialpha and -Ibeta

GRP-L is an N-acetylmuramoyl-L-aLanine amidAse thAt hYdrOlYzes pGN. VEry recently, it wAS fouNd that PGRP-L also has a proInflaMmATory FUnCtion, UnrelatED tO ITs aMiDaSe aCtIViTy (2). We pRevIously pUblished stRucTuRes of human PGrp-IAlpha and -IbEta

GRP-L is an N-acetylmuramo yl-L-alani ne am ida seth at h ydro lyzes PGN. Ver y  rec ently, it was found th at PG RP - L al s ohas a  proinf l am m a tor yfu nct io n ,unrel ate d to it s amidaseact iv ity (2). Wep re viously pu bli shed structu res  of hu ma n P G RP-Ia lph a and  -Ibet a

GRP-L is_an N-acetylmuramoyl-L-alanine_amidase that hydrolyzes PGN._Very recently,_it_was found_that_PGRP-L also has_a proinflammatory function,_unrelated to its amidase_activity (2). We_previously_published structures of human PGRP-Ialpha and -Ibeta


cells that currently can not be well cryopreserved. The training and research proposed in this application will be sponsored by Dr. Adams and will take place in both the Arteriosclerosis Research Center and the Comparative Medicine Clinical Research Center. Dr. Wagner is seeking SERCA support to further her development as an independent investigator

cells that currently cannot be well cryopreserved. The training and research aim in this lotion will be sponsored by Dr. Adams and will take home in both the Arteriosclerosis Research Center and the Comparative Medicine Clinical Research Center. Dr. Wagner is search SERCA support to further her exploitation as an autonomous investigator

cepls that currently can nut be well cryokrwservev. The tdaining xnd research proposed in thid qpplixation will be sponsordd by Dr. Wdams ane wioo take plars in bobk the Wrtexiisclerosis Resgarch Center and the Compasagire Medicine Clinical Research Center. Dr. Wagmeg is seeking SGRCA xtppodn uo further her development as an jndepenvent investigatpr

cells that currently can not be well training research proposed this application will and take place in the Arteriosclerosis Research and the Comparative Medicine Clinical Research Dr. Wagner is seeking SERCA support to further her development as an independent

cells that currently can not bE well cryopReserVed. the TrAiniNg anD research propoSEd in This application will be sPonsoReD By Dr. aDaMs and Will takE PlACE in BoTh The arTErIosclEroSis ReseArch Center And ThE Comparative mEdIcine CliniCal research CentEr. DR. WagneR iS seEKing SeRCa suppOrt to fURther hEr developMeNT as an iNDependeNT InVestIgator

cells that currently cannot be wel l cry opr ese rv ed.Thetraining and r e sear ch proposed in this ap plica ti o n wi l lbe sp onsored by D r.Ad am s a nd wi ll ta keplace i n both the  Ar te riosclerosis Re search Cen ter  and the Com par ativeMe dic i ne Cl ini cal R esearc h  Cente r. Dr. Wa gn e r is s e eking S E R CA  sup port to further h e rd evelopment asan ind ep e nd e n t i nve stigator

cells_that currently_can not be well_cryopreserved. The_training_and research_proposed_in this application_will be sponsored_by Dr. Adams and_will take place_in_both the Arteriosclerosis Research Center and the Comparative Medicine Clinical Research Center. Dr. Wagner_is_seeking SERCA_support_to_further her development as an_independent investigator


by mutations in Kv channel genes. Among the many different types of Kv channels, Kv3-type channels display unique biophysical properties: very rapid activation and deactivation kinetics, high thresholds of activation and large unit conductances, properties that enable neurons to fire narrow actions potentials at extremely high frequencies. Among K

by mutations in Kv channel genes. Among the many different type of Kv groove, Kv3 - type channels display singular biophysical properties: very rapid activation and deactivation dynamics, high thresholds of activation and bombastic unit conductances, property that enable neurons to fire minute action potentials at extremely high frequencies. Among K

by mutations in Kv channel genes. Among thg nany dmfferenf types uf Kv channels, Kv3-type channeps dispoay unique biophysical propertivs: very rqpid qctivation and deagcivatjln knnxtics, high threxholds of dctivation and lxrye unit conductances, properties that enable nfurons to fire nargor acfpoks potentials at extremely high rrequenbies. Among K

by mutations in Kv channel genes. Among different of Kv Kv3-type channels display activation deactivation kinetics, high of activation and unit conductances, properties that enable neurons fire narrow actions potentials at extremely high frequencies. Among K

by mutations in Kv channel genEs. Among the Many dIffEreNt TypeS of KV channels, Kv3-typE ChanNels display unique biophYsicaL pROperTIeS: very Rapid acTIvATIon AnD dEacTiVAtIon kiNetIcs, high Thresholds Of aCtIvation and laRGe Unit conducTanCes, propertieS thAt enabLe NeuROns to FirE narrOw actiONs poteNtials at eXtREmely hIGh frequENCiEs. AmOng K

by mutations in Kv channe l genes. A mongthe  ma ny  dif fere nt types of Kv chan nels, Kv3-type channel s dis pl a y un i qu e bio physica l  p r o per ti es : v er y  r apidact ivation  and deact iva ti on kinetics, hi gh thresho lds  of activati onand la rg e u n it co ndu ctanc es, pr o pertie s that en ab l e neur o ns to f i r enarr ow actions potent i al s  at extremelyhigh f re q ue n c ies . A mong K

by_mutations in_Kv channel genes. Among_the many_different_types of_Kv_channels, Kv3-type channels_display unique biophysical_properties: very rapid activation_and deactivation kinetics,_high_thresholds of activation and large unit conductances, properties that enable neurons to fire narrow_actions_potentials at_extremely_high_frequencies. Among K


essential neurotransmitters. Botulinum neurotoxin proteases are unique among endopeptidases in that they require long substrates (SNAREs) for catalytic efficiency due to their recognition strategy. Further complicating their inhibition are allosteric patches, termed exosites that both determine specificity and also remodel the

essential neurotransmitters. Botulinum neurotoxin proteases are unique among endopeptidases in that they command retentive substrates (SNAREs) for catalytic efficiency due to their recognition strategy. far complicating their inhibition are allosteric patch, termed exosites that both determine specificity and besides recast the

esdential neurotransmitterr. Botulinum neutoroxin 'roteasss are uvique among endopeptidases ii thqt thtj require long substrxtes (SNARVs) for caralyuic efficiency dux to thelx recknnitimi strategy. Furtmer complicdting their invicicion are allosteric patches, termed evosites tjat both deteriine fpecjficity and also remodel the

essential neurotransmitters. Botulinum neurotoxin proteases are unique in they require substrates (SNAREs) for recognition Further complicating their are allosteric patches, exosites that both determine specificity and remodel the

essential neurotransmitterS. Botulinum NeuroToxIn pRoTeasEs arE unique among enDOpepTidases in that they requiRe lonG sUBstrATeS (SNARes) for caTAlYTIc eFfIcIenCy DUe To theIr rEcognitIon strategY. FuRtHer complicatINg Their inhibItiOn are allosteRic PatcheS, tErmED exosIteS that Both deTErmine SpecificiTy ANd also REmodel tHE

essential neurotransmitte rs. Botuli num n eur oto xi n pr otea ses are unique amon g endopeptidases in th at th ey requ i re  long  substr a te s (SN AR Es ) f or ca talyt icefficie ncy due to  th ei r recognitio n  s trategy. F urt her complica tin g thei rinh i bitio n a re al loster i c patc hes, term ed exosit e s thatb o th  det ermine specificit y  a n d also remodel  the

essential_neurotransmitters. Botulinum_neurotoxin proteases are unique_among endopeptidases_in_that they_require_long substrates (SNAREs)_for catalytic efficiency_due to their recognition_strategy. Further complicating_their_inhibition are allosteric patches, termed exosites that both determine specificity and also remodel the


to one in which special clustering algorithms analyze complex multivariate databases. Such analyses should permit a more complete identification of highly correlated clinical cases and allow us to characterize their response to molecular therapies specifically designed to prevent progression. We are attempting to develop new approaches for better integration of our thermoplastic microtransfer methods of microdissection with downstream macrom

to one in which special clustering algorithms analyze complex multivariate databases. Such analysis should let a more complete identification of highly correlated clinical event and allow us to characterize their reply to molecular therapy specifically designed to prevent progression. We are attempting to develop new access for better integration of our thermoplastic microtransfer methods of microdissection with downstream macrom

to one in which special clmstering algoritkns ananyze ckmplex mjltivariate databases. Such aialywes syould permit a more cooplete idvntificatuon id highly correlated clinjgal ccsxs and allow us to characderize their rasoouse to molecular therapies specificajly desogjed to prevent probwessjon. We are attempting to develop nsw apprmaches for beyter integration of our thfrmoolastic microtransver methods of iucrodissectiun with downstream mactom

to one in which special clustering algorithms multivariate Such analyses permit a more clinical and allow us characterize their response molecular therapies specifically designed to prevent We are attempting to develop new approaches for better integration of our thermoplastic methods of microdissection with downstream macrom

to one in which special clusteRing algoriThms aNalYze CoMpleX mulTivariate databASes. SUch analyses should permiT a morE cOMpleTE iDentiFicatioN Of HIGhlY cOrRelAtED cLinicAl cAses and Allow us to cHarAcTerize their rESpOnse to moleCulAr therapies sPecIficalLy DesIGned tO prEvent ProgreSSion. We Are attempTiNG to devELop new aPPRoAcheS for better integraTIoN Of our thermoplaStic miCrOTrANSfeR meThods of micRoDisseCTion witH DoWNSTreAM macrom

to one in which special c lusteringalgor ith msan alyz e co mplex multivar i atedatabases. Such analys es sh ou l d pe r mi t a m ore com p le t e  id en ti fic at i on  of h igh ly corr elated cli nic al  cases and a l lo w us to ch ara cterize thei r r espons etom olecu lar  ther apiess pecifi cally des ig n ed top reventp r og ress ion. We are attem p ti n g to develop n ew app ro a ch e s  fo r b etter inte gr ation of ourt he r m o pla s tic microtran sfer method s  of  micro di sse c tion w ith d ow n str eam macrom

to_one in_which special clustering algorithms_analyze complex_multivariate_databases. Such_analyses_should permit a_more complete identification_of highly correlated clinical_cases and allow_us_to characterize their response to molecular therapies specifically designed to prevent progression. We are_attempting_to develop_new_approaches_for better integration of our_thermoplastic microtransfer methods of microdissection_with downstream_macrom


and alcohol problems in young adulthood, to test multiple models for understanding the mechanisms and directions of influence among these key constructs, and to identify possible points of prevention and intervention. NOT-OD-09-058: NIH Announces the Availability of Recovery Act Funds for Competitive Revision Application The immune system has the potential

and alcohol problems in young adulthood, to test multiple models for understand the mechanism and directions of influence among these key constructs, and to name possible points of prevention and intervention. NOT - OD-09 - 058: NIH announce the Availability of Recovery Act Funds for Competitive Revision Application The immune system have the potential

anf alcohol problems in yomng adulthood, to test mnltiple models wor understanding the mechanmsms and eirections of influencd among tjese key conwrructs, and to idenbnfy pkdsibnx points of preyention and intervention. TOG-OB-09-058: NIH Announces the Availability of Wecoveru Wct Funds for Sompttieive Geyision Application The immune syatem hav the potentisl

and alcohol problems in young adulthood, to models understanding the and directions of and identify possible points prevention and intervention. NIH Announces the Availability of Recovery Funds for Competitive Revision Application The immune system has the potential

and alcohol problems in young Adulthood, tO test MulTipLe ModeLs foR understanding THe meChanisms and directions oF inflUeNCe amONg These Key consTRuCTS, anD tO iDenTiFY pOssibLe pOints of Prevention And InTervention. NOt-oD-09-058: nIH AnnouncEs tHe AvailabiliTy oF RecovErY AcT funds For compeTitive rEvisioN ApplicatIoN the immUNe systeM HAs The pOtential

and alcohol problems in y oung adult hood,  to  te st  mul tipl e models for u n ders tanding the mechanisms  anddi r ecti o ns  of i nfluenc e  a m o ngth es e k ey co nstru cts , and t o identify  po ss ible pointso fprevention  an d interventi on.  NOT-O D- 09- 0 58: N IHAnnou nces t h e Avai labilityof Recove r y Act F u n ds  for  Competitive Revi s io n  Application T he imm un e  s y s tem  ha s the pote nt ial

and_alcohol problems_in young adulthood, to_test multiple_models_for understanding_the_mechanisms and directions_of influence among_these key constructs, and_to identify possible_points_of prevention and intervention. NOT-OD-09-058: NIH Announces the Availability of Recovery Act Funds for_Competitive_Revision Application_The_immune_system has the potential


,8-tetra-chlorodibenzo-p-dioxin (TCDD), the prototypical AHR agonist. In mice, TCDD inhibits prostatic bud formation by the fetal urogenital sinus (UGS), prevents the ventral prostate lobe from forming, and permanently alters the structure and function

, 8 - tetra - chlorodibenzo - p - dioxin (TCDD), the prototypical AHR agonist. In mice, TCDD inhibit prostate bud formation by the fetal urogenital sinus (UGS), prevent the adaxial prostate lobe from forming, and permanently alters the social organization and routine

,8-tetga-chlorodibenzo-p-dioxin (TGDD), the prototypnxal AHC agoniat. In mize, TCDD inhibits prostatic bnd firmatuon by the fetal urogevital sinls (UGS), prwvenus the ventral prostate lobe frkl foxmmng, and permanektly alters the structure avd function

,8-tetra-chlorodibenzo-p-dioxin (TCDD), the prototypical AHR agonist. In inhibits bud formation the fetal urogenital prostate from forming, and alters the structure function

,8-tetra-chlorodibenzo-p-dioxin (tCDD), the proTotypIcaL AHr aGoniSt. In Mice, TCDD inhibiTS proStatic bud formation by thE fetaL uROgenITaL sinuS (UGS), preVEnTS The VeNtRal PrOStAte loBe fRom formIng, and permAneNtLy alters the sTRuCture and fuNctIon

,8-tetra-chlorodibenzo-p-d ioxin (TCD D), t hepro to typi calAHR agonist. I n  mic e, TCDD inhibits prost aticbu d  for m at ion b y the f e ta l uro ge ni tal  s i nu s (UG S),  preven ts the ven tra lprostate lob e  f rom formin g,and permanen tly  alter sthe struc tur e and  funct i on

,8-tetra-chlorodibenzo-p-dioxin (TCDD),_the prototypical_AHR agonist. In mice,_TCDD inhibits_prostatic_bud formation_by_the fetal urogenital_sinus (UGS), prevents_the ventral prostate lobe_from forming, and_permanently_alters the structure and function


of the Boston University Multidisciplinary Clinical Research Center grant which was established in 2001 and built on a strong foundation of outstanding epidemiology and clinical research. The strong record of accomplishment in patient oriented medical research at Boston University has been not only maintained in the last four years but expanded. What we propose creates new directions and areas of

of the Boston University Multidisciplinary Clinical Research Center grant which was established in 2001 and built on a strong initiation of great epidemiology and clinical research. The strong phonograph record of skill in patient oriented medical research at Boston University has been not merely maintained in the last four old age but expanded. What we propose create new directions and area of

of the Boston University Mmltidisciplinary Clinicel Resezrch Cenger grant which was establisied un 2001 abd built on a strong fuundation of outsrandmng epidemiology and clikncal dcseareh. The strong regord of accmmplishment in pxtnent oriented medical research at Bofton Unovfrsity has beeg nou ogly jaintained in the last four years gut expended. What we ptopose creates new directilns wnd areas of

of the Boston University Multidisciplinary Clinical Research which established in and built on epidemiology clinical research. The record of accomplishment patient oriented medical research at Boston has been not only maintained in the last four years but expanded. What propose creates new directions and areas of

of the Boston University MultIdisciplinAry ClIniCal reSearCh CeNter grant which WAs esTablished in 2001 and built on a StronG fOUndaTIoN of ouTstandiNG ePIDemIoLoGy aNd CLiNical ResEarch. ThE strong recOrd Of AccomplishmeNT iN patient orIenTed medical reSeaRch at BOsTon uNiverSitY has bEen not ONly maiNtained in ThE Last foUR years bUT ExPandEd. What we propose crEAtES new directions And areAs OF

of the Boston UniversityMultidisci plina ryCli ni calRese arch Center gr a nt w hich was established i n 200 1a nd b u il t ona stron g  f o u nda ti on  of  o u ts tandi ngepidemi ology andcli ni cal research .  T he strongrec ord of accom pli shment  i n p a tient  or iente d medi c al res earch atBo s ton Un i versity h as  bee n not only mainta i ne d  in the last f our ye ar s  b u t  ex pan ded. Whatwe  prop o se crea t es n e w d i rections andareas of

of_the Boston_University Multidisciplinary Clinical Research_Center grant_which_was established_in_2001 and built_on a strong_foundation of outstanding epidemiology_and clinical research._The_strong record of accomplishment in patient oriented medical research at Boston University has been_not_only maintained_in_the_last four years but expanded._What we propose creates new_directions and_areas of


Sfanos et al., Nat. Rev. Urol. 9:111-118, 2012). b. Development of a new MLV infectivity assay and further applications of the iGLuc infectivity assay strategy As part of our continuing studies on XMRV, we adapted a retrotransposition assay (Cur

Sfanos et al. , Nat. Rev. Urol. 9:111 - 118, 2012). b. Development of a new MLV infectivity assay and further applications of the iGLuc infectivity assay strategy As character of our stay studies on XMRV, we adapt a retrotransposition assay (Cur

Sfwnos et al., Nat. Rev. Urol. 9:111-118, 2012). b. Development of a nxw MLV jnfectivkty assay and further applicetiobs of the iGLuc infectivity assay stgategy As paru of our continuiif studicf on WMRV, ce adapted a rettotransposithon assay (Cur

Sfanos et al., Nat. Rev. Urol. 9:111-118, Development a new infectivity assay and infectivity strategy As part our continuing studies XMRV, we adapted a retrotransposition assay

Sfanos et al., Nat. Rev. Urol. 9:111-118, 2012). b. DeveLopment of a New MLv inFecTiVity AssaY and further appLIcatIons of the iGLuc infectivIty asSaY StraTEgY As paRt of our COnTINuiNg StUdiEs ON XmRV, we AdaPted a reTrotranspoSitIoN assay (Cur

Sfanos et al., Nat. Rev.Urol. 9:11 1-118 , 2 012 ).  b.Deve lopment of a n e w ML V infectivity assay an d fur th e r ap p li catio ns of t h ei G Luc  i nf ect iv i ty  assa y s trategy  As part o f o ur  continuings tu dies on XM RV,  we adapteda r etrotr an spo s ition  as say ( Cur

Sfanos_et al.,_Nat. Rev. Urol. 9:111-118,_2012). b._Development_of a_new_MLV infectivity assay_and further applications_of the iGLuc infectivity_assay strategy As_part_of our continuing studies on XMRV, we adapted a retrotransposition assay (Cur


fill out questionnaires after these medical visits. A home visit will occur one month after the audio-taped visit. Children will be interviewed during the home visits, asked to demonstrate inhaler and peak flow technique a second time, and have their lung function examined using spirometry. Caregivers will fill out questionnaires

fill out questionnaires after these medical visits. A base sojourn will occur one month after the sound recording - taped sojourn. Children will be interviewed during the family visit, asked to show inhaler and peak flow proficiency a second time, and have their lung function examined use spirometry. Caregivers will fill up out questionnaires

fipl out questionnaires afuer these medical visits. A homs visit dill occur one month after tie aydio-tqped visit. Children wiul be intvrviewed euriig the home visiva, asked to dejlnstxave inhaler and keak flow tewhnique a secotd tnme, and have their lung function exaiined uxijg spirometry. Sarebyvera will fill out questionnaires

fill out questionnaires after these medical visits. visit occur one after the audio-taped during home visits, asked demonstrate inhaler and flow technique a second time, and their lung function examined using spirometry. Caregivers will fill out questionnaires

fill out questionnaires afteR these mediCal viSitS. A hOmE visIt wiLl occur one montH AfteR the audio-taped visit. ChiLdren WiLL be iNTeRviewEd durinG ThE HOme ViSiTs, aSkED tO demoNstRate inhAler and peaK flOw Technique a seCOnD time, and haVe tHeir lung funcTioN examiNeD usINg spiRomEtry. CAregivERs will Fill out quEsTIonnaiREs

fill out questionnaires a fter these  medi cal  vi si ts.A ho me visit willo ccur  one month after the a udio- ta p ed v i si t. Ch ildrenw il l bein te rvi ew e ddurin g t he home  visits, a ske dto demonstra t einhaler an d p eak flow tec hni que ase con d  time , a nd ha ve the i r lung  function  e x amined using s p i ro metr y. Caregivers wil l  f i ll out questio nnaire s

fill_out questionnaires_after these medical visits._A home_visit_will occur_one_month after the_audio-taped visit. Children_will be interviewed during_the home visits,_asked_to demonstrate inhaler and peak flow technique a second time, and have their lung_function_examined using_spirometry._Caregivers_will fill out questionnaires


solution at physiological pH and pH = 8.5, using different [NAC]/[Mn+] ratios and [Mn+] = 10 and 100 mM. In this study, we will combine the results from different spectroscopic techniques, such as extended x-ray-absorption fine structure (EXAFS), multi-

solution at physiological pH and pH = 8.5, using different [ NAC]/[Mn+ ] ratios and [ Mn+ ] = 10 and 100 mM. In this discipline, we will compound the results from different spectroscopic techniques, such as run x - ray - preoccupation all right structure (EXAFS), multi-

sopution at physiological kH and pH = 8.5, using differxnt [NAC]/[Jn+] ratior and [Mn+] = 10 and 100 mM. In this svudy, we wull combine the resultr from divferent wpecuroscopic techniqnss, such as exfcnded e-ray-absorption nine structgre (EXAFS), multh-

solution at physiological pH and pH = different ratios and = 10 and we combine the results different spectroscopic techniques, as extended x-ray-absorption fine structure (EXAFS),

solution at physiological pH And pH = 8.5, using DiffeRenT [NAc]/[MN+] ratIos aNd [Mn+] = 10 and 100 mM. In thiS StudY, we will combine the resulTs froM dIFferENt SpectRoscopiC TeCHNiqUeS, sUch As EXtEnded X-raY-absorpTion fine stRucTuRe (EXAFS), multi-

solution at physiological  pH and pH  = 8. 5,usi ng  dif fere nt [NAC]/[Mn+] rati os and [Mn+] = 10 and100 m M. In t h is  stud y, we w i ll c omb in ethe  r e su lts f rom  differ ent spectr osc op ic technique s ,such as ex ten ded x-ray-ab sor ptionfi nes truct ure  (EXA FS), m u lti-

solution_at physiological_pH and pH =_8.5, using_different_[NAC]/[Mn+] ratios_and_[Mn+] = 10_and 100 mM._In this study, we_will combine the_results_from different spectroscopic techniques, such as extended x-ray-absorption fine structure (EXAFS), multi-


monkey virus that is the closest relative to HCV. In addition, we have prepared challenge pools of GBV-B and have determined the infectivity titer of these in tamarins. We plan to use the GBV-B tamarin system to study characteristics of the virus that it shares with HCV, which must

monkey virus that is the closest relative to HCV. In addition, we have prepared challenge pool of GBV - B and have determine the infectivity titer of these in tamarins. We plan to use the GBV - b-complex vitamin tamarin system to study characteristic of the virus that it share with HCV, which must

mojkey virus that is the cuosest relative to HCV. In adsition, wd have prepared challenge pollw of TBV-B and have determindd the invectivitt tiuer of these in tejarins. We plah to bsx the GBV-B tamatin system tm study characdefidtics of the virus that it shares wyth HCV, wjich must

monkey virus that is the closest relative In we have challenge pools of infectivity of these in We plan to the GBV-B tamarin system to study of the virus that it shares with HCV, which must

monkey virus that is the closeSt relative To HCV. in aDdiTiOn, we Have Prepared challeNGe poOls of GBV-B and have determIned tHe INfecTIvIty tiTer of thESe IN TamArInS. We PlAN tO use tHe GbV-B tamaRin system tO stUdY characterisTIcS of the viruS thAt it shares wiTh HcV, whicH mUst

monkey virus that is theclosest re lativ e t o H CV . In  add ition, we have prep ared challenge pools o f GBV -B andh av e det ermined th e inf ec ti vit yt it er of  th ese intamarins.Wepl an to use th e  G BV-B tamar insystem to st udy  chara ct eri s ticsofthe v irus t h at itshares wi th HCV, w h ich mus t

monkey_virus that_is the closest relative_to HCV._In_addition, we_have_prepared challenge pools_of GBV-B and_have determined the infectivity_titer of these_in_tamarins. We plan to use the GBV-B tamarin system to study characteristics of the_virus_that it_shares_with_HCV, which must


A. Both genetic studies and studies using inhibitors of protein phosphatases (e.g. okadaic acid) indicate protein phosphatases play an important role(s) in the regulation of cell cycle progression and processes implicated in tumor promotion. PP5 has been shown to play a negative regulatory role in a p53-

A. Both genetic studies and studies using inhibitor of protein phosphatase (for example okadaic acid) indicate protein phosphatases play an crucial role(s) in the regulation of cell bicycle progress and processes implicate in tumor promotion. PP5 has been shown to toy a negative regulatory role in a p53-

A. Blth genetic studies and rtudies using iuyibitocs of pdotein pfosphatases (e.g. okadaic acid) mndixate kgotein phosphatases puay an imiortant rile(s) un the regnmation of celm cycnx progression akd processev implicated it gulor promotion. PP5 has been shown to [lay a mehative regulatjry goje ih a p53-

A. Both genetic studies and studies using protein (e.g. okadaic indicate protein phosphatases the of cell cycle and processes implicated tumor promotion. PP5 has been shown play a negative regulatory role in a p53-

A. Both genetic studies and stuDies using iNhibiTorS of PrOteiN phoSphatases (e.g. okaDAic aCid) indicate protein phosPhataSeS Play AN iMportAnt role(S) In THE reGuLaTioN oF CeLl cycLe pRogressIon and procEssEs Implicated in TUmOr promotioN. PP5 Has been shown To pLay a neGaTivE RegulAtoRy rolE in a p53-

A. Both genetic studies an d studiesusing  in hib it orsof p rotein phospha t ases  (e.g. okadaic acid) i ndica te prot e in  phos phatase s  p l a y a nim por ta n trole( s)in theregulation  of  c ell cycle pr o gr ession and  pr ocesses impl ica ted in  t umo r  prom oti on. P P5 has been s hown to p la y  a neg a tive re g u la tory  role in a p53-

A. Both_genetic studies_and studies using inhibitors_of protein_phosphatases_(e.g. okadaic_acid)_indicate protein phosphatases_play an important_role(s) in the regulation_of cell cycle_progression_and processes implicated in tumor promotion. PP5 has been shown to play a negative_regulatory_role in_a_p53-


GS from various species use metal ions. This will involve the preparation of a number of PBGSs from various sources, with various combinations of Zn(2+), Mg(2+), Mn(2+), followed by analysis of metal ligation by EXAFS and ESR, and function. The inhibition of these several

GS from various species use metallic element ion. This will involve the preparation of a numeral of PBGSs from respective sources, with various combination of Zn(2 +), Mg(2 +), Mn(2 +), trace by analysis of metallic element ligation by EXAFS and ESR, and function. The inhibition of these respective

GS vrom various species use metal ions. This will mnvolve the preoaration of a number of PBGSd drom carious sources, with vxrious colbinatiobs oh Zn(2+), Mg(2+), Mn(2+), folloxsd by akclysia of kxtal ligation bi EXAFS and ASR, and functimn. Tke inhibition of these several

GS from various species use metal ions. involve preparation of number of PBGSs combinations Zn(2+), Mg(2+), Mn(2+), by analysis of ligation by EXAFS and ESR, and The inhibition of these several

GS from various species use meTal ions. ThiS will InvOlvE tHe prEparAtion of a number OF PBGss from various sources, wiTh varIoUS comBInAtionS of Zn(2+), Mg(2+), mN(2+), fOLLowEd By AnaLySIs Of metAl lIgation By EXAFS and eSR, AnD function. The INhIbition of tHesE several

GS from various species us e metal io ns. T his  wi ll  inv olve  the preparati o n of  a number of PBGSs fro m var io u s so u rc es, w ith var i ou s com bi na tio ns of  Zn(2 +),  Mg(2+) , Mn(2+),fol lo wed by analy s is  of metallig ation by EXA FSand ES R,  an d  func tio n. Th e inhi b itionof thesese v eral

GS from_various species_use metal ions. This_will involve_the_preparation of_a_number of PBGSs_from various sources,_with various combinations of_Zn(2+), Mg(2+), Mn(2+),_followed_by analysis of metal ligation by EXAFS and ESR, and function. The inhibition of_these_several


hippocampus will be correlated with their susceptibility to epilepsy associated damage. Similar studies will be carried out in rats with seizures induced by graded electrical stimulation. Because the hippocampal somatostatin interneuron appears to be an early excitotoxic target, and thus of possible significance in the pathogenesis of TLE, we will particularly focus on the

hippocampus will be correlated with their susceptibility to epilepsy associated damage. Similar report will be carry out in rats with seizures induced by grade electrical stimulation. Because the hippocampal somatostatin interneuron appear to be an early excitotoxic aim, and thus of potential meaning in the pathogenesis of TLE, we will particularly focus on the

hiopocampus will be correlxted with their suscepvibilitg to epiuepsy associated damage. Simipae stueies will be carried ojt in ratd with swizuces induced by gczded elcetriczp stnmnlation. Because the hippowampal somatosdagiu interneuron appears to be an early excitoyodic target, and thux of lossible significance in the pathofenesis of TLE, we wikl particularly focus on tje

hippocampus will be correlated with their susceptibility associated Similar studies be carried out by electrical stimulation. Because hippocampal somatostatin interneuron to be an early excitotoxic target, thus of possible significance in the pathogenesis of TLE, we will particularly focus the

hippocampus will be correlatEd with theiR suscEptIbiLiTy to EpilEpsy associated DAmagE. Similar studies will be cArrieD oUT in rATs With sEizures INdUCEd bY gRaDed ElECtRical StiMulatioN. Because thE hiPpOcampal somatOStAtin internEurOn appears to bE an Early eXcItoTOxic tArgEt, and Thus of POssiblE significAnCE in the PAthogenESIs Of TLe, we will particularLY fOCus on the

hippocampus will be corre lated with  thei r s usc ep tibi lity  to epilepsy a s soci ated damage. Similar s tudie sw illb ecarri ed outi nr a tswi th  se iz u re s ind uce d by gr aded elect ric al  stimulation .  B ecause the  hi ppocampal so mat ostati nint e rneur onappea rs tob e an e arly exci to t oxic t a rget, a n d  t husof possible signi f ic a nce in the pat hogene si s  o f TLE , w e will par ti cular l y focus on t h e

hippocampus_will be_correlated with their susceptibility_to epilepsy_associated_damage. Similar_studies_will be carried_out in rats_with seizures induced by_graded electrical stimulation._Because_the hippocampal somatostatin interneuron appears to be an early excitotoxic target, and thus of_possible_significance in_the_pathogenesis_of TLE, we will particularly_focus on the


flexor digitorum tendon transfer replace the posterior tibial tendon muscle unit and does it leave muscle imbalance and increased strain in the arch?; 3) does a bony procedure, like a medial calcaneal displacement osteotomy, adequately assist the flexor digitorum tendon transfer?; and, most importantly, 4)

flexor digitorum tendon transfer replace the posterior tibial tendon muscle unit and does it bequeath muscleman imbalance and increased strain in the arch? ; 3) perform a bony procedure, like a medial calcaneal supplanting osteotomy, adequately assist the flexor digitorum tendon transfer? ; and, most importantly, 4 )

flfxor digitorum tendon trxnsfer replace jhw postxrior tjbial tevdon muscle unit and does it lwave nuscle imbalance and ivcreased dtrain ib tht arch?; 3) does a boig procedure, ljne a nedial calcanesl displacament osteotomf, xdzquately assist the flexor digitorum tendon tgansfer?; and, moft ik[ortzntly, 4)

flexor digitorum tendon transfer replace the posterior muscle and does leave muscle imbalance arch?; does a bony like a medial displacement osteotomy, adequately assist the flexor tendon transfer?; and, most importantly, 4)

flexor digitorum tendon tranSfer replacE the pOstEriOr TibiAl teNdon muscle unit ANd doEs it leave muscle imbalanCe and InCReasED sTrain In the arCH?; 3) dOES a bOnY pRocEdURe, Like a MedIal calcAneal displAceMeNt osteotomy, aDEqUately assiSt tHe flexor digiTorUm tendOn TraNSfer?; aNd, mOst imPortanTLy, 4)

flexor digitorum tendon t ransfer re place  th e p os teri or t ibial tendon m u scle  unit and does it leav e mus cl e  imb a la nce a nd incr e as e d  st ra in  in  t h earch? ; 3 ) doesa bony pro ced ur e, like a me d ia l calcanea l d isplacementost eotomy ,ade q uatel y a ssist  the f l exor d igitorumte n don tr a nsfer?; a nd , mo st importantly, 4 )

flexor_digitorum tendon_transfer replace the posterior_tibial tendon_muscle_unit and_does_it leave muscle_imbalance and increased_strain in the arch?;_3) does a_bony_procedure, like a medial calcaneal displacement osteotomy, adequately assist the flexor digitorum tendon transfer?;_and,_most importantly,_4)


aggravate AIDS-associated CNS dysfunctions. The results obtained in this proposal will allow the generation of data on direct effects of the drug on cells, relative susceptibility of different cell types to direct actions, and on pathways, aiming a future R01 application on modulation of oxidative stress in Meth abuse in vivo. These will lead

aggravate AIDS - associated CNS dysfunctions. The result prevail in this proposal will allow the generation of datum on direct effects of the drug on cells, proportional susceptibility of unlike cell types to direct actions, and on pathways, calculate a future R01 application on modulation of oxidative tension in Meth abuse in vivo. These will lead

aghravate AIDS-associated CKS dysfunctions. Jhw resunts obfained iv this proposal will allow tie gwneraupon of data on direct effects lf the deug ib cells, relative smfcepflbilicy of different gell types do direct actimnr, cnd on pathways, aiming a future R01 ap[licatipn on modulation of pvidafpvt stress in Meth abuse in vivo. Thsse wiln lead

aggravate AIDS-associated CNS dysfunctions. The results obtained proposal allow the of data on on relative susceptibility of cell types to actions, and on pathways, aiming a R01 application on modulation of oxidative stress in Meth abuse in vivo. These lead

aggravate AIDS-associated CNs dysfunctiOns. ThE reSulTs ObtaIned In this proposal WIll aLlow the generation of datA on diReCT effECtS of thE drug on CElLS, RelAtIvE suScEPtIbiliTy oF differEnt cell typEs tO dIrect actions, ANd On pathways, AimIng a future R01 aPplIcatioN oN moDUlatiOn oF oxidAtive sTRess in meth abuse In VIvo. TheSE will leAD

aggravate AIDS-associated  CNS dysfu nctio ns.  Th eresu ltsobtained in th i s pr oposal will allow thegener at i on o f  d ata o n direc t  e f f ect sof  th ed ru g oncel ls, rel ative susc ept ib ility of dif f er ent cell t ype s to directact ions,an d o n  path way s, ai ming a future  R01 appl ic a tion o n  modula t i on  ofoxidative stressi nM eth abuse in v ivo. T he s ew i lllea d

aggravate_AIDS-associated CNS_dysfunctions. The results obtained_in this_proposal_will allow_the_generation of data_on direct effects_of the drug on_cells, relative susceptibility_of_different cell types to direct actions, and on pathways, aiming a future R01 application_on_modulation of_oxidative_stress_in Meth abuse in vivo._These will lead


M. tuberculosis. In the Aim 2, we will study the relationship between PE and PPE protein secretion, post-translational modification and the immunogenicity of these proteins. This work will refine our model of how PE and PPE proteins generate antigenic diversity in M. tuberculosis. Together, these data will dramatically increase

M. tuberculosis. In the Aim 2, we will study the relationship between PE and PPE protein secretion, post - translational modification and the immunogenicity of these proteins. This workplace will polish our model of how PE and PPE proteins generate antigenic diverseness in M. tuberculosis. Together, these data will dramatically increase

M. huberculosis. In the Aim 2, we will study jhw relavionshil betweev PE and PPE protein secretiln, post-uganslational modificagion and nhe immunigenmcity of these pckteins. Bkis wkvk wino refine our mpdel of hof PE and PPE psogenns generate antigenic diversity in I. tubervuposis. Together, thexq dafa will dramatically increase

M. tuberculosis. In the Aim 2, we the between PE PPE protein secretion, of proteins. This work refine our model how PE and PPE proteins generate diversity in M. tuberculosis. Together, these data will dramatically increase

M. tuberculosis. In the Aim 2, we wiLl study the RelatIonShiP bEtweEn PE And PPE protein sECretIon, post-translational moDificAtIOn anD ThE immuNogenicITy OF TheSe PrOteInS. thIs worK wiLl refinE our model oF hoW Pe and PPE proteINs Generate anTigEnic diversitY in m. tuberCuLosIS. TogeTheR, thesE data wILl dramAtically iNcREase

M. tuberculosis. In the A im 2, we w ill s tud y t he  rel atio nship betweenP E an d PPE protein secretio n, po st - tran s la tiona l modif i ca t i onan dthe  i m mu nogen ici ty of t hese prote ins .This work wi l lrefine our  mo del of how P E a nd PPE  p rot e ins g ene rateantige n ic div ersity in  M .  tuber c ulosis. T og ethe r, these data wil l  d r amatically inc rease

M._tuberculosis. In_the Aim 2, we_will study_the_relationship between_PE_and PPE protein_secretion, post-translational modification_and the immunogenicity of_these proteins. This_work_will refine our model of how PE and PPE proteins generate antigenic diversity in_M._tuberculosis. Together,_these_data_will dramatically increase


Cs) from patients, have challenged this traditional model of metastasis. The new technologies indicate that metastatic ability is acquired at much earlier stages of tumor progression than predicted by the Darwinian model, is encoded throughout the bulk of the primary tumor, it is highly plastic and involves transient changes in gene expression. These results have led to

Cs) from patients, have challenged this traditional model of metastasis. The new technology bespeak that metastatic ability is acquired at much earlier degree of tumor progression than predicted by the Darwinian mannequin, is encode throughout the bulk of the primary tumor, it is highly plastic and involves transient change in gene expression. These results have led to

Cs) vrom patients, have challtnged this traditninal mmdel or metastxsis. The new technologies invicare thqt metastatic ability ks acquirvd at mucy eaclier stages of vhmor progressjln tkai predicted by jhe Darwiniat model, is encmddd throughout the bulk of the primary tumor, ot is highly plaftic wnd jnvolves transient changes in gene expresvion. These rexults have led to

Cs) from patients, have challenged this traditional metastasis. new technologies that metastatic ability stages tumor progression than by the Darwinian is encoded throughout the bulk of primary tumor, it is highly plastic and involves transient changes in gene expression. results have led to

Cs) from patients, have challenGed this traDitioNal ModEl Of meTastAsis. The new techNOlogIes indicate that metastaTic abIlITy is ACqUired At much eARlIER stAgEs Of tUmOR pRogreSsiOn than pRedicted by The daRwinian model, IS eNcoded throUghOut the bulk of The PrimarY tUmoR, It is hIghLy plaStic anD InvolvEs transieNt CHanges IN gene exPREsSion. these results have lED tO

Cs) from patients, have ch allenged t his t rad iti on al m odel  of metastasis .  The  new technologies indi cateth a t me t as tatic  abilit y  i s acq ui re d a tm uc h ear lie r stage s of tumor  pr og ression than pr edicted by  th e Darwinianmod el, is  e nco d ed th rou ghout  the b u lk ofthe prima ry tumor, it is h i g hl y pl astic and involve s  t r ansient change s in g en e  e x p res sio n. These r es ultsh ave led to

Cs) from_patients, have_challenged this traditional model_of metastasis._The_new technologies_indicate_that metastatic ability_is acquired at_much earlier stages of_tumor progression than_predicted_by the Darwinian model, is encoded throughout the bulk of the primary tumor, it_is_highly plastic_and_involves_transient changes in gene expression._These results have led to


scientists and community members across all levels from schoolchildren to retirees. LEARNMEM2018 will have substantial impact on the field by accelerating the pace of team science and leapfrogging towards a more complete fundamental understanding of learning and memory mechanisms as well as novel therapeutic and preventative approaches to treating brain illness and promoting brain

scientists and community members across all levels from schoolchildren to retiree. LEARNMEM2018 will take substantial impact on the sphere by accelerate the pace of team science and leapfrogging towards a more arrant cardinal understanding of learning and memory mechanisms as well as novel curative and preventative approaches to treating brain illness and promote brain

sclentists and community mtmbers across all levels from achoolchkldren to retirees. LEARNMEM2018 xill have substantial impact on the fielf by accwlereting the pace oh team sgnence wnd nxapfrogging towsrds a mora complete fungaoeutal understanding of learning and mqmory mrcjanisms as welj as govem therapeutic and preventative appdoaches to treating nrain illness and promotinh brwin

scientists and community members across all levels to LEARNMEM2018 will substantial impact on pace team science and towards a more fundamental understanding of learning and memory as well as novel therapeutic and preventative approaches to treating brain illness and brain

scientists and community memBers across All leVelS frOm SchoOlchIldren to retireES. LEArNMEM2018 will have substantiAl impAcT On thE FiEld by AccelerATiNG The PaCe Of tEaM ScIence And LeapfroGging towarDs a MoRe complete fuNDaMental undeRstAnding of learNinG and meMoRy mEChaniSms As welL as novEL theraPeutic and PrEVentatIVe approACHeS to tReating brain illneSS aND promoting braiN

scientists and communitymembers ac rossall  le ve ls f romschoolchildren to r etirees. LEARNMEM2018willha v e su b st antia l impac t  o n the  f ie ldby ac celer ati ng thepace of te amsc ience and le a pf rogging to war ds a more co mpl ete fu nd ame n tal u nde rstan ding o f  learn ing and m em o ry mec h anismsa s  w ellas novel therapeu t ic and preventati ve app ro a ch e s  to  tr eating bra in  illn e ss andp ro m o t ing brain

scientists_and community_members across all levels_from schoolchildren_to_retirees. LEARNMEM2018_will_have substantial impact_on the field_by accelerating the pace_of team science_and_leapfrogging towards a more complete fundamental understanding of learning and memory mechanisms as well_as_novel therapeutic_and_preventative_approaches to treating brain illness_and promoting brain


R action in the adipocyte. Understanding the roles of corepressors in adipocyte biology is crucial if we are to design novel approaches to the treatment of obesity and diabetes. Relevance: Obesity is a risk factor for the development of type 2 diabetes mellitus, and diabetes is a major cause or blindness, kidney disease

R action in the adipocyte. Understanding the roles of corepressors in adipocyte biota is all-important if we are to plan novel approaches to the treatment of obesity and diabetes. Relevance: fleshiness is a risk factor for the development of character 2 diabetes mellitus, and diabetes is a major causal agent or blindness, kidney disease

R aftion in the adipocyte. Ukderstanding the roles mf corspressorr in adipocyte biology is crnciao if qe are to design novel approachvs to the treetment of obesitb and diabetes. Velevcnre: Obesity is a risk factmr for the devaluplent of type 2 diabetes mellitus, and diabetrs is a major caose og flinsness, kidney disease

R action in the adipocyte. Understanding the corepressors adipocyte biology crucial if we to treatment of obesity diabetes. Relevance: Obesity a risk factor for the development type 2 diabetes mellitus, and diabetes is a major cause or blindness, kidney

R action in the adipocyte. UndeRstanding tHe rolEs oF coRePresSors In adipocyte bioLOgy iS crucial if we are to desigN noveL aPProaCHeS to thE treatmENt OF ObeSiTy And DiABeTes. ReLevAnce: ObeSity is a risK faCtOr for the deveLOpMent of type 2 DiaBetes mellituS, anD diabeTeS is A Major CauSe or bLindneSS, kidneY disease

R action in the adipocyte.  Understan dingthe  ro le s of  cor epressors in a d ipoc yte biology is crucial  if w ea re t o  d esign  novela pp r o ach es  t o t he tr eatme ntof obes ity and di abe te s. Relevance :  O besity isa r isk factor f orthe de ve lop m ent o f t ype 2  diabe t es mel litus, an dd iabete s  is a m a j or  cau se or blindness,k id n ey disease

R action_in the_adipocyte. Understanding the roles_of corepressors_in_adipocyte biology_is_crucial if we_are to design_novel approaches to the_treatment of obesity_and_diabetes. Relevance: Obesity is a risk factor for the development of type 2 diabetes_mellitus,_and diabetes_is_a_major cause or blindness, kidney_disease


. A basic understanding of the nature of keratin modification in MB should allow designing rational experiments to determine if changes in keratins are essential for alcohol induced injury and if such changes can be reversed. Our hypothesis is that Mallory Body formation may result from alterations in glycosylation and/or phosphorylation of hepatocyte keratins

. A basic understanding of the nature of keratin modification in MB should allow design intellectual experiments to determine if change in keratin are essential for alcohol induced injury and if such change can be reversed. Our hypothesis is that Mallory Body constitution may result from alterations in glycosylation and/or phosphorylation of hepatocyte keratin

. A hasic understanding of tme nature of kercrin movificatjon in MC should allow designing ratmonao exptgiments to determine kf changed in kerqtinw are essenvjal for alcohkp inbured injury and lf such chatges can be reeefszd. Our hypothesis is that Mallory Boqy formstlon may result frok altsgauions in glycosylation and/or phoslhorylauion of hepatocyte keratins

. A basic understanding of the nature modification MB should designing rational experiments keratins essential for alcohol injury and if changes can be reversed. Our hypothesis that Mallory Body formation may result from alterations in glycosylation and/or phosphorylation of keratins

. A basic understanding of the nAture of kerAtin mOdiFicAtIon iN MB sHould allow desiGNing Rational experiments to dEtermInE If chANgEs in kEratins ARe ESSenTiAl For AlCOhOl indUceD injury And if such cHanGeS can be reversED. OUr hypothesIs iS that Mallory bodY formaTiOn mAY resuLt fRom alTeratiONs in glYcosylatiOn ANd/or phOSphorylATIoN of hEpatocyte keratins

. A basic understanding of  the natur e ofker ati nmodi fica tion in MB sho u ld a llow designing rationa l exp er i ment s  t o det erminei fc h ang es  i n k er a ti ns ar e e ssentia l for alco hol  i nduced injur y  a nd if such  ch anges can be  re versed .Our hypot hes is is  thatM allory  Body for ma t ion ma y  result f ro m al terations in glyc o sy l ation and/or p hospho ry l at i o n o f h epatocyteke ratin s

. A_basic understanding_of the nature of_keratin modification_in_MB should_allow_designing rational experiments_to determine if_changes in keratins are_essential for alcohol_induced_injury and if such changes can be reversed. Our hypothesis is that Mallory Body_formation_may result_from_alterations_in glycosylation and/or phosphorylation of_hepatocyte keratins


to apply. Proposals will be reviewed by scientists not competing for pilot project funding. These reviews will be discussed by the Center's Internal Advisory Committee, which will make final decisions. Recipients will be required to write annual progress reports, and will be contacted beyond the end of the funding to document publications, grants

to apply. Proposals will be reviewed by scientists not compete for pilot burner project funding. These follow-up will be hash out by the Center's Internal Advisory Committee, which will make final decision. recipient role will be required to publish annual progress reports, and will be touch beyond the end of the funding to text file publications, grants

to apply. Proposals will be reviewed by scnwntistv not dompetine for pilot project funding. Vhesw revuews will be discussed by the Cvnter's Inrernel Advisory Commmftee, whleh wimp manx final decisioks. Recipiends will be reqgifeb to write annual progress reports, agd will bf contacted beiond uhe end of the funding to document publicztions, jrants

to apply. Proposals will be reviewed by competing pilot project These reviews will Internal Committee, which will final decisions. Recipients be required to write annual progress and will be contacted beyond the end of the funding to document publications,

to apply. Proposals will be revIewed by sciEntisTs nOt cOmPetiNg foR pilot project fUNdinG. These reviews will be disCusseD bY The CENtEr's InTernal ADViSORy COmMiTteE, wHIcH will MakE final dEcisions. ReCipIeNts will be reqUIrEd to write aNnuAl progress rePorTs, and wIlL be COntacTed BeyonD the enD Of the fUnding to dOcUMent puBLicatioNS, GrAnts

to apply. Proposals willbe reviewe d bysci ent is ts n ot c ompeting for p i lotproject funding. These  revi ew s  wil l  b e dis cussedb yt h e C en te r's  I n te rnalAdv isory C ommittee,whi ch  will make f i na l decision s.Recipients w ill  be re qu ire d  to w rit e ann ual pr o gressreports,an d  willb e conta c t ed  bey ond the end of th e  f u nding to docum ent pu bl i ca t i ons , g rants

to_apply. Proposals_will be reviewed by_scientists not_competing_for pilot_project_funding. These reviews_will be discussed_by the Center's Internal_Advisory Committee, which_will_make final decisions. Recipients will be required to write annual progress reports, and will_be_contacted beyond_the_end_of the funding to document_publications, grants


. These changes in GALT are not adequately reflected in peripheral blood analysis. The kinetics and mechanisms of CD4+ T cell restoration and function in GALT following ART have not been fully determined. Simian immunodeficiency virus (SIV) infected rhesus macaques provide an excellent animal model to study the gut mucosal

. These changes in GALT are not adequately reflected in peripheral blood analysis. The dynamics and mechanism of CD4 + T cell restoration and affair in GALT postdate ART have not been fully determined. Simian immunodeficiency virus (SIV) infect rhesus macaque provide an excellent animal model to study the gut mucosal

. Thfse changes in GALT are kot adequately rgfoected in pedipheral blood analysis. The kinetics abd mexhanisms of CD4+ T cell festoratiln and fynctmon in GALT following ARB havs not ueen fully detetmined. Simiat immunodeficianzy virus (SIV) infected rhesus macaques providr wn excellent agimak modsl to study the gut mucosal

. These changes in GALT are not in blood analysis. kinetics and mechanisms and in GALT following have not been determined. Simian immunodeficiency virus (SIV) infected macaques provide an excellent animal model to study the gut mucosal

. These changes in GALT are not aDequately rEflecTed In pErIpheRal bLood analysis. ThE KineTics and mechanisms of CD4+ T Cell rEsTOratIOn And fuNction iN gAlt FolLoWiNg ArT HAvE not bEen Fully deTermined. SiMiaN iMmunodeficieNCy Virus (SIV) inFecTed rhesus macAquEs provIdE an EXcellEnt AnimaL model TO study The gut mucOsAL

. These changes in GALT ar e not adeq uatel y r efl ec tedin p eripheral bloo d  ana lysis. The kinetics an d mec ha n isms of  CD4+  T cell re s t ora ti on  an df un ction  in  GALT f ollowing A RTha ve not beenf ul ly determi ned . Simian imm uno defici en cyv irus(SI V) in fected rhesus  macaques  p r ovidea n excel l e nt  ani mal model to stud y  t h e gut mucosal

. These_changes in_GALT are not adequately_reflected in_peripheral_blood analysis._The_kinetics and mechanisms_of CD4+ T_cell restoration and function_in GALT following_ART_have not been fully determined. Simian immunodeficiency virus (SIV) infected rhesus macaques provide an_excellent_animal model_to_study_the gut mucosal


these cells, although they have lost expression of insulin, retain to a large extend the same modifications found in the active beta cells of islets, strongly supporting the idea that they are poised for expression of insulin. In contrast, other cell types show no such modifications.[unreadable] [unreadable] We are now exploring the long-

these cells, although they have lost expression of insulin, retain to a large extend the like modification found in the active beta cells of isle, strongly defend the idea that they are poised for saying of insulin. In contrast, other cellular telephone type show no such modifications.[unreadable ] [ indecipherable ] We are now exploring the long-

thfse cells, although they mave lost expression of insuljn, retaiv to a large extend the same midifixations found in the aztive betw cells if iwoets, stronjmy supporting bhe ibee that they are poised fos expression ox kndulin. In contrast, other cell types fhow no skch modificatijns.[umweadzble] [unreadable] We are now explorihg the nong-

these cells, although they have lost expression retain a large the same modifications cells islets, strongly supporting idea that they poised for expression of insulin. In other cell types show no such modifications.[unreadable] [unreadable] We are now exploring the

these cells, although they havE lost expreSsion Of iNsuLiN, retAin tO a large extend tHE samE modifications found in tHe actIvE Beta CElLs of iSlets, stROnGLY suPpOrTinG tHE iDea thAt tHey are pOised for exPreSsIon of insulin. iN cOntrast, othEr cEll types show No sUch modIfIcaTIons.[uNreAdablE] [unreaDAble] We Are now expLoRIng the LOng-

these cells, although the y have los t exp res sio nof i nsul in, retain toa  lar ge extend the same mod ifica ti o ns f o un d inthe act i ve b eta  c el lsof is lets,  st ronglysupporting  th eidea that th e yare poised  fo r expression  of  insul in . I n  cont ras t, ot her ce l l type s show no  s u ch mod i ficatio n s .[ unre adable] [unreadab l e] We are now exp loring  t h el o ng-

these_cells, although_they have lost expression_of insulin,_retain_to a_large_extend the same_modifications found in_the active beta cells_of islets, strongly_supporting_the idea that they are poised for expression of insulin. In contrast, other cell_types_show no_such_modifications.[unreadable]_[unreadable] We are now exploring_the long-


kinetics and toxicology. These hypotheses will be tested by accomplishing the following Specific Aims: Specific Aim 1: Quantify the influence of DCA, at exposure levels ranging from environmental, [unreadable]g/kg/d to clinical, mg/kg/d, on human liver MAAI and tyrosine catabolism

kinetics and toxicology. These hypotheses will be tested by accomplishing the follow Specific Aims: Specific purpose 1: Quantify the influence of DCA, at exposure levels ranging from environmental, [ unreadable]g / kg / d to clinical, mg / kg / d, on human liver MAAI and tyrosine catabolism

kijetics and toxicology. Thtse hypotheses will be txsted bg accompuishing the following Specifmc Aums: Skvcific Aim 1: Quantify ghe influvnce of DXA, au exposure levels ranging from skviroumxntal, [unreadablg]g/kg/d to clitical, mg/kg/d, on hjmcn liver MAAI and tyrosine catabolisi

kinetics and toxicology. These hypotheses will be accomplishing following Specific Specific Aim 1: at levels ranging from [unreadable]g/kg/d to clinical, on human liver MAAI and tyrosine

kinetics and toxicology. ThesE hypotheseS will Be tEstEd By acCompLishing the follOWing specific Aims: Specific AiM 1: QuanTiFY the INfLuencE of DCA, aT ExPOSurE lEvEls RaNGiNg froM enVironmeNtal, [unreadAblE]g/Kg/d to clinicaL, Mg/Kg/d, on human LivEr MAAI and tyrOsiNe cataBoLisM

kinetics and toxicology.These hypo these s w ill  b e te sted  by accomplish i ng t he following SpecificAims:  S p ecif i cAim 1 : Quant i fy t hein fl uen ce of  DCA,  at  exposu re levelsran gi ng from envi r on mental, [u nre adable]g/kg/ d t o clin ic al, mg/kg /d,  on h uman l i ver MA AI and ty ro s ine ca t abolism

kinetics_and toxicology._These hypotheses will be_tested by_accomplishing_the following_Specific_Aims: Specific Aim_1: Quantify the_influence of DCA, at_exposure levels ranging_from_environmental, [unreadable]g/kg/d to clinical, mg/kg/d, on human liver MAAI and tyrosine catabolism


, lipid-anchored ectodomains of the alpha subunit are sufficient to demonstrate this effect. 2) A receptor-less mast cell-like line has been successfully transfected with various mutant receptors and studied with respect to the early biochemical events associated with aggregation of the wildtype receptors for IgE. Truncation of the cytoplasmic

, lipid - anchored ectodomains of the alpha subunit are sufficient to demonstrate this effect. 2) A sense organ - less mast cellular telephone - comparable line has been successfully transfected with diverse mutant sense organ and studied with respect to the early biochemical consequence consort with aggregation of the wildtype receptors for IgE. Truncation of the cytoplasmic

, lioid-anchored ectodomains uf the alpha suyynit ace suffjcient tu demonstrate this effect. 2) A rwceptir-less mast cell-like lkne has bven succewsfuooy transferfed witm varjlus kntant receptors and studiad with respecd go the early biochemical events assocyated wotj aggregation jf tnq wimdtype receptors for IgE. Truncatioh of tht cytoplasmic

, lipid-anchored ectodomains of the alpha subunit to this effect. A receptor-less mast transfected various mutant receptors studied with respect the early biochemical events associated with of the wildtype receptors for IgE. Truncation of the cytoplasmic

, lipid-anchored ectodomains oF the alpha sUbuniT arE suFfIcieNt to Demonstrate thiS EffeCt. 2) A receptor-less mast celL-like LiNE has BEeN succEssfullY TrANSfeCtEd WitH vARiOus muTanT receptOrs and studIed WiTh respect to tHE eArly biocheMicAl events assoCiaTed witH aGgrEGatioN of The wiLdtype REceptoRs for IgE. TRuNCation OF the cytOPLaSmic

, lipid-anchored ectodomai ns of thealpha  su bun it  are  suf ficient to dem o nstr ate this effect. 2) Arecep to r -les s  m ast c ell-lik e  l i n e h as  b een  s u cc essfu lly  transf ected with  va ri ous mutant r e ce ptors andstu died with re spe ct toth e e a rly b ioc hemic al eve n ts ass ociated w it h  aggre g ation o f th e wi ldtype receptorsf or IgE. Truncatio n of t he cy t o pla smi c

, lipid-anchored_ectodomains of_the alpha subunit are_sufficient to_demonstrate_this effect._2)_A receptor-less mast_cell-like line has_been successfully transfected with_various mutant receptors_and_studied with respect to the early biochemical events associated with aggregation of the wildtype_receptors_for IgE._Truncation_of_the cytoplasmic


functioning and immune functioning, as measured by CD4 cell count and prevalence of gynecological problems, over time and how depression may mediate these links, in both HIV+ and HIV- heterosexual Latinas. Its results will thus be useful in understanding and creating new public health prevention and intervention methods aimed at ethnic minority women.

functioning and immune functioning, as measured by CD4 cell count and preponderance of gynecological trouble, over time and how depression may intercede these links, in both HIV+ and HIV- heterosexual Latinas. Its resultant role will thus be useful in agreement and creating new public health prevention and interposition methods aimed at heathen minority women.

fujctioning and immune fungtioning, as measorwd by RD4 cell count avd prevalence of gynecologicel peoblens, over time and how ddpression may meduate rhese links, in botm HIV+ wnd KIT- heterosexual Katinas. Itv results will tfud be useful in understanding and crqating mea public healtr prtvegtioh and intervention methods aimed af ethnib minority women.

functioning and immune functioning, as measured by count prevalence of problems, over time these in both HIV+ HIV- heterosexual Latinas. results will thus be useful in and creating new public health prevention and intervention methods aimed at ethnic minority

functioning and immune functIoning, as meAsureD by cD4 cElL couNt anD prevalence of gYNecoLogical problems, over timE and hOw DEpreSSiOn may Mediate THeSE LinKs, In BotH Hiv+ aNd HIV- HetErosexuAl Latinas. ITs rEsUlts will thus BE uSeful in undErsTanding and crEatIng new PuBliC HealtH prEventIon and INterveNtion methOdS Aimed aT Ethnic mINOrIty wOmen.

functioning and immune fu nctioning,  as m eas ure dby C D4 c ell count andp reva lence of gynecological  prob le m s, o v er  time  and ho w  d e p res si on  ma ym ed iatethe se link s, in both  HI V+  and HIV- he t er osexual La tin as. Its resu lts  willth usb e use ful  in u nderst a ndingand creat in g  new p u blic he a l th  pre vention and inter v en t ion methods ai med at  e t hn i c  mi nor ity women.

functioning_and immune_functioning, as measured by_CD4 cell_count_and prevalence_of_gynecological problems, over_time and how_depression may mediate these_links, in both_HIV+_and HIV- heterosexual Latinas. Its results will thus be useful in understanding and creating_new_public health_prevention_and_intervention methods aimed at ethnic_minority women.


- binding protein in translation. Indeed, mutants of PAB1 deleting the part of the protein that interacts with eIF4G have no effect on the growth of cells. [unreadable] We are re-examining the importance of the polyA binding protein in the polyA requirement for translation. We find that

- binding protein in translation. Indeed, mutants of PAB1 deleting the character of the protein that interact with eIF4 G have no effect on the increase of cell. [ unreadable ] We are re - examining the importance of the polyA tie down protein in the polyA requirement for translation. We recover that

- blnding protein in translxtion. Indeed, mujabts of PAB1 dsleting ghe part of the protein that ibteraxts with eIF4G have no dffect on the groqth id cells. [uncsadable] We ars re-eranining the impprtance of the polyA bingivg protein in the polyA requirement fjr tranxlwtion. We find jhat

- binding protein in translation. Indeed, mutants deleting part of protein that interacts on growth of cells. We are re-examining importance of the polyA binding protein the polyA requirement for translation. We find that

- binding protein in translatiOn. Indeed, muTants Of PaB1 dElEtinG the Part of the proteIN thaT interacts with eIF4G have No effEcT On thE GrOwth oF cells. [uNReADAblE] WE aRe rE-eXAmIning The ImportaNce of the poLyA BiNding protein IN tHe polyA reqUirEment for tranSlaTion. We FiNd tHAt

- binding protein in tran slation. I ndeed , m uta nt s of  PAB 1 deleting the part  of the protein that i ntera ct s  wit h  e IF4Ghave no ef f e cton  t hegr o wt h ofcel ls. [un readable]Wear e re-examini n gthe import anc e of the pol yAbindin gpro t ein i n t he po lyA re q uireme nt for tr an s lation .  We fin d th at

-_binding protein_in translation. Indeed, mutants_of PAB1_deleting_the part_of_the protein that_interacts with eIF4G_have no effect on_the growth of_cells._[unreadable] We are re-examining the importance of the polyA binding protein in the polyA_requirement_for translation._We_find_that


areas are obvious. MAP kinases are key regulatory components acting on many cellular processes such as embryogenesis, differentiation, proliferation, cell death, and acute hormonal responses. MAP kinases are activated by a protein kinase cascade, consisting of a MAP/ERK kinase kinase (MEKK), which activates a MEK which activates a MAP kinase

areas are obvious. MAP kinases are key regulatory component act on many cellular processes such as embryogenesis, specialization, proliferation, cell end, and acute hormonal responses. MAP kinase are activated by a protein kinase cascade, consisting of a MAP / ERK kinase kinase (MEKK), which trip a MEK which activates a MAP kinase

arfas are obvious. MAP kinares are key regolqtory romponehts activg on many cellular processed wuch qs embryogenesis, diffefentiatioj, prolifwratmon, cell death, ais acute hormohwl rzs'onses. MAP kinaxes are acdivated by a psogenn kinase cascade, consisting of a MA[/ERK kimade kinase (MEKK), whibh actjnaues a MEK which activates a MAP kjnase

areas are obvious. MAP kinases are key acting many cellular such as embryogenesis, acute responses. MAP kinases activated by a kinase cascade, consisting of a MAP/ERK kinase (MEKK), which activates a MEK which activates a MAP kinase

areas are obvious. MAP kinases Are key reguLatorY coMpoNeNts aCtinG on many cellulaR ProcEsses such as embryogenesIs, difFeREntiATiOn, proLiferatIOn, CELl dEaTh, And AcUTe HormoNal ResponsEs. MAP kinasEs aRe Activated by a PRoTein kinase CasCade, consistiNg oF a MAP/ErK KinASe kinAse (mEKK), wHich acTIvates A MEK which AcTIvates A mAP kinaSE

areas are obvious. MAP ki nases arekey r egu lat or y co mpon ents acting on many  cellular processes su ch as  e m bryo g en esis,  differ e nt i a tio n,  p rol if e ra tion,  ce ll deat h, and acu teho rmonal respo n se s. MAP kin ase s are activa ted  by apr ote i n kin ase  casc ade, c o nsisti ng of a M AP / ERK ki n ase kin a s e(MEK K), which activat e sa  MEK which act ivates  a MA P kin ase

areas_are obvious._MAP kinases are key_regulatory components_acting_on many_cellular_processes such as_embryogenesis, differentiation, proliferation,_cell death, and acute_hormonal responses. MAP_kinases_are activated by a protein kinase cascade, consisting of a MAP/ERK kinase kinase (MEKK),_which_activates a_MEK_which_activates a MAP kinase


sympatho-excitatory state in dogs with HF. Therefore, the specific aims of this project are to: 1) determine if the central gain of the cardiac sympathetic afferent reflex in dogs with HF is related to increased levels of central Ang II or to changes in Ang II type1 receptor density or both, 2)

sympatho - excitatory state in dogs with HF. Therefore, the specific aims of this undertaking are to: 1) settle if the central gain of the cardiac charitable sensory nerve reflex in dogs with HF is related to increased level of central Ang II or to changes in Ang II type1 sense organ concentration or both, 2 )

sylpatho-excitatory state ik dogs with HF. Tkwreforx, the slecific xims of this project are to: 1) dwtermune if the central gaiv of the bardiac stmpauhetic afferent rxrlex in dogs slth HY ms related to ikcreased leeels of centran Xny II or to changes in Ang II type1 reseptor cejsity or both, 2)

sympatho-excitatory state in dogs with HF. Therefore, aims this project to: 1) determine the sympathetic afferent reflex dogs with HF related to increased levels of central II or to changes in Ang II type1 receptor density or both, 2)

sympatho-excitatory state in Dogs with HF. thereForE, thE sPeciFic aIms of this projeCT are To: 1) determine if the centraL gain Of THe caRDiAc symPathetiC AfFERenT rEfLex In DOgS with hF iS relateD to increasEd lEvEls of central aNg iI or to chanGes In Ang II type1 rEcePtor deNsIty OR both, 2)

sympatho-excitatory state  in dogs w ith H F.The re fore , th e specific aim s  ofthis project are to: 1 ) det er m inei fthe c entralg ai n ofth ecar di a csympa the tic aff erent refl exin  dogs with H F  i s relatedtoincreased le vel s of c en tra l  AngIIor to  chang e s in A ng II typ e1 recept o r densi t y  o r bo th, 2)

sympatho-excitatory_state in_dogs with HF. Therefore,_the specific_aims_of this_project_are to: 1)_determine if the_central gain of the_cardiac sympathetic afferent_reflex_in dogs with HF is related to increased levels of central Ang II or_to_changes in_Ang_II_type1 receptor density or both,_2)