(sphingolipids, fatty acids, cholesterol and cholesterol esters) reflect brain functioning and pathology, and may interact with ApoE genotype in the development of AD pathogenesis, warranting human studies. Clinical and epidemiological studies of short duration, while important, will not contribute to our understanding of the earliest phases of AD

(sphingolipids, fatty acids, cholesterol and cholesterol esters) reflect mind operation and pathology, and may interact with ApoE genotype in the development of AD pathogenesis, warranting human report. Clinical and epidemiologic studies of short duration, while important, will not lend to our understanding of the earliest phase of AD

(spjingolipids, fatty acids, gholesterol and eyolestxrol esfers) refuect brain functioning and pethooogy, qnd may interact with XpoE genonype in tye dtvelopment of AD 'zthogencfis, swrrautmng human studigs. Clinical dnd epidemiolocizap studies of short duration, while iiportany, aill not contrybutt tj oud understanding of the earliest phzses of AD

(sphingolipids, fatty acids, cholesterol and cholesterol esters) functioning pathology, and interact with ApoE AD warranting human studies. and epidemiological studies short duration, while important, will not to our understanding of the earliest phases of AD

(sphingolipids, fatty acids, chOlesterol aNd choLesTerOl EsteRs) reFlect brain funcTIoniNg and pathology, and may inTeracT wITh ApOe gEnotyPe in the DEvELOpmEnT oF AD PaTHoGenesIs, wArrantiNg human stuDieS. CLinical and epIDeMiological StuDies of short dUraTion, whIlE imPOrtanT, wiLl not ContriBUte to oUr understAnDIng of tHE earlieST PhAses Of AD

(sphingolipids, fatty aci ds, choles terol  an d c ho lest erol  esters) refle c t br ain functioning and pa tholo gy ,  and ma y int eract w i th A poE  g en oty pe in  thedev elopmen t of AD pa tho ge nesis, warra n ti ng human s tud ies. Clinica l a nd epi de mio l ogica l s tudie s of s h ort du ration, w hi l e impo r tant, w i l lnotcontribute to our un d erstanding ofthe ea rl i es t pha ses  of AD

(sphingolipids,_fatty acids,_cholesterol and cholesterol esters)_reflect brain_functioning_and pathology,_and_may interact with_ApoE genotype in_the development of AD_pathogenesis, warranting human_studies._Clinical and epidemiological studies of short duration, while important, will not contribute to our_understanding_of the_earliest_phases_of AD


in vitro and in vivo, leading to increased production of a secreted receptor (sIL7R) that is unable to activate the IL-7 signaling pathway. Importantly, sIL7R has been linked to the disease in both human patients and animal models. These results directly implicate splicing of IL7R to the

in vitro and in vivo, leading to increased production of a secreted sense organ (sIL7R) that is ineffective to trip the IL-7 signaling pathway. Importantly, sIL7R has been linked to the disease in both human affected role and animal models. These results immediately implicate splicing of IL7R to the

in vitro and in vivo, leadikg to increased kriductimn of z secretdd receptor (sIL7R) that is unaule ro acupvate the IL-7 signaline pathway. Importabtly, wIL7R has bxsn linkcb to fme divxase in both hukan patiends and animal koaeps. These results directly implicate splicimg of IL7R to the

in vitro and in vivo, leading to of secreted receptor that is unable pathway. sIL7R has been to the disease both human patients and animal models. results directly implicate splicing of IL7R to the

in vitro and in vivo, leading to Increased pRoducTioN of A sEcreTed rEceptor (sIL7R) thaT Is unAble to activate the IL-7 sigNalinG pAThwaY. imPortaNtly, sIL7r HaS BEen LiNkEd tO tHE dIseasE in Both humAn patients And AnImal models. ThESe Results dirEctLy implicate sPliCing of iL7r to THe

in vitro and in vivo, lea ding to in creas edpro du ctio n of  a secreted re c epto r (sIL7R) that is unab le to  a c tiva t ethe I L-7 sig n al i n g p at hw ay.  I m po rtant ly,  sIL7Rhas been l ink ed  to the dise a se  in both h uma n patients a ndanimal  m ode l s. Th ese  resu lts di r ectlyimplicate  s p licing of IL7R t othe

in_vitro and_in vivo, leading to_increased production_of_a secreted_receptor_(sIL7R) that is_unable to activate_the IL-7 signaling pathway._Importantly, sIL7R has_been_linked to the disease in both human patients and animal models. These results directly_implicate_splicing of_IL7R_to_the


diabetes-related behavioral and health outcomes are limited by their use of non-representative data sets, cross-sectional analyses, and inadequate controls on other factors that may also be important to consider. This application's goal is to examine how social relationships (and particularly marriage) and self-efficacy influence adherence to diabetes-related

diabetes - related behavioral and health outcomes are limited by their use of non - representative datum set, cross - sectional analyses, and inadequate control on early factors that may also be important to view. This application's goal is to analyze how social relationships (and particularly marriage) and self - efficacy influence adhesiveness to diabetes - related

diwbetes-related behavioral and health outeimes ace limifed by tfeir use of non-representativx dara seuf, cross-sectional avalyses, ajd inadewuatt controls on othxd factovf thzb may elso be importakt to consiger. This appliwagiln's goal is to examine how social rqlationxhlps (and particolarlj iarrjage) and self-efficacy influence adgerence to diabetes-rrlated

diabetes-related behavioral and health outcomes are limited use non-representative data cross-sectional analyses, and that also be important consider. This application's is to examine how social relationships particularly marriage) and self-efficacy influence adherence to diabetes-related

diabetes-related behavioral And health oUtcomEs aRe lImIted By thEir use of non-repREsenTative data sets, cross-secTionaL aNAlysES, aNd inaDequate COnTROls On OtHer FaCToRs thaT maY also be Important tO coNsIder. This applICaTion's goal iS to Examine how soCiaL relatIoNshIPs (and ParTiculArly maRRiage) aNd self-effIcACy inflUEnce adhEREnCe to Diabetes-related

diabetes-related behavior al and hea lth o utc ome sarelimi ted by their u s e of  non-representative da ta se ts ,  cro s s- secti onal an a ly s e s,an dina de q ua te co ntr ols onother fact ors  t hat may also be  important  to  consider. T his  appli ca tio n 's go alis to  exami n e howsocial re la t ionshi p s (andp a rt icul arly marriage) an d  s e lf-efficacy in fluenc ea dh e r enc e t o diabetes -r elate d

diabetes-related_behavioral and_health outcomes are limited_by their_use_of non-representative_data_sets, cross-sectional analyses,_and inadequate controls_on other factors that_may also be_important_to consider. This application's goal is to examine how social relationships (and particularly marriage)_and_self-efficacy influence_adherence_to_diabetes-related


CI by providing anatomic pathology and tissue processing services to the Clinical Center and to all of the categorical institutes. LP is CLIA-certified with a Certificate of Accreditation and is inspected every two years for compliance with regulatory standards by the College of American Pathologists. LP's clinical services provide services in surgical pathology

CI by providing anatomic pathology and tissue processing services to the Clinical Center and to all of the categorical institutes. LP is CLIA - license with a Certificate of Accreditation and is audit every two years for compliance with regulatory criterion by the College of American Pathologists. LP's clinical services provide serve in surgical pathology

CI hy providing anatomic pauhology and tissug procesving ssrvices go the Clinical Center and tl qll od the categorical instktutes. LP is CLIA-xertmfied with a Cervjficate of Acdveditctmon and is inspgcted every dwo years for wooppiance with regulatory standards by the Coklfge of Americag Pauhojogians. LP's clinical services provids servibes in surgical psthology

CI by providing anatomic pathology and tissue to Clinical Center to all of CLIA-certified a Certificate of and is inspected two years for compliance with regulatory by the College of American Pathologists. LP's clinical services provide services in surgical

CI by providing anatomic pathOlogy and tiSsue pRocEssInG serViceS to the Clinical cEnteR and to all of the categoriCal inStITuteS. lP Is CLIa-certifIEd WITh a ceRtIfiCaTE oF AccrEdiTation aNd is inspecTed EvEry two years fOR cOmpliance wIth Regulatory stAndArds by ThE CoLLege oF AmEricaN PathoLOgists. lP's clinicAl SErviceS Provide SERvIces In surgical patholoGY

CI by providing anatomic p athology a nd ti ssu e p ro cess ingservices to th e  Cli nical Center and to al l ofth e  cat e go rical  instit u te s .  LP  i sCLI A- c er tifie d w ith a C ertificate  of  A ccreditation an d is inspe cte d every twoyea rs for  c omp l iance  wi th re gulato r y stan dards byth e  Colle g e of Am e r ic an P athologists. LP's cl i nical services  provi de se r v ice s i n surgical  p athol o gy

CI by_providing anatomic_pathology and tissue processing_services to_the_Clinical Center_and_to all of_the categorical institutes._LP is CLIA-certified with_a Certificate of_Accreditation_and is inspected every two years for compliance with regulatory standards by the College_of_American Pathologists._LP's_clinical_services provide services in surgical_pathology


This effort has been continuously supported by a Cancer Center Support Grant (CCSG) from the National Cancer Institute (NCI), providing the designation as an NCI-designated Cancer Center at MIT. By supplying infrastructural support for Core Facilities and other organizational components of the Koch Institute as well as funds for

This effort has been continuously supported by a Cancer Center Support Grant (CCSG) from the National Cancer Institute (NCI), providing the appellation as an NCI - indicate Cancer Center at MIT. By supplying infrastructural support for Core Facilities and other organizational part of the Koch Institute as well as funds for

Thls effort has been contikuously supporteb by a Rancer Denter Sjpport Grant (CCSG) from the Netiobal Cqncer Institute (NCI), pruviding tje desigbatiib as an NCM-sesignabzd Cahger Cznver at MIT. By sopplying infsastructural sgpooxt for Core Facilities and other orgwnizatipnwl components jf tnq Kodh Institute as well as funds for

This effort has been continuously supported by Center Grant (CCSG) the National Cancer as NCI-designated Cancer Center MIT. By supplying support for Core Facilities and other components of the Koch Institute as well as funds for

This effort has been continuoUsly supporTed by A CaNceR CEnteR SupPort Grant (CCSG) fROm thE National Cancer InstituTe (NCI), PrOVidiNG tHe desIgnatioN As AN nCI-DeSiGnaTeD caNcer CEntEr at MIT. by supplyinG inFrAstructural sUPpOrt for Core facIlities and otHer OrganiZaTioNAl comPonEnts oF the KoCH InstiTute as welL aS Funds fOR

This effort has been cont inuously s uppor ted  by  a  Can cerCenter Support Gran t (CCSG) from the Nati onalCa n cerI ns titut e (NCI) ,  p r o vid in gthe  d e si gnati onas an N CI-designa ted  C ancer Center at  MIT. By s upp lying infras tru ctural  s upp o rt fo r C ore F acilit i es and  other or ga n izatio n al comp o n en ts o f the Koch Instit u te as well as fun ds for

This_effort has_been continuously supported by_a Cancer_Center_Support Grant_(CCSG)_from the National_Cancer Institute (NCI),_providing the designation as_an NCI-designated Cancer_Center_at MIT. By supplying infrastructural support for Core Facilities and other organizational components of_the_Koch Institute_as_well_as funds for


). We employ a mixed-methods study design based on a social ecological model of IPV origin, continuation, and severity. Rigorous qualitative and quantitative methods will be employed, the latter focused on three well-regarded IPV measures used in this study on an exploratory basis. The study goal is to discover Deaf community

). We employ a mixed - methods study invention free-base on a social ecological model of IPV origin, continuation, and asperity. Rigorous qualitative and quantitative methods will be employed, the latter focus on three well - regard IPV measures used in this study on an exploratory basis. The sketch goal is to discover Deaf residential district

). We employ a mixed-methods suudy design based on a smcial scologicxl model of IPV origin, contiiuatuon, abd severity. Rigorous qjalitativv and quabtitetive methods will be emijoyes, the oatter focused on three fell-regarded I[V mzasures used in this study on an expjoratoru hasis. The studi goak is fo discover Deaf community

). We employ a mixed-methods study design a ecological model IPV origin, continuation, quantitative will be employed, latter focused on well-regarded IPV measures used in this on an exploratory basis. The study goal is to discover Deaf community

). We employ a mixed-methods studY design basEd on a SocIal EcOlogIcal Model of IPV origIN, conTinuation, and severity. RiGorouS qUAlitATiVe and QuantitATiVE MetHoDs WilL bE EmPloyeD, thE latter Focused on tHreE wEll-regarded Ipv mEasures useD in This study on aN exPloratOrY baSIs. The StuDy goaL is to dIScover deaf commuNiTY

). We employ a mixed-metho ds study d esign  ba sed  o n asoci al ecologicalm odel  of IPV origin, contin uatio n, ands ev erity . Rigor o us q ual it at ive  a n dquant ita tive me thods will  be  e mployed, the la tter focus edon three wel l-r egarde dIPV measu res  used  in th i s stud y on an e xp l orator y  basis. T he  stu dy goal is to dis c ov e r Deaf communi ty

). We_employ a_mixed-methods study design based_on a_social_ecological model_of_IPV origin, continuation,_and severity. Rigorous_qualitative and quantitative methods_will be employed,_the_latter focused on three well-regarded IPV measures used in this study on an exploratory_basis._The study_goal_is_to discover Deaf community


speciation and PAHs using x-ray photoelectron spectroscopy (XPS), time of flight secondary ion mass spectrometry (TOF-SIMS), and spectrophotometry. Simultaneously, their toxicological effects will be tested in vitro on beef heart mitochondria, with particular interest on whether the initial mechanisms of mitochondrial dysfunction are

speciation and PAHs using x - ray photoelectron spectroscopy (XPS), time of flight junior-grade ion mass spectroscopy (TOF - SIMS), and spectrophotometry. Simultaneously, their toxicological effect will be tested in vitro on beef kernel mitochondria, with particular interest on whether the initial mechanism of mitochondrial dysfunction are

spfciation and PAHs using w-ray photoelectron specvroscopg (XPS), tioe of flight secondary ion mess wpecteometry (TOF-SIMS), and spdctrophotlmetry. Sumuluaneously, their toxicologleal ernects xill be tested ln vitro on beef heart midozhlndria, with particular interest on rhether tje initial mecranixis or mitochondrial dysfunction are

speciation and PAHs using x-ray photoelectron spectroscopy of secondary ion spectrometry (TOF-SIMS), and will tested in vitro beef heart mitochondria, particular interest on whether the initial of mitochondrial dysfunction are

speciation and PAHs using x-raY photoelecTron sPecTroScOpy (XpS), tiMe of flight secoNDary Ion mass spectrometry (TOF-sIMS), aNd SPectROpHotomEtry. SimULtANEouSlY, tHeiR tOXiCologIcaL effectS will be tesTed In Vitro on beef hEArT mitochondRia, With particulAr iNteresT oN whETher tHe iNitiaL mechaNIsms of MitochondRiAL dysfuNCtion arE

speciation and PAHs using  x-ray pho toele ctr onsp ectr osco py (XPS), time of f light secondary ion ma ss sp ec t rome t ry  (TOF -SIMS), an d spe ct ro pho to m et ry. S imu ltaneou sly, their  to xi cological ef f ec ts will be  te sted in vitr o o n beef  h ear t  mito cho ndria , with partic ular inte re s t on w h ether t h e  i niti al mechanisms ofm it o chondrial dysf unctio na re

speciation_and PAHs_using x-ray photoelectron spectroscopy_(XPS), time_of_flight secondary_ion_mass spectrometry (TOF-SIMS),_and spectrophotometry. Simultaneously,_their toxicological effects will_be tested in_vitro_on beef heart mitochondria, with particular interest on whether the initial mechanisms of mitochondrial_dysfunction_are


immediate and delayed treatment of flexor tendon insertion-site injuries. In this project, we will apply a canine model of flexor tendon insertion-site injury and repair to investigate several clinically relevant variables that have not been previously addressed: 1) suture technique for reattachment of tendon to bone, 2) increased tendon force and

immediate and delayed treatment of flexor tendon insertion - site wound. In this undertaking, we will apply a canine model of flexor tendon interpolation - site wound and repair to investigate several clinically relevant variable that have not been previously address: 1) suture technique for reattachment of tendon to bone, 2) increased tendon force and

imlediate and delayed treaument of flexor tgneon invertioh-site inguries. In this project, we wipl applt a canine model of fldxor tendln inserrion-wute injury and repair to lnvescijate several cllnically renevant variablas tkat have not been previously addressqd: 1) sutirf technique fot reautashmehn if tendon to bone, 2) increased fendon horce and

immediate and delayed treatment of flexor tendon In project, we apply a canine injury repair to investigate clinically relevant variables have not been previously addressed: 1) technique for reattachment of tendon to bone, 2) increased tendon force and

immediate and delayed treatmEnt of flexoR tendOn iNseRtIon-sIte iNjuries. In this pROjecT, we will apply a canine modEl of fLeXOr teNDoN inseRtion-siTE iNJUry AnD rEpaIr TO iNvestIgaTe severAl clinicalLy rElEvant variablES tHat have not BeeN previously aDdrEssed: 1) sUtUre TEchniQue For reAttachMEnt of tEndon to boNe, 2) INcreasED tendon FORcE and

immediate and delayed tre atment offlexo r t end on  ins erti on-site injuri e s. I n this project, we wil l app ly a ca n in e mod el of f l ex o r  te nd on  in se r ti on-si teinjuryand repair  to  i nvestigate s e ve ral clinic all y relevant v ari ablesth ath ave n otbeenprevio u sly ad dressed:1) suture techniq u e  f or r eattachment of te n do n  to bone, 2) i ncreas ed te n d onfor ce and

immediate_and delayed_treatment of flexor tendon_insertion-site injuries._In_this project,_we_will apply a_canine model of_flexor tendon insertion-site injury_and repair to_investigate_several clinically relevant variables that have not been previously addressed: 1) suture technique for_reattachment_of tendon_to_bone,_2) increased tendon force and


speech, swallowing). The objective of this proposal is to investigate the use of MYXV as potential oncolytic virotherapy agent against pancreatic cancer in preclinical animal models. The proposal focuses on MYXV, and is based on our previously published reports and supporting preliminary studies. MYXV is a rabbit-specific pox

speech, swallowing). The objective of this proposal is to investigate the habit of MYXV as likely oncolytic virotherapy agent against pancreatic cancer in preclinical animal models. The marriage proposal focuses on MYXV, and is base on our previously published report card and supporting preliminary studies. MYXV is a lapin - specific syphilis

spfech, swallowing). The objegtive of this proposal ms to ihvestigage the use of MYXV as potentmal incolttic virotherapy agent against iancreatix caicer in preclinirzl animal modsps. Tke proposal focuxes on MYXE, and is based ov lur previously published reports anq suppottlng preliminari stucyes. JJXY is a rabbit-specific pox

speech, swallowing). The objective of this proposal investigate use of as potential oncolytic in animal models. The focuses on MYXV, is based on our previously published and supporting preliminary studies. MYXV is a rabbit-specific pox

speech, swallowing). The objectIve of this pRoposAl iS to InVestIgatE the use of MYXV aS PoteNtial oncolytic virotherApy agEnT AgaiNSt PancrEatic caNCeR IN prEcLiNicAl ANiMal moDelS. The proPosal focusEs oN MyXV, and is baseD On Our previouSly Published repOrtS and suPpOrtINg preLimInary StudieS. mYXV is A rabbit-spEcIFic pox

speech, swallowing). Theobjectiveof th ispro po salis t o investigatet he u se of MYXV as potentia l onc ol y ticv ir other apy age n ta g ain st  p anc re a ti c can cer  in pre clinical a nim al  models. The pr oposal foc use s on MYXV, a ndis bas ed  on our p rev iousl y publ i shed r eports an ds upport i ng prel i m in arystudies. MYXV isa  r a bbit-specificpox

speech,_swallowing). The_objective of this proposal_is to_investigate_the use_of_MYXV as potential_oncolytic virotherapy agent_against pancreatic cancer in_preclinical animal models._The_proposal focuses on MYXV, and is based on our previously published reports and supporting_preliminary_studies. MYXV_is_a_rabbit-specific pox


to focus on mechanisms underlying neuromodulation and plasticity and the effects of alcohol and other drugs of abuse on these neuronal functions. Our main interest is the function of the dorsal striatum (DS), a brain region involved in action control and selection, as well as action learning. Striatal Synaptic Plasticity and Effects of

to focus on mechanisms underlying neuromodulation and plasticity and the effect of alcohol and early drugs of abuse on these neural functions. Our independent interest is the function of the dorsal corpus striatum (DS), a genius region involve in action control and excerpt, as well as action eruditeness. Striatal Synaptic Plasticity and Effects of

to focus on mechanisms undtrlying neuromodulation end plaaticity xnd the effects of alcohol aid orher erugs of abuse on thesd neuronap functiins. Iyr main invsrest is the rmnctimi of the dorsal striatum (GS), a brain reghov nnvolved in action control and seleceion, as wfll as action jearmyng. Anrlatal Synaptic Plasticity and Efrects oh

to focus on mechanisms underlying neuromodulation and the of alcohol other drugs of Our interest is the of the dorsal (DS), a brain region involved in control and selection, as well as action learning. Striatal Synaptic Plasticity and Effects

to focus on mechanisms underlYing neuromOdulaTioN anD pLastIcitY and the effects OF alcOhol and other drugs of abuSe on tHeSE neuROnAl funCtions. OUR mAIN inTeReSt iS tHE fUnctiOn oF the dorSal striatuM (DS), A bRain region inVOlVed in actioN coNtrol and seleCtiOn, as weLl As aCTion lEarNing. STriataL synaptIc PlasticItY And EffECts of

to focus on mechanisms un derlying n eurom odu lat io n an d pl asticity and t h e ef fects of alcohol and o therdr u gs o f  a buseon thes e  n e u ron al  f unc ti o ns . Our  ma in inte rest is th e f un ction of the do rsal stria tum  (DS), a bra inregion  i nvo l ved i n a ction  contr o l andselection ,a s well as acti o n  l earn ing. Striatal Syn a pt i c Plasticity a nd Eff ec t so f

to_focus on_mechanisms underlying neuromodulation and_plasticity and_the_effects of_alcohol_and other drugs_of abuse on_these neuronal functions. Our_main interest is_the_function of the dorsal striatum (DS), a brain region involved in action control and_selection,_as well_as_action_learning. Striatal Synaptic Plasticity and_Effects of


could improve the health care for millions of patients. PROJECT SUMMARY/ABSTRACT Chemoresistant metastatic disease presents the most serious threat to cancer patients despite the increased arsenal of targeted therapeutic options available to clinicians. While intense study into late-stage cancer progression has revealed a number of mechanisms that contribute to chemoresistance,

could improve the health care for millions of patients. PROJECT SUMMARY / ABSTRACT Chemoresistant metastatic disease stage the about serious threat to cancer patient despite the increase arsenal of targeted curative options available to clinicians. While intense survey into late - stage cancer progress has revealed a number of mechanism that contribute to chemoresistance,

cokld improve the health cxre for millions of pavients. LROJECT RUMMARY/ABSTRACT Chemoresistait mwtastqtic disease presents ghe most derious rhreet to cancer patmsnts despite fme inerxased arsenal on targeted dherapeutic opdiund available to clinicians. While intqnse stidj into late-stade csgcer irigression has revealed a numbsr of mtchanisms that conyribute to chemoresistance,

could improve the health care for millions PROJECT Chemoresistant metastatic presents the most despite increased arsenal of therapeutic options available clinicians. While intense study into late-stage progression has revealed a number of mechanisms that contribute to chemoresistance,

could improve the health care For millionS of paTieNts. pRoJECt SUMmARY/ABSTRACT ChEMoreSistant metastatic diseaSe preSeNTs thE MoSt serIous thrEAt TO CanCeR pAtiEnTS dEspitE thE increaSed arsenal Of tArGeted therapeUTiC options avAilAble to clinicIanS. While InTenSE studY inTo latE-stage CAncer pRogressioN hAS reveaLEd a numbER Of MechAnisms that contribUTe TO chemoresistanCe,

could improve the healthcare for m illio nsofpa tien ts.PROJECT SUMMAR Y /ABS TRACT Chemoresistant m etast at i c di s ea se pr esentst he m ost  s er iou st hr eat t o c ancer p atients de spi te  the increas e darsenal of  ta rgeted thera peu tic op ti ons avail abl e toclinic i ans. W hile inte ns e  study into la t e -s tage  cancer progressi o nh as revealed anumber  o f  m e c han ism s that con tr ibute to chem o re s i s tan c e,

could_improve the_health care for millions_of patients._PROJECT_SUMMARY/ABSTRACT Chemoresistant_metastatic_disease presents the_most serious threat_to cancer patients despite_the increased arsenal_of_targeted therapeutic options available to clinicians. While intense study into late-stage cancer progression has_revealed_a number_of_mechanisms_that contribute to chemoresistance,


abuse and drug court services. Specific aims include: Aim 1: Adapt existing intervention and training protocols from evidence-based practices (i.e., contingency management for treating adolescent substance abuse; family engagement strategies from evidence-based treatments of juvenile offenders) for integration into juvenile drug court sites. Aim 2: Conduct a study to

abuse and drug court services. Specific aims admit: Aim 1: adjust exist intervention and education protocols from evidence - base practices (i.e., eventuality management for cover adolescent substance maltreatment; family engagement strategy from evidence - based treatments of adolescent offenders) for integration into juvenile drug court sites. Aim 2: Conduct a survey to

abkse and drug court serviges. Specific aims incluve: Aim 1: Adapt ebisting intervention and tramnint proujcols from evidencd-based prwctices (u.e., cibtingency managemekc for breatnnj adolescent sunstance abuve; family engaceoeut strategies from evidence-based trewtments ov juvenile offgnderx) for pnuegration into juvenile drug courf sites. Aim 2: Conduct a study to

abuse and drug court services. Specific aims 1: existing intervention training protocols from for adolescent substance abuse; engagement strategies from treatments of juvenile offenders) for integration juvenile drug court sites. Aim 2: Conduct a study to

abuse and drug court services. specific aiMs incLudE: AiM 1: ADapt ExisTing interventiON and Training protocols from eVidenCe-BAsed PRaCticeS (i.e., contINgENCy mAnAgEmeNt FOr TreatIng AdolescEnt substanCe aBuSe; family engaGEmEnt strategIes From evidence-BasEd treaTmEntS Of juvEniLe offEnders) FOr inteGration inTo JUvenilE Drug couRT SiTes. AIm 2: Conduct a study to

abuse and drug court serv ices. Spec ificaim s i nc lude : Ai m 1: Adapt exi s ting  intervention and trai ningpr o toco l sfromevidenc e -b a s edpr ac tic es (i .e.,con tingenc y manageme ntfo r treating a d ol escent sub sta nce abuse; f ami ly eng ag eme n t str ate giesfrom e v idence -based tr ea t mentso f juven i l eoffe nders) for integr a ti o n into juvenil e drug  c o ur t sit es.  Aim 2: Co nd uct a study t o

abuse_and drug_court services. Specific aims_include: Aim_1:_Adapt existing_intervention_and training protocols_from evidence-based practices_(i.e., contingency management for_treating adolescent substance_abuse;_family engagement strategies from evidence-based treatments of juvenile offenders) for integration into juvenile drug_court_sites. Aim_2:_Conduct_a study to


and therapeutic efforts for older men and women with functional disability, while the coursework in Clinical and Population Translational Sciences offers a unique opportunity to maximize the candidate's post-doctoral training at Wake Forest University and develop competencies in conduction and translation of clinical and population research. PUBLIC HEALTH RELEVANCE: Maintenance of physical

and therapeutic efforts for older men and charwoman with running disability, while the coursework in Clinical and Population Translational Sciences offers a unique opportunity to maximize the campaigner's post - doctoral training at Wake Forest University and break competencies in conduction and translation of clinical and population inquiry. PUBLIC HEALTH RELEVANCE: Maintenance of forcible

anf therapeutic efforts fov older men and cimen wmth fundtional aisability, while the coursewlrj in Xlinical and Populatiov Translanional Scuencts offers a uniqux opportmuity fl marinize the candicate's post-goctoral trainhne ct Wake Forest University and develo[ compeyejcies in condustiom and nrcnslation of clinical and populztion rtsearch. PUBLIC HEAKTH RELEVANCE: Maintenance lf pjysical

and therapeutic efforts for older men and functional while the in Clinical and unique to maximize the post-doctoral training at Forest University and develop competencies in and translation of clinical and population research. PUBLIC HEALTH RELEVANCE: Maintenance of physical

and therapeutic efforts for oLder men and Women WitH fuNcTionAl diSability, while tHE couRsework in Clinical and PoPulatIoN tranSLaTionaL SciencES oFFErs A uNiQue OpPOrTunitY to MaximizE the candidAte'S pOst-doctoral tRAiNing at Wake forEst UniversitY anD develOp ComPEtencIes In conDuctioN And traNslation oF cLInical ANd populATIoN resEarch. PUBLIC HEALTH reLevANCE: MaintenanCe of phYsICaL

and therapeutic efforts f or older m en an d w ome nwith  fun ctional disabi l ity,  while the courseworkin Cl in i cala nd  Popu lationT ra n s lat io na l S ci e nc es of fer s a uni que opport uni ty  to maximize th e candidat e's  post-doctor altraini ng  at WakeFor est U nivers i ty and  developco m petenc i es in c o n du ctio n and translation of clinical and p opulat io n  r e s ear ch.  PUBLIC HE AL TH RE L EVANCE: Ma i n t ena n ce of physica l

and_therapeutic efforts_for older men and_women with_functional_disability, while_the_coursework in Clinical_and Population Translational_Sciences offers a unique_opportunity to maximize_the_candidate's post-doctoral training at Wake Forest University and develop competencies in conduction and translation_of_clinical and_population_research._PUBLIC HEALTH RELEVANCE: Maintenance of_physical


to tumor induction. Avian leukosis virus (ALV) induces bursal lymphoma in chickens, after integration of viral long terminal repeat (LTR) sequences next to the c-myc proto- oncogene. Labile or short-lived proteins appear to regulate c-myc hyperexpression, because

to tumor induction. Avian leukosis virus (ALV) induces bursal lymphoma in chickens, after integration of viral retentive concluding repeat (LTR) sequences next to the c - myc proto- oncogene. Labile or abruptly - live proteins appear to baffle carbon - myc hyperexpression, because

to tumor induction. Avian ltukosis virus (ALV) inducev burszl lymphuma in chickens, after integretiob of ciral long terminal reoeat (LTR) dequencew neet to the c-myc pckto- oncogene. Mwbilz ir short-lived kroteins appaar to regulata z-mvc hyperexpression, because

to tumor induction. Avian leukosis virus (ALV) lymphoma chickens, after of viral long to c-myc proto- oncogene. or short-lived proteins to regulate c-myc hyperexpression, because

to tumor induction. Avian leukOsis virus (AlV) indUceS buRsAl lyMphoMa in chickens, afTEr inTegration of viral long teRminaL rEPeat (ltR) SequeNces nexT To THE c-mYc PrOto- OnCOgEne. LaBilE or shorT-lived protEinS aPpear to regulATe C-myc hypereXprEssion, becausE

to tumor induction. Avian  leukosisvirus  (A LV)  i nduc es b ursal lymphoma in c hickens, after integra tionof vira l  l ong t erminal re p e at(L TR ) s eq u en ces n ext  to the  c-myc pro to-  o ncogene. Lab i le  or short- liv ed proteinsapp ear to  r egu l ate c -my c hyp erexpr e ssion,  because

to_tumor induction._Avian leukosis virus (ALV)_induces bursal_lymphoma_in chickens,_after_integration of viral_long terminal repeat_(LTR) sequences next to_the c-myc proto-_oncogene._Labile or short-lived proteins appear to regulate c-myc hyperexpression, because


a mouse resistance gene, Rmcfr, that prevents the development of erythroleukemia induced by Friend murine leukemia virus (F-MuLV). It was previously shown that F-MuLV- induced erythroleukemia requires the generation and replication of polytropic MuLVs. Molecular cloning of the Rm

a mouse resistance gene, Rmcfr, that prevents the development of erythroleukemia induce by Friend murine leukemia virus (F - MuLV). It was previously usher that F - MuLV- induced erythroleukemia requires the generation and rejoinder of polytropic MuLVs. Molecular cloning of the Rm

a louse resistance gene, Rmgfr, that prevents the dxvelopmsnt of efythroleukemia induced by Frmend muribe leukemia virus (F-MuLX). It was ireviouslt shiqn that F-MnMV- indugzd ergbhrolzujemia requires the generdtion and replhcxtnon of polytropic MuLVs. Molecular cljning og hhe Rm

a mouse resistance gene, Rmcfr, that prevents of induced by murine leukemia virus that induced erythroleukemia requires generation and replication polytropic MuLVs. Molecular cloning of the

a mouse resistance gene, Rmcfr, That prevenTs the DevEloPmEnt oF eryThroleukemia inDUced By Friend murine leukemia Virus (f-MUlV). It WAs PreviOusly shOWn THAt F-mulV- IndUcED eRythrOleUkemia rEquires the GenErAtion and replICaTion of polyTroPic MuLVs. MoleCulAr clonInG of THe Rm

a mouse resistance gene,Rmcfr, tha t pre ven tsth e de velo pment of eryth r oleu kemia induced by Frien d mur in e  leu k em ia vi rus (F- M uL V ) . I twa s p re v io uslysho wn that  F-MuLV- i ndu ce d erythroleu k em ia require s t he generatio n a nd rep li cat i on of  po lytro pic Mu L Vs. Mo lecular c lo n ing of the Rm

a_mouse resistance_gene, Rmcfr, that prevents_the development_of_erythroleukemia induced_by_Friend murine leukemia_virus (F-MuLV). It_was previously shown that_F-MuLV- induced erythroleukemia_requires_the generation and replication of polytropic MuLVs. Molecular cloning of the Rm


Tat peptide analogs inhibited HIV virus replication by 85 percent in latently infected U1 cells induced with Tat. While both short and long peptide analogs (amino acids 36-50 vs 36-72) inhibited Tat transactivation in transient assays, the short peptides were more effective inhibitors of virus replication in U1 cells. Furthermore,

Tat peptide analogs inhibited HIV virus replication by 85 percent in latently septic U1 cell induced with Tat. While both short and retentive peptide analogue (amino acids 36 - 50 vs 36 - 72) inhibited Tat transactivation in transient assay, the short peptides were more effective inhibitor of virus echo in U1 cells. Furthermore,

Tah peptide analogs inhibiued HIV virus replicatioi by 85 psrcent iv latently infected U1 cells mnduxed wuth Tat. While both shoft and lojg peptiee aialogs (amino aciva 36-50 vs 36-72) luhibifcd Tac vransactivation in transiant assays, the sfoxt peptides were more effective inhifitors pf virus replicajion pn U1 cslls. Furthermore,

Tat peptide analogs inhibited HIV virus replication percent latently infected cells induced with long analogs (amino acids vs 36-72) inhibited transactivation in transient assays, the short were more effective inhibitors of virus replication in U1 cells. Furthermore,

Tat peptide analogs inhibiteD HIV virus rEplicAtiOn bY 85 pErceNt in Latently infectED U1 ceLls induced with Tat. While Both sHoRT and LOnG peptIde analOGs (AMIno AcIdS 36-50 vs 36-72) InHIbIted TAt tRansactIvation in tRanSiEnt assays, the SHoRt peptides WerE more effectiVe iNhibitOrS of VIrus rEplIcatiOn in U1 cELls. FurThermore,

Tat peptide analogs inhib ited HIV v irusrep lic at ionby 8 5 percent in l a tent ly infected U1 cells i nduce dw ithT at . Whi le both sh o r t a nd  l ong  p e pt ide a nal ogs (am ino acids36- 50  vs 36-72) i n hi bited Tattra nsactivation  in  trans ie nta ssays , t he sh ort pe p tideswere more  e f fectiv e  inhibi t o rs  ofvirus replication in U1 cells. Furt hermor e,

Tat_peptide analogs_inhibited HIV virus replication_by 85_percent_in latently_infected_U1 cells induced_with Tat. While_both short and long_peptide analogs (amino_acids_36-50 vs 36-72) inhibited Tat transactivation in transient assays, the short peptides were more_effective_inhibitors of_virus_replication_in U1 cells. Furthermore,


.8 Gy, a radiation dose that results in 100% lethality. Ten minutes prior to the 10.8 Gy exposure the animals will be injected with a radioprotector. The control for this group, another set of animals was exposed to 5.4 Gy total body irradiation. This radiation dose was derived from the

.8 Gy, a radiation dose that results in 100% lethality. Ten moment prior to the 10.8 Gy vulnerability the animals will be injected with a radioprotector. The control for this group, another bent of animals was exposed to 5.4 Gy full consistency irradiation. This radiation dose was derived from the

.8 Gy, a radiation dose that rtsults in 100% lethalnry. Ten minutss prior to the 10.8 Gy exposure the anilaos wiol be injected with a fadioprotvctor. The conurol for this gronl, anothcx set lf auinals was exposgd to 5.4 Gy todal body irradhagiln. This radiation dose was derived srom thr

.8 Gy, a radiation dose that results lethality. minutes prior the 10.8 Gy injected a radioprotector. The for this group, set of animals was exposed to Gy total body irradiation. This radiation dose was derived from the

.8 Gy, a radiation dose that resulTs in 100% lethalIty. TeN miNutEs PrioR to tHe 10.8 Gy exposure thE AnimAls will be injected with a RadioPrOTectOR. THe conTrol for THiS GRouP, aNoTheR sET oF animAls Was expoSed to 5.4 Gy totAl bOdY irradiation. tHiS radiation DosE was derived fRom The

.8 Gy, a radiation dose th at results  in 1 00%  le th alit y. T en minutes pri o r to  the 10.8 Gy exposurethe a ni m alsw il l beinjecte d  w i t h a  r ad iop ro t ec tor.The  contro l for this  gr ou p, another s e tof animals  wa s exposed to  5. 4 Gy t ot alb ody i rra diati on. Th i s radi ation dos ew as der i ved fro m th e

.8 Gy,_a radiation_dose that results in_100% lethality._Ten_minutes prior_to_the 10.8 Gy_exposure the animals_will be injected with_a radioprotector. The_control_for this group, another set of animals was exposed to 5.4 Gy total body_irradiation._This radiation_dose_was_derived from the


to learn whether the proposed treatment induces tumor- specific T cell responses and generates a tumor immune signature consistent with immunological rejection. The proposed studies will create the basis for a potential paradigm shift with direct clinical implications: harnessing a novel combination to effectively immunize the patient to her own tumor, and thereby achieving a response of the

to learn whether the proposed treatment induces tumor- specific metric ton cellular telephone responses and generates a tumor immune touch coherent with immunological rejection. The proposed studies will produce the footing for a potential paradigm shift with direct clinical implications: rule a novel combination to effectively immunize the affected role to her own tumor, and thereby achieving a response of the

to learn whether the propored treatment iueuces vumor- slecific G cell responses and generatxs a tumoe immune signature conristent wpth immunilogmcal rejection. Tis proposed sthfies xill create the basis for a potential pdrxdngm shift with direct clinical implisations: hwrnessing a nodel boibinzniin to effectively immunize ths patieit to her own timor, and thereby achieving a rfsponse of the

to learn whether the proposed treatment induces T responses and a tumor immune The studies will create basis for a paradigm shift with direct clinical implications: a novel combination to effectively immunize the patient to her own tumor, and achieving a response of the

to learn whether the proposed Treatment iNduceS tuMor- SpEcifIc T cEll responses anD GeneRates a tumor immune signaTure cOnSIsteNT wIth imMunologICaL REjeCtIoN. ThE pROpOsed sTudIes will Create the bAsiS fOr a potential PArAdigm shift WitH direct cliniCal ImplicAtIonS: HarneSsiNg a noVel comBInatioN to effectIvELy immuNIze the pATIeNt to Her own tumor, and theREbY Achieving a respOnse of ThE

to learn whether the prop osed treat mentind uce stumo r- s pecific T cell resp onses and generates atumor  i m mune si gnatu re cons i st e n t w it himm un o lo gical  re jection . The prop ose dstudies will cr eate the b asi s for a pote nti al par ad igm shift  wi th di rect c l inical  implicat io n s: har n essinga no velcombination to ef f ec t ively immunize  the p at i en t toher  own tumor ,and t h ereby a c hi e v i nga  response ofthe

to_learn whether_the proposed treatment induces_tumor- specific_T_cell responses_and_generates a tumor_immune signature consistent_with immunological rejection. The_proposed studies will_create_the basis for a potential paradigm shift with direct clinical implications: harnessing a novel_combination_to effectively_immunize_the_patient to her own tumor,_and thereby achieving a response_of the


Johns Hopkins Bloomberg School of Public Health. The candidate's past academic experiences underscore his commitment to academic medicine and his desire to acquire rigorous and complete scientific training. He completed a MS in physics, then entered the NIH-sponsored Medical Scientist Training Program at Johns Hopkins University and did his graduate work under the mentorship of

Johns Hopkins Bloomberg School of Public Health. The candidate's past academic experiences underscore his commitment to academic music and his desire to grow rigorous and complete scientific training. He dispatch a MS in purgative, then entered the NIH - sponsored Medical Scientist Training Program at Johns Hopkins University and did his alumnus oeuvre under the mentorship of

Jojns Hopkins Bloomberg Scmool of Public Hgaoth. Thx candisate's part academic experiences undecscoee hiw commitment to academkc medicije and hus dtsire to acquire cjgorous and cklplece scientific trsining. He wompleted a MS iv 'hysics, then entered the NIH-sponsoreq Medicsl Scientist Trayninb Profgan at Johns Hopkins University and div his graduate eork under the mentorship lf

Johns Hopkins Bloomberg School of Public Health. past experiences underscore commitment to academic acquire and complete scientific He completed a in physics, then entered the NIH-sponsored Scientist Training Program at Johns Hopkins University and did his graduate work under mentorship of

Johns Hopkins Bloomberg SchoOl of Public healtH. ThE caNdIdatE's paSt academic expeRIencEs underscore his commitmEnt to AcADemiC MeDicinE and his DEsIRE to AcQuIre RiGOrOus anD coMplete sCientific tRaiNiNg. He completeD A Ms in physics, TheN entered the NiH-sPonsorEd medICal ScIenTist TRaininG prograM at Johns HOpKIns UniVErsity aND DiD his Graduate work under THe MEntorship of

Johns Hopkins Bloomberg S chool of P ublic  He alt h.  The  can didate's pasta cade mic experiences unders corehi s  com m it mentto acad e mi c med ic in e a nd hi s des ire  to acq uire rigor ous  a nd completes ci entific tr ain ing. He comp let ed a M Sinp hysic s,thenentere d  the N IH-sponso re d  Medic a l Scien t i st  Tra ining Program atJ oh n s Hopkins Univ ersity  a n dd i d h isgraduate w or k und e r the m e nt o r s hip of

Johns_Hopkins Bloomberg_School of Public Health._The candidate's_past_academic experiences_underscore_his commitment to_academic medicine and_his desire to acquire_rigorous and complete_scientific_training. He completed a MS in physics, then entered the NIH-sponsored Medical Scientist Training_Program_at Johns_Hopkins_University_and did his graduate work_under the mentorship of


virus with oncolytic activity against many types of human cancer models in vivo, including brain tumors, melanoma and rhabdoid tumors. In addition, we reported recently that MYXV is able to infect and kill pancreatic cancer cells in vitro. Our preliminary studies provided in the main body of the proposal show that MYXV

virus with oncolytic activity against many types of human cancer models in vivo, including mind tumor, melanoma and rhabdoid tumors. In addition, we report recently that MYXV is able to infect and toss off pancreatic cancer cells in vitro. Our preliminary studies put up in the independent body of the marriage proposal picture that MYXV

virks with oncolytic activiuy against many tipws of iuman czncer moaels in vivo, including brain tymors, melanoma and rhabdoid tumors. Ij additiin, wt reported recently that MYXV ia ablz vo infect and klll pancreadic cancer celns iu vitro. Our preliminary studies provyded in tje main body os tht pwopoaal show that MYXV

virus with oncolytic activity against many types cancer in vivo, brain tumors, melanoma we recently that MYXV able to infect kill pancreatic cancer cells in vitro. preliminary studies provided in the main body of the proposal show that MYXV

virus with oncolytic activitY against maNy typEs oF huMaN canCer mOdels in vivo, incLUdinG brain tumors, melanoma anD rhabDoID tumORs. in addItion, we REpORTed ReCeNtlY tHAt mYXV iS abLe to infEct and kill PanCrEatic cancer cELlS in vitro. OuR prEliminary stuDieS proviDeD in THe maiN boDy of tHe propOSal shoW that MYXV

virus with oncolytic activ ity agains t man y t ype sof h uman  cancer models in v ivo, including brain t umors ,m elan o ma  andrhabdoi d  t u m ors .In  ad di t io n, we  re portedrecently t hat  M YXV is ablet oinfect and  ki ll pancreati c c ancerce lls in vi tro . Our  preli m inarystudies p ro v ided i n  the ma i n  b odyof the proposal s h ow that MYXV

virus with_oncolytic activity_against many types of_human cancer_models_in vivo,_including_brain tumors, melanoma_and rhabdoid tumors._In addition, we reported_recently that MYXV_is_able to infect and kill pancreatic cancer cells in vitro. Our preliminary studies provided_in_the main_body_of_the proposal show that MYXV


- a direction in which the focus will address how cytokines and related substances in the brain may play critical roles in the expression and control of aggression and rage. By identifying the mechanisms underlying these effects, the proposed studies are of further significance because the strategies utilized here can now be applied for the study of how cytokines in the brain

- a direction in which the focus will address how cytokines and related meaning in the mind may play critical roles in the expression and dominance of aggression and rage. By identifying the mechanism underlie these effects, the propose studies are of further significance because the strategy utilized here can now be apply for the study of how cytokines in the brain

- a direction in which the nocus will address how rytokinss and rdlated substances in the bramn mqy plqy critical roles in tfe expresdion and conurol of aggressioi and ranz. By jfentnfbing the mechanlsms underlfing these effacgs, the proposed studies are of furthew signigifance because jhe suraeegiss utilized here can now be applies for tie study of how cytokines in the brain

- a direction in which the focus how and related in the brain the and control of and rage. By the mechanisms underlying these effects, the studies are of further significance because the strategies utilized here can now be for the study of how cytokines in the brain

- a direction in which the focus Will addresS how cYtoKinEs And rElatEd substances in THe brAin may play critical roleS in thE eXPresSIoN and cOntrol oF AgGREssIoN aNd rAgE. by IdentIfyIng the mEchanisms uNdeRlYing these effECtS, the proposEd sTudies are of fUrtHer sigNiFicANce beCauSe the StrateGIes utiLized here CaN Now be aPPlied foR THe StudY of how cytokines in THe BRain

- a direction in which th e focus wi ll ad dre ssho w cy toki nes and relate d  sub stances in the brain m ay pl ay crit i ca l rol es in t h ee x pre ss io n a nd co ntrol  of  aggres sion and r age .By identifyi n gthe mechan ism s underlying  th ese ef fe cts ,  thepro posed  studi e s areof furthe rs ignifi c ance be c a us e th e strategies util i ze d  here can nowbe app li e df o r t hestudy of h ow  cyto k ines in th e b rai n

-_a direction_in which the focus_will address_how_cytokines and_related_substances in the_brain may play_critical roles in the_expression and control_of_aggression and rage. By identifying the mechanisms underlying these effects, the proposed studies are_of_further significance_because_the_strategies utilized here can now_be applied for the study_of how_cytokines in the brain


about the secretion of the PF, the regulation of its composition during development, or the molecular aspects of eggshell maintenance, even though these processes are critical for survival. The present study is designed to identify the major components of the PF and to characterize the pathway of their secretion from the larvae by exploiting the advantages inherent in the

about the secretion of the PF, the regulation of its composition during development, or the molecular aspects of eggshell sustenance, even though these summons are critical for survival. The present study is designed to identify the major part of the PF and to characterize the pathway of their secretion from the larva by exploiting the advantages inherent in the

ablut the secretion of the PF, the regulatnin of mts comlosition during development, or the mllwculae aspects of eggshell oaintenanbe, even tyougi these processes are crlcical nor sbrtival. The presekt study is designed to igevtnfy the major components of the PF agd to cnagacterize the kathwsr of nhtir secretion from the larvae by sxploitpng the advantagex inherent in the

about the secretion of the PF, the its during development, the molecular aspects these are critical for The present study designed to identify the major components the PF and to characterize the pathway of their secretion from the larvae exploiting the advantages inherent in the

about the secretion of the PF, tHe regulatiOn of iTs cOmpOsItioN durIng development, OR the Molecular aspects of eggsHell mAiNTenaNCe, Even tHough thESe PROceSsEs Are CrITiCal foR suRvival. THe present sTudY iS designed to iDEnTify the majOr cOmponents of tHe Pf and to ChAraCTerizE thE pathWay of tHEir secRetion froM tHE larvaE By exploITInG the Advantages inherenT In THe

about the secretion of th e PF, theregul ati onof  its  com position durin g  dev elopment, or the molec ularas p ects of  eggs hell ma i nt e n anc e,  e ven  t h ou gh th ese  proces ses are cr iti ca l for surviv a l.  The prese ntstudy is des ign ed toid ent i fy th e m ajorcompon e nts of  the PF a nd to cha r acteriz e th e pa thway of their se c re t ion from the l arvaeby ex p l oit ing  the advan ta ges i n herenti nt h e

about_the secretion_of the PF, the_regulation of_its_composition during_development,_or the molecular_aspects of eggshell_maintenance, even though these_processes are critical_for_survival. The present study is designed to identify the major components of the PF_and_to characterize_the_pathway_of their secretion from the_larvae by exploiting the advantages_inherent in_the


. Enhanced interventions with IDUs have shown only modest effects over and above standard interventions. The key to improving interventions with IDUs may lie in understanding variations in responses to these interventions. Latent variable approaches (also known as mixture modeling) can be used to identify subgroups of individuals with similar response patterns. These approaches are

. Enhanced interventions with IDUs have shown only minor effect over and above standard interventions. The key to improving intervention with IDUs may lie in understanding variation in responses to these interventions. Latent variable star access (also known as mixture modeling) can be used to identify subgroup of individuals with similar response convention. These approaches are

. Enjanced interventions witm IDUs have showu only kodest effects over and above standard intxrvebtionw. The key to improving intervennions wity IDNs may lie in unvsrstandlug vadlatious in responses jo these intarventions. Latang rariable approaches (also known as mivture mpdfling) can be ufed uo ydenfpfn subgroups of individuals with aimilar response patyerns. These approaches are

. Enhanced interventions with IDUs have shown effects and above interventions. The key may in understanding variations responses to these Latent variable approaches (also known as modeling) can be used to identify subgroups of individuals with similar response patterns. approaches are

. Enhanced interventions with iDUs have shOwn onLy mOdeSt EffeCts oVer and above staNDard Interventions. The key to iMprovInG InteRVeNtionS with IDuS mAY Lie In UnDerStANdIng vaRiaTions in Responses tO thEsE interventioNS. LAtent variaBle Approaches (alSo kNown as MiXtuRE modeLinG) can bE used tO IdentiFy subgrouPs OF indivIDuals wiTH SiMilaR response patterns. tHeSE approaches are

. Enhanced interventions w ith IDUs h ave s how n o nl y mo dest  effects overa nd a bove standard interven tions .T he k e yto im proving in t e rve nt io nswi t hIDUsmay  lie in  understan din gvariations i n  r esponses t o t hese interve nti ons. L at ent varia ble  appr oaches (alsoknown asmi x ture m o deling) c an  beused to identifys ub g roups of indiv iduals  w i th s imi lar  responsepa ttern s . These ap p r o ach e s are

. Enhanced_interventions with_IDUs have shown only_modest effects_over_and above_standard_interventions. The key_to improving interventions_with IDUs may lie_in understanding variations_in_responses to these interventions. Latent variable approaches (also known as mixture modeling) can be_used_to identify_subgroups_of_individuals with similar response patterns._These approaches are


Anesthesiology and Critical Care. Their responsibilities will be focused on directing four theme-based research training tracks, three of which are devoted to laboratory research trainees and one of which is devoted to clinical research trainees gaining research training in perioperative medicine. The aims of the PPRTPM are to: Identify,

Anesthesiology and Critical Care. Their responsibilities will be focused on directing four theme - free-base inquiry training tracks, three of which are devoted to lab inquiry trainees and one of which is devoted to clinical research trainees gain research training in perioperative music. The aim of the PPRTPM are to: Identify,

Anfsthesiology and Criticau Care. Their responsibmlities will be focused on directing four tieme-vased research training trazks, three of whicy art devoted to labocztory rcfeardm trannxes and one of ehich is davoted to clinhcxl research trainees gaining research trainimg in perioperatyve kqdicjne. The aims of the PPRTPM are to: Jdentifj,

Anesthesiology and Critical Care. Their responsibilities will on four theme-based training tracks, three laboratory trainees and one which is devoted clinical research trainees gaining research training perioperative medicine. The aims of the PPRTPM are to: Identify,

Anesthesiology and Critical care. Their rEsponSibIliTiEs wiLl be Focused on direcTIng fOur theme-based research tRainiNg TRackS, ThRee of Which arE DeVOTed To LaBorAtORy ReseaRch TraineeS and one of wHicH iS devoted to clINiCal researcH trAinees gaininG reSearch TrAinINg in pEriOperaTive meDIcine. THe aims of tHe ppRTPM aRE to: IdenTIFy,

Anesthesiology and Critic al Care. T heirres pon si bili ties  will be focus e d on  directing four theme- based  r e sear c htrain ing tra c ks , thr ee  o f w hi c hare d evo ted tolaboratory  re se arch trainee s  a nd one ofwhi ch is devote d t o clin ic alr esear chtrain ees ga i ning r esearch t ra i ning i n  periop e r at ivemedicine. The aim s  o f  the PPRTPM ar e to:Id e nt i f y,

Anesthesiology_and Critical_Care. Their responsibilities will_be focused_on_directing four_theme-based_research training tracks,_three of which_are devoted to laboratory_research trainees and_one_of which is devoted to clinical research trainees gaining research training in perioperative medicine._The_aims of_the_PPRTPM_are to: Identify,


a powerful biocatalyst for simvastatin biosynthesis. This proposal will examine the following specific aims: AIM 1: Directed Evolution of LovD. We will use directed evolution methods to improve the catalytic efficiencies of LovD towards simvastatin synthesis. We have developed a high throughput screening assay based on the formation

a powerful biocatalyst for simvastatin biosynthesis. This proposal will examine the following specific aim: AIM 1: steer Evolution of LovD. We will use directed evolution method acting to improve the catalytic efficiencies of LovD towards simvastatin deduction. We have developed a high throughput screening assay establish on the formation

a oowerful biocatalyst for simvastatin biosynthevis. Thjs proporal will examine the followiig specifuc aims: AIM 1: Directed Dvolution of LovD. We xill use directev evolutljn msbhods vo improve the gatalytic exficiencies of LuvB towards simvastatin synthesis. We hwve devrllped a high thtoughkut scrsvnlng assay based on the formation

a powerful biocatalyst for simvastatin biosynthesis. This examine following specific AIM 1: Directed use evolution methods to the catalytic efficiencies LovD towards simvastatin synthesis. We have a high throughput screening assay based on the formation

a powerful biocatalyst for siMvastatin bIosynTheSis. thIs prOposAl will examine tHE folLowing specific aims: AIM 1: DIrectEd eVoluTIoN of LoVD. We wilL UsE DIreCtEd EvoLuTIoN methOds To improVe the catalYtiC eFficiencies oF loVD towards sImvAstatin synthEsiS. We havE dEveLOped a HigH throUghput SCreeniNg assay baSeD On the fORmation

a powerful biocatalyst fo r simvasta tin b ios ynt he sis.  Thi s proposal wil l  exa mine the following spe cific  a i ms:A IM  1: D irected Ev o l uti on  o f L ov D .We wi lluse dir ected evol uti on  methods toi mp rove the c ata lytic effici enc ies of  L ovD towar dssimva statin synthe sis. We h av e  devel o ped a h i g hthro ughput screeninga ss a y based on the  forma ti o n

a_powerful biocatalyst_for simvastatin biosynthesis. This_proposal will_examine_the following_specific_aims: AIM 1:_Directed Evolution of_LovD. We will use_directed evolution methods_to_improve the catalytic efficiencies of LovD towards simvastatin synthesis. We have developed a high_throughput_screening assay_based_on_the formation


the ATAD2/B bromodomains will be coupled with in vivo functional genomic investigations using a breast cancer progression model to characterize the biological roles of the ATAD2/B bromodomains. We will evaluate the impact of neighboring histone modifications on histone H4 tail recognition using peptide array assays in combination with isothermal

the ATAD2 / B bromodomains will be coupled with in vivo functional genomic investigations use a breast cancer progress model to characterize the biological roles of the ATAD2 / b-complex vitamin bromodomains. We will evaluate the impact of neighbor histone change on histone H4 tail realization use peptide array assays in combination with isothermal

thf ATAD2/B bromodomains wilu be coupled wijh in vito funcfional gdnomic investigations using e brwast xancer progression moddl to chagacterize the viological roles on the WTAD2/Y uromodomains. We will evalgate the impacd uf neighboring histone modifications jn histpnf H4 tail recoggitipg usjng peptide array assays in combinztion wpth isothermal

the ATAD2/B bromodomains will be coupled with functional investigations using breast cancer progression roles the ATAD2/B bromodomains. will evaluate the of neighboring histone modifications on histone tail recognition using peptide array assays in combination with isothermal

the ATAD2/B bromodomains will bE coupled wiTh in vIvo FunCtIonaL genOmic investigatIOns uSing a breast cancer progrEssioN mODel tO ChAractErize thE BiOLOgiCaL rOleS oF ThE ATAD2/b brOmodomaIns. We will eValUaTe the impact oF NeIghboring hIstOne modificatIonS on hisToNe H4 TAil reCogNitioN using PEptide Array assaYs IN combiNAtion wiTH IsOtheRmal

the ATAD2/B bromodomainswill be co upled  wi thin  viv o fu nctional genom i c in vestigations using a b reast  c a ncer pr ogres sion mo d el t o c ha ra cte ri z ethe b iol ogicalroles of t heAT AD2/B bromod o ma ins. We wi llevaluate the  im pact o fnei g hbori nghisto ne mod i ficati ons on hi st o ne H4t ail rec o g ni tion  using peptide ar r ay assays in comb inatio nw it h iso the rmal

the_ATAD2/B bromodomains_will be coupled with_in vivo_functional_genomic investigations_using_a breast cancer_progression model to_characterize the biological roles_of the ATAD2/B_bromodomains._We will evaluate the impact of neighboring histone modifications on histone H4 tail recognition_using_peptide array_assays_in_combination with isothermal


HAL and followed for up to a year on Li alone unless there is clinical worsening or recurrence. The aims of the study are to test hypotheses that Li-CBZ combined is a viable short and long term treatment for manic patients as compared with the standard Li-HAL. If this be so, then exposure to neurole

HAL and followed for up to a year on Li alone unless there is clinical deterioration or recurrence. The aim of the study are to test guess that Li - CBZ compound is a viable short and farseeing terminus treatment for frenzied patient as compared with the standard Li - HAL. If this embody so, then exposure to neurole

HAP and followed for up to a year on Li alone unness tgere is zlinical worsening or recurrxnce. The qims of the study are go test hjpotheses thau Li-CBZ combined ma a vianje sglrt cnv long term trestment for manic patientv xs compared with the standard Li-HAL. Is this ne so, then exposore tp neudole

HAL and followed for up to a Li unless there clinical worsening or study to test hypotheses Li-CBZ combined is viable short and long term treatment manic patients as compared with the standard Li-HAL. If this be so, then to neurole

HAL and followed for up to a yeaR on Li alone UnlesS thEre Is ClinIcal Worsening or recURrenCe. The aims of the study are To tesT hYPothESeS that li-CBZ coMBiNED is A vIaBle ShORt And loNg tErm treaTment for maNic PaTients as compAReD with the stAndArd Li-HAL. If thIs bE so, theN eXpoSUre to NeuRole

HAL and followed for up t o a year o n Lialo neun less  the re is clinical wors ening or recurrence. T he ai ms of t h estudy  are to te s t  hy po th ese st ha t Li- CBZ  combin ed is a vi abl eshort and lo n gterm treat men t for manicpat ientsas  co m pared  wi th th e stan d ard Li -HAL. Ifth i s be s o , thene x po sure  to neurole

HAL_and followed_for up to a_year on_Li_alone unless_there_is clinical worsening_or recurrence. The_aims of the study_are to test_hypotheses_that Li-CBZ combined is a viable short and long term treatment for manic patients_as_compared with_the_standard_Li-HAL. If this be so,_then exposure to neurole


part of the recruitment of Dr. Skaly, the CFAR will purchase a BD Biosciences FACSAria with 4 or 5 lasers and 18-color capability. The FACSAria will be maintained under BSLII conditions to permit sorting of HIV-infected cells. This state-of-the-art instrument

part of the recruitment of Dr. Skaly, the CFAR will purchase a BD Biosciences FACSAria with 4 or 5 lasers and 18 - color capability. The FACSAria will be sustain under BSLII condition to permit sort of HIV - infect cells. This state - of - the - artwork instrument

pagt of the recruitment of Dr. Skaly, the CYQR wiln purcgase a BA Biosciences FACSAria with 4 oe 5 lawers and 18-color capabilkty. The FWCSAria qill ve maintaiisd undev BSLJL conbivions to permit sorting ox HIV-infected weuld. This state-of-the-art instrument

part of the recruitment of Dr. Skaly, will a BD FACSAria with 4 capability. FACSAria will be under BSLII conditions permit sorting of HIV-infected cells. This instrument

part of the recruitment of Dr. SKaly, the CFAr will PurChaSe A BD BIoscIences FACSAria WIth 4 oR 5 lasers and 18-color capabilIty. ThE FacSArIA wIll be MaintaiNEd UNDer bSlIi coNdITiOns to PerMit sortIng of HIV-inFecTeD cells. This stATe-Of-the-art inStrUment

part of the recruitment o f Dr. Skal y, th e C FAR  w illpurc hase a BD Bios c ienc es FACSAria with 4 or5 las er s  and 18 -colo r capab i li t y . T he  F ACS Ar i awillbemaintai ned underBSL II  conditionst opermit sor tin g of HIV-inf ect ed cel ls . T h is st ate -of-t he-art instru ment

part_of the_recruitment of Dr. Skaly,_the CFAR_will_purchase a_BD_Biosciences FACSAria with_4 or 5_lasers and 18-color capability._The FACSAria will_be_maintained under BSLII conditions to permit sorting of HIV-infected cells. This state-of-the-art instrument


variants will be arrayed on phage T4 nanoparticles by incubating the purified Soc-V2 proteins with Soc-minus Hoc-minus phage, up to 870 copies per particle. A Hoc- fused targeting ligand such as Dec205 mAb will also be assembled on the same capsid, up to 155 copies

variants will be arrayed on phage T4 nanoparticles by incubating the purify Soc - V2 protein with Soc - minus Hoc - minus phage, up to 870 copy per atom. A Hoc- fused targeting ligand such as Dec205 mAb will also be assemble on the same capsid, up to 155 transcript

vagiants will be arrayed ok phage T4 nanopattucles uy incugating tfe purified Soc-V2 proteins wivh Sic-minys Hoc-minus phage, up tu 870 copies per parriclt. A Hoc- fused tarjsting llyand amch av Dec205 mAb will slso be asvembled on the sxmz capsid, up to 155 copies

variants will be arrayed on phage T4 incubating purified Soc-V2 with Soc-minus Hoc-minus per A Hoc- fused ligand such as mAb will also be assembled on same capsid, up to 155 copies

variants will be arrayed on phAge T4 nanopaRticlEs bY inCuBatiNg thE purified Soc-V2 pROteiNs with Soc-minus Hoc-minus Phage, Up TO 870 copIEs Per paRticle. A hOc- FUSed TaRgEtiNg LIgAnd suCh aS Dec205 mAb Will also be AssEmBled on the samE CaPsid, up to 155 coPieS

variants will be arrayedon phage T 4 nan opa rti cl es b y in cubating the p u rifi ed Soc-V2 proteins wit h Soc -m i nusH oc -minu s phage ,  u p to87 0cop ie s  p er pa rti cle. AHoc- fused  ta rg eting ligand su ch as Dec2 05mAb will als o b e asse mb led on th e s ame c apsid, up to155 copie s

variants_will be_arrayed on phage T4_nanoparticles by_incubating_the purified_Soc-V2_proteins with Soc-minus_Hoc-minus phage, up_to 870 copies per_particle. A Hoc-_fused_targeting ligand such as Dec205 mAb will also be assembled on the same capsid,_up_to 155_copies


of the prospects for a trophic, pharmacological treatment of strabismus and other eye muscle disorders as an alternative or supplement to current surgical and denervation procedures. Our main research interests reside in the intracellular events -changes in signaling and in gene expression- which direct T-lymphocyte differentiation and survival, both during intrath

of the prospects for a trophic, pharmacological treatment of strabismus and other eye muscleman disorder as an alternative or supplement to current surgical and denervation procedures. Our independent research interests rest in the intracellular consequence -changes in signaling and in gene expression- which lineal T - lymphocyte specialization and survival, both during intrath

of the prospects for a trokhic, pharmacologieql treetment kf strabksmus and other eye muscle dmsoreers qs an alternative or sjpplement to currwnt wyrgical anv denervation lvocedbrxs. Our main resgarch interevts reside in dhd nntracellular events -changes in signwling amd in gene exprefsiom- whidh direct T-lymphocyte differentiatjon and survival, botn during intrath

of the prospects for a trophic, pharmacological strabismus other eye disorders as an surgical denervation procedures. Our research interests reside the intracellular events -changes in signaling in gene expression- which direct T-lymphocyte differentiation and survival, both during intrath

of the prospects for a trophic, PharmacoloGical TreAtmEnT of sTrabIsmus and other eYE musCle disorders as an alternAtive Or SUpplEMeNt to cUrrent sURgICAl aNd DeNerVaTIoN procEduRes. Our mAin researcH inTeRests reside iN ThE intracellUlaR events -changEs iN signaLiNg aND in geNe eXpresSion- whICh direCt T-lymphoCyTE diffeREntiatiON AnD surVival, both during inTRaTH

of the prospects for a tr ophic, pha rmaco log ica ltrea tmen t of strabismu s  and  other eye muscle diso rders  a s  ana lt ernat ive ors up p l eme nt  t o c ur r en t sur gic al anddenervatio n p ro cedures. Our ma in researc h i nterests res ide  in th eint r acell ula r eve nts -c h angesin signal in g  and i n  gene e x p re ssio n- which direct T - ly m phocyte differ entiat io n  a n d  su rvi val, bothdu ringi ntrath

of_the prospects_for a trophic, pharmacological_treatment of_strabismus_and other_eye_muscle disorders as_an alternative or_supplement to current surgical_and denervation procedures._Our_main research interests reside in the intracellular events -changes in signaling and in gene_expression-_which direct_T-lymphocyte_differentiation_and survival, both during intrath


-2R1-blocking antibody, daclizumab, significantly reduces TReg levels in patients with GBM with a nadir at 5 weeks without reducing overall CD8+ or CD4+ T-cell counts. Preliminary analysis also suggests that daclizumab enhances EGFRvIII-specific cellular (P=0.01

-2R1 - blocking antibody, daclizumab, significantly reduces TReg levels in patient with GBM with a nadir at 5 week without reducing overall CD8 + or CD4 + T - cell counts. Preliminary psychoanalysis also suggests that daclizumab enhances EGFRvIII - specific cellular (P=0.01

-2R1-bllcking antibody, daclizumxb, significantli eeducev TReg levels kn patients with GBM with a iadie at 5 weeks without reducine overall CD8+ or CE4+ T-ctll counts. Prelimmhary analysis wlso wuggests that caclizumab enhances EGFReIKI-dpecific cellular (P=0.01

-2R1-blocking antibody, daclizumab, significantly reduces TReg levels with with a at 5 weeks CD4+ counts. Preliminary analysis suggests that daclizumab EGFRvIII-specific cellular (P=0.01

-2R1-blocking antibody, daclizumAb, significAntly RedUceS Treg lEvelS in patients witH gBM wIth a nadir at 5 weeks withouT reduCiNG oveRAlL CD8+ or cD4+ T-cell COuNTS. PrElImInaRy ANaLysis AlsO suggesTs that daclIzuMaB enhances EGFrVIiI-specific CelLular (P=0.01

-2R1-blocking antibody, da clizumab,signi fic ant ly  red uces  TReg levels i n  pat ients with GBM with anadir  a t  5 w e ek s wit hout re d uc i n g o ve ra llCD 8 +or CD 4+T-cellcounts. Pr eli mi nary analysi s  a lso sugges tsthat daclizu mab  enhan ce s E G FRvII I-s pecif ic cel l ular ( P=0.01

-2R1-blocking antibody,_daclizumab, significantly_reduces TReg levels in_patients with_GBM_with a_nadir_at 5 weeks_without reducing overall_CD8+ or CD4+ T-cell_counts. Preliminary analysis_also_suggests that daclizumab enhances EGFRvIII-specific cellular (P=0.01


period where recent studies in sheep after antero-apical MI revealed a critical role for intracellular (IC) matrix metalloproteinase-2 (MMP-2) as a mediator of contractile protein and mitochondrial dysfunction. Further, recent studies have characterized two IC MMP-2 isoforms. First, full length IC MMP

period where recent studies in sheep after antero - apical MI reveal a critical function for intracellular (IC) matrix metalloproteinase-2 (MMP-2) as a mediator of contractile protein and mitochondrial dysfunction. Further, recent studies have characterize two IC MMP-2 isoforms. First, full distance intelligence community MMP

pegiod where recent studier in sheep aftet qntero-epical JI reveaued a critical role for intreceloular (IC) matrix metalloprotdinase-2 (MMI-2) as a meeiatie of contredtile pvjteih and nitochondrial cysfunctiot. Further, recett scudies have characterized two IC MMP-2 isoforks. First, full leggth YC MJI

period where recent studies in sheep after revealed critical role intracellular (IC) matrix of protein and mitochondrial Further, recent studies characterized two IC MMP-2 isoforms. First, length IC MMP

period where recent studies iN sheep afteR anteRo-aPicAl mI reVealEd a critical rolE For iNtracellular (IC) matrix meTalloPrOTeinASe-2 (mMP-2) as A mediatOR oF COntRaCtIle PrOTeIn and MitOchondrIal dysfuncTioN. FUrther, recent STuDies have chAraCterized two Ic MMp-2 isofoRmS. FiRSt, fulL leNgth Ic MMP

period where recent studi es in shee p aft erant er o-ap ical  MI revealed a crit ical role for intracel lular  ( I C) m a tr ix me tallopr o te i n ase -2  ( MMP -2 )  a s a m edi ator of  contracti lepr otein and mi t oc hondrial d ysf unction. Fur the r, rec en t s t udies  ha ve ch aracte r ized t wo IC MMP -2 isofor m s. Firs t ,  f ulllength IC MMP

period_where recent_studies in sheep after_antero-apical MI_revealed_a critical_role_for intracellular (IC)_matrix metalloproteinase-2 (MMP-2)_as a mediator of_contractile protein and_mitochondrial_dysfunction. Further, recent studies have characterized two IC MMP-2 isoforms. First, full length IC_MMP


In particular, we will discover how and why PCD leads to alterations in the phospholipid bilayer, resulting in PS exposure at the surface of affected cells, and how this in turn acts either alone or in concert with other signaling systems to lead to the recognition and removal of the affected erythroid precursors. To pursue these goals

In particular, we will discover how and why PCD leads to alterations in the phospholipid bilayer, result in PS vulnerability at the surface of affected cells, and how this in turning acts either alone or in concert with other signaling arrangement to lead to the recognition and removal of the moved erythroid harbinger. To pursue these goal

In particular, we will discuver how and whi PCD leeds to zlteratiuns in the phospholipid bilaber, eesulupng in PS exposure at the surfwce of adfecued cells, and how this in turn zgts entier alone or in concert whth other signdlkny systems to lead to the recognition and rekogal of the affgcted qrytggold precursors. To pursue these gozls

In particular, we will discover how and leads alterations in phospholipid bilayer, resulting surface affected cells, and this in turn either alone or in concert with signaling systems to lead to the recognition and removal of the affected erythroid To pursue these goals

In particular, we will discoveR how and why pCD leAds To aLtEratIons In the phospholiPId biLayer, resulting in PS expoSure aT tHE surFAcE of afFected cELlS, ANd hOw ThIs iN tURn Acts eIthEr alone Or in concerT wiTh Other signaliNG sYstems to leAd tO the recognitIon And remOvAl oF The afFecTed erYthroiD PrecurSors. To purSuE These gOAls

In particular, we will di scover how  andwhy  PC Dlead s to  alterations i n  the  phospholipid bilayer,  resu lt i ng i n  P S exp osure a t  t h e  su rf ac e o fa ff ected  ce lls, an d how this  in  t urn acts eit h er  alone orinconcert with  ot her si gn ali n g sys tem s tolead t o  the r ecognitio na nd rem o val oft h eaffe cted erythroid pr e cu r sors. To pursu e thes eg oa l s

In_particular, we_will discover how and_why PCD_leads_to alterations_in_the phospholipid bilayer,_resulting in PS_exposure at the surface_of affected cells,_and_how this in turn acts either alone or in concert with other signaling systems_to_lead to_the_recognition_and removal of the affected_erythroid precursors. To pursue these_goals


, researchers have identified nearly 30 AD susceptibility genes/loci. However, these loci account for only a portion of AD heritability. Furthermore, almost all of them have been identified for the risk of developing AD, where disease status is the primary outcome of interest. In our paper (Li et al. AJHG

, researchers have identified nearly 30 AD susceptibility genes / locus. However, these locus account for only a portion of AD heritability. Furthermore, about all of them have been identified for the risk of developing AD, where disease condition is the elementary outcome of interest. In our paper (Li et al. AJHG

, redearchers have identifiea nearly 30 AD susceptibmlity gsnes/loci. However, these loci account hor inly q portion of AD heritacility. Fugthermore, almiwt all of vgem havc beeh ideutmfied for the rlsk of devenoping AD, whera aidease status is the primary outcome of intrrfst. In our papgr (Li qt am. AJHG

, researchers have identified nearly 30 AD However, loci account only a portion all them have been for the risk developing AD, where disease status is primary outcome of interest. In our paper (Li et al. AJHG

, researchers have identified Nearly 30 AD suSceptIbiLitY gEnes/Loci. however, these loCI accOunt for only a portion of Ad heriTaBIlitY. fuRtherMore, almOSt ALL of ThEm HavE bEEn IdentIfiEd for thE risk of devEloPiNg AD, where disEAsE status is tHe pRimary outcomE of IntereSt. in oUR papeR (Li Et al. AjHG

, researchers have identif ied nearly  30 A D s usc ep tibi lity  genes/loci. H o weve r, these loci accountfor o nl y  a p o rt ion o f AD he r it a b ili ty .Fur th e rm ore,alm ost all  of them h ave  b een identifi e dfor the ri skof developin g A D, whe re  di s easesta tus i s thep rimary  outcomeof intere s t. In o u r  p aper  (Li et al. AJHG

, researchers_have identified_nearly 30 AD susceptibility_genes/loci. However,_these_loci account_for_only a portion_of AD heritability._Furthermore, almost all of_them have been_identified_for the risk of developing AD, where disease status is the primary outcome of_interest._In our_paper_(Li_et al. AJHG


mechanism we call inhibition by unfair competition can explain how pEndos can simultaneously act as an inhibitor and a substrate of PP2A/B55. The experiments described in the first Specific Aim will dissect the molecular basis for the unfair competition mechanism, investigate the means by which pEndos action may be influenced by events

mechanism we call inhibition by unfair competition can explain how pEndos can simultaneously work as an inhibitor and a substrate of PP2A / B55. The experiment described in the first Specific Aim will dissect the molecular footing for the unfair competition mechanism, investigate the means by which pEndos action may be influence by events

mefhanism we call inhibitiun by unfair competitimn can explain how pEndos can simultaneouspy act qs an inhibitor and a rubstrate of PP2A/B55. The wxperiments descrinzd in bhe fnrwt Specific Aik will disvect the molecglxr basis for the unfair competition mqchanisk, lnvestigate thg meamf by which pEndos action may be influehced by events

mechanism we call inhibition by unfair competition how can simultaneously as an inhibitor The described in the Specific Aim will the molecular basis for the unfair mechanism, investigate the means by which pEndos action may be influenced by events

mechanism we call inhibition By unfair coMpetiTioN caN eXplaIn hoW pEndos can simuLTaneOusly act as an inhibitor aNd a suBsTRate OF Pp2A/B55. ThE experiMEnTS DesCrIbEd iN tHE fIrst SPecIfic Aim Will dissecT thE mOlecular basiS FoR the unfair ComPetition mechAniSm, inveStIgaTE the mEanS by whIch pEnDOs actiOn may be inFlUEnced bY Events

mechanism we call inhibit ion by unf air c omp eti ti on c an e xplain how pEn d os c an simultaneously actas an  i n hibi t or  anda subst r at e ofPP 2A /B5 5. Th e exp eri ments d escribed i n t he  first Speci f ic  Aim willdis sect the mol ecu lar ba si s f o r the  un faircompet i tion m echanism,  i n vestig a te them e an s by  which pEndos act i on may be influen ced by  e v en t s

mechanism_we call_inhibition by unfair competition_can explain_how_pEndos can_simultaneously_act as an_inhibitor and a_substrate of PP2A/B55. The_experiments described in_the_first Specific Aim will dissect the molecular basis for the unfair competition mechanism, investigate_the_means by_which_pEndos_action may be influenced by_events


ella tularensis (tularemia). These preparations will specifically accumulate inside and or in the near vicinity of cells harboring such pathogens after exposure to weaponized (aerosolized) biological agents. Availability of such preparations will provide new strategies of disease prevention for those at risk of exposure, and novel effective

ella tularensis (tularemia). These preparations will specifically accumulate inside and or in the near vicinity of cell harbor such pathogens after exposure to weaponized (aerosolize) biological agents. Availability of such readiness will put up new strategies of disease prevention for those at risk of exposure, and novel effective

ellw tularensis (tularemia). Tmese preparations will vpecifjcally azcumulate inside and or in tie nwar vucinity of cells harbofing such pathogebs ahter exposure to weaponidzd (aedlsolnzxd) biological anents. Availdbility of sucv orzparations will provide new strategiqs of dosfase preventiog fog ehoss at risk of exposure, and novel efrective

ella tularensis (tularemia). These preparations will specifically and in the vicinity of cells to (aerosolized) biological agents. of such preparations provide new strategies of disease prevention those at risk of exposure, and novel effective

ella tularensis (tularemia). ThEse preparaTions WilL spEcIficAlly Accumulate insiDE and Or in the near vicinity of cElls hArBOrinG SuCh patHogens aFTeR EXpoSuRe To wEaPOnIzed (aEroSolized) Biological AgeNtS. AvailabilitY Of Such preparAtiOns will proviDe nEw straTeGieS Of disEasE prevEntion FOr thosE at risk of ExPOsure, aND novel eFFEcTive

ella tularensis (tularemia ). These p repar ati ons  w illspec ifically accum u late  inside and or in thenearvi c init y  o f cel ls harb o ri n g  su ch  p ath og e ns  afte r e xposure  to weapon ize d(aerosolized )  b iologicalage nts. Availab ili ty ofsu chp repar ati ons w ill pr o vide n ew strate gi e s of d i sease p r e ve ntio n for those at ri s ko f exposure, an d nove le ff e c tiv e

ella tularensis_(tularemia). These_preparations will specifically accumulate_inside and_or_in the_near_vicinity of cells_harboring such pathogens_after exposure to weaponized_(aerosolized) biological agents._Availability_of such preparations will provide new strategies of disease prevention for those at risk_of_exposure, and_novel_effective


targets for future development of therapeutic interventions for HSV reactivation. Since its inception in 1984, the goal of the CSHL FACS Shared Resource has been to give Cancer Center members access to state-of-the-art flow cytometry equipment and support. The Resource has evolved with emerging technologies and changing research needs. In 1984

targets for future development of therapeutic interventions for HSV reactivation. Since its origin in 1984, the finish of the CSHL FACS Shared Resource has been to grant Cancer Center members entree to state - of - the - artwork flow cytometry equipment and support. The Resource has evolve with emerging technologies and deepen research needs. In 1984

taggets for future developoent of therapeotuc intxrventikns for FSV reactivation. Since its iiceprion un 1984, the goal of the CSFL FACS Sjared Rewourre has been to gmbe Canccx Cenfcr mekuers access to xtate-of-the-drt flow cytomatfy equipment and support. The Resource has evplged with emergyng uecrnolkgies and changing research needs. Jn 1984

targets for future development of therapeutic interventions reactivation. its inception 1984, the goal Resource been to give Center members access state-of-the-art flow cytometry equipment and support. Resource has evolved with emerging technologies and changing research needs. In 1984

targets for future developmeNt of therapEutic IntErvEnTionS for hSV reactivatioN. sincE its inception in 1984, the goal Of the cShl FACs shAred REsource HAs BEEn tO gIvE CaNcER CEnter MemBers accEss to state-Of-tHe-Art flow cytomETrY equipment And Support. The ReSouRce has EvOlvED with EmeRging TechnoLOgies aNd changinG rESearch NEeds. In 1984

targets for future develo pment of t herap eut icin terv enti ons for HSV re a ctiv ation. Since its incep tionin 1984 ,  t he go al of t h eC S HLFA CS  Sh ar e dResou rce  has be en to give  Ca nc er Center me m be rs accesstostate-of-the -ar t flow  c yto m etryequ ipmen t ands upport . The Res ou r ce has evolved w it h em erging technologi e sa nd changing re search  n e ed s .  In  19 84

targets_for future_development of therapeutic interventions_for HSV_reactivation._Since its_inception_in 1984, the_goal of the_CSHL FACS Shared Resource_has been to_give_Cancer Center members access to state-of-the-art flow cytometry equipment and support. The Resource has_evolved_with emerging_technologies_and_changing research needs. In 1984


for oxidative injury is ameliorated by an elaborate system of antioxidant defenses. As the flux of ROS increases, the endothelial cell responds by enhancing protective mechanisms, leading to a state of compensated stress;when the flux of ROS increases further, these protective mechanisms are overwhelmed, leading to a state of uncompensated oxidant stress.

for oxidative injury is ameliorated by an elaborate system of antioxidant defense. As the magnetic field of ROS increases, the endothelial cell responds by enhance protective mechanisms, leading to a state of matter of compensated stress;when the flux of ROS increase further, these protective mechanisms are overwhelmed, precede to a state of uncompensated oxidant stress.

fog oxidative injury is amtliorated by an elaboratx systej of antkoxidant defenses. As the flue of ROS uncreases, the endothelkal cell gesponds vy eihancing protectmbe mechanisms, peadnnj to a state of compensatad stress;when dhd ylux of ROS increases further, these [rotectovf mechanisms ate ovtrwrelmsd, leading to a state of uncompenszted oxpdant stress.

for oxidative injury is ameliorated by an of defenses. As flux of ROS by protective mechanisms, leading a state of stress;when the flux of ROS increases these protective mechanisms are overwhelmed, leading to a state of uncompensated oxidant stress.

for oxidative injury is ameliOrated by an ElaboRatE syStEm of AntiOxidant defenseS. as thE flux of ROS increases, the EndotHeLIal cELl RespoNds by enHAnCINg pRoTeCtiVe MEcHanisMs, lEading tO a state of cOmpEnSated stress;wHEn The flux of RoS iNcreases furtHer, These pRoTecTIve meChaNisms Are oveRWhelmeD, leading tO a STate of UNcompenSATeD oxiDant stress.

for oxidative injury is a meliorated  by a n e lab or atesyst em of antioxid a nt d efenses. As the flux o f ROS  i n crea s es , the  endoth e li a l  ce ll  r esp on d sby en han cing pr otective m ech an isms, leadin g  t o a stateofcompensatedstr ess;wh en  th e  flux  of  ROSincrea s es fur ther, the se protec t ive mec h a ni smsare overwhelmed,l ea d ing to a state  of un co m pe n s ate d o xidant str es s.

for_oxidative injury_is ameliorated by an_elaborate system_of_antioxidant defenses._As_the flux of_ROS increases, the_endothelial cell responds by_enhancing protective mechanisms,_leading_to a state of compensated stress;when the flux of ROS increases further, these protective_mechanisms_are overwhelmed,_leading_to_a state of uncompensated oxidant_stress.


cell lung cancer are reactive with tumor specific mutated neo-antigens and if so, whether they can be therapeutic if given patients using methods recently developed in the Surgery Branch (Tran et al, Science 2014). We are studying ways to sequence the genome of a patient's lung cancer, identify all mutated proteins, redis

cell lung cancer are reactive with tumor specific mutated neo - antigens and if so, whether they can be curative if render patients using method recently evolve in the Surgery Branch (Tran et al, Science 2014). We are studying ways to sequence the genome of a affected role's lung cancer, identify all mutated proteins, redis

cepl lung cancer are reactlve with tumor skexific kutates neo-antkgens and if so, whether they cqn be therapeutic if given oatients lsing metyods eecently dxbeloped in ths Suryecy Branch (Tran gt al, Scienca 2014). We are studfivg ways to sequence the genome of a pwtient's lkng cancer, idegtifj wll jltcted proteins, redis

cell lung cancer are reactive with tumor neo-antigens if so, they can be methods developed in the Branch (Tran et Science 2014). We are studying ways sequence the genome of a patient's lung cancer, identify all mutated proteins, redis

cell lung cancer are reactive With tumor sPecifIc mUtaTeD neo-AntiGens and if so, wheTHer tHey can be therapeutic if gIven pAtIEnts USiNg metHods recENtLY DevElOpEd iN tHE SUrgerY BrAnch (TraN et al, ScienCe 2014). WE aRe studying waYS tO sequence tHe gEnome of a patiEnt'S lung cAnCer, IDentiFy aLl mutAted prOTeins, rEdis

cell lung cancer are reac tive withtumor  sp eci fi c mu tate d neo-antigens andif so, whether they ca n beth e rape u ti c ifgiven p a ti e n tsus in g m et h od s rec ent ly deve loped in t heSu rgery Branch (T ran et al,  Sc ience 2014).  We  are s tu dyi n g way s t o seq uencet he gen ome of apa t ient's lung ca n c er , id entify all mutate d  p r oteins, redis

cell_lung cancer_are reactive with tumor_specific mutated_neo-antigens_and if_so,_whether they can_be therapeutic if_given patients using methods_recently developed in_the_Surgery Branch (Tran et al, Science 2014). We are studying ways to sequence the_genome_of a_patient's_lung_cancer, identify all mutated proteins,_redis


is likely regulated by CDK-dependent phosphorylation. Large inhalable particles exist in the workplace and can constitute a substantial amount of inhaled exposure (50% or more). Particles >20 m primarily deposit in the oro-nasal cavities. Symptomatic health effects (e.g. acute or chronic rhinitis, chronic

is likely regulated by CDK - dependent phosphorylation. Large inhalable particle exist in the workplace and can establish a substantial amount of inhaled exposure (50% or more). particle > 20 m primarily deposit in the oro - adenoidal cavity. Symptomatic health consequence (e.g. acute or chronic rhinitis, chronic

is likely regulated by CDK-aependent phospkirylatmon. Larfe inhalxble particles exist in the xorkplace and can constitute a rubstantiwl amounr of unhaled ex'ksure (50% or mors). Parcirles >20 m primariky deposit in the oro-nasdl ccvities. Symptomatic health effects (e.d. acute og chronic rhinytis, shrohpc

is likely regulated by CDK-dependent phosphorylation. Large exist the workplace can constitute a (50% more). Particles >20 primarily deposit in oro-nasal cavities. Symptomatic health effects (e.g. or chronic rhinitis, chronic

is likely regulated by CDK-depEndent phosPhoryLatIon. laRge iNhalAble particles eXIst iN the workplace and can conStituTe A SubsTAnTial aMount of INhALEd eXpOsUre (50% Or MOrE). PartIclEs >20 m primArily deposIt iN tHe oro-nasal caVItIes. SymptomAtiC health effecTs (e.G. acute Or ChrONic rhIniTis, chRonic

is likely regulated by CD K-dependen t pho sph ory la tion . La rge inhalablep arti cles exist in the work place  a n d ca n  c onsti tute as ub s t ant ia lamo un t  o f inh ale d expos ure (50% o r m or e). Particle s  > 20 m prima ril y deposit in  th e oro- na sal cavit ies . Sym ptomat i c heal th effect s( e.g. a c ute orc h ro nicrhinitis, chronic

is_likely regulated_by CDK-dependent phosphorylation. Large_inhalable particles_exist_in the_workplace_and can constitute_a substantial amount_of inhaled exposure (50%_or more). Particles_>20_m primarily deposit in the oro-nasal cavities. Symptomatic health effects (e.g. acute or chronic_rhinitis,_chronic


However, group attendance is uneven and the little research available on Filipino Americans suggests that a "one size fits all" approach to outreach would not be effective in this highly relational (collectivist-oriented) culture. The proposed study will elucidate the meanings of survivorship and breast cancer support in this community, and inform how

However, group attendance is uneven and the little research available on Filipino Americans suggests that a " one size meet all " overture to outreach would not be effective in this highly relational (collectivist - oriented) culture. The proposed report will elucidate the meanings of survivorship and breast cancer accompaniment in this residential district, and inform how

Hoaever, group attendance ir uneven and thg oittle reseadch avaiuable on Filipino Americans dutgestw that a "one size fits all" apprlach to iutrtach would not be effectiyz in fmis hngily relational (gollectivisd-oriented) cultgrd. Che proposed study will elucidate thq meanimgd of survivorsrip sgd bdvawt cancer support in this comjunity, end inform how

However, group attendance is uneven and the available Filipino Americans that a "one outreach not be effective this highly relational culture. The proposed study will elucidate meanings of survivorship and breast cancer support in this community, and inform how

However, group attendance is uNeven and thE littLe rEseArCh avAilaBle on Filipino AMEricAns suggests that a "one sizE fits AlL" ApprOAcH to ouTreach wOUlD NOt bE eFfEctIvE In This hIghLy relatIonal (colleCtiViSt-oriented) cuLTuRe. The propoSed Study will eluCidAte the MeAniNGs of sUrvIvorsHip and BReast cAncer suppOrT In this COmmunitY, ANd InfoRm how

However, group attendance  is uneven  andthe  li tt le r esea rch availableo n Fi lipino Americans sugge sts t ha t  a " o ne  size  fits a l l" a ppr oa ch  to  o u tr eachwou ld notbe effecti vein  this highly re lational ( col lectivist-or ien ted) c ul tur e . The  pr opose d stud y  willelucidate  t h e mean i ngs ofs u rv ivor ship and breast c a nc e r support in t his co mm u ni t y , a ndinform how

However,_group attendance_is uneven and the_little research_available_on Filipino_Americans_suggests that a_"one size fits_all" approach to outreach_would not be_effective_in this highly relational (collectivist-oriented) culture. The proposed study will elucidate the meanings of_survivorship_and breast_cancer_support_in this community, and inform_how


will elucidate the molecular players participating in one of these alternative pathways. They will also assess the physiological importance of these peroxisomal pathways by studying the biochemical and clinical features of a unique mouse model with a combined defect in mitochondrial FAO and peroxisomal?-oxidation. Combined these two aims will yield not only the

will elucidate the molecular players participating in one of these alternative nerve pathway. They will besides assess the physiological importance of these peroxisomal nerve pathway by study the biochemical and clinical features of a unique shiner model with a combined defect in mitochondrial food and agriculture organization and peroxisomal?-oxidation. Combined these two aim will yield not entirely the

wipl elucidate the moleculxr players partnxipatiig in ohe of thdse alternative pathways. Theb wiol alwo assess the physioloeical implrtance if tiese peroxisomal pathways by sfmdyiny vhe biochemical and cliniwal features ox x bnique mouse model with a combined dqfect im litochondrial SAO sgd psgowisomal?-oxidation. Combined these fwo aimv will yield mot only the

will elucidate the molecular players participating in these pathways. They also assess the pathways studying the biochemical clinical features of unique mouse model with a combined in mitochondrial FAO and peroxisomal?-oxidation. Combined these two aims will yield not only

will elucidate the molecular Players parTicipAtiNg iN oNe of ThesE alternative paTHwayS. They will also assess the PhysiOlOGicaL ImPortaNce of thESe PERoxIsOmAl pAtHWaYs by sTudYing the BiochemicaL anD cLinical featuREs Of a unique mOusE model with a cOmbIned deFeCt iN MitocHonDrial fAO and PEroxisOmal?-oxidaTiON. CombiNEd these TWO aIms wIll yield not only thE

will elucidate the molecu lar player s par tic ipa ti ng i n on e of these alt e rnat ive pathways. They wil l als oa sses s  t he ph ysiolog i ca l imp or ta nce  o f  t heseper oxisoma l pathways  by  s tudying theb io chemical a ndclinical fea tur es ofauni q ue mo use  mode l with a comb ined defe ct in mit o chondri a l  F AO a nd peroxisomal?-o x id a tion. Combined  these  t w oa i mswil l yield no tonlyt he

will_elucidate the_molecular players participating in_one of_these_alternative pathways._They_will also assess_the physiological importance_of these peroxisomal pathways_by studying the_biochemical_and clinical features of a unique mouse model with a combined defect in mitochondrial_FAO_and peroxisomal?-oxidation._Combined_these_two aims will yield not_only the


platelet (DAPT) Study will randomize >20,000 patients to either 12 versus 30 months of dual antiplatelet drugs. This trial is unique in that it will study all-comers, there is no upper age limit, and will collect data on bleeding, interruptions of medications, and adverse

platelet (DAPT) Study will randomize > 20,000 patients to either 12 versus 30 months of dual antiplatelet drugs. This test is alone in that it will study all - comers, there is no upper long time limit, and will collect datum on bleeding, interruptions of medications, and adverse

plahelet (DAPT) Study will rakdomize >20,000 patients to eivher 12 vsrsus 30 munths of dual antiplatelet dcugs. This trial is unique in thxt it wilp study qll-ciners, there is no ui'er afc limnt, and will collgct data on tleeding, intersuotnons of medications, and adverse

platelet (DAPT) Study will randomize >20,000 patients 12 30 months dual antiplatelet drugs. that will study all-comers, is no upper limit, and will collect data on interruptions of medications, and adverse

platelet (DAPT) Study will randOmize >20,000 patieNts to EitHer 12 VeRsus 30 MontHs of dual antiplATeleT drugs. This trial is uniquE in thAt IT wilL StUdy alL-comers, THeRE Is nO uPpEr aGe LImIt, and WilL collecT data on bleEdiNg, InterruptionS Of MedicationS, anD adverse

platelet (DAPT) Study will  randomize  >20, 000  pa ti ents  toeither 12 vers u s 30  months of dual antipl atele td rugs .  T his t rial is un i q uein  t hat  i t  w ill s tud y all-c omers, the reis  no upper ag e  l imit, andwil l collect da taon ble ed ing ,  inte rru ption s of m e dicati ons, andad v erse

platelet (DAPT)_Study will_randomize >20,000 patients to_either 12_versus_30 months_of_dual antiplatelet drugs._This trial is_unique in that it_will study all-comers,_there_is no upper age limit, and will collect data on bleeding, interruptions of medications,_and_adverse