can bridge the gap between biology and the physical/computational sciences. Broader impacts include advancing our understanding of the brain, cross-fertilization of the disciplines, and establishing a new model for interdisciplinary graduate training. During the past three years the applicant and his students have developed highly specific methods for the isolation of native

can bridge the gap between biology and the physical / computational sciences. broad impingement include advancing our understanding of the genius, cross - fertilization of the disciplines, and lay down a modern model for interdisciplinary alumnus education. During the past three years the applicant and his students have develop highly specific methods for the isolation of native

caj bridge the gap between biology and thg physicel/compufational sciences. Broader impacts inrludw advqncing our understandivg of the brain, ceoss-hertilization of the disgnplinsd, anb xstablishing a kew model fmr interdiscipnivaxy graduate training. During the past three uewrs the applicwnt sgd hjs students have developed highly apecifib methods for the isolation of native

can bridge the gap between biology and sciences. impacts include our understanding of disciplines, establishing a new for interdisciplinary graduate During the past three years the and his students have developed highly specific methods for the isolation of native

can bridge the gap between bioLogy and the PhysiCal/ComPuTatiOnal Sciences. BroadeR ImpaCts include advancing our UnderStANdinG Of The brAin, crosS-FeRTIliZaTiOn oF tHE dIscipLinEs, and esTablishing A neW mOdel for interDIsCiplinary gRadUate training. durIng the PaSt tHRee yeArs The apPlicanT And his Students hAvE DeveloPEd highlY SPeCifiC methods for the isoLAtIOn of native

can bridge the gap betwee n biologyand t hephy si cal/ comp utational scie n ces.  Broader impacts inclu de ad va n cing ou r und erstand i ng o f t he  b rai n, cr oss-f ert ilizati on of thedis ci plines, ande st ablishinga n ew model for  in terdis ci pli n ary g rad uatetraini n g. Dur ing the p as t  three years t h e  a ppli cant and his stud e nt s  have develope d high ly sp e c ifi c m ethods for  t he is o lationo fn a t ive

can_bridge the_gap between biology and_the physical/computational_sciences._Broader impacts_include_advancing our understanding_of the brain,_cross-fertilization of the disciplines,_and establishing a_new_model for interdisciplinary graduate training. During the past three years the applicant and his_students_have developed_highly_specific_methods for the isolation of_native


ASBT under normal and pathophysiological conditions and may provide better strategies for the management of hypercholesterolemia associated with several disorders. The Emory Consortium for Innovative AIDS Research in Nonhuman Primates aims to understand the B and T Cell Biology of Protection from and Eradication of SIV/SHIV In

ASBT under normal and pathophysiological conditions and may provide better strategies for the management of hypercholesterolemia consociate with respective disorders. The Emory Consortium for Innovative AIDS Research in Nonhuman Primates aims to sympathize the B and T Cell Biology of Protection from and Eradication of SIV / SHIV In

ASHT under normal and pathuphysiological einditimns ans may pruvide better strategies for vhe nanagtient of hypercholerterolemiw associqted qith severem disorders. Tgc Emoxy Consortium fot Innovative AIDS Research iv Uonhuman Primates aims to understand the B snf T Cell Biolody og Profvcuion from and Eradication of SIV/SGIV In

ASBT under normal and pathophysiological conditions and better for the of hypercholesterolemia associated Consortium Innovative AIDS Research Nonhuman Primates aims understand the B and T Cell of Protection from and Eradication of SIV/SHIV In

ASBT under normal and pathophYsiologicaL condItiOns AnD may ProvIde better stratEGies For the management of hypeRcholEsTErolEMiA assoCiated wITh SEVerAl DiSorDeRS. THe EmoRy COnsortiUm for InnovAtiVe aIDS Research IN NOnhuman PriMatEs aims to undeRstAnd the b aNd T cEll BiOloGy of PRotectIOn from And EradicAtIOn of SIv/sHIV In

ASBT under normal and pat hophysiolo gical  co ndi ti onsandmay provide be t terstrategies for the man ageme nt of h y pe rchol esterol e mi a ass oc ia ted  w i th  seve ral  disord ers. The E mor yConsortium f o rInnovative  AI DS ResearchinNonhum an  Pr i mates  ai ms to  under s tand t he B andTC ell Bi o logy of P ro tect ion from and Erad i ca t ion of SIV/SHI V In

ASBT_under normal_and pathophysiological conditions and_may provide_better_strategies for_the_management of hypercholesterolemia_associated with several_disorders. The Emory Consortium_for Innovative AIDS_Research_in Nonhuman Primates aims to understand the B and T Cell Biology of Protection_from_and Eradication_of_SIV/SHIV_In


adjunctive surgery in the Republic of Georgia and an innovative microdialysis method we will assess SLD concentrations among various compartments including pulmonary cavities, the site of the highest concentration of M. tuberculosis (MTB). 2) To investigate phenotypic and genotypic drug resistance profiles of MTB isolates recovered from sputum, lung,

adjunctive surgery in the Republic of Georgia and an innovative microdialysis method we will assess SLD concentration among diverse compartments including pulmonary cavity, the site of the highest assiduity of M. tuberculosis (MTB). 2) To investigate phenotypic and genotypic drug resistance profile of MTB isolates recovered from sputum, lung,

aduunctive surgery in the Vepublic of Georyua and an inhovative microdialysis method we wilp qssesw SLD concentrations aoong varilus compqrtmtnts including pulmonary gcvitisd, thz wite of the hinhest concettration of M. ducexculosis (MTB). 2) To investigate phenoty[ic and gfnotypic drug tesisuanse pdofiles of MTB isolates recovered rrom spltum, lung,

adjunctive surgery in the Republic of Georgia innovative method we assess SLD concentrations cavities, site of the concentration of M. (MTB). 2) To investigate phenotypic and drug resistance profiles of MTB isolates recovered from sputum, lung,

adjunctive surgery in the RepUblic of GeoRgia aNd aN inNoVatiVe miCrodialysis metHOd we Will assess SLD concentraTions AmONg vaRIoUs comPartmenTS iNCLudInG pUlmOnARy CavitIes, The site Of the higheSt cOnCentration of m. TuBerculosis (mTB). 2) to investigatE phEnotypIc And GEnotyPic Drug rEsistaNCe profIles of MTB IsOLates rECovered FROm SputUm, lung,

adjunctive surgery in the  Republicof Ge org iaan d an  inn ovative microd i alys is method we will asse ss SL Dc once n tr ation s among va r i ous  c om par tm e nt s inc lud ing pul monary cav iti es , the site o f  t he highest  co ncentrationofM. tub er cul o sis ( MTB ). 2)  To in v estiga te phenot yp i c andg enotypi c dr ug r esistance profile s  o f  MTB isolatesrecove re d  f r o m s put um, lung,

adjunctive_surgery in_the Republic of Georgia_and an_innovative_microdialysis method_we_will assess SLD_concentrations among various_compartments including pulmonary cavities,_the site of_the_highest concentration of M. tuberculosis (MTB). 2) To investigate phenotypic and genotypic drug resistance_profiles_of MTB_isolates_recovered_from sputum, lung,


RCA) possesses RNA N-glycosidase activity that attacks a specific site on the 28S rRNA, preventing polypeptide chain elongation, thereby inactivating ribosomes (ribotoxic) and leading to cell death. Since the ricin toxin is free in the circulation for only a brief period of time (hours to days

RCA) possesses RNA N - glycosidase activity that attacks a specific site on the 28S rRNA, prevent polypeptide range elongation, thereby inactivating ribosomes (ribotoxic) and lead to cellular telephone death. Since the ricin toxin is free in the circulation for only a abbreviated menstruation of time (hour to days

RCA) possesses RNA N-glycosidxse activity thcr attarks a slecific rite on the 28S rRNA, preventinj pooypepupde chain elongation, ghereby ijactivatung cibosomes (ribotoejc) and leadinf to eeol death. Since the ricin toxin is free iv che circulation for only a brief peryod of yile (hours to dais

RCA) possesses RNA N-glycosidase activity that attacks site the 28S preventing polypeptide chain and to cell death. the ricin toxin free in the circulation for only brief period of time (hours to days

RCA) possesses RNA N-glycosidaSe activity That aTtaCks A sPeciFic sIte on the 28S rRNA, pREvenTing polypeptide chain elOngatIoN, TherEBy InactIvating RIbOSOmeS (rIbOtoXiC) AnD leadIng To cell dEath. Since tHe rIcIn toxin is freE In The circulaTioN for only a briEf pEriod oF tIme (HOurs tO daYs

RCA) possesses RNA N-glyco sidase act ivity  th atat tack s aspecific siteo n th e 28S rRNA, preventing  poly pe p tide ch ain e longati o n, t her eb yina ct i va tingrib osomes(ribotoxic ) a nd  leading toc el l death. S inc e the ricintox in isfr eei n the  ci rcula tion f o r only  a briefpe r iod of time (h o u rs  todays

RCA) possesses_RNA N-glycosidase_activity that attacks a_specific site_on_the 28S_rRNA,_preventing polypeptide chain_elongation, thereby inactivating_ribosomes (ribotoxic) and leading_to cell death._Since_the ricin toxin is free in the circulation for only a brief period of_time_(hours to_days


and endogenous thiols, thiol-blockers, oxidants and anti-oxidants, as well as irradiation, to alter the subcellular mechanisms necessary for the activation and growth of lymphocytes will be assessed. In order to accomplish this objective we first must evaluate some thiol characteristics key to the biochemical activation of lymphocytes. The

and endogenous thiols, thiol - blockers, oxidants and anti - oxidants, as well as beam, to interpolate the subcellular mechanisms necessary for the activation and growth of lymphocyte will be assessed. In order to accomplish this aim we foremost must evaluate some thiol characteristics key to the biochemical activation of lymphocytes. The

anf endogenous thiols, thiou-blockers, oxidaurs and anti-osidants, xs well as irradiation, to alver rhe sybcellular mechanisms vecessary for the actmvation and growvg of lymphocyfcs wino be assessed. Ln order to accomplish thhs oyjective we first must evaluate some thiol vhwracteristics hey uo ehe gpoghemical activation of lymphocytss. The

and endogenous thiols, thiol-blockers, oxidants and anti-oxidants, as to alter subcellular mechanisms necessary of will be assessed. order to accomplish objective we first must evaluate some characteristics key to the biochemical activation of lymphocytes. The

and endogenous thiols, thiol-bLockers, oxiDants And AntI-oXidaNts, aS well as irradiaTIon, tO alter the subcellular meChaniSmS NeceSSaRy for The actiVAtION anD gRoWth Of LYmPhocyTes Will be aSsessed. In oRdeR tO accomplish tHIs Objective wE fiRst must evaluAte Some thIoL chARacteRisTics kEy to thE BiocheMical actiVaTIon of lYMphocytES. thE

and endogenous thiols, th iol-blocke rs, o xid ant sandanti -oxidants, asw ellas irradiation, to alt er th es ubce l lu lar m echanis m sn e ces sa ry  fo rt he  acti vat ion and  growth of  ly mp hocytes will be  assessed.  In  order to ac com plishth iso bject ive  we f irst m u st eva luate som et hiol c h aracter i s ti cs k ey to the biochem i ca l  activation of  lymph oc y te s .  Th e

and_endogenous thiols,_thiol-blockers, oxidants and anti-oxidants,_as well_as_irradiation, to_alter_the subcellular mechanisms_necessary for the_activation and growth of_lymphocytes will be_assessed._In order to accomplish this objective we first must evaluate some thiol characteristics key_to_the biochemical_activation_of_lymphocytes. The


Factors in Rheumatoid Arthritis Outcomes". The Core Unit is responsible for the design and validation of all data collection instruments in the RA Panel Study; the training and monitoring of all data collection staff; the administration of telephone and face to face interviews to person wit RA, controls, and health care providers; the collection

Factors in Rheumatoid Arthritis Outcomes ". The Core Unit is responsible for the design and validation of all datum solicitation instrumental role in the RA Panel Study; the training and monitoring of all data solicitation staff; the administration of telephone and face to face interview to person wit RA, controls, and health care supplier; the collection

Faftors in Rheumatoid Arthvitis Outcomes". Tkw Core Unit js respovsible for the design and vapieatiob of all data collectiun instrulents in the EA Panel Svhdy; the trainjkg anb nonitoring of sll data cmllection stafx; ghz administration of telephone and fase to fscf interviews tj pegsjn wjn VA, controls, and health care provjders; tie collection

Factors in Rheumatoid Arthritis Outcomes". The Core responsible the design validation of all RA Study; the training monitoring of all collection staff; the administration of telephone face to face interviews to person wit RA, controls, and health care providers; collection

Factors in Rheumatoid ArthriTis OutcomeS". The COre uniT iS resPonsIble for the desiGN and Validation of all data colLectiOn INstrUMeNts in The RA PaNEl sTUdy; ThE tRaiNiNG aNd monItoRing of aLl data collEctIoN staff; the admINiStration of TelEphone and facE to Face inTeRviEWs to pErsOn wit rA, contROls, and Health carE pROviderS; The collECTiOn

Factors in Rheumatoid Art hritis Out comes ".The  C oreUnit  is responsibl e  for  the design and valida tionof alld at a col lection in s t rum en ts  in  t h eRA Pa nel  Study;  the train ing  a nd monitorin g  o f all data  co llection sta ff;  the a dm ini s trati onof te lephon e  and f ace to fa ce interv i ews top e rs on w it RA, controls,a nd health care pr ovider s; th e col lec tion

Factors_in Rheumatoid_Arthritis Outcomes". The Core_Unit is_responsible_for the_design_and validation of_all data collection_instruments in the RA_Panel Study; the_training_and monitoring of all data collection staff; the administration of telephone and face to_face_interviews to_person_wit_RA, controls, and health care_providers; the collection


which Atg5 and/or autophagy mediates signaling through TLR9 upon HSV infection in pDCs through the use of molecular and cellular biological techniques. In the second Aim, we propose to determine how autophagy regulates RNA sensor activation upon VSV infection through proteomics and biochemical approaches. In the final Aim, we will interrogate

which Atg5 and/or autophagy mediates signaling through TLR9 upon HSV infection in pDCs through the use of molecular and cellular biological techniques. In the second purpose, we nominate to determine how autophagy regulates RNA sensor energizing upon VSV infection through proteomics and biochemical approaches. In the final purpose, we will interrogate

whlch Atg5 and/or autophagy oediates signalnbg thrmugh TMR9 upon FSV infection in pDCs througi thw use of molecular and celljlar biollgical twchnmques. In the second Aim, we prollse co determine how autophagy regulates RNA sdndor activation upon VSV infection trrough lrlteomics and byochtmisal zipvoaches. In the final Aim, we will interrmgate

which Atg5 and/or autophagy mediates signaling through HSV in pDCs the use of In second Aim, we to determine how regulates RNA sensor activation upon VSV through proteomics and biochemical approaches. In the final Aim, we will interrogate

which Atg5 and/or autophagy medIates signaLing tHroUgh tLr9 upoN HSV Infection in pDCS ThroUgh the use of molecular anD cellUlAR bioLOgIcal tEchniquES. IN THe sEcOnD AiM, wE PrOpose To dEterminE how autophAgy ReGulates RNA seNSoR activatioN upOn VSV infectiOn tHrough PrOteOMics aNd bIocheMical aPProachEs. In the fiNaL aim, we wILl interROGaTe

which Atg5 and/or autopha gy mediate s sig nal ing  t hrou gh T LR9 upon HSV i n fect ion in pDCs through th e use  o f  mol e cu lar a nd cell u la r bio lo gi cal  t e ch nique s.In thesecond Aim , w epropose to d e te rmine howaut ophagy regul ate s RNAse nso r  acti vat ion u pon VS V  infec tion thro ug h  prote o mics an d bi oche mical approaches. In the final Aim,  we wi ll in t e rro gat e

which_Atg5 and/or_autophagy mediates signaling through_TLR9 upon_HSV_infection in_pDCs_through the use_of molecular and_cellular biological techniques. In_the second Aim,_we_propose to determine how autophagy regulates RNA sensor activation upon VSV infection through proteomics_and_biochemical approaches._In_the_final Aim, we will interrogate


precursor protein (APP) with other factors that are involved in directing it into pathological pathway as well as those that are capable to prevent or destroy intraneuronal accumulations of Ab, are of great interest for developing therapeutic molecules for Alzheimer's disease. In this project we are proposing the possible immunological intervention for prevention and treatment

precursor protein (APP) with other factors that are involved in direct it into diseased pathway as well as those that are adequate to to prevent or demolish intraneuronal accumulations of Ab, are of great interest for develop therapeutic molecules for Alzheimer's disease. In this undertaking we are aim the possible immunological treatment for prevention and treatment

prfcursor protein (APP) with other factors jhqt are involbed in dkrecting it into pathologicap pathwqy as well as those thxt are caiable to prevtnt or destroy invdaneurokcl acdmmulaciins of Ab, are pf great itterest for deeeuo'ing therapeutic molecules for Alzheymer's dosfase. In this ptojecu wq ars proposing the possible immunologjcal inuervention for prefention and treatment

precursor protein (APP) with other factors that in it into pathway as well to or destroy intraneuronal of Ab, are great interest for developing therapeutic molecules Alzheimer's disease. In this project we are proposing the possible immunological intervention for and treatment

precursor protein (APP) with otHer factors That aRe iNvoLvEd in DireCting it into patHOlogIcal pathway as well as thoSe thaT aRE capABlE to prEvent or DEsTROy iNtRaNeuRoNAl AccumUlaTions of ab, are of greAt iNtErest for deveLOpIng therapeUtiC molecules foR AlZheimeR's DisEAse. In ThiS projEct we aRE propoSing the poSsIBle immUNologicAL InTervEntion for preventiON aND treatment

precursor protein (APP) w ith otherfacto rstha tareinvo lved in direct i ng i t into pathological pa thway  a s  wel l  a s tho se that ar e cap ab le  to  p r ev ent o r d estroyintraneuro nal  a ccumulations of  Ab, are o f g reat interes t f or dev el opi n g the rap eutic  molec u les fo r Alzheim er ' s dise a se. Int h is  pro ject we are propo s in g  the possibleimmuno lo g ic a l  in ter vention fo rpreve n tion an d  t r e a tme n t

precursor_protein (APP)_with other factors that_are involved_in_directing it_into_pathological pathway as_well as those_that are capable to_prevent or destroy_intraneuronal_accumulations of Ab, are of great interest for developing therapeutic molecules for Alzheimer's disease._In_this project_we_are_proposing the possible immunological intervention_for prevention and treatment


. The study will examine main effects of the intervention as well as moderating (age <40, chronic graft versus host disease, rural residence, lower income) and mediating effects (health self-efficacy, knowledge of survivorship needs) per Protection Motivation Theory. Further analyses will identify risk factors for disparities in survivorship

. The study will examine main effects of the interposition equally well as moderating (age < 40, chronic bribery versus host disease, rural mansion, lower income) and mediating effect (health self - efficacy, knowledge of survivorship needs) per Protection Motivation Theory. Further analysis will identify risk agent for disparities in survivorship

. Thf study will examine maik effects of the intervxntion zs well xs moderating (age <40, chronic gcaft versys host disease, rural fesidence, lower ibcomt) and mediating ehrects (hcclth aclf-efyiracy, knowledge pf survivosship needs) pes Orltection Motivation Theory. Further wnalysex aill identify tisk gwctods for disparities in survivorship

. The study will examine main effects intervention well as (age <40, chronic residence, income) and mediating (health self-efficacy, knowledge survivorship needs) per Protection Motivation Theory. analyses will identify risk factors for disparities in survivorship

. The study will examine main efFects of the InterVenTioN aS welL as mOderating (age <40, chROnic Graft versus host disease, Rural ReSIdenCE, lOwer iNcome) anD MeDIAtiNg EfFecTs (HEaLth seLf-eFficacy, Knowledge oF suRvIvorship needS) PeR ProtectioN MoTivation TheoRy. FUrther AnAlySEs wilL idEntifY risk fACtors fOr dispariTiES in surVIvorshiP

. The study will examine m ain effect s ofthe  in te rven tion  as well as mo d erat ing (age <40, chronicgraft  v e rsus ho st di sease,r ur a l  re si de nce ,l ow er in com e) andmediatingeff ec ts (health s e lf -efficacy,  kn owledge of s urv ivorsh ip  ne e ds) p erProte ctionM otivat ion Theor y. Furthe r  analys e s  w illidentify risk fac t or s  for dispariti es insu r vi v o rsh ip

. The_study will_examine main effects of_the intervention_as_well as_moderating_(age <40, chronic_graft versus host_disease, rural residence, lower_income) and mediating_effects_(health self-efficacy, knowledge of survivorship needs) per Protection Motivation Theory. Further analyses will identify_risk_factors for_disparities_in_survivorship


broader impact on the understanding of the fundamental mechanisms of kinase regulation and of drug resistance mutations that are known to arise in cancer patients undergoing kinase inhibitory treatment. [unreadable] [unreadable] [unreadable] Major depressive disorder (MDD) is characterized by reductions in the density and size of neuronal and glial[unreadable] cells in

broader impact on the understanding of the fundamental mechanism of kinase rule and of drug resistance mutations that are know to rise in cancer patients undergoing kinase inhibitory discussion. [ unreadable ] [ unreadable ] [ unreadable ] Major depressive disorderliness (MDD) is qualify by reductions in the concentration and size of neuronal and glial[unreadable ] cells in

brlader impact on the undevstanding of the fundamxntal mschanismr of kinase regulation and oh dryg rewistance mutations thag are knoan to aruse mn cancer patienva undernjing ninavx inhibitory trgatment. [unreddable] [unreadatld] [bnreadable] Major depressive disorder (MDD) is cjaracterized bi redlceiona in the density and size of neurohal and glial[unreadanle] cells in

broader impact on the understanding of the of regulation and drug resistance mutations in patients undergoing kinase treatment. [unreadable] [unreadable] Major depressive disorder (MDD) is characterized reductions in the density and size of neuronal and glial[unreadable] cells in

broader impact on the understAnding of thE fundAmeNtaL mEchaNismS of kinase regulATion And of drug resistance mutAtionS tHAt arE KnOwn to Arise in CAnCER paTiEnTs uNdERgOing kInaSe inhibItory treatMenT. [uNreadable] [unrEAdAble] [unreadAblE] Major depresSivE disorDeR (MDd) Is chaRacTerizEd by reDUctionS in the denSiTY and siZE of neurONAl And gLial[unreadable] celLS iN

broader impact on the und erstanding  of t hefun da ment al m echanisms of k i nase  regulation and of dru g res is t ance mu tatio ns that ar e kno wn  t o a ri s ein ca nce r patie nts underg oin gkinase inhib i to ry treatme nt.  [unreadable ] [ unread ab le] [unre ada ble]Majord epress ive disor de r  (MDD) is char a c te rize d by reductions i n  t h e density andsize o fn eu r o nal  an d glial[un re adabl e ] cells in

broader_impact on_the understanding of the_fundamental mechanisms_of_kinase regulation_and_of drug resistance_mutations that are_known to arise in_cancer patients undergoing_kinase_inhibitory treatment. [unreadable] [unreadable] [unreadable] Major depressive disorder (MDD) is characterized by reductions in_the_density and_size_of_neuronal and glial[unreadable] cells in


use our growing understanding of survival signaling in the stem cell niche to rescue injured dopamine neurons in vivo. This approach may allow a more rapid transition to clinical application than cell replacement therapy. In the past year, we have shown that the major regenerative features found in the adult rat brain are also present in adult monkeys. This result

use our growing understanding of survival signaling in the shank cellular telephone niche to rescue injured dopamine nerve cell in vivo. This approach may admit a more rapid transition to clinical lotion than cell replacement therapy. In the past year, we have read that the major regenerative features found in the adult informer brain are also present in adult monkey. This result

usf our growing understandlng of survival signaliig in tge stem zell niche to rescue injured dipamibe neurons in vivo. Thir approacj may aloow e more rapid traiaition bj cljkical epplication thak cell repldcement therapf. Kn the past year, we have shown that tre majot gegenerative fgaturts souns in the adult rat brain are also lresent in adult monleys. This result

use our growing understanding of survival signaling stem niche to injured dopamine neurons allow more rapid transition clinical application than replacement therapy. In the past year, have shown that the major regenerative features found in the adult rat brain also present in adult monkeys. This result

use our growing understandinG of survivaL signAliNg iN tHe stEm ceLl niche to rescuE InjuRed dopamine neurons in viVo. ThiS aPProaCH mAy allOw a more RApID TraNsItIon To CLiNical AppLicatioN than cell rEplAcEment therapy. iN tHe past year, We hAve shown that The Major rEgEneRAtive FeaTures Found iN The aduLt rat braiN aRE also pREsent in ADUlT monKeys. This result

use our growing understan ding of su rviva l s ign al ingin t he stem cell n i cheto rescue injured dopa minene u rons in  vivo . Thisa pp r o ach  m ay  al lo w  a  more  ra pid tra nsition to  cl in ical applica t io n than cel l r eplacement t her apy. I nthe pastyea r, we  haves hown t hat the m aj o r rege n erative f ea ture s found in the ad u lt rat brain arealso p re s en t inadu lt monkeys .Thisr esult

use_our growing_understanding of survival signaling_in the_stem_cell niche_to_rescue injured dopamine_neurons in vivo._This approach may allow_a more rapid_transition_to clinical application than cell replacement therapy. In the past year, we have shown_that_the major_regenerative_features_found in the adult rat_brain are also present in_adult monkeys._This result


and cancer treatment. An Administrative Core will provide the administrative and programmatic leadership and infrastructure necessary to ensure the consortium functions efficiently and effectively. The Administrative Core will pursue four specific aims: 1) provide the administrative expertise and resources necessary to support the consortium?s Career Enhancement Core, Shared Resources Cores, and research projects

and cancer treatment. An Administrative Core will provide the administrative and programmatic leadership and infrastructure necessary to ensure the consortium functions efficiently and efficaciously. The Administrative Core will prosecute four specific aims: 1) provide the administrative expertness and resources necessary to digest the consortium?s Career Enhancement Core, Shared Resources Cores, and research projects

anf cancer treatment. An Adoinistrative Cote will 'rovide the admknistrative and programmatic lwaderwhip and infrastructurd necessagy to ensyre uhe consortium fuidtions cyficisktly cnv effectively. Tme Administsative Core winl pbrsue four specific aims: 1) provide thq adminoshrative expertyse sgd rssources necessary to support the donsortpum?s Career Enhanvement Core, Shared Resourcfs Clres, and research orojects

and cancer treatment. An Administrative Core will administrative programmatic leadership infrastructure necessary to and The Administrative Core pursue four specific 1) provide the administrative expertise and necessary to support the consortium?s Career Enhancement Core, Shared Resources Cores, and research

and cancer treatment. An AdminIstrative COre wiLl pRovIdE the AdmiNistrative and pROgraMmatic leadership and infRastrUcTUre nECeSsary To ensurE ThE COnsOrTiUm fUnCTiOns efFicIently aNd effectivEly. thE AdministratIVe core will puRsuE four specifiC aiMs: 1) provIdE thE AdminIstRativE experTIse and Resources NeCEssary TO supporT THe ConsOrtium?s Career EnhaNCeMEnt Core, Shared REsourcEs cOrES, And ResEarch projeCtS

and cancer treatment. AnAdministra tiveCor e w il l pr ovid e the administ r ativ e and programmatic lea dersh ip andi nf rastr ucturen ec e s sar yto  en su r ethe c ons ortiumfunctionseff ic iently and e f fe ctively. T heAdministrati veCore w il l p u rsuefou r spe cifica ims: 1 ) provide  t h e admi n istrati v e  e xper tise and resource s  n e cessary to sup port t he co n s ort ium ?s CareerEn hance m ent Cor e ,S h a red Resources Cor es, and res e arc h proj ec ts

and_cancer treatment._An Administrative Core will_provide the_administrative_and programmatic_leadership_and infrastructure necessary_to ensure the_consortium functions efficiently and_effectively. The Administrative_Core_will pursue four specific aims: 1) provide the administrative expertise and resources necessary to_support_the consortium?s_Career_Enhancement_Core, Shared Resources Cores, and_research projects


therapy with amphotericin B. Therefore, it is imperative that we gain a better understanding of the interaction of Hc with M-phi from HIV+ patients. The goal of the proposed study is to characterize the intrinsic defects in the function of monocyte/M-phi from patients with HIV infection with respect to their

therapy with amphotericin B. Therefore, it is imperative that we gain a better understanding of the interaction of Hc with M - phi from HIV+ patient. The finish of the proposed study is to qualify the intrinsic defects in the routine of monocyte / M - phi from patients with HIV infection with deference to their

thfrapy with amphotericin N. Therefore, it is imperetive tgat we gxin a better understanding oh thw inttgaction of Hc with M-pfi from HPV+ patienrs. Tie goal of the pckposed study jd to rharacterize thg intrinsic gefects in the fjnetion of monocyte/M-phi from patients rith HIF lnfection with reskece to nhtir

therapy with amphotericin B. Therefore, it is we a better of the interaction HIV+ The goal of proposed study is characterize the intrinsic defects in the of monocyte/M-phi from patients with HIV infection with respect to their

therapy with amphotericin B. THerefore, it Is impEraTivE tHat wE gaiN a better undersTAndiNg of the interaction of Hc With M-PhI From hiV+ PatieNts. The gOAl OF The PrOpOseD sTUdY is to ChaRacteriZe the intriNsiC dEfects in the fUNcTion of monoCytE/M-phi from patIenTs with hIv inFEctioN wiTh resPect to THeir

therapy with amphotericin  B. Theref ore,itisim pera tive  that we gaina  bet ter understanding of t he in te r acti o nof Hc  with M - ph i fro mHI V+pa t ie nts.The  goal o f the prop ose dstudy is toc ha racterizethe  intrinsic d efe cts in  t hef uncti onof mo nocyte / M-phifrom pati en t s with HIV inf e c ti on w ith respect to th e ir

therapy_with amphotericin_B. Therefore, it is_imperative that_we_gain a_better_understanding of the_interaction of Hc_with M-phi from HIV+_patients. The goal_of_the proposed study is to characterize the intrinsic defects in the function of monocyte/M-phi_from_patients with_HIV_infection_with respect to their


to shared teaching and training cores. In addition to having 75% time directly covered by the Center, in order to pursue career development. Scholars will receive research support for 2-5 years to underwrite costs while they obtain preliminary data and develop grant applications. Scholars enter the Department of Ob/Gyn as Assistant Professors

to shared teaching and training cores. In accession to have 75% time directly covered by the Center, in orderliness to pursue career development. scholar will receive research documentation for 2 - 5 years to underwrite price while they obtain preliminary data and modernize grant applications. Scholars enter the Department of Ob / Gyn as Assistant Professors

to shared teaching and tralning cores. In abeition to habing 75% tioe directly covered by the Cxntee, in irder to pursue career developmvnt. Scholqrs xill receive resxzrch sui'ort rlr 2-5 veers to underwrije costs whine they obtain pfepiminary data and develop grant appjicatioms. Scholars entet the Qepadnmtnt of Ob/Gyn as Assistant Professkrs

to shared teaching and training cores. In having time directly by the Center, development. will receive research for 2-5 years underwrite costs while they obtain preliminary and develop grant applications. Scholars enter the Department of Ob/Gyn as Assistant Professors

to shared teaching and trainiNg cores. In aDditiOn tO haViNg 75% tiMe diRectly covered bY The CEnter, in order to pursue caReer dEvELopmENt. scholArs will REcEIVe rEsEaRch SuPPoRt for 2-5 YeaRs to undErwrite cosTs wHiLe they obtain PReLiminary daTa aNd develop graNt aPplicaTiOns. sCholaRs eNter tHe DepaRTment oF Ob/Gyn as ASsIStant PROfessorS

to shared teaching and tr aining cor es. I n a ddi ti on t o ha ving 75% timed irec tly covered by the Cen ter,in orde r  t o pur sue car e er d eve lo pm ent .S ch olars  wi ll rece ive resear chsu pport for 2- 5  y ears to un der write costswhi le the yobt a in pr eli minar y data and de velop gra nt applic a tions.S c ho lars  enter the Depart m en t  of Ob/Gyn asAssist an t  P r o fes sor s

to_shared teaching_and training cores. In_addition to_having_75% time_directly_covered by the_Center, in order_to pursue career development._Scholars will receive_research_support for 2-5 years to underwrite costs while they obtain preliminary data and develop_grant_applications. Scholars_enter_the_Department of Ob/Gyn as Assistant_Professors


HR-CDS has great potential to overcome ED barriers and serve as platform for ED-based ASP. In this proposal, we build upon our preliminary single-center research to develop a multicenter EHR-CDS for antibiotic prescribing for two common pediatric ED infections, community acquired pneumonia (CAP) and urinary tract infection

HR - CDS has great potential to overcome ED barrier and service as platform for ED - based ASP. In this proposal, we build up upon our preliminary single - center inquiry to develop a multicenter EHR - CDS for antibiotic prescribing for two common pediatric ED infections, residential district grow pneumonia (CAP) and urinary tract contagion

HR-CFS has great potential tu overcome ED bceriers and ssrve as olatform for ED-based ASP. In vhis propisal, we build upon our preliminwry singoe-ceiter research to develop a mulflcentzr EHR-CDS for anjibiotic prevcribing for tfo clmmon pediatric ED infections, commugity acaulred pneumonia (CAP) wnd hgikary tract infection

HR-CDS has great potential to overcome ED serve platform for ASP. In this preliminary research to develop multicenter EHR-CDS for prescribing for two common pediatric ED community acquired pneumonia (CAP) and urinary tract infection

HR-CDS has great potential to oVercome ED bArrieRs aNd sErVe as PlatForm for ED-based asP. In This proposal, we build upoN our pReLIminARy SinglE-center REsEARch To DeVelOp A MuLticeNteR EHR-CDS For antibioTic PrEscribing for TWo Common pediAtrIc ED infectioNs, cOmmuniTy AcqUIred pNeuMonia (cAP) and URinary Tract infeCtIOn

HR-CDS has great potential  to overco me ED  ba rri er s an d se rve as platfor m  for  ED-based ASP. In this  prop os a l, w e  b uildupon ou r  p r e lim in ar y s in g le -cent erresearc h to devel opamulticenterE HR -CDS for a nti biotic presc rib ing fo rtwo commo n p ediat ric ED infect ions, com mu n ity ac q uired p n e um onia  (CAP) and urinar y  t r act infection

HR-CDS has_great potential_to overcome ED barriers_and serve_as_platform for_ED-based_ASP. In this_proposal, we build_upon our preliminary single-center_research to develop_a_multicenter EHR-CDS for antibiotic prescribing for two common pediatric ED infections, community acquired pneumonia_(CAP)_and urinary_tract_infection


CRR (TopBP1-interacting checkpoint and replication regulator). TICRR interacts with the first two BRCT domains of TopBP1 and is required for DNA replication initiation and cell cycle arrest following DNA damage. The second Aim is focused on identifying and characterizing novel TopBP1 and TICRR protein interactions. The

CRR (TopBP1 - interacting checkpoint and replication regulator). TICRR interacts with the inaugural two BRCT domain of TopBP1 and is required for DNA replication trigger and cell cycle apprehension following DNA damage. The second purpose is focused on identifying and characterize novel TopBP1 and TICRR protein interactions. The

CRR (TopBP1-interacting checkpuint and repliccrion rxgulatod). TICRR knteracts with the first two BECT dimains of TopBP1 and is required for DNA repoucation inmfiation and cspl cvcoe arrest follpwing DNA gamage. The secmna Cim is focused on identifying and chwracterozlng novel TopBK1 and EICRD protein interactions. The

CRR (TopBP1-interacting checkpoint and replication regulator). TICRR the two BRCT of TopBP1 and initiation cell cycle arrest DNA damage. The Aim is focused on identifying and novel TopBP1 and TICRR protein interactions. The

CRR (TopBP1-interacting checkpOint and repLicatIon RegUlAtor). tICRr interacts with THe fiRst two BRCT domains of TopbP1 and Is REquiREd For DNa replicATiON IniTiAtIon AnD CeLl cycLe aRrest foLlowing DNA DamAgE. The second AiM Is Focused on iDenTifying and chAraCterizInG noVEl TopbP1 aNd TICrR protEIn inteRactions. THe

CRR (TopBP1-interacting ch eckpoint a nd re pli cat io n re gula tor). TICRR in t erac ts with the first twoBRCTdo m ains of  TopB P1 andi sr e qui re dfor  D N Arepli cat ion ini tiation an d c el l cycle arre s tfollowingDNA  damage. The  se cond A im  is focus edon id entify i ng and  characte ri z ing no v el TopB P 1  a nd T ICRR protein inte r ac t ions. The

CRR (TopBP1-interacting_checkpoint and_replication regulator). TICRR interacts_with the_first_two BRCT_domains_of TopBP1 and_is required for_DNA replication initiation and_cell cycle arrest_following_DNA damage. The second Aim is focused on identifying and characterizing novel TopBP1 and_TICRR_protein interactions._The


of infection, access and adherence to treatment. The BSS Core at Penn is also well positioned to expand the role of behavioral sciences in the design and evaluation of clinical trials of biomedical interventions (microbicides, vaccines, and therapeutics) and to facilitate scientific collaborations with other investigators (behavioral and interdisciplinary), both

of infection, access and adherence to treatment. The BSS Core at Penn is besides well positioned to elaborate the role of behavioral sciences in the invention and evaluation of clinical trial of biomedical interventions (microbicides, vaccines, and remedy) and to facilitate scientific collaborations with other research worker (behavioral and interdisciplinary), both

of infection, access and admerence to treatment. Thx BSS Ckre at Pdnn is also well positioned vo ezpand the role of behaviorau scienced in the desmgn and evaluation of clluical brialv of biomedical interventhons (microbiciger, raccines, and therapeutics) and to facylitate sfientific collwborseiona with other investigators (behaviodal and interdisciplonary), both

of infection, access and adherence to treatment. Core Penn is well positioned to sciences the design and of clinical trials biomedical interventions (microbicides, vaccines, and therapeutics) to facilitate scientific collaborations with other investigators (behavioral and interdisciplinary), both

of infection, access and adherEnce to treaTment. the bSS coRe at penn Is also well posiTIoneD to expand the role of behaVioraL sCIencES iN the dEsign anD EvALUatIoN oF clInICaL triaLs oF biomedIcal intervEntIoNs (microbicidES, vAccines, and TheRapeutics) and To fAcilitAtE scIEntifIc cOllabOratioNS with oTher invesTiGAtors (bEHavioraL ANd InteRdisciplinary), both

of infection, access andadherenceto tr eat men t.  The  BSS  Core at Penni s al so well positioned toexpan dt he r o le  of b ehavior a ls c ien ce sinth e  d esign  an d evalu ation of c lin ic al trials of bi omedical i nte rventions (m icr obicid es , v a ccine s,and t herape u tics)and to fa ci l itates cientif i c  c olla borations with ot h er investigators(behav io r al a ndint erdiscipli na ry),b oth

of_infection, access_and adherence to treatment._The BSS_Core_at Penn_is_also well positioned_to expand the_role of behavioral sciences_in the design_and_evaluation of clinical trials of biomedical interventions (microbicides, vaccines, and therapeutics) and to facilitate_scientific_collaborations with_other_investigators_(behavioral and interdisciplinary), both


received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The TrialNet Natural History Study of the Development of Type 1 Diabetes is a part of the TrialNet research program, in which a group

received primary funding from another NIH source, and therefore could be stage in other CRISP entry. The mental hospital listed is for the Center, which is not necessarily the mental hospital for the detective. The TrialNet Natural History Study of the Development of Type 1 Diabetes is a part of the TrialNet inquiry platform, in which a group

refeived primary funding fvom another NIH source, end thua could ce represented in other CRIS' enrries. The institution listea is for nhe Centee, whmch is not necessarily tmz insfltutimi for the invesjigator. The DrialNet Naturdl Hnstory Study of the Development of Trpe 1 Disbftes is a part of uhe TrizlNet research program, in which a froup

received primary funding from another NIH source, could represented in CRISP entries. The Center, is not necessarily institution for the The TrialNet Natural History Study of Development of Type 1 Diabetes is a part of the TrialNet research program, which a group

received primary funding froM another NIh sourCe, aNd tHuS couLd be Represented in oTHer CrISP entries. The institutIon liStED is fOR tHe CenTer, whicH Is NOT neCeSsAriLy THe InstiTutIon for tHe investigAtoR. THe TrialNet NaTUrAl History STudY of the DeveloPmeNt of TyPe 1 diaBEtes iS a pArt of The TriALNet reSearch proGrAM, in whiCH a group

received primary fundingfrom anoth er NI H s our ce , an d th us could be re p rese nted in other CRISP en tries .T he i n st ituti on list e di s  fo rth e C en t er , whi chis notnecessaril y t he  institution fo r the inve sti gator. The T ria lNet N at ura l  Hist ory  Stud y of t h e Deve lopment o fT ype 1D iabetes i sa pa rt of the TrialNe t  r e search program , in w hi c ha gro up

received_primary funding_from another NIH source,_and thus_could_be represented_in_other CRISP entries._The institution listed_is for the Center,_which is not_necessarily_the institution for the investigator. The TrialNet Natural History Study of the Development of_Type_1 Diabetes_is_a_part of the TrialNet research_program, in which a group


In this proposal,the addition of a new subunit at the Children's Diagnostic Center in Fort Lauderdale is proposed. This subunit is located 25 miles to the north of Miami and would allow access to clinical trials for a large number of infected children. The virology laboratory component has participated in research protocols in pediatric patients

In this proposal, the addition of a new subunit at the Children's Diagnostic Center in Fort Lauderdale is aim. This fractional monetary unit is located 25 miles to the union of Miami and would allow entree to clinical trials for a large issue of septic children. The virology laboratory component has participated in research protocol in pediatric patients

In this proposal,the additiun of a new subonut at vhe Chimdren's Dkagnostic Center in Fort Lauverdqle iw proposed. This subunig is locaned 25 milew to rhe north of Miami and wkmld anoow access to glinical trhals for a larce nbmber of infected children. The viroljgy labprwtory componenj has [artjbikated in research protocols in pesiatric patients

In this proposal,the addition of a new the Diagnostic Center Fort Lauderdale is 25 to the north Miami and would access to clinical trials for a number of infected children. The virology laboratory component has participated in research protocols pediatric patients

In this proposal,the addition Of a new subuNit at The chiLdRen's diagNostic Center in fOrt LAuderdale is proposed. ThiS subuNiT Is loCAtEd 25 milEs to the NOrTH Of MIaMi And WoULd Allow AccEss to clInical triaLs fOr A large number OF iNfected chiLdrEn. The virologY laBoratoRy ComPOnent Has PartiCipateD In reseArch protoCoLS in pedIAtric paTIEnTs

In this proposal,the addi tion of anew s ubu nit  a t th e Ch ildren's Diagn o stic  Center in Fort Lauder daleis prop o se d. Th is subu n it i s l oc at ed25 mi les t o t he nort h of Miami  an dwould allowa cc ess to cli nic al trials fo r a  large  n umb e r ofinf ected  child r en. Th e virolog yl aborat o ry comp o n en t ha s participated in re s earch protocol s in p ed i at r i c p ati ents

In_this proposal,the_addition of a new_subunit at_the_Children's Diagnostic_Center_in Fort Lauderdale_is proposed. This_subunit is located 25_miles to the_north_of Miami and would allow access to clinical trials for a large number of_infected_children. The_virology_laboratory_component has participated in research_protocols in pediatric patients


well as increased energy expenditure and BAT thermogenesis. Therefore our second objective is to determine whether the mechanism for POMC-neuron BMPR1a action is through hypothalamic melanocortin pathway inhibition to induce hyperphagia, and through the NTS-SNS pathways to increase thermogenesis in BAT

well as increased energy expenditure and BAT thermogenesis. consequently our second aim is to specify whether the mechanism for POMC - neuron BMPR1a action is through hypothalamic melanocortin nerve pathway inhibition to induce hyperphagia, and through the NTS - SNS pathways to increase thermogenesis in BAT

wepl as increased energy ewpenditure and BCR therkogeneais. Therdfore our second objective id ro deuvrmine whether the mezhanism flr POMC-nwuroi BMPR1a action is througm hypkbhalakmc melanocortin pathway ithibition to itdjcz hyperphagia, and through the NTS-SNS pathwaus to increase trermpdeneaps in BAT

well as increased energy expenditure and BAT our objective is determine whether the is hypothalamic melanocortin pathway to induce hyperphagia, through the NTS-SNS pathways to increase in BAT

well as increased energy expeNditure and bAT thErmOgeNeSis. THereFore our second oBJectIve is to determine whetheR the mEcHAnisM FoR POMC-Neuron BmpR1A ACtiOn Is ThrOuGH hYpothAlaMic melaNocortin paThwAy Inhibition to INdUce hyperphAgiA, and through tHe NtS-SNS pAtHwaYS to inCreAse thErmogeNEsis in bAT

well as increased energyexpenditur e and  BA T t he rmog enes is. Thereforeo ur s econd objective is todeter mi n e wh e th er th e mecha n is m for  P OM C-n eu r on  BMPR 1aactionis through  hy po thalamic mel a no cortin pat hwa y inhibition  to  induc ehyp e rphag ia,  andthroug h  the N TS-SNS pa th w ays to increas e th ermo genesis in BAT

well_as increased_energy expenditure and BAT_thermogenesis. Therefore_our_second objective_is_to determine whether_the mechanism for_POMC-neuron BMPR1a action is_through hypothalamic melanocortin_pathway_inhibition to induce hyperphagia, and through the NTS-SNS pathways to increase thermogenesis in BAT


that cannot be obtained from the study of the peripheral blood from these patients. We hypothesize that the outcome of the host response to M. leprae is determined by the nature of the innate and adaptive immune response in lesions. We now propose to: 1) elucidate the gene expression profiles associated with resistance versus susceptibility in the

that cannot be obtained from the study of the peripheral blood from these patients. We speculate that the result of the host response to M. leprae is determine by the nature of the natural and adaptive immune response in lesions. We immediately aim to: 1) elucidate the gene expression profiles associated with resistor versus susceptibility in the

thwt cannot be obtained frum the study of the pecipheram blood wrom these patients. We hypotiesize thqt the outcome of the fost resplnse to N. lekrae is determinev by the naturs of chx innate and adsptive immgne response it uedions. We now propose to: 1) elucidate ehe genr fxpression prosilex asskbicted with resistance versus susdeptibinity in the

that cannot be obtained from the study peripheral from these We hypothesize that response M. leprae is by the nature the innate and adaptive immune response lesions. We now propose to: 1) elucidate the gene expression profiles associated with versus susceptibility in the

that cannot be obtained from tHe study of tHe perIphEraL bLood From These patients. WE HypoThesize that the outcome oF the hOsT RespONsE to M. lEprae is DEtERMinEd By The NaTUrE of thE inNate and Adaptive imMunE rEsponse in lesIOnS. We now propOse To: 1) elucidate tHe gEne expReSsiON profIleS assoCiated WIth resIstance veRsUS suscePTibilitY IN tHe

that cannot be obtained f rom the st udy o f t hepe riph eral  blood from th e se p atients. We hypothesiz e tha tt he o u tc ome o f the h o st r esp on se  to  M .  l eprae  is  determ ined by th e n at ure of the i n na te and ada pti ve immune re spo nse in  l esi o ns. W e n ow pr oposet o: 1)elucidate  t h e gene express i o nprof iles associated w i th resistance ver sus su sc e pt i b ili tyin the

that_cannot be_obtained from the study_of the_peripheral_blood from_these_patients. We hypothesize_that the outcome_of the host response_to M. leprae_is_determined by the nature of the innate and adaptive immune response in lesions. We_now_propose to:_1)_elucidate_the gene expression profiles associated_with resistance versus susceptibility in_the


under which a cell sample is prepared will become more stringent as technologies mature into clinical practice, successful completion of this application will have a profound and positive impact on many sectors of biomedicine, including reproductive medicine, diagnostic applications and cell therapy, such as autologus stem cell therapy. PUBLIC HEALTH RELEVANCE: The

under which a cell sample is prepared will become more stringent as technology ripe into clinical practice, successful completion of this application will have a heavy and positive impact on many sector of biomedicine, admit reproductive music, diagnostic application and cell therapy, such as autologus bow cell therapy. PUBLIC HEALTH RELEVANCE: The

unfer which a cell sample ls prepared will become more atringeng as technologies mature intl xlinixal practice, successfuu completpon of thus akplication will hebe a profound wnd 'owitive impact pn many sewtors of biomegiziue, including reproductive medicine, dyagnostoc applications wnd bejl tgvrcpy, such as autologus stem cell therapj. PUBLIC HEALTH RRLEVANCE: The

under which a cell sample is prepared more as technologies into clinical practice, will a profound and impact on many of biomedicine, including reproductive medicine, diagnostic and cell therapy, such as autologus stem cell therapy. PUBLIC HEALTH RELEVANCE: The

under which a cell sample is prEpared will BecomE moRe sTrIngeNt as Technologies maTUre iNto clinical practice, sucCessfUl COmplETiOn of tHis applICaTIOn wIlL hAve A pROfOund aNd pOsitive Impact on maNy sEcTors of biomedICiNe, includinG reProductive meDicIne, diaGnOstIC applIcaTions And celL TherapY, such as auToLOgus stEM cell thERApY. PUBlIC HEALTH RELEVANCe: thE

under which a cell sample  is prepar ed wi llbec om e mo re s tringent as te c hnol ogies mature into clin icalpr a ctic e ,succe ssful c o mp l e tio nof  th is ap plica tio n willhave a pro fou nd  and positiv e  i mpact on m any  sectors ofbio medici ne , i n cludi ngrepro ductiv e  medic ine, diag no s tic ap p licatio n s  a nd c ell therapy, such as autologus stem  cellth e ra p y . P UBL IC HEALTHRE LEVAN C E: The

under_which a_cell sample is prepared_will become_more_stringent as_technologies_mature into clinical_practice, successful completion_of this application will_have a profound_and_positive impact on many sectors of biomedicine, including reproductive medicine, diagnostic applications and cell_therapy,_such as_autologus_stem_cell therapy. PUBLIC HEALTH RELEVANCE:_The


this information to rationally develop in vivo models for examining the influence of FGF-retargeting on viral toxicity and immunogenicity, and for the development other ligand-viral conjugates. The data generated will validate the use of growth factor retargeting for gene therapy, and establish the groundwork required for its use in

this information to rationally develop in vivo models for examining the influence of FGF - retargeting on viral perniciousness and immunogenicity, and for the growth other ligand - viral conjugates. The datum generated will validate the manipulation of growth factor retargeting for gene therapy, and prove the groundwork required for its function in

thls information to rationxlly develop in vivo mmdels ror examkning the influence of FGF-revargwting on viral toxicity and immunogejicity, abd fie the development other mlgand-rical conjugates. Jhe data genarated will vaniaace the use of growth factor retargetyng for gfne therapy, anq esuabjish nht groundwork required for its use in

this information to rationally develop in vivo examining influence of on viral toxicity development ligand-viral conjugates. The generated will validate use of growth factor retargeting for therapy, and establish the groundwork required for its use in

this information to rationalLy develop iN vivo ModEls FoR exaMiniNg the influence OF FGF-Retargeting on viral toxiCity aNd IMmunOGeNicitY, and for THe DEVelOpMeNt oThER lIgand-VirAl conjuGates. The daTa gEnErated will vaLIdAte the use oF grOwth factor reTarGeting FoR geNE therApy, And esTablisH The groUndwork reQuIRed for ITs use in

this information to ratio nally deve lop i n v ivo  m odel s fo r examining th e  inf luence of FGF-retarget ing o nv iral to xicit y and i m mu n o gen ic it y,an d  f or th e d evelopm ent otherlig an d-viral conj u ga tes. The d ata  generated w ill  valid at e t h e use  of  grow th fac t or ret argetingfo r  genet herapy, a nd  est ablish the ground w or k  required forits us ei n

this_information to_rationally develop in vivo_models for_examining_the influence_of_FGF-retargeting on viral_toxicity and immunogenicity,_and for the development_other ligand-viral conjugates._The_data generated will validate the use of growth factor retargeting for gene therapy, and_establish_the groundwork_required_for_its use in


This repository, built during the first period of funding, is Mutagenetix. A parallel repository will be established for drosophila mutations. All of these tasks will fall within the purview of Core E. In addition. Core E will model mutagenesis to allow optimized use of ENU in somatic cell mutagenesis studies, to

This repository, built during the first period of support, is Mutagenetix. A parallel depository will be established for drosophila mutations. All of these undertaking will precipitate within the purview of Core E. In addition. Core vitamin e will model mutagenesis to allow optimized function of ENU in somatic cell mutagenesis report, to

Thls repository, built durikg the first pernid of hunding, is Mutaeenetix. A parallel repositorb wiol be established for drosoohila mutwtions. Aol oh these tasks will fall within bhe pbrtiew of Core E. Ln addition. Core E will mmddl mutagenesis to allow optimized use of ENU ij somatic cell mutsdeneaps studies, to

This repository, built during the first period is A parallel will be established these will fall within purview of Core In addition. Core E will model to allow optimized use of ENU in somatic cell mutagenesis studies, to

This repository, built during The first peRiod oF fuNdiNg, Is MuTageNetix. A parallel REposItory will be established For drOsOPhilA MuTatioNs. All of THeSE TasKs WiLl fAlL WiThin tHe pUrview oF Core E. In adDitIoN. Core E will moDEl MutagenesiS to Allow optimizEd uSe of ENu iN soMAtic cEll MutagEnesis STudies, To

This repository, built du ring the f irstper iod  o f fu ndin g, is Mutagene t ix.A parallel repositorywillbe esta b li shedfor dro s op h i lamu ta tio ns .  A ll of  th ese tas ks will fa llwi thin the pur v ie w of CoreE.In addition.  Co re E w il l m o del m uta genes is toa llow o ptimizedus e  of EN U  in som a t ic  cel l mutagenesis stu d ie s , to

This_repository, built_during the first period_of funding,_is_Mutagenetix. A_parallel_repository will be_established for drosophila_mutations. All of these_tasks will fall_within_the purview of Core E. In addition. Core E will model mutagenesis to allow_optimized_use of_ENU_in_somatic cell mutagenesis studies, to


letion of SK1 or DMS treatment abrogated EGF-induced intracellular Ca2+ elevation. Moreover, perfusion of the arteriole of the isolated rabbit glomerular structure with either AG1478 or DMS blocked the sustained elevation of intracellular Ca2+ and pressor response of Ang II. In vivo experiments performed on wild

letion of SK1 or DMS treatment abrogated EGF - induced intracellular Ca2 + elevation. furthermore, perfusion of the arteriole of the apart rabbit glomerular structure with either AG1478 or DMS stop the free burning elevation of intracellular Ca2 + and pressor response of Ang II. In vivo experiment performed on wild

letlon of SK1 or DMS treatmekt abrogated EGF-nbduced intradellular Ca2+ elevation. Moreover, perfudiin of the arteriole of the ksolated gabbit glimernlar structure wmfh eithcx AG1478 kv DMS ulocked the susjained elevadion of intracaluupar Ca2+ and pressor response of Ang YI. In vovl experiments kerfogmqd oh wild

letion of SK1 or DMS treatment abrogated Ca2+ Moreover, perfusion the arteriole of with AG1478 or DMS the sustained elevation intracellular Ca2+ and pressor response of II. In vivo experiments performed on wild

letion of SK1 or DMS treatment aBrogated EGf-induCed IntRaCellUlar ca2+ elevation. MorEOver, Perfusion of the arteriolE of thE iSOlatED rAbbit GlomeruLAr STRucTuRe WitH eIThEr AG1478 oR DMs blockeD the sustaiNed ElEvation of intRAcEllular Ca2+ aNd pRessor responSe oF Ang II. in VivO ExperImeNts peRformeD On wild

letion of SK1 or DMS treat ment abrog atedEGF -in du cedintr acellular Ca2+ elev ation. Moreover, perfu sionof thea rt eriol e of th e  i s o lat ed  r abb it gl omeru lar  struct ure with e ith er  AG1478 or D M Sblocked th e s ustained ele vat ion of  i ntr a cellu lar  Ca2+  and p r essorresponseof Ang II .  In viv o ex peri ments performed o n  w i ld

letion of_SK1 or_DMS treatment abrogated EGF-induced_intracellular Ca2+_elevation._Moreover, perfusion_of_the arteriole of_the isolated rabbit_glomerular structure with either_AG1478 or DMS_blocked_the sustained elevation of intracellular Ca2+ and pressor response of Ang II. In vivo_experiments_performed on_wild


-12 teachers and biomedical, public health, biomedical engineering and educational researchers to develop learner-centered, career focused educational modules that will attract and motivate students, particularly those who are traditionally underrepresented in science, medicine and technology. 3. To provide rigorous professional development for K-12 teachers in TX, through an established

-12 teachers and biomedical, public health, biomedical engineering and educational researchers to develop apprentice - center, career focused educational modules that will attract and motivate student, peculiarly those who are traditionally underrepresented in science, medicine and technology. 3. To supply rigorous professional development for K-12 teachers in TX, through an establish

-12 tewchers and biomedical, punlic health, biomgducal eigineerjng and dducational researchers to dxvelip leqrner-centered, career fucused edlcational modnles that will avfract akb motjyate vvudents, particukarly thosa who are tradhtkoually underrepresented in science, meqicine snf technology. 3. Jo prpdide ginorous professional development ror K-12 ttachers in TX, throigh an established

-12 teachers and biomedical, public health, biomedical educational to develop career focused educational motivate particularly those who traditionally underrepresented in medicine and technology. 3. To provide professional development for K-12 teachers in TX, through an established

-12 teachers and biomedical, publIc health, biOmediCal EngInEeriNg anD educational reSEarcHers to develop learner-ceNtereD, cAReer FOcUsed eDucatioNAl MODulEs ThAt wIlL AtTract And MotivatE students, pArtIcUlarly those wHO aRe traditioNalLy underrepreSenTed in sCiEncE, MedicIne And teChnoloGY. 3. To proVide rigorOuS ProfesSIonal deVELoPmenT for K-12 teachers in TX, THrOUgh an establishEd

-12 teachers and biomedica l, publichealt h,bio me dica l en gineering ande duca tional researchers todevel op lear n er -cent ered, c a re e r  fo cu se d e du c at ional  mo dules t hat will a ttr ac t and motiva t estudents,par ticularly th ose  who a re  tr a ditio nal ly un derrep r esente d in scie nc e , medi c ine and t ec hnol ogy. 3. To provid e  r i gorous profess ionalde v el o p men t f or K-12 te ac hersi n TX, t h ro u g h  an established

-12 teachers_and biomedical,_public health, biomedical engineering_and educational_researchers_to develop_learner-centered,_career focused educational_modules that will_attract and motivate students,_particularly those who_are_traditionally underrepresented in science, medicine and technology. 3. To provide rigorous professional development for_K-12_teachers in_TX,_through_an established


research engineers are adequately trained to navigate the waters of successful translational research in neural engineering. This will effectively provide a smoother/faster path to market for the clinical application of exciting neural engineering technological breakthroughs aimed at improving diagnostic and therapeutic success for diseases of the nervous system. The proposed symposia titled "Translational

research engineers are adequately trained to navigate the body of water of successful translational inquiry in neural engineering. This will efficaciously provide a placid / faster path to grocery store for the clinical application of exciting neural technology technical breakthroughs aimed at better diagnostic and therapeutic success for diseases of the skittish system. The proposed symposia titled " Translational

redearch engineers are adeduately trained to navmgate tge waterr of successful translationap eeseaech in neural engineerkng. This aill effwctitely provide a smoother/faster lwth co market for thg clinical a[plication of axzicing neural engineering technologicaj breakyhgoughs aimed aj impgoding diagnostic and therapeutic succesa for dpseases of the netvous system. The proposed dymplsia titled "Translwtional

research engineers are adequately trained to navigate of translational research neural engineering. This path market for the application of exciting engineering technological breakthroughs aimed at improving and therapeutic success for diseases of the nervous system. The proposed symposia titled

research engineers are adequAtely trainEd to nAviGatE tHe waTers Of successful trANslaTional research in neural EnginEeRIng. THIs Will eFfectivELy PROviDe A sMooThER/fAster PatH to markEt for the clIniCaL application OF eXciting neuRal Engineering tEchNologiCaL brEAkthrOugHs aimEd at imPRoving DiagnostiC aND theraPEutic suCCEsS for Diseases of the nervOUs SYstem. The proposEd sympOsIA tITLed "traNslational

research engineers are ad equately t raine d t o n av igat e th e waters of su c cess ful translational rese archin neur a lengin eering. Th i s  wi ll  e ffe ct i ve ly pr ovi de a sm oother/fas ter  p ath to marke t  f or the cli nic al applicati onof exc it ing neura l e ngine eringt echnol ogical br ea k throug h s aimed a timpr oving diagnostica nd therapeutic su ccessfo r  d i s eas esof the ner vo us sy s tem. Th e  p r o p ose d  symposia tit led "Transl a tio nal

research_engineers are_adequately trained to navigate_the waters_of_successful translational_research_in neural engineering._This will effectively_provide a smoother/faster path_to market for_the_clinical application of exciting neural engineering technological breakthroughs aimed at improving diagnostic and therapeutic_success_for diseases_of_the_nervous system. The proposed symposia_titled "Translational


BD2 and chemokine MIP-31 (CCL20) bind to their cellular receptor, CCR6, they induce an intracellular antiviral activity against HIV that is absent in cells that do not express CCR6. While direct inactivation of enveloped viruses including HIV has been implicated as one mechanism of defensins, to our

BD2 and chemokine MIP-31 (CCL20) bind to their cellular receptor, CCR6, they induce an intracellular antiviral activity against HIV that is absent in cells that do not carry CCR6. While lineal inactivation of enveloped virus include HIV has been implicated as one mechanism of defensins, to our

BD2 wnd chemokine MIP-31 (CCL20) bikd to their cellolqr recxptor, CDR6, they knduce an intracellular antitirao actuvity against HIV that is absenn in cellw thet do not express CCR6. Whlje djvect nnectivation of ekveloped visuses includinc FIR has been implicated as one mechanifm of drffnsins, to our

BD2 and chemokine MIP-31 (CCL20) bind to receptor, they induce intracellular antiviral activity in that do not CCR6. While direct of enveloped viruses including HIV has implicated as one mechanism of defensins, to our

BD2 and chemokine MIP-31 (CCL20) bind tO their cellUlar rEcePtoR, CcR6, thEy inDuce an intracelLUlar Antiviral activity againSt HIV ThAT is aBSeNt in cElls thaT Do NOT exPrEsS CCr6. WHIlE direCt iNactivaTion of enveLopEd Viruses incluDInG HIV has beeN imPlicated as onE meChanisM oF deFEnsinS, to Our

BD2 and chemokine MIP-31 ( CCL20) bin d tothe irce llul ar r eceptor, CCR6, they  induce an intracellul ar an ti v iral ac tivit y again s tH I V t ha tisab s en t incel ls that  do not ex pre ss  CCR6. While di rect inact iva tion of enve lop ed vir us esi nclud ing  HIVhas be e n impl icated as  o n e mech a nism of d ef ensi ns, to our

BD2 and_chemokine MIP-31_(CCL20) bind to their_cellular receptor,_CCR6,_they induce_an_intracellular antiviral activity_against HIV that_is absent in cells_that do not_express_CCR6. While direct inactivation of enveloped viruses including HIV has been implicated as one_mechanism_of defensins,_to_our


between the central terminals of the trigeminal nerve (trigeminal afferents) and neurons located in the spinal trigeminal nucleus caudalis (Vc), a brainstem region implicated in nociceptive processing for the face. We hypothesize that synaptic connectivity of individual trigeminal afferents and neurons in the V

between the central terminals of the trigeminal nerve (trigeminal afferents) and nerve cell locate in the spinal trigeminal nucleus caudalis (Vc), a brainstem region implicated in nociceptive processing for the grimace. We speculate that synaptic connectivity of individual trigeminal afferents and neurons in the V

behween the central terminxls of the triggmunal nxrve (trjgeminal afferents) and neurons locatxd ib the spinal trigeminal nucueus caudwlis (Vc), q breinstem region implicated in nkgicepcite processing fpr the faca. We hypothesise tkat synaptic connectivity of individtal tribelinal afferentf anc neudons in the V

between the central terminals of the trigeminal afferents) neurons located the spinal trigeminal region in nociceptive processing the face. We that synaptic connectivity of individual trigeminal and neurons in the V

between the central terminalS of the trigEminaL neRve (TrIgemInal Afferents) and neURons Located in the spinal trigEminaL nUCleuS CaUdaliS (Vc), a braINsTEM reGiOn ImpLiCAtEd in nOciCeptive Processing For ThE face. We hypotHEsIze that synAptIc connectiviTy oF indivIdUal TRigemInaL affeRents aND neuroNs in the V

between the central termi nals of th e tri gem ina lnerv e (t rigeminal affe r ents ) and neurons locatedin th es pina l  t rigem inal nu c le u s  ca ud al is(V c ),  a br ain stem re gion impli cat ed  in nocicept i ve  processin g f or the face.  We  hypot he siz e  that  sy napti c conn e ctivit y of indi vi d ual tr i geminal a ff eren ts and neurons in th e  V

between_the central_terminals of the trigeminal_nerve (trigeminal_afferents)_and neurons_located_in the spinal_trigeminal nucleus caudalis_(Vc), a brainstem region_implicated in nociceptive_processing_for the face. We hypothesize that synaptic connectivity of individual trigeminal afferents and neurons_in_the V


of military service including blast injury. The objectives of this proposal are to improve the prevention and treatment of SNHL in veterans. Research Design: To improve our understanding of cellular processes underlying hair cell (HC) damage and loss, the contributions of molecular isoforms within known HC damage and survival pathways will be evaluated by determining their expression

of military service including blast injury. The aim of this marriage proposal are to improve the prevention and treatment of SNHL in veteran. Research Design: To better our understanding of cellular processes underlie haircloth cell (HC) price and loss, the contributions of molecular isoforms within know HC damage and survival pathways will be evaluated by determining their expression

of military service includlng blast injury. The oboectivea of thir proposal are to improve thx prwventuon and treatment of SVHL in venerans. Rewearrh Design: To impckve our underabandiug of cellular ptocesses undarlying hair calu (KC) damage and loss, the contributions of molrcklar isoforms rithpn knosn HC damage and survival pathways will bt evaluated by detrrmining their expression

of military service including blast injury. The this are to the prevention and Research To improve our of cellular processes hair cell (HC) damage and loss, contributions of molecular isoforms within known HC damage and survival pathways will be by determining their expression

of military service includinG blast injuRy. The ObjEctIvEs of This Proposal are to iMProvE the prevention and treatMent oF SnhL in VEtErans. researcH deSIGn: TO iMpRovE oUR uNdersTanDing of cEllular proCesSeS underlying hAIr Cell (HC) damaGe aNd loss, the conTriButionS oF moLEculaR isOformS withiN Known Hc damage anD sURvival PAthways WILl Be evAluated by determinINg THeir expression

of military service inclu ding blast  inju ry.  Th eobje ctiv es of this pro p osal  are to improve the pr event io n  and tr eatme nt of S N HL i n v et er ans .R es earch  De sign: T o improveour  u nderstanding of  cellularpro cesses under lyi ng hai rcel l  (HC)  da mageand lo s s, the  contribu ti o ns ofm olecula r is ofor ms within known H C  d a mage and survi val pa th w ay s wil l b e evaluate dby de t erminin g  t h e i r e x pression

of_military service_including blast injury. The_objectives of_this_proposal are_to_improve the prevention_and treatment of_SNHL in veterans. Research_Design: To improve_our_understanding of cellular processes underlying hair cell (HC) damage and loss, the contributions of_molecular_isoforms within_known_HC_damage and survival pathways will_be evaluated by determining their_expression


. 'fake' variable binding ("Every man loves his wife" vs. "The men bought presents for their wives;" b) the processing of `world variables,' essentially implicatures that some state of affairs is not true in the actual world; and c) the determination of the domain over which a variable is quantified (

.' fake' variable binding (" Every man love his wife " vs. " The man bought presents for their wives; " b) the processing of 'earth variables,' essentially implicatures that some state of matter of affairs is not true in the actual universe; and c) the determination of the domain over which a variable star is quantified (

. 'fane' variable binding ("Evern man loves his cufe" vs. "The msn boughg presents for their wives;" b) tye pricessing of `world varixbles,' essvntially umplmcatures that some state of afrwirs ms not true in jhe actual wmrld; and c) the ddtzrmination of the domain over which w varianlf is quantifieq (

. 'fake' variable binding ("Every man loves vs. men bought for their wives;" variables,' implicatures that some of affairs is true in the actual world; and the determination of the domain over which a variable is quantified (

. 'fake' variable binding ("Every mAn loves his Wife" vS. "ThE meN bOughT preSents for their wIVes;" b) The processing of `world vaRiablEs,' ESsenTIaLly imPlicatuREs THAt sOmE sTatE oF AfFairs Is nOt true iN the actual WorLd; And c) the deterMInAtion of the DomAin over which A vaRiable Is QuaNTifieD (

. 'fake' variable binding("Every ma n lov eshis  w ife"  vs.  "The men boug h t pr esents for their wives ;" b)  t h e pr o ce ssing  of `wo r ld v ari ab le s,'  e s se ntial lyimplica tures that  so me  state of af f ai rs is nottru e in the act ual  world ;and c) th e d eterm inatio n  of th e domainov e r whic h  a vari a b le  isquantified (

. 'fake'_variable binding_("Every man loves his_wife" vs._"The_men bought_presents_for their wives;"_b) the processing_of `world variables,' essentially_implicatures that some_state_of affairs is not true in the actual world; and c) the determination of_the_domain over_which_a_variable is quantified (


the formal POR research training. The Cardiovascular Risk Intervention Program and the Division of General Internal Medicine will provide study subjects. The General Clinical Research Center will provide ancillary support including nurses, a dietitian, a biostatistical programmer and laboratory services. At USP, the Department of Pharmacognosy will

the formal POR research training. The Cardiovascular Risk Intervention Program and the Division of General Internal Medicine will provide discipline discipline. The General Clinical Research Center will provide ancillary support include nurses, a dietitian, a biostatistical programmer and testing ground serve. At USP, the Department of Pharmacognosy will

thf formal POR research trxining. The Cardnivascunar Riak Interxention Program and the Dividiin of General Internal Medizine will provide stuvy subjects. The Jsneral Gjinidwl Rzsxarch Center wikl provide ancillary sup[oft including nurses, a dietitian, a bioftatistocwl programmer wnd kwborznovy services. At USP, the Departmenf of Phermacognosy wilk

the formal POR research training. The Cardiovascular Program the Division General Internal Medicine General Research Center will ancillary support including a dietitian, a biostatistical programmer and services. At USP, the Department of Pharmacognosy will

the formal POR research trainIng. The CardIovasCulAr RIsK IntErveNtion Program anD The DIvision of General InternAl MedIcINe wiLL pRovidE study sUBjECTs. THe geNerAl cLiNical resEarch CeNter will prOviDe Ancillary supPOrT including NurSes, a dietitiaN, a bIostatIsTicAL progRamMer anD laborATory seRvices. At UsP, THe DepaRTment of pHArMacoGnosy will

the formal POR research t raining. T he Ca rdi ova sc ular  Ris k Intervention Prog ram and the Division o f Gen er a l In t er nal M edicine wi l l  pr ov id e s tu d ysubje cts . The G eneral Cli nic al  Research Ce n te r will pro vid e ancillarysup port i nc lud i ng nu rse s, adietit i an, abiostatis ti c al pro g rammera n dlabo ratory services.A tU SP, the Depart ment o fP ha r m aco gno sy will

the_formal POR_research training. The Cardiovascular_Risk Intervention_Program_and the_Division_of General Internal_Medicine will provide_study subjects. The General_Clinical Research Center_will_provide ancillary support including nurses, a dietitian, a biostatistical programmer and laboratory services. At_USP,_the Department_of_Pharmacognosy_will


ality. To be maximally effective, IPV intervention and prevention strategies must be responsive to the language, culture, and other characteristics of the target population. Moreover, if, as our clinical and research experience suggests, IPV perpetrator characteristics and manifestations of IPV affecting the Deaf community differ from general population norms in significant

ality. To be maximally effective, IPV intervention and prevention strategies must be responsive to the language, acculturation, and early characteristics of the target population. furthermore, if, as our clinical and research experience indicate, IPV perpetrator characteristics and expression of IPV feign the Deaf community disagree from cosmopolitan population norms in significant

alihy. To be maximally effecuive, IPV intervenjiin and prevehtion stfategies must be responsive vo tye labguage, culture, and othdr characneristics of uhe target populavjon. Morcjver, lf, as iur clinical akd research experience sucgdscs, IPV perpetrator characteristics agd manigedtations of IPD afgqctihg the Deaf community differ from feneral population nprms in significant

ality. To be maximally effective, IPV intervention strategies be responsive the language, culture, target Moreover, if, as clinical and research suggests, IPV perpetrator characteristics and manifestations IPV affecting the Deaf community differ from general population norms in significant

ality. To be maximally effectiVe, IPV interVentiOn aNd pReVentIon sTrategies must bE RespOnsive to the language, culTure, aNd OTher CHaRacteRistics OF tHE TarGeT pOpuLaTIoN. MoreOveR, if, as ouR clinical aNd rEsEarch experieNCe Suggests, IPv peRpetrator chaRacTeristIcS anD ManifEstAtionS of IPV AFfectiNg the Deaf CoMMunity DIffer frOM GeNeraL population norms iN SiGNificant

ality. To be maximally eff ective, IP V int erv ent io n an d pr evention strat e gies  must be responsive to  thela n guag e ,cultu re, and ot h e r c ha ra cte ri s ti cs of  th e targe t populati on.  M oreover, if, as  our clini cal  and researc h e xperie nc e s u ggest s,IPV p erpetr a tor ch aracteris ti c s andm anifest a t io ns o f IPV affecting t h eD eaf communitydiffer  f r om g ene ral  populatio nnorms in sign i fi c a n t

ality. To_be maximally_effective, IPV intervention and_prevention strategies_must_be responsive_to_the language, culture,_and other characteristics_of the target population._Moreover, if, as_our_clinical and research experience suggests, IPV perpetrator characteristics and manifestations of IPV affecting the_Deaf_community differ_from_general_population norms in significant


elements of an individual patient's complex genetic blueprint with targeted pharmacotherapies to which that individual may optimally respond. The purpose of this proposed research is to apply pharmacogenetic techniques to predict which alcohol dependent patients will respond favorably to a trial of a selective serotonin re-uptake inhibitor (SSRI) for the prevention

elements of an individual patient's complex genetic blueprint with targeted pharmacotherapies to which that person may optimally react. The purpose of this proposed inquiry is to apply pharmacogenetic proficiency to predict which alcohol dependent patient will respond favorably to a trial of a selective serotonin rhenium - uptake inhibitor (SSRI) for the prevention

elfments of an individual katient's complex ywnetic bluepdint witf targeted pharmacotherapies ti whixh that individual may optimallj respond. The purpose of this proposed veseaxci is to apply pmarmacogenedic techniques tu 'redict which alcohol dependent patiqnts wikl respond favorwbly eo a nrlal of a selective serotonin re-ultake iihibitor (SSRI) fpr the prevention

elements of an individual patient's complex genetic targeted to which individual may optimally proposed is to apply techniques to predict alcohol dependent patients will respond favorably a trial of a selective serotonin re-uptake inhibitor (SSRI) for the prevention

elements of an individual patIent's complEx genEtiC blUePrinT witH targeted pharmACothErapies to which that indiViduaL mAY optIMaLly reSpond. ThE PuRPOse Of ThIs pRoPOsEd resEarCh is to aPply pharmaCogEnEtic techniquES tO predict whIch Alcohol depenDenT patieNtS wiLL respOnd FavorAbly to A Trial oF a selectiVe SErotonIN re-uptaKE InHibiTor (SSRI) for the prevENtIOn

elements of an individual  patient's  comp lex  ge ne ticblue print with tar g eted  pharmacotherapies towhich  t h at i n di vidua l may o p ti m a lly  r es pon d. Th e pur pos e of th is propose d r es earch is toa pp ly pharmac oge netic techni que s to p re dic t  whic h a lcoho l depe n dent p atients w il l  respo n d favor a b ly  toa trial of a sele c ti v e serotonin re -uptak ei nh i b ito r ( SSRI) forth e pre v ention

elements_of an_individual patient's complex genetic_blueprint with_targeted_pharmacotherapies to_which_that individual may_optimally respond. The_purpose of this proposed_research is to_apply_pharmacogenetic techniques to predict which alcohol dependent patients will respond favorably to a trial_of_a selective_serotonin_re-uptake_inhibitor (SSRI) for the prevention


regulatory" T-cells that inhibit immune responses to these related normal proteins will enhance the effectiveness of the vaccine without inducing deleterious autoimmunity. PHS 398/2590 (Rev. 11/07) Page 1 Continuation Format Page To investigate the physiological function of nonmuscle myosin heavy chain II-B (

regulatory " T - cells that inhibit immune answer to these relate normal proteins will enhance the effectiveness of the vaccine without inducing deleterious autoimmunity. PHS 398/2590 (Rev. 11/07) Page 1 Continuation Format Page To investigate the physiologic function of nonmuscle myosin heavy chain II - B (

regklatory" T-cells that inhinit immune respouwes to these related normal proteins will enhancx thw efftbtiveness of the vacckne witholt inducibg dtleterious autoimmunity. PMF 398/2590 (Rsy. 11/07) Paye 1 Continuation Format Pace To investigdtd che physiological function of nonmussle myoxij heavy chain YI-B (

regulatory" T-cells that inhibit immune responses to normal will enhance effectiveness of the PHS (Rev. 11/07) Page Continuation Format Page investigate the physiological function of nonmuscle heavy chain II-B (

regulatory" T-cells that inhibIt immune reSponsEs tO thEsE relAted Normal proteins WIll eNhance the effectiveness Of the VaCCine WItHout iNducing DElETEriOuS aUtoImMUnIty. PHs 398/2590 (ReV. 11/07) Page 1 CoNtinuation forMaT Page To invesTIgAte the physIolOgical functiOn oF nonmuScLe mYOsin hEavY chaiN II-B (

regulatory" T-cells that i nhibit imm une r esp ons es  tothes e related norm a l pr oteins will enhance th e eff ec t iven e ss  of t he vacc i ne w ith ou tind uc i ng  dele ter ious au toimmunity . P HS  398/2590 (R e v.  11/07) Pa ge1 Continuati onFormat  P age To in ves tigat e thep hysiol ogical fu nc t ion of nonmusc l e  m yosi n heavy chain II- B  (

regulatory" T-cells_that inhibit_immune responses to these_related normal_proteins_will enhance_the_effectiveness of the_vaccine without inducing_deleterious autoimmunity. PHS 398/2590_(Rev. 11/07) Page_1_Continuation Format Page To investigate the physiological function of nonmuscle myosin heavy chain II-B_(


an educational component which features value clarification and decision making exercises, and which is devised for neighborhood groups, skill-training centers and schools; a training component enabling particpants to develop drug education projects within neighborhoods; an evaluation component which aims at providing pre- and post program analyses, sophisticated attitude probes and feedback mechanisms. As

an educational component which features value clarification and decision make exercise, and which is devised for neighborhood groups, skill - education centers and schools; a training part enable particpants to develop drug education projects within neighborhoods; an evaluation component which calculate at providing pre- and post broadcast analysis, sophisticated position probes and feedback mechanism. As

an educational component wmich features value clacificatjon and aecision making exercises, anv whuch iw devised for neighborfood grouis, skill-teainmng centers and schools; a traihlng cmnponent enablikg particpatts to develop dfuy education projects within neighborroods; am fvaluation comkonenu wrich aims at providing pre- and post prkgram aialyses, sophistocated attitude probes and feefback mechanisms. Ad

an educational component which features value clarification making and which devised for neighborhood a component enabling particpants develop drug education within neighborhoods; an evaluation component which at providing pre- and post program analyses, sophisticated attitude probes and feedback mechanisms.

an educational component whiCh features Value ClaRifIcAtioN and Decision making EXercIses, and which is devised fOr neiGhBOrhoOD gRoups, Skill-trAInING ceNtErS anD sCHoOls; a tRaiNing comPonent enabLinG pArticpants to DEvElop drug edUcaTion projects WitHin neiGhBorHOods; aN evAluatIon comPOnent wHich aims aT pROvidinG Pre- and pOST pRogrAm analyses, sophistICaTEd attitude probEs and fEeDBaCK MecHanIsms. As

an educational componentwhich feat uresval uecl arif icat ion and decisi o n ma king exercises, and wh ich i sd evis e dfor n eighbor h oo d gro up s,  sk il l -t raini ngcenters  and schoo ls;  a  training co m po nent enabl ing  particpants  to  devel op  dr u g edu cat ion p roject s  withi n neighbo rh o ods; a n  evalua t i on  com ponent which aims at providing pre-  and p os t  p r o gra m a nalyses, s op histi c ated at t it u d e  pr o bes and feedb ack mechani s ms.  As

an_educational component_which features value clarification_and decision_making_exercises, and_which_is devised for_neighborhood groups, skill-training_centers and schools; a_training component enabling_particpants_to develop drug education projects within neighborhoods; an evaluation component which aims at providing_pre-_and post_program_analyses,_sophisticated attitude probes and feedback_mechanisms. As


isve elements-IREs)in iron metabolism transcripts. This non-physiologic increase in IRE-binding activity of IRP1 in turn leads to abnormal repression of ferritin synthesis and abnormal increases in transferrin receptor synthesis and potentially toxic cytosolic labile iron concentrations. Based on our cell culture

isve elements - IREs)in iron metabolism transcripts. This non - physiologic increase in IRE - binding natural process of IRP1 in twist leads to abnormal repression of ferritin synthesis and abnormal increases in transferrin sense organ synthesis and potentially toxic cytosolic labile iron concentrations. Based on our cellular telephone polish

isvf elements-IREs)in iron meuabolism transcriktw. This non-phgsiologiz increase in IRE-binding actmvitt of URP1 in turn leads to acnormal rvpression of herritin synthesma and anuormam incxeeses in transfetrin receptos synthesis ang oocentially toxic cytosolic labile irog concemtgations. Based jn olr celm culture

isve elements-IREs)in iron metabolism transcripts. This non-physiologic IRE-binding of IRP1 turn leads to and increases in transferrin synthesis and potentially cytosolic labile iron concentrations. Based on cell culture

isve elements-IREs)in iron metAbolism traNscriPts. thiS nOn-phYsioLogic increase iN iRE-bInding activity of IRP1 in tUrn leAdS To abNOrMal rePressioN Of FERriTiN sYntHeSIs And abNorMal incrEases in traNsfErRin receptor sYNtHesis and poTenTially toxic cYtoSolic lAbIle IRon coNceNtratIons. BaSEd on ouR cell cultUrE

isve elements-IREs)iniron metab olism  tr ans cr ipts . Th is non-physiol o gicincrease in IRE-bindin g act iv i ty o f  I RP1 i n turnl ea d s  to  a bn orm al re press ion  of fer ritin synt hes is  and abnorma l  i ncreases i n t ransferrin r ece ptor s yn the s is an d p otent iallyt oxic c ytosolicla b ile ir o n conce n t ra tion s. Based on our c e ll culture

isve elements-IREs)in_iron metabolism_transcripts. This non-physiologic increase_in IRE-binding_activity_of IRP1_in_turn leads to_abnormal repression of_ferritin synthesis and abnormal_increases in transferrin_receptor_synthesis and potentially toxic cytosolic labile iron concentrations. Based on our cell culture


of MAP3K8 occur in lung cancer and contribute to disease progression. We have recently shown that increased protein expression of MAP3K8 in lung tumor cell lines leads to changes in downstream signaling pathways and ultimately transcription of important genes in cell survival. To test the effects of MAP3K8 over expression on survival in

of MAP3K8 occur in lung cancer and contribute to disease progression. We have recently shown that increase protein formula of MAP3K8 in lung tumor cell lines leads to change in downstream signaling pathways and ultimately recording of crucial genes in cell survival. To test the effects of MAP3K8 over construction on survival in

of MAP3K8 occur in lung canctr and contribute to disxase prkgressiov. We have recently shown thav inxreastb protein expression of MAP3K8 pn lung tymor xell lines leads to chanfcs in vownstream signsling pathfays and ultimdtdlv transcription of important genes ig cell xugvival. To test the qffedns of MAP3K8 over expression on shrvival in

of MAP3K8 occur in lung cancer and disease We have shown that increased lung cell lines leads changes in downstream pathways and ultimately transcription of important in cell survival. To test the effects of MAP3K8 over expression on survival

of MAP3K8 occur in lung cancer anD contributE to diSeaSe pRoGresSion. we have recently SHown That increased protein exPressIoN Of MAp3k8 iN lung Tumor ceLL lINEs lEaDs To cHaNGeS in doWnsTream siGnaling patHwaYs And ultimatelY TrAnscriptioN of Important genEs iN cell sUrVivAL. To teSt tHe effEcts of maP3K8 oveR expressiOn ON surviVAl in

of MAP3K8 occur in lung c ancer andcontr ibu teto  dis ease  progression.W e ha ve recently shown that  incr ea s ed p r ot ein e xpressi o no f  MA P3 K8  in  l u ng  tumo r c ell lin es leads t o c ha nges in down s tr eam signal ing  pathways an d u ltimat el y t r anscr ipt ion o f impo r tant g enes in c el l  survi v al. Tot e st  the  effects of MAP3K 8  o v er expressionon sur vi v al i n

of_MAP3K8 occur_in lung cancer and_contribute to_disease_progression. We_have_recently shown that_increased protein expression_of MAP3K8 in lung_tumor cell lines_leads_to changes in downstream signaling pathways and ultimately transcription of important genes in cell_survival._To test_the_effects_of MAP3K8 over expression on_survival in


dependent insulin receptor (IR) signaling pathway in rod photoreceptors. We have discovered that IR activation is functionally important for rod survival, since its deletion in rods resulted in the loss of neuroprotective survival signaling. This novel pathway uses growth factor receptor bound protein (Grb14), an upstream regulator of IR, and requires phot

dependent insulin receptor (IR) signaling pathway in gat photoreceptors. We have discover that IR activation is functionally important for rod survival, since its omission in rods resulted in the loss of neuroprotective survival sign. This novel pathway use growth factor sense organ bound protein (Grb14), an upstream regulator of IR, and requires phot

depfndent insulin receptor (LR) signaling patkqay in rod pgotoreceotors. We have discovered thav IR actication is functionally importann for rod surtival, since its vsletion in rosd revnlted in the loxs of neurmprotective susvkvcl signaling. This novel pathway uses growth fwctor receptor boumq prkneln (Grb14), an upstream regulator of JR, and gequires phot

dependent insulin receptor (IR) signaling pathway in We discovered that activation is functionally its in rods resulted the loss of survival signaling. This novel pathway uses factor receptor bound protein (Grb14), an upstream regulator of IR, and requires phot

dependent insulin receptor (Ir) signaling PathwAy iN roD pHotoRecePtors. We have disCOverEd that IR activation is fuNctioNaLLy imPOrTant fOr rod suRViVAL, siNcE iTs dElETiOn in rOds ResulteD in the loss Of nEuRoprotective SUrVival signaLinG. This novel paThwAy uses GrOwtH FactoR reCeptoR bound PRotein (grb14), an upstReAM regulATor of IR, AND rEquiRes phot

dependent insulin receptor  (IR) sign aling  pa thw ay  inrodphotoreceptors .  Wehave discovered that I R act iv a tion is  func tionall y  i m p ort an tfor  r o dsurvi val , since  its delet ion  i n rods resul t ed  in the lo ssof neuroprot ect ive su rv iva l  sign ali ng. T his no v el pat hway uses  g r owth f a ctor re c e pt or b ound protein (Grb 1 4) ,  an upstream r egulat or of I R,and  requiresph ot

dependent insulin_receptor (IR)_signaling pathway in rod_photoreceptors. We_have_discovered that_IR_activation is functionally_important for rod_survival, since its deletion_in rods resulted_in_the loss of neuroprotective survival signaling. This novel pathway uses growth factor receptor bound_protein_(Grb14), an_upstream_regulator_of IR, and requires phot


, I have a unique opportunity to purse my career development by working with outstanding scientists in fields that will enhance my abilities and intellect. I plan to achieve my objective through course work at Rutgers University, attendance of basic science conferences, and regular meetings with my mentor and advisors designed to monitor and enhance my progress. This program

, I have a unique opportunity to purse my career development by working with great scientist in discipline that will enhance my ability and reason. I plan to achieve my objective through class oeuvre at Rutgers University, attendance of basic science conference, and regular meetings with my mentor and adviser designed to monitor and enhance my progress. This program

, I jave a unique opportunitn to purse my catewr devxlopmenf by worying with outstanding scientmsts in fuelds that will enhancd my abilpties and inttllect. I plan to edhieve my objsgtive vhrough course eork at Rudgers Universidy, actendance of basic science conferencqs, and tehular meetings witn my jvnuor and advisors designed to monifor and enhance my ptogress. This program

, I have a unique opportunity to career by working outstanding scientists in abilities intellect. I plan achieve my objective course work at Rutgers University, attendance basic science conferences, and regular meetings with my mentor and advisors designed to and enhance my progress. This program

, I have a unique opportunity to Purse my carEer deVelOpmEnT by wOrkiNg with outstandINg scIentists in fields that wiLl enhAnCE my aBIlIties And inteLLeCT. i plAn To AchIeVE mY objeCtiVe throuGh course woRk aT RUtgers UniverSItY, attendancE of Basic science ConFerencEs, And REgulaR meEtingS with mY Mentor And advisoRs DEsigneD To monitOR AnD enhAnce my progress. ThiS PrOGram

, I have a unique opportun ity to pur se my  ca ree rdeve lopm ent by working with  outstanding scientist s infi e ldst ha t wil l enhan c em y  ab il it ies  a n dintel lec t. I pl an to achi eve  m y objectivet hr ough cours e w ork at Rutge rsUniver si ty, atten dan ce of  basic scienc e confere nc e s, and regular m ee ting s with my mentora nd advisors desig ned to  m o ni t o r a ndenhance my  p rogre s s. This pr o g r am

, I_have a_unique opportunity to purse_my career_development_by working_with_outstanding scientists in_fields that will_enhance my abilities and_intellect. I plan_to_achieve my objective through course work at Rutgers University, attendance of basic science conferences,_and_regular meetings_with_my_mentor and advisors designed to_monitor and enhance my progress._This program


PIL proteins will be further characterized. Cloned CDNAS for these interstitial proteins will be isolated and their structure characterized. Moreover, specific probes will be generated for use in determining both physiological and aberrant expression of these proteins in vivo and in vitro studies. Regulation of these interstitial proteins will be studied by analysis of their M

PIL proteins will be further characterized. Cloned CDNAS for these interstitial proteins will be sequester and their social organization characterized. Moreover, specific probe will be render for use in determining both physiologic and aberrant expression of these proteins in vivo and in vitro studies. rule of these interstitial protein will be studied by analysis of their megabyte

PIP proteins will be furthtr characterized. Eooned RDNAS fkr these interstitial proteins will ue iwolattb and their structurd charactvrized. Moeeovtr, specific probes will bc gensvated hor use in detetmining both physiological avd aberrant expression of these proteyns in figo and in vitrj stldyes. Dvgmlation of these interstitial prkteins xill be studied by analysis of their M

PIL proteins will be further characterized. Cloned these proteins will isolated and their will generated for use determining both physiological aberrant expression of these proteins in and in vitro studies. Regulation of these interstitial proteins will be studied by of their M

PIL proteins will be further cHaracterizEd. CloNed cDNaS For tHese Interstitial prOTeinS will be isolated and theiR struCtURe chARaCteriZed. MoreOVeR, SPecIfIc ProBeS WiLl be gEneRated foR use in deteRmiNiNg both physioLOgIcal and abeRraNt expression Of tHese prOtEinS In vivO anD in viTro stuDIes. RegUlation of ThESe inteRStitial PROtEins Will be studied by anALySIs of their M

PIL proteins will be furt her charac teriz ed.  Cl on ed C DNAS  for these int e rsti tial proteins will beisola te d  and th eir s tructur e  c h a rac te ri zed .M or eover , s pecific  probes wi llbe  generated f o ruse in det erm ining both p hys iologi ca l a n d abe rra nt ex pressi o n of t hese prot ei n s in v i vo andi n  v itro  studies. Regulat i on of these inter stitia lp ro t e ins  wi ll be stud ie d bya nalysis of t h eir M

PIL_proteins will_be further characterized. Cloned_CDNAS for_these_interstitial proteins_will_be isolated and_their structure characterized._Moreover, specific probes will_be generated for_use_in determining both physiological and aberrant expression of these proteins in vivo and in_vitro_studies. Regulation_of_these_interstitial proteins will be studied_by analysis of their M