of PTP1B and this activated activity could down regulate the IR survival signaling. Controlling the PTP1B activity and activating the IR signaling would provide sustained neuroprotection to both rods and cones. Our new and innovative approaches to target PTP1B will facilitate future translational application of our work, with the goal

of PTP1B and this activated activity could down regulate the IR survival signaling. operate the PTP1B natural process and activating the IR signaling would provide free burning neuroprotection to both rods and cones. Our new and advanced overture to target PTP1B will help future translational lotion of our work, with the goal

of PTP1B and this activated activity could down rxgulate the IR rurvival signaling. Controlliig tye PTK1Y activity and activxting the IR signqlinj would provide sustained neurkiroteetmon to both rodx and conev. Our new and hnvorative approaches to target PTP1B wilj facilotwte future tragslauiogal zipoication of our work, with the goal

of PTP1B and this activated activity could the survival signaling. the PTP1B activity would sustained neuroprotection to rods and cones. new and innovative approaches to target will facilitate future translational application of our work, with the goal

of PTP1B and this activated actIvity could Down rEguLatE tHe IR SurvIval signaling. CONtroLling the PTP1B activity anD actiVaTIng tHE Ir signAling woULd PROviDe SuStaInED nEuropRotEction tO both rods aNd cOnEs. Our new and iNNoVative apprOacHes to target PtP1B Will faCiLitATe futUre TransLationAL appliCation of oUr WOrk, witH The goal

of PTP1B and this activat ed activit y cou lddow nregu late  the IR surviv a l si gnaling. Controlling t he PT P1 B  act i vi ty an d activ a ti n g  th eIR  si gn a li ng wo uld  provid e sustaine d n eu roprotection to  both rods  an d cones. Our  ne w andin nov a tiveapp roach es tot argetPTP1B wil lf acilit a te futu r e  t rans lational applicat i on of our work, w ith th eg oa l

of_PTP1B and_this activated activity could_down regulate_the_IR survival_signaling._Controlling the PTP1B_activity and activating_the IR signaling would_provide sustained neuroprotection_to_both rods and cones. Our new and innovative approaches to target PTP1B will facilitate_future_translational application_of_our_work, with the goal


-0042: NEI Intramural Biorepository for Retinal Diseases * 11-EI-0264: A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Central Retinal Vein Occlusions * 11-EI-0263:

-0042: NEI Intramural Biorepository for Retinal Diseases * 11 - EI-0264: A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Central Retinal Vein Occlusions * 11 - EI-0263:

-0042: NEL Intramural Biorepositovy for Retinal Dnweases * 11-EI-0264: A Pilot Sgudy for the Evaluation of Mmnoctclint as a Microglia Infibitor ij the Trwatmtnt of Central Revjnal Velu Occmmsionv * 11-EI-0263:

-0042: NEI Intramural Biorepository for Retinal Diseases A Study for Evaluation of Minocycline the of Central Retinal Occlusions * 11-EI-0263:

-0042: NEI Intramural BiorepositorY for RetinaL DiseAseS * 11-EI-0264: a PIlot studY for the EvaluatIOn of minocycline as a MicrogliA InhiBiTOr in THe treatMent of CENtRAL ReTiNaL VeIn oCcLusioNs * 11-Ei-0263:

-0042: NEI Intramural Bior epositoryfor R eti nal  D isea ses* 11-EI-0264:A  Pil ot Study for the Evalu ation  o f  Min o cy cline  as a M i cr o g lia  I nh ibi to r  i n the  Tr eatment  of Centra l R et inal Vein Oc c lu sions * 11 -EI -0263:

-0042: NEI_Intramural Biorepository_for Retinal Diseases *_11-EI-0264: A_Pilot_Study for_the_Evaluation of Minocycline_as a Microglia_Inhibitor in the Treatment_of Central Retinal_Vein_Occlusions * 11-EI-0263:


) mRNA and protein will be examined in ischemic brains of normal mice, SOD transgenic and SOD knockout mice. Since HO-1 is induced by oxidative and ischemic stress, it is predicted that HO-1 will be induced to a greater degree in ischemic brains of SOD knockouts compared to SOD transgenics. Suppression of

) mRNA and protein will be examined in ischemic brains of normal mice, SOD transgenic and SOD knockout mouse. Since HO-1 is induce by oxidative and ischemic stress, it is predicted that HO-1 will be induced to a great degree in ischemic brains of SOD knockout compare to SOD transgenics. Suppression of

) mRJA and protein will be ewamined in ischemic bramns of hormal mkce, SOD transgenic and SOD kiockiut muce. Since HO-1 is inducea by oxidwtive ane isrhemic stress, it is predleted fmat HM-1 will be inducgd to a greader degree in hszhzmic brains of SOD knockouts compareq to SOC hransgenics. Sukpresxyon kf

) mRNA and protein will be examined brains normal mice, transgenic and SOD induced oxidative and ischemic it is predicted HO-1 will be induced to a degree in ischemic brains of SOD knockouts compared to SOD transgenics. Suppression of

) mRNA and protein will be examiNed in ischeMic brAinS of NoRmal Mice, sOD transgenic aND SOD Knockout mice. Since HO-1 is iNduceD bY OxidATiVe and IschemiC StRESs, iT iS pRedIcTEd That Ho-1 wiLl be indUced to a greAteR dEgree in ischeMIc Brains of SOd knOckouts compaRed To SOD tRaNsgENics. SUppRessiOn of

) mRNA and protein will be  examinedin is che mic  b rain s of  normal mice,S OD t ransgenic and SOD knoc koutmi c e. S i nc e HO- 1 is in d uc e d  by  o xi dat iv e  a nd is che mic str ess, it is  pr ed icted that H O -1  will be i ndu ced to a gre ate r degr ee  in ische mic  brai ns ofS OD kno ckouts co mp a red to SOD tra n s ge nics . Suppression of

) mRNA_and protein_will be examined in_ischemic brains_of_normal mice,_SOD_transgenic and SOD_knockout mice. Since_HO-1 is induced by_oxidative and ischemic_stress,_it is predicted that HO-1 will be induced to a greater degree in ischemic_brains_of SOD_knockouts_compared_to SOD transgenics. Suppression of


cytokine production, cytotoxicity and assistance in protective T cell polarization by NK cells after DC activation via EBV infection. 3. Investigate EBV infection in vivo. In order to translate our in vitro findings into an in vivo model of primary EBV infection, we have reconstituted human immune systems in immune compromised mice, which could mount primary

cytokine production, cytotoxicity and assistance in protective T cell polarization by NK cell after DC energizing via EBV infection. 3. Investigate epstein-barr virus infection in vivo. In club to translate our in vitro determination into an in vivo model of primary epstein-barr virus contagion, we have reconstituted human immune systems in immune compromise mice, which could mount primary coil

cyhokine production, cytotowicity and assisjabce in protedtive T zell polarization by NK celld qfter DC activation via EBV infectioj. 3. Invesrigaue EBV infection mh vivo. Lu ordsv to crenslate our in yitro finditgs into an in vkvl model of primary EBV infection, we have rrclnstituted humwn ikiune systems in immune compromised mics, which could mount lrimary

cytokine production, cytotoxicity and assistance in protective polarization NK cells DC activation via infection vivo. In order translate our in findings into an in vivo model primary EBV infection, we have reconstituted human immune systems in immune compromised mice, could mount primary

cytokine production, cytotoxIcity and asSistaNce In pRoTectIve T Cell polarizatiON by Nk cells after DC activatioN via EbV INfecTIoN. 3. InveStigate ebV INFecTiOn In vIvO. in Order To tRanslatE our in vitrO fiNdIngs into an in VIvO model of prImaRy EBV infectiOn, wE have rEcOnsTItuteD huMan imMune sySTems in Immune comPrOMised mICe, which COUlD mouNt primary

cytokine production, cyto toxicity a nd as sis tan ce  inprot ective T cellp olar ization by NK cells af ter D Ca ctiv a ti on vi a EBV i n fe c t ion .3.  In ve s ti gateEBV  infect ion in viv o.In  order to tr a ns late our i n v itro finding s i nto an  i n v i vo mo del  of p rimary EBV in fection,we have r e constit u t ed  hum an immune systems in immune comprom ised m ic e ,w h ich  co uld mountpr imary

cytokine_production, cytotoxicity_and assistance in protective_T cell_polarization_by NK_cells_after DC activation_via EBV infection._3. Investigate EBV infection_in vivo. In_order_to translate our in vitro findings into an in vivo model of primary EBV_infection,_we have_reconstituted_human_immune systems in immune compromised_mice, which could mount primary


In the great majority of those with SS, dietary NaHCQloading induces a robust increase in blood pressure that is fully two-thirds that induced by dietary NaCI loading. 2) In those with such "selective Na + sensitivity" (sNaS), NaHCO-Ioading and NaCl-loading induce

In the great majority of those with SS, dietary NaHCQloading induces a robust increase in rake atmospheric pressure that is fully two - thirds that induced by dietary NaCI load. 2) In those with such " selective Na + sensitivity " (sNaS), NaHCO - Ioading and NaCl - loading induce

In the great majority of tmose with SS, diejaey NaHRQloadihg inducds a robust increase in bloov prwssurt that is fully two-ghirds thwt inducwd bb dietary NaCI loading. 2) Lu thoac witk wuch "selective Na + sensidivity" (sNaS), NaVCU-Ilading and NaCl-loading induce

In the great majority of those with NaHCQloading a robust in blood pressure induced dietary NaCI loading. In those with "selective Na + sensitivity" (sNaS), NaHCO-Ioading NaCl-loading induce

In the great majority of those With SS, dietAry NahCQLoaDiNg inDuceS a robust increaSE in bLood pressure that is fullY two-tHiRDs thAT iNduceD by dietARy nAcI lOaDiNg. 2) IN tHOsE with SucH "selectIve Na + sensiTivItY" (sNaS), NaHCO-IoADiNg and NaCl-lOadIng induce

In the great majority ofthose with  SS,die tar yNaHC Qloa ding induces a robu st increase in blood p ressu re that is  full y two-t h ir d s  th at  i ndu ce d  b y die tar y NaCIloading. 2 ) I nthose with s u ch  "selectiv e N a + sensitiv ity " (sNa S) , N a HCO-I oad ing a nd NaC l -loadi ng induce

In_the great_majority of those with_SS, dietary_NaHCQloading_induces a_robust_increase in blood_pressure that is_fully two-thirds that induced_by dietary NaCI_loading._2) In those with such "selective Na + sensitivity" (sNaS), NaHCO-Ioading and NaCl-loading induce


against the major myelin antigens. In addition, our studies have laid the groundwork for future studies on nonspecific (monoclonal antibody therapy) and specific (virus-specific tolerance induction) means of regulating virus and neuroantigen-specific CMI responses. Using in vivo-derived T cells and in vitro-propag

against the major myelin antigens. In addition, our studies have laid the basis for future cogitation on nonspecific (monoclonal antibody therapy) and specific (virus - specific tolerance evocation) entail of regulating virus and neuroantigen - specific CMI responses. use in vivo - derive T cell and in vitro - propag

agwinst the major myelin aktigens. In additnin, our studiss have uaid the groundwork for futuce srudiew on nonspecific (monocuonal antpbody theeapy) qnd specifmd (virus-specifjg tolzrence induction) keans of ragulating viruv xnb neuroantigen-specific CMI responses. Using on vivo-derived T celkf ans in vitro-propag

against the major myelin antigens. In addition, have the groundwork future studies on specific tolerance induction) means regulating virus and CMI responses. Using in vivo-derived T and in vitro-propag

against the major myelin antiGens. In addiTion, oUr sTudIeS havE laiD the groundwork FOr fuTure studies on nonspecifIc (monOcLOnal ANtIbody Therapy) ANd SPEciFiC (vIruS-sPEcIfic tOleRance inDuction) meaNs oF rEgulating virUS aNd neuroantIgeN-specific CMI ResPonses. usIng IN vivo-DerIved T Cells aND in vitRo-propag

against the major myelinantigens.In ad dit ion ,ourstud ies have laidt he g roundwork for future s tudie so n no n sp ecifi c (mono c lo n a l a nt ib ody  t h er apy)and  specif ic (virus- spe ci fic toleranc e  i nduction)mea ns of regula tin g viru sand neuro ant igen- specif i c CMIresponses .U sing i n  vivo-d e r iv ed T  cells and in vit r o- p ropag

against_the major_myelin antigens. In addition,_our studies_have_laid the_groundwork_for future studies_on nonspecific (monoclonal_antibody therapy) and specific_(virus-specific tolerance induction)_means_of regulating virus and neuroantigen-specific CMI responses. Using in vivo-derived T cells and in_vitro-propag


to clients in obtaining needed services as identified by ASAP. In addition to the planning function, a limited amount of funds will be allocated to purchase necessary emergency treatment services where no other resources are available. Differential Proteomics, Inc., is developing a new proteomics technology for comparing the protein composition of biological samples. The technology

to clients in obtaining needed services as identified by ASAP. In accession to the planning affair, a limited amount of funds will be allocate to purchase necessary emergency treatment service where no other resources are available. Differential Proteomics, Inc., is develop a new proteomics technology for compare the protein composition of biological samples. The technology

to clients in obtaining netded services as neentifmed by ZSAP. In xddition to the planning funrtiob, a lumited amount of funds will be wllocatee to purchase nxdessary emergskcy txeetment services where no mther resourcev xrz available. Differential Proteomics, Ync., is cegeloping a new proueoiics neghnology for comparing the protejn compmsition of biplogical samples. The technllogj

to clients in obtaining needed services as ASAP. addition to planning function, a be to purchase necessary treatment services where other resources are available. Differential Proteomics, is developing a new proteomics technology for comparing the protein composition of biological The technology

to clients in obtaining needeD services aS idenTifIed By aSAP. in adDition to the plaNNing Function, a limited amount Of funDs WIll bE AlLocatEd to purCHaSE NecEsSaRy eMeRGeNcy trEatMent serVices where No oThEr resources aRE aVailable. DiFfeRential ProteOmiCs, Inc., iS dEveLOping A neW protEomics TEchnolOgy for comPaRIng the PRotein cOMPoSitiOn of biological samPLeS. the technology

to clients in obtaining n eeded serv icesaside nt ifie d by  ASAP. In addi t ionto the planning functi on, a  l i mite d  a mount  of fun d sw i llbe  a llo ca t ed  to p urc hase ne cessary em erg en cy treatment se rvices whe reno other res our ces ar eava i lable . D iffer ential Proteo mics, Inc ., is dev e lopinga ne w pr oteomics technolo g yf or comparing t he pro te i nc o mpo sit ion of bio lo gical samples .  T h e tec h nology

to_clients in_obtaining needed services as_identified by_ASAP._In addition_to_the planning function,_a limited amount_of funds will be_allocated to purchase_necessary_emergency treatment services where no other resources are available. Differential Proteomics, Inc., is developing_a_new proteomics_technology_for_comparing the protein composition of_biological samples. The technology


the United States. Since smoking cessation is a major public health initiative, former smokers will increasingly account for a higher percentage of lung cancer cases. Therefore, two high-risk population groups exist for lung cancer and improved disease management can be beneficial to both current and former smokers. Additionally, the prognosis for lung cancer patients is very

the United States. Since smoking cessation is a major public health initiative, former smokers will increasingly report for a eminent percentage of lung cancer cases. consequently, two high - hazard population groups exist for lung cancer and improved disease management can be beneficial to both current and early stag party. Additionally, the prognosis for lung cancer patients is very

thf United States. Since smuking cessation is a mejor puglic heauth initiative, former smokerd qill uncreasingly account fur a highvr percenrage if lung caider cascf. Thsveforz, vwo high-risk pokulation grogps exist for nuvg cancer and improved disease manageient cam he beneficial jo bouh surrsnt and former smokers. Additionallg, the pgognosis for lung cancer patients is very

the United States. Since smoking cessation is public initiative, former will increasingly account lung cases. Therefore, two population groups exist lung cancer and improved disease management be beneficial to both current and former smokers. Additionally, the prognosis for lung patients is very

the United States. Since smokiNg cessatioN is a mAjoR puBlIc heAlth Initiative, formER smoKers will increasingly acCount FoR A higHEr PerceNtage of LUnG CAncEr CaSes. thEReFore, tWo hIgh-risk Population GroUpS exist for lunG CaNcer and impRovEd disease manAgeMent caN bE beNEficiAl tO both CurrenT And forMer smokerS. ADDitionALly, the pROGnOsis For lung cancer patiENtS Is very

the United States. Sincesmoking ce ssati onisamajo r pu blic health in i tiat ive, former smokers wi ll in cr e asin g ly  acco unt for ah i ghe rpe rce nt a ge  of l ung  cancer  cases. Th ere fo re, two high - ri sk populat ion  groups exis t f or lun gcan c er an d i mprov ed dis e ase ma nagementca n  be be n eficial t oboth  current and form e rs mokers. Additi onally ,t he p rog nos is for lun gcance r  patien t si s ver y

the_United States._Since smoking cessation is_a major_public_health initiative,_former_smokers will increasingly_account for a_higher percentage of lung_cancer cases. Therefore,_two_high-risk population groups exist for lung cancer and improved disease management can be beneficial_to_both current_and_former_smokers. Additionally, the prognosis for_lung cancer patients is very


7th leading cause of blindness in the U.S. The emmetropization mechanism has at least three main components: 1) the retina, which responds to the sign and amount of defocus (or other visual cues); 2) a signaling cascade that originates in the retina, travels through the retinal pigment epithelium (

7th leading cause of blindness in the U.S. The emmetropization mechanism has at least three chief component: 1) the retina, which responds to the sign and amount of defocus (or early visual cues); 2) a signaling shower that originate in the retina, travels through the retinal pigment epithelium (

7th leading cause of blindntss in the U.S. The emmetrmpizatjon mechxnism has at least three maii conponebts: 1) the retina, which fesponds no the sitn aid amount of defocus (or other blsual rues); 2) a signalikg cascade dhat originatev kn the retina, travels through the retynal pibmfnt epithelium (

7th leading cause of blindness in the emmetropization has at three main components: to sign and amount defocus (or other cues); 2) a signaling cascade that in the retina, travels through the retinal pigment epithelium (

7th leading cause of blindness In the U.S. The EmmetRopIzaTiOn meChanIsm has at least tHRee mAin components: 1) the retina, Which ReSPondS To The siGn and amOUnT OF deFoCuS (or OtHEr VisuaL cuEs); 2) a signAling cascaDe tHaT originates iN ThE retina, traVelS through the rEtiNal pigMeNt ePIthelIum (

7th leading cause of blin dness in t he U. S.The  e mmet ropi zation mechani s m ha s at least three maincompo ne n ts:1 )the r etina,w hi c h  re sp on dsto th e sig n a nd amou nt of defo cus  ( or other vis u al  cues); 2)  asignaling ca sca de tha tori g inate s i n the  retin a , trav els throu gh the re t inal pi g m en t ep ithelium (

7th_leading cause_of blindness in the_U.S. The_emmetropization_mechanism has_at_least three main_components: 1) the_retina, which responds to_the sign and_amount_of defocus (or other visual cues); 2) a signaling cascade that originates in the_retina,_travels through_the_retinal_pigment epithelium (


and substantial surgical therapy. The work of the IBD Genetics Consortium will enable us to identify important predisposing and disease modifying genes contributing to the pathogenesis of IBD which has the promise to: (1) identify persons at risk for disease, (2) predict disease course, (3) aid in selection of treatment, (

and substantial surgical therapy. The work of the IBD Genetics Consortium will enable us to identify important predisposing and disease change gene contributing to the pathogenesis of IBD which has the promise to: (1) name persons at hazard for disease, (2) predict disease course, (3) care in selection of treatment, (

anf substantial surgical tmerapy. The work of the MBD Genstics Covsortium will enable us to iventufy inportant predisposing xnd diseade modifting tenes contcjbuting to ths patkojenesis of IBD ehich has dhe promise to: (1) kdzntify persons at risk for disease, (2) [redict dlsease course, (3) aid yn sslection of treatment, (

and substantial surgical therapy. The work of Genetics will enable to identify important contributing the pathogenesis of which has the to: (1) identify persons at risk disease, (2) predict disease course, (3) aid in selection of treatment, (

and substantial surgical theRapy. The worK of thE IBd GeNeTics consOrtium will enabLE us tO identify important predIsposInG And dISeAse moDifying GEnES ConTrIbUtiNg TO tHe patHogEnesis oF IBD which hAs tHe Promise to: (1) ideNTiFy persons aT riSk for disease, (2) PreDict diSeAse COurse, (3) Aid In selEction OF treatMent, (

and substantial surgicaltherapy. T he wo rkofth e IB D Ge netics Consort i um w ill enable us to ident ify i mp o rtan t  p redis posinga nd d ise as emod if y in g gen escontrib uting to t hepa thogenesis o f  I BD which h asthe promiseto:  (1) i de nti f y per son s atrisk f o r dise ase, (2)pr e dict d i sease c o u rs e, ( 3) aid in selecti o no f treatment, (

and_substantial surgical_therapy. The work of_the IBD_Genetics_Consortium will_enable_us to identify_important predisposing and_disease modifying genes contributing_to the pathogenesis_of_IBD which has the promise to: (1) identify persons at risk for disease, (2)_predict_disease course,_(3)_aid_in selection of treatment, (


imaging of functional conditions of extremities soft tissue. There is an important clinical need to develop an effective, rapid and cost-effective method of non-invasive assessing or imaging of extremities soft tissue viability. The overall goal of the project is to validate the feasibility of a microwave tomographic (MWT) imaging technology for assessment of

imaging of functional conditions of extremities piano tissue. There be an important clinical need to develop an effective, rapid and price - effective method of non - invasive assessing or imagination of extremities soft tissue viability. The overall goal of the undertaking is to validate the feasibility of a microwave tomographic (MWT) image technology for judgment of

imwging of functional condltions of extremnries smft tiasue. Thefe is an important clinical ieed to dtnelop an effective, raoid and clst-effecrive nethod of ikn-invaslre asacssiny ir imaging of gxtremities voft tissue vidbklnty. The overall goal of the project ys to vslldate the feasybilptr of a microwave tomographic (MWT) imagihg techiology for assexsment of

imaging of functional conditions of extremities soft is important clinical to develop an of assessing or imaging extremities soft tissue The overall goal of the project to validate the feasibility of a microwave tomographic (MWT) imaging technology for assessment

imaging of functional conditIons of extrEmitiEs sOft TiSsue. therE is an important CLiniCal need to develop an effeCtive, RaPId anD CoSt-effEctive mEThOD Of nOn-InVasIvE AsSessiNg oR imaginG of extremiTieS sOft tissue viaBIlIty. The overAll Goal of the proJecT is to vAlIdaTE the fEasIbiliTy of a mICrowavE tomograpHiC (mWT) imaGIng techNOLoGy foR assessment of

imaging of functional con ditions of  extr emi tie ssoft  tis sue. There isa n im portant clinical needto de ve l op a n  e ffect ive, ra p id a ndco st -ef fe c ti ve me tho d of no n-invasive  as se ssing or ima g in g of extre mit ies soft tis sue  viabi li ty. The o ver all g oal of the pr oject isto valida t e the f e a si bili ty of a microwave to m ographic (MWT)  imagi ng te c h nol ogy  for asses sm ent o f

imaging_of functional_conditions of extremities soft_tissue. There_is_an important_clinical_need to develop_an effective, rapid_and cost-effective method of_non-invasive assessing or_imaging_of extremities soft tissue viability. The overall goal of the project is to validate_the_feasibility of_a_microwave_tomographic (MWT) imaging technology for_assessment of


to characterize the haplotype specific nature of suppression of EAE using F1 restricted T cell lines and clones. These experiments will define the genetic and antigenetic specifity of inhibition of disease using auto antigens and synthetic antigens whos immune response is under IR gene control. At present, the mechanism by which IR genes confer susceptibility

to characterize the haplotype specific nature of suppression of EAE using F1 restricted metric ton cellular telephone lines and clones. These experiment will specify the genetic and antigenetic specifity of inhibition of disease use car antigens and synthetic antigens who s immune response is under IR gene control. At present, the mechanism by which IR gene confer susceptibility

to characterize the haplotnpe specific natorw of snppressjon of EXE using F1 restricted T cell lunes qnd clones. These experkments wipl definw tht genetic and antmfenetic specirlty oy mnhibition of dlsease usinc auto antigenv xnb synthetic antigens whos immune res[onse ix knder IR gene sontgoj. At irtsent, the mechanism by which IR gsnes coifer susceptibikity

to characterize the haplotype specific nature of EAE F1 restricted cell lines and the and antigenetic specifity inhibition of disease auto antigens and synthetic antigens whos response is under IR gene control. At present, the mechanism by which IR confer susceptibility

to characterize the haplotypE specific nAture Of sUppReSsioN of EaE using F1 restriCTed T Cell lines and clones. ThesE expeRiMEnts WIlL defiNe the geNEtIC And AnTiGenEtIC sPecifIty Of inhibItion of disEasE uSing auto antiGEnS and syntheTic Antigens whos ImmUne resPoNse IS undeR IR Gene cOntrol. aT preseNt, the mechAnISm by whICh IR genES CoNfer Susceptibility

to characterize the haplo type speci fic n atu reof  sup pres sion of EAE us i ng F 1 restricted T cell li nes a nd clon e s.  Thes e exper i me n t s w il ldef in e  t he ge net ic andantigeneti c s pe cifity of in h ib ition of d ise ase using au toantige ns  an d  synt het ic an tigens whos i mmune res po n se isu nder IR g en e co ntrol. At present ,  t h e mechanism by  which  I R  g e n escon fer suscep ti bilit y

to_characterize the_haplotype specific nature of_suppression of_EAE_using F1_restricted_T cell lines_and clones. These_experiments will define the_genetic and antigenetic_specifity_of inhibition of disease using auto antigens and synthetic antigens whos immune response is_under_IR gene_control._At_present, the mechanism by which_IR genes confer susceptibility


isolated hepatic metastases. These tumors often cause debilitating symptoms due to excessive hormonal secretion. Besides surgery, there are limited curative and palliative treatments available to patients with metastatic NE tumors, emphasizing the need for development of other forms of therapy. In this proposal, we will present data illustrating that GSK3B inhibition may be a

isolated hepatic metastases. These tumors often induce enfeeble symptom due to excessive hormonal secretion. Besides surgery, there be circumscribed curative and palliative treatments available to patients with metastatic NE tumor, underscore the need for growth of other forms of therapy. In this marriage proposal, we will present data illustrating that GSK3B inhibition may be a

isllated hepatic metastaser. These tumors often ceuse degilitativg symptoms due to excessive hirmonql secretion. Besides sjrgery, thvre are lumittd curative and pemliativc trezbmentv available to katients witv metastatic NA gulors, emphasizing the need for develjpment pf other forms os thtra[y. Ih this proposal, we will present dafa illuvtrating that GSK3B inhibition may be a

isolated hepatic metastases. These tumors often cause due excessive hormonal Besides surgery, there treatments to patients with NE tumors, emphasizing need for development of other forms therapy. In this proposal, we will present data illustrating that GSK3B inhibition may a

isolated hepatic metastases. these tumorS ofteN caUse DeBiliTatiNg symptoms due tO ExceSsive hormonal secretion. besidEs SUrgeRY, tHere aRe limitED cURAtiVe AnD paLlIAtIve trEatMents avAilable to pAtiEnTs with metastATiC NE tumors, eMphAsizing the neEd fOr deveLoPmeNT of otHer Forms Of therAPy. In thIs proposaL, wE Will prESent datA ILlUstrAting that GSK3B inhiBItIOn may be a

isolated hepatic metastas es. Thesetumor s o fte ncaus e de bilitating sym p toms  due to excessive horm onalse c reti o n.  Besi des sur g er y ,  th er eare  l i mi ted c ura tive an d palliati vetr eatments ava i la ble to pat ien ts with meta sta tic NE  t umo r s, em pha sizin g then eed fo r develop me n t of o t her for m s  o f th erapy. In this pr o po s al, we will pr esentda t ai l lus tra ting thatGS K3B i n hibitio n  m a y bea

isolated_hepatic metastases._These tumors often cause_debilitating symptoms_due_to excessive_hormonal_secretion. Besides surgery,_there are limited_curative and palliative treatments_available to patients_with_metastatic NE tumors, emphasizing the need for development of other forms of therapy. In_this_proposal, we_will_present_data illustrating that GSK3B inhibition_may be a


conversion of HDL subspecies; 4) CETP will be studied using surface balance techniques to elucidate the mechanisms of the reaction and the role of apo A-IV in lipid exchange phenomena. The investigation of the structure and function of the plasma apolipoproteins has led to major advances in the diagnosis, treatment, and prevention

conversion of HDL subspecies; 4) CETP will be studied using surface balance technique to clarify the mechanisms of the reaction and the role of apo A - IV in lipid rally phenomena. The investigation of the social organization and function of the plasma apolipoproteins has led to major advances in the diagnosis, discussion, and prevention

congersion of HDL subspecier; 4) CETP will be studiev using surface balance techniques to elucivate the nechanisms of the reacgion and nhe role if ako A-IV in lipid eedhange ikenomska. Thz mnvestigation on the strucdure and functhov lf the plasma apolipoproteins has lqd to msjlr advances in the qiaghosis, treatment, and prevention

conversion of HDL subspecies; 4) CETP will using balance techniques elucidate the mechanisms role apo A-IV in exchange phenomena. The of the structure and function of plasma apolipoproteins has led to major advances in the diagnosis, treatment, and prevention

conversion of HDL subspecies; 4) cETP will be StudiEd uSinG sUrfaCe baLance techniqueS To elUcidate the mechanisms of The reAcTIon aND tHe rolE of apo A-iv iN LIpiD eXcHanGe PHeNomenA. ThE investIgation of tHe sTrUcture and funCTiOn of the plaSma ApolipoproteIns Has led To MajOR advaNceS in thE diagnOSis, treAtment, and PrEVentioN

conversion of HDL subspeci es; 4) CET P wil l b e s tu died  usi ng surface bal a ncetechniques to elucidat e the  m e chan i sm s ofthe rea c ti o n  an dth e r ol e  o f apo  A- IV in l ipid excha nge  p henomena. Th e  i nvestigati onof the struc tur e andfu nct i on of  th e pla sma ap o lipopr oteins ha sl ed tom ajor ad v a nc es i n the diagnosis,t re a tment, and pre ventio n

conversion of_HDL subspecies;_4) CETP will be_studied using_surface_balance techniques_to_elucidate the mechanisms_of the reaction_and the role of_apo A-IV in_lipid_exchange phenomena. The investigation of the structure and function of the plasma apolipoproteins has_led_to major_advances_in_the diagnosis, treatment, and prevention


, and saves significant cost. The result is improved patient outcomes and improved lab operating performance. Phase IIB aims address application to clinical human specimens along with development of instruments and media appropriate for commercial use. The objectives of this proposal reflect the major goals required to achieve commercial entry of the SpecID smart culture system into commercial,

, and saves significant cost. The result is better patient result and improved lab operating performance. Phase IIB aims savoir-faire application to clinical human specimens along with development of instrumental role and media appropriate for commercial use. The aim of this proposal reflect the major goal required to achieve commercial entry of the SpecID bright acculturation system into commercial,

, anf saves significant cost. The result is nnprovev patieht outcooes and improved lab operatiig pwrfornance. Phase IIB aims aadress apilication to rlinical human s'scimens along aith vevelopment of lnstruments and media appsoornate for commercial use. The objectivqs of tnid proposal refject ehe jajor goals required to achieve cojmercian entry of thr SpecID smart culture syshem lnto commercial,

, and saves significant cost. The result patient and improved operating performance. Phase clinical specimens along with of instruments and appropriate for commercial use. The objectives this proposal reflect the major goals required to achieve commercial entry of the smart culture system into commercial,

, and saves significant cost. ThE result is iMprovEd pAtiEnT outComeS and improved laB OperAting performance. Phase IiB aimS aDDresS ApPlicaTion to cLInICAl hUmAn SpeCiMEnS alonG wiTh develOpment of inStrUmEnts and media APpRopriate foR coMmercial use. THe oBjectiVeS of THis prOpoSal reFlect tHE major Goals requIrED to achIEve commERCiAl enTry of the SpecID smaRT cULture system intO commeRcIAl,

, and saves significant co st. The re sultisimp ro vedpati ent outcomes a n d im proved lab operating p erfor ma n ce.P ha se II B aimsa dd r e ssap pl ica ti o nto cl ini cal hum an specime nsal ong with dev e lo pment of i nst ruments andmed ia app ro pri a te fo r c ommer cial u s e. The  objectiv es of thi s  propos a l  r efle ct the major goal s  r e quired to achi eve co mm e rc i a l e ntr y of the S pe cID s m art cul t ur e s yst e m into commer cial,

, and_saves significant_cost. The result is_improved patient_outcomes_and improved_lab_operating performance. Phase_IIB aims address_application to clinical human_specimens along with_development_of instruments and media appropriate for commercial use. The objectives of this proposal reflect_the_major goals_required_to_achieve commercial entry of the_SpecID smart culture system into_commercial,


. The study will also include monthly support forums. Statistical analysis of the instrumentation responses and interpretive analysis of interview texts will be used. Story Sharing promises to offer a new caring intervention for NAs as they develop empathic and mutual care relationships that recognize the uniqueness and dignity of each resident. Juvenile and adult

. The study will also include monthly support forum. Statistical psychoanalysis of the instrumentation responses and interpretative analysis of consultation texts will be used. report Sharing promise to offer a fresh caring intervention for NAs as they build up empathic and mutual care relationship that greet the uniqueness and dignity of each house physician. Juvenile and adult

. Thf study will also includt monthly support forums. Statiatical avalysis of the instrumentatiln respinses and interpretive analysis of inteeviex texts will be naed. Stovv Shadlng pxonises to offer a new carhng interventimn flr NAs as they develop empathic and mutual cwre relationshyps uhae redognize the uniqueness and dignity of eaci resident. Juvemile and adult

. The study will also include monthly Statistical of the responses and interpretive be Story Sharing promises offer a new intervention for NAs as they develop and mutual care relationships that recognize the uniqueness and dignity of each resident. and adult

. The study will also include moNthly suppoRt forUms. staTiSticAl anAlysis of the insTRumeNtation responses and intErpreTiVE anaLYsIs of iNtervieW TeXTS wiLl Be UseD. STOrY SharIng PromiseS to offer a nEw cArIng interventIOn For NAs as thEy dEvelop empathIc aNd mutuAl CarE RelatIonShips That reCOgnize The uniqueNeSS and diGNity of eACH rEsidEnt. Juvenile and aduLT

. The study will also incl ude monthl y sup por t f or ums.  Sta tistical analy s is o f the instrumentationrespo ns e s an d  i nterp retivea na l y sis  o fint er v ie w tex tswill be  used. Sto rySh aring promis e sto offer a  ne w caring int erv ention  f orN As as  th ey de velope mpathi c and mut ua l  carer elation s h ip s th at recognize theu ni q ueness and dig nity o fe ac h res ide nt. Juveni le  anda dult

. The_study will_also include monthly support_forums. Statistical_analysis_of the_instrumentation_responses and interpretive_analysis of interview_texts will be used._Story Sharing promises_to_offer a new caring intervention for NAs as they develop empathic and mutual care_relationships_that recognize_the_uniqueness_and dignity of each resident._Juvenile and adult


Our data also reveal that cocaine down regulates two anti-HIV cellular microRNAs (miRNAs), miR-125b and miR-328 in primary CD4+ T cells. Since these miRNAs target the 3'UTR of HIV-1 mRNA, we believe cocaine may target post-transcription steps of HIV-1 replication

Our data also reveal that cocaine down regulates two anti - HIV cellular microRNAs (miRNAs), miR-125b and miR-328 in basal CD4 + metric ton cells. Since these miRNAs target the 3'UTR of HIV-1 mRNA, we believe cocaine may target post - transcription steps of HIV-1 rejoinder

Oug data also reveal that gocaine down regolqtes txo anti-GIV celljlar microRNAs (miRNAs), miR-125b aid muR-328 in primary CD4+ T cells. Sivce these miRNAs rargtt the 3'UTR of HIV-1 mRNA, we beliebc cocciie may target ppst-transcrhption steps ox FIR-1 replication

Our data also reveal that cocaine down anti-HIV microRNAs (miRNAs), and miR-328 in these target the 3'UTR HIV-1 mRNA, we cocaine may target post-transcription steps of replication

Our data also reveal that cocaIne down regUlateS twO anTi-hIV cElluLar microRNAs (mirnAs), mIR-125b and miR-328 in primary CD4+ T cElls. SInCE theSE mIRNAs Target tHE 3'Utr Of HiV-1 MRnA, wE bELiEve coCaiNe may taRget post-trAnsCrIption steps oF hIv-1 replicatiOn

Our data also reveal that  cocaine d own r egu lat es  two  ant i-HIV cellular micr oRNAs (miRNAs), miR-12 5b an dm iR-3 2 8in pr imary C D 4+ T  ce ll s.  Si nc e  t hesemiR NAs tar get the 3' UTR  o f HIV-1 mRNA ,  w e believecoc aine may tar get  post- tr ans c ripti onsteps  of HI V -1 rep lication

Our_data also_reveal that cocaine down_regulates two_anti-HIV_cellular microRNAs_(miRNAs),_miR-125b and miR-328_in primary CD4+_T cells. Since these_miRNAs target the_3'UTR_of HIV-1 mRNA, we believe cocaine may target post-transcription steps of HIV-1 replication


near the 2q break will determine if a gene (s) is altered by this familial RCC-associated chromosome translocation. Deletion of the short arm of chromosome 5 was the sole structural alteration identified in a case of testicular lymphoma and it may harbor a tumor suppressor gene implicated in this malignancy. In the past year two studies

near the 2q break will determine if a gene (s) is altered by this familial RCC - associated chromosome translocation. omission of the light arm of chromosome 5 was the sole geomorphologic revision identified in a case of testicular lymphoma and it may harbor a tumor suppressor gene entail in this malignity. In the past year two studies

newr the 2q break will detevmine if a gene (s) is alvered bg this fxmilial RCC-associated chromodone trqnslocation. Deletion ow the shogt arm of chrinosome 5 was the sole strhgturan alteration idgntified in d case of testhcjlcr lymphoma and it may harbor a tumow supprrsdor gene implisatec in fhis malignancy. In the past year tso studpes

near the 2q break will determine if (s) altered by familial RCC-associated chromosome arm chromosome 5 was sole structural alteration in a case of testicular lymphoma it may harbor a tumor suppressor gene implicated in this malignancy. In the year two studies

near the 2q break will determinE if a gene (s) iS alteRed By tHiS famIliaL RCC-associated CHromOsome translocation. DeleTion oF tHE shoRT aRm of cHromosoME 5 wAS The SoLe StrUcTUrAl altEraTion ideNtified in a CasE oF testicular lYMpHoma and it mAy hArbor a tumor sUppRessor GeNe iMPlicaTed In thiS maligNAncy. In The past yeAr TWo studIEs

near the 2q break will de termine if  a ge ne(s)  i s al tere d by this fami l ialRCC-associated chromos ome t ra n sloc a ti on. D eletion of t hesh or t a rm of  chro mos ome 5 w as the sol e s tr uctural alte r at ion identi fie d in a caseoftestic ul arl ympho maand i t mayh arbora tumor s up p ressor gene im p l ic ated  in this malignan c y. In the past ye ar two  s t ud i e s

near_the 2q_break will determine if_a gene_(s)_is altered_by_this familial RCC-associated_chromosome translocation. Deletion_of the short arm_of chromosome 5_was_the sole structural alteration identified in a case of testicular lymphoma and it may_harbor_a tumor_suppressor_gene_implicated in this malignancy. In_the past year two studies


that novel CAP-DTG combination nano-microbicide reduce cytotoxicity of DTG to cells. In vitro HIV prophylaxis using HIV indicator TZM-bl cells show that CAP-DTG combination nano-microbicide offers significantly higher protection from HIV-1 infection as compared to DTG solution and CAP nanoparticles indicating

that novel CAP - DTG combination nano - microbicide reduce cytotoxicity of DTG to cells. In vitro HIV prophylaxis using HIV index TZM - bl cell show that CAP - DTG combination nano - microbicide offers importantly higher security from HIV-1 infection as compare to DTG solution and CAP nanoparticles indicating

thwt novel CAP-DTG combinatlon nano-microbicnee rednce cytktoxicith of DTG to cells. In vitro HMV peophyoaxis using HIV indicagor TZM-bl cells syow uhat CAP-DTG combiiztion nano-micdlbicndx offers signiflcantly higver protection ffol HIV-1 infection as compared to DTG folutiom wnd CAP nanopatticlts yndidating

that novel CAP-DTG combination nano-microbicide reduce cytotoxicity to In vitro prophylaxis using HIV CAP-DTG nano-microbicide offers significantly protection from HIV-1 as compared to DTG solution and nanoparticles indicating

that novel CAP-DTG combinatioN nano-microBicidE reDucE cYtotOxicIty of DTG to cellS. in viTro HIV prophylaxis using hIV inDiCAtor tzM-Bl celLs show tHAt cap-DTg cOmBinAtIOn Nano-mIcrObicide Offers signIfiCaNtly higher prOTeCtion from HiV-1 iNfection as coMpaRed to DtG SolUTion aNd CaP nanOpartiCLes indIcating

that novel CAP-DTG combin ation nano -micr obi cid eredu ce c ytotoxicity of DTGto cells. In vitro HIV  prop hy l axis us ing H IV indi c at o r  TZ M- bl  ce ll s  s how t hat  CAP-DT G combinat ion  n ano-microbic i de  offers si gni ficantly hig her  prote ct ion fromHIV -1 in fectio n  as co mpared to  D T G solu t ion and C AP  nan oparticles indica t in g

that_novel CAP-DTG_combination nano-microbicide reduce cytotoxicity_of DTG_to_cells. In_vitro_HIV prophylaxis using_HIV indicator TZM-bl_cells show that CAP-DTG_combination nano-microbicide offers_significantly_higher protection from HIV-1 infection as compared to DTG solution and CAP nanoparticles indicating


PI:Uc), we are finding that drivers with PD perform worse than elderly drivers without neurological disease in driving tasks conducted on-road in an instrumented vehicle (IV) and on experimental driving scenarios presented on a high-fidelity driving simulator. Even drivers with early PD of mild severity have impairments on cognitive and visual

PI: Uc), we are finding that drivers with PD perform worse than elderly driver without neurological disease in drive tasks conducted on - road in an instrumented vehicle (IV) and on experimental drive scenarios presented on a high - fidelity drive simulator. Even drivers with early PD of meek severity have impairment on cognitive and visual

PI:Kc), we are finding that dvivers with PD pgrdorm wmrse tgan eldefly drivers without neurologmcal diseqse in driving tasks cunducted ln-road ib an unstrumentxs vehicle (IV) zkd on xxperimental drlving scenasios presented ov c high-fidelity driving simulator. Eveg drivets with early PD of kyld avvtrity have impairments on cognitibe and nisual

PI:Uc), we are finding that drivers with worse elderly drivers neurological disease in an vehicle (IV) and experimental driving scenarios on a high-fidelity driving simulator. Even with early PD of mild severity have impairments on cognitive and visual

PI:Uc), we are finding that driveRs with PD peRform WorSe tHaN eldErly Drivers without NEuroLogical disease in drivinG taskS cONducTEd On-roaD in an inSTrUMEntEd VeHicLe (iv) aNd on eXpeRimentaL driving scEnaRiOs presented oN A hIgh-fidelitY drIving simulatOr. EVen driVeRs wITh earLy Pd of miLd seveRIty havE impairmeNtS On cognITive and VISuAl

PI:Uc), we are finding th at drivers  with  PD  pe rf ormwors e than elderly driv ers without neurologic al di se a se i n  d rivin g tasks co n d uct ed  o n-r oa d  i n anins trument ed vehicle  (I V)  and on expe r im ental driv ing  scenarios p res entedon  ah igh-f ide litydrivin g  simul ator. Eve nd rivers with ea r l yPD o f mild severity h a ve impairments on  cogni ti v ea n d v isu al

PI:Uc),_we are_finding that drivers with_PD perform_worse_than elderly_drivers_without neurological disease_in driving tasks_conducted on-road in an_instrumented vehicle (IV)_and_on experimental driving scenarios presented on a high-fidelity driving simulator. Even drivers with early_PD_of mild_severity_have_impairments on cognitive and visual


, Differential Capture Proteomics (DCP), is designed to circumvent serious limitations in the current capabilities of current proteomics technology, notably DCP can identify the protein differences between two body fluid or tissue samples and simultaneously generate an affinity reagent for each identified difference protein. The DCP approach utilizes phage display libraries of peptides from

, Differential Capture Proteomics (DCP), is designed to circumvent serious limitations in the current capability of current proteomics engineering, notably DCP can identify the protein differences between two soundbox fluid or tissue sample distribution and simultaneously generate an affinity reagent for each identified deviation protein. The DCP approach utilizes bacteriophage display library of peptides from

, Divferential Capture Proteumics (DCP), is designed vo circhmvent sdrious limitations in the cucrenr capqbilities of current pfoteomics technoligy, iotably DCP can msentify the pdlteiu vifferences beteeen two bmdy fluid or thsruz samples and simultaneously generatq an afgijity reagent fjr essh isvnuified difference protein. The DCP approabh utilizes phage display libraries of peptldes from

, Differential Capture Proteomics (DCP), is designed serious in the capabilities of current identify protein differences between body fluid or samples and simultaneously generate an affinity for each identified difference protein. The DCP approach utilizes phage display libraries of from

, Differential Capture ProteoMics (DCP), is dEsignEd tO ciRcUmveNt seRious limitatioNS in tHe current capabilities oF currEnT ProtEOmIcs teChnologY, NoTABly dCp cAn iDeNTiFy the ProTein difFerences beTweEn Two body fluid OR tIssue samplEs aNd simultaneoUslY generAtE an AFfiniTy rEagenT for eaCH identIfied diffErENce proTEin. The Dcp ApProaCh utilizes phage diSPlAY libraries of pePtides FrOM

, Differential Capture Pro teomics (D CP),isdes ig nedto c ircumvent seri o us l imitations in the curr ent c ap a bili t ie s ofcurrent pr o t eom ic stec hn o lo gy, n ota bly DCP  can ident ify  t he protein d i ff erences be twe en two bodyflu id orti ssu e  samp les  andsimult a neousl y generat ea n affi n ity rea g e nt  for  each identifiedd if f erence protein . TheDC P  a p p roa chutilizes p ha ge di s play li b ra r i e s o f  peptides fro m

, Differential_Capture Proteomics_(DCP), is designed to_circumvent serious_limitations_in the_current_capabilities of current_proteomics technology, notably_DCP can identify the_protein differences between_two_body fluid or tissue samples and simultaneously generate an affinity reagent for each identified_difference_protein. The_DCP_approach_utilizes phage display libraries of_peptides from


using an in vivo model of Abeta-induced neurotoxicity. Results should allow us to determine if genotype affects post-trauma pathology and will provide information on how ApoE4 produces its effects at the molecular level. The effect of genetic makeup on the extent of the inflammatory activity in the brain will be an

using an in vivo model of Abeta - induced neurotoxicity. Results should leave us to settle if genotype affects post - trauma pathology and will provide information on how ApoE4 produce its effects at the molecular level. The impression of genic makeup on the extent of the incendiary natural process in the brain will be an

uslng an in vivo model of Xbeta-induced neoritoxicmty. Reshlts shojld allow us to determine if gwnotykv affects post-trauma oathology and wilo pricide information ok how WpoE4 'roduces its efnects at tha molecular leeeu. Che effect of genetic makeup on the qxtent pf the inflammatjry sstivjny in the brain will be an

using an in vivo model of Abeta-induced should us to if genotype affects information how ApoE4 produces effects at the level. The effect of genetic makeup the extent of the inflammatory activity in the brain will be an

using an in vivo model of Abeta-Induced neuRotoxIciTy. REsUlts ShouLd allow us to detERminE if genotype affects post-TraumA pATholOGy And wiLl proviDE iNFOrmAtIoN on HoW apOE4 proDucEs its efFects at the MolEcUlar level. The EFfEct of genetIc mAkeup on the exTenT of the InFlaMMatorY acTivitY in the BRain wiLl be an

using an in vivo model of  Abeta-ind ucedneu rot ox icit y. R esults shoulda llow  us to determine if ge notyp ea ffec t spost- traumap at h o log yan d w il l  p rovid e i nformat ion on how  Ap oE 4 produces i t seffects at  th e molecularlev el. Th eeff e ct of  ge netic  makeu p  on th e extentof the in f lammato r y  a ctiv ity in the brainw il l  be an

using_an in_vivo model of Abeta-induced_neurotoxicity. Results_should_allow us_to_determine if genotype_affects post-trauma pathology_and will provide information_on how ApoE4_produces_its effects at the molecular level. The effect of genetic makeup on the extent_of_the inflammatory_activity_in_the brain will be an


epitopes of membrane- bound receptors. Many of the receptors and epitopes that we will target are difficult or, in some cases, impossible to target using traditional methods, including activated receptor conformations and intracellular structures. Lipoparticles present a unique technology for the development of important new classes of antibodies and vaccine candidates. This proposal focuses

epitopes of membrane- bound receptors. Many of the receptors and antigenic determinant that we will target are unmanageable or, in some case, impossible to target use traditional method acting, including activated sense organ conformations and intracellular structures. Lipoparticles present a alone technology for the development of authoritative new classes of antibody and vaccine candidates. This proposal concenter

epltopes of membrane- bound receptors. Many of the recepfors and epitopes that we will targev arw difdicult or, in some caser, impossihle to tqrgeu using traditionem methods, incmmding ectivated recepjor conformadions and intrdcdlpular structures. Lipoparticles presqnt a umieue technology for ehe svvtlopment of important new classes of antpbodies and vaccime candidates. This proposap fofuses

epitopes of membrane- bound receptors. Many of and that we target are difficult to using traditional methods, activated receptor conformations intracellular structures. Lipoparticles present a unique for the development of important new classes of antibodies and vaccine candidates. This focuses

epitopes of membrane- bound reCeptors. ManY of thE reCepToRs anD epiTopes that we wilL TargEt are difficult or, in some Cases, ImPOssiBLe To tarGet usinG TrADItiOnAl MetHoDS, iNcludIng ActivatEd receptor ConFoRmations and iNTrAcellular sTruCtures. LipopaRtiCles prEsEnt A UniquE teChnolOgy for THe deveLopment of ImPOrtant NEw classES Of AntiBodies and vaccine cANdIDates. This propoSal focUsES

epitopes of membrane- bou nd recepto rs. M any  of  t he r ecep tors and epito p es t hat we will target are  diff ic u lt o r ,in so me case s ,i m pos si bl e t ot ar get u sin g tradi tional met hod s,  including a c ti vated rece pto r conformati ons  and i nt rac e llula r s truct ures.L ipopar ticles pr es e nt a u n ique te c h no logy  for the developm e nt of important n ew cla ss e so f  an tib odies andva ccine candida t es . T his proposal focu ses

epitopes_of membrane-_bound receptors. Many of_the receptors_and_epitopes that_we_will target are_difficult or, in_some cases, impossible to_target using traditional_methods,_including activated receptor conformations and intracellular structures. Lipoparticles present a unique technology for the_development_of important_new_classes_of antibodies and vaccine candidates._This proposal focuses


in the construction of our test statistics (Aim 6). This proposal is a continuation of our ongoing studies of lipid metabolism, focusing on the action of a lipid mediator: 1-0-alkyl-2- acetyl-glycerophosphocholine (platelet-activating factor, PAF). We have found, in

in the construction of our test statistics (Aim 6). This proposal is a good continuation of our ongoing cogitation of lipid metabolism, concenter on the natural process of a lipid mediator: 1 - 0 - alkyl-2- acetyl - glycerophosphocholine (platelet - activating factor, PAF). We have establish, in

in the construction of our test statistics (Aim 6). Vhis prkposal ir a continuation of our ongomng wtuditf of lipid metabolksm, focuspng on thw acuion of a lipid mxsiator: 1-0-alkyl-2- zgetyl-ylbcerophosphochokine (platenet-activating xaztlr, PAF). We have found, in

in the construction of our test statistics This is a of our ongoing on action of a mediator: 1-0-alkyl-2- acetyl-glycerophosphocholine factor, PAF). We have found, in

in the construction of our tesT statisticS (Aim 6). THis ProPoSal iS a coNtinuation of ouR OngoIng studies of lipid metabOlism, FoCUsinG On The acTion of a LIpID MedIaToR: 1-0-alKyL-2- AcEtyl-gLycErophosPhocholine (PlaTeLet-activatinG FaCtor, PAF). We hAve Found, in

in the construction of ou r test sta tisti cs(Ai m6).This  proposal is a cont inuation of our ongoin g stu di e s of li pid m etaboli s m, f ocu si ng  on  t h eactio n o f a lip id mediato r:1- 0-alkyl-2- a c et yl-glycero pho sphocholine(pl atelet -a cti v ating  fa ctor,  PAF). We hav e found,in

in_the construction_of our test statistics_(Aim 6)._This_proposal is_a_continuation of our_ongoing studies of_lipid metabolism, focusing on_the action of_a_lipid mediator: 1-0-alkyl-2- acetyl-glycerophosphocholine (platelet-activating factor, PAF). We have found, in


, and the excitatory neurotransmitter glutamate. The quantitative neuroanatomic analyses rely on computer-assisted microscopy and involve studies of cell distribution as well as morphologic and intracellular characteristics of individual neurons. An important underlying assumption in this proposal is that the selective vulnerability in Alzheimer's Disease is related to the molecular and anatomic heterogeneity of

, and the excitatory neurotransmitter glutamate. The quantitative neuroanatomic analyses rely on computer - assisted microscopy and imply cogitation of cell distribution equally well as morphologic and intracellular characteristic of individual neurons. An important implicit in assumption in this proposal is that the selective vulnerability in Alzheimer's Disease is associate to the molecular and anatomic heterogeneity of

, anf the excitatory neurotrxnsmitter glutamate. Thx quantjtative veuroanatomic analyses rely ln compyter-assisted microscoph and invllve stueies if cell distribution as scll av morphologic akd intracelnular charactesirtncs of individual neurons. An importagt undetljing assumptiog in ehis iriposal is that the selective bulnerauility in Alzheomer's Disease is related tl thf molecular and anwtomic hetetkgegwity of

, and the excitatory neurotransmitter glutamate. The analyses on computer-assisted and involve studies as and intracellular characteristics individual neurons. An underlying assumption in this proposal is the selective vulnerability in Alzheimer's Disease is related to the molecular and anatomic of

, and the excitatory neurotranSmitter gluTamatE. ThE quAnTitaTive Neuroanatomic aNAlysEs rely on computer-assistEd micRoSCopy ANd InvolVe studiES oF CEll DiStRibUtIOn As welL as MorpholOgic and intRacElLular charactERiStics of indIviDual neurons. AN imPortanT uNdeRLying AssUmptiOn in thIS propoSal is that ThE SelectIVe vulneRABiLity In Alzheimer's DiseaSE iS Related to the moLeculaR aND aNATomIc hEterogeneiTy Of

, and the excitatory neuro transmitte r glu tam ate .Thequan titative neuro a nato mic analyses rely on c omput er - assi s te d mic roscopy an d inv ol ve  st ud i es  of c ell  distri bution aswel las morpholog i cand intrac ell ular charact eri sticsof  in d ividu alneuro ns. An import ant under ly i ng ass u mptioni n  t hisproposal is thatt he selective vuln erabil it y  i n Alz hei mer's Dise as e isr elatedt ot h e  mo l ecular and an atomic hete r oge neityof

, and_the excitatory_neurotransmitter glutamate. The quantitative_neuroanatomic analyses_rely_on computer-assisted_microscopy_and involve studies_of cell distribution_as well as morphologic_and intracellular characteristics_of_individual neurons. An important underlying assumption in this proposal is that the selective vulnerability_in_Alzheimer's Disease_is_related_to the molecular and anatomic_heterogeneity of


involved with the practice of quantitative sciences in cancer and are typically in residence at the DFCI. All trainees are required to actively participate in the a working group seminar series on quantitative issues in cancer research, which serves as a primary forum at Harvard to discuss current issues and challenges on this topic, as well as in several

involved with the practice of quantitative sciences in cancer and are typically in residence at the DFCI. All trainee are command to actively participate in the a working group seminar serial on quantitative issues in cancer inquiry, which serves as a primary forum at Harvard to hash out current exit and challenges on this topic, as well as in several

ingolved with the practice of quantitativg wciencxs in czncer ana are typically in residence ar the DFCI. All trainees are required to acticely participatx in the a worilng gxonp seminar serigs on quantidative issues hn ccncer research, which serves as a priiary fotul at Harvard tj dixsuss buvrent issues and challenges on tgis toppc, as well as in xeveral

involved with the practice of quantitative sciences and typically in at the DFCI. actively in the a group seminar series quantitative issues in cancer research, which as a primary forum at Harvard to discuss current issues and challenges on topic, as well as in several

involved with the practice of QuantitatiVe sciEncEs iN cAnceR and Are typically in REsidEnce at the DFCI. All traineEs are ReQUireD To ActivEly partICiPATe iN tHe A woRkINg Group SemInar serIes on quantItaTiVe issues in caNCeR research, wHicH serves as a prImaRy foruM aT HaRVard tO diScuss CurrenT Issues And challeNgES on thiS Topic, as WELl As in Several

involved with the practic e of quant itati vesci en cesin c ancer and aret ypic ally in residence at t he DF CI .  All tr ainee s are r e qu i r edto  a cti ve l yparti cip ate inthe a work ing  g roup seminar se ries on qu ant itative issu esin can ce r r e searc h,which  serve s  as aprimary f or u m at H a rvard t o di scus s current issuesa nd challenges onthis t op i c, a s w ell  as in sev er al

involved_with the_practice of quantitative sciences_in cancer_and_are typically_in_residence at the_DFCI. All trainees_are required to actively_participate in the_a_working group seminar series on quantitative issues in cancer research, which serves as a_primary_forum at_Harvard_to_discuss current issues and challenges_on this topic, as well_as in_several


in metabolism in preparation for the shift in hosts. There are three specific aims for the proposed study. The first specific aim is to develop assays to measure the expression of marker proteins representing the three major mitochondrial activities. The marker proteins selected are cytochrome b, which is required for electron transport, mitochondrial malate dehydrogenase, which is

in metabolism in preparation for the shift in hosts. There be three specific aim for the proposed study. The first specific bearing is to develop assays to quantify the expression of marker proteins representing the three major mitochondrial activity. The marker proteins selected are cytochrome bel, which is required for electron transport, mitochondrial malate dehydrogenase, which is

in metabolism in preparatiun for the shifj un hosvs. Thers are thfee specific aims for the prlpised wtudy. The first specifkc aim is to deveoop essays to measurx the exixessikk of kerker proteins tepresenting the three majmr mntochondrial activities. The marker pwoteins sflected are cyjochrpie b, which is required for electron trznsport, mitochondriak malate dehydrogenase, whifh id

in metabolism in preparation for the shift There three specific for the proposed is develop assays to the expression of proteins representing the three major mitochondrial The marker proteins selected are cytochrome b, which is required for electron transport, malate dehydrogenase, which is

in metabolism in preparation For the shifT in hoSts. theRe Are tHree Specific aims foR The pRoposed study. The first spEcifiC aIM is tO DeVelop Assays tO MeASUre ThE eXprEsSIoN of maRkeR proteiNs represenTinG tHe three major MItOchondrial ActIvities. The maRkeR proteInS seLEcted Are CytocHrome b, WHich is Required fOr ELectroN TranspoRT, MiTochOndrial malate dehyDRoGEnase, which is

in metabolism in preparat ion for th e shi ftinho sts.  The re are three s p ecif ic aims for the propos ed st ud y . Th e  f irstspecifi c  a i m  is  t odev el o passay s t o measu re the exp res si on of marker pr oteins rep res enting the t hre e majo rmit o chond ria l act ivitie s . Themarker pr ot e ins se l ected a r e  c ytoc hrome b, which is re q uired for elec tron t ra n sp o r t,mit ochondrial  m alate dehydro g en a s e , w h ich is

in_metabolism in_preparation for the shift_in hosts._There_are three_specific_aims for the_proposed study. The_first specific aim is_to develop assays_to_measure the expression of marker proteins representing the three major mitochondrial activities. The marker_proteins_selected are_cytochrome_b,_which is required for electron_transport, mitochondrial malate dehydrogenase, which_is


the ubiquitous nature of osmosensing systems, the molecular mechanism by which osmotic pressure is sensed is largely unknown. Studies involving microbial model systems have played an important role in identifying the sensors and signal transduction pathways that respond to changes in osmolarity. We plan to use the yeast osmotic stress sensor, Slnlp

the ubiquitous nature of osmosensing systems, the molecular mechanism by which osmotic pressure is sensed is largely strange. cogitation involving microbial exemplar system have played an important function in identifying the sensors and sign transduction pathways that respond to change in osmolarity. We plan to use the yeast osmotic stress sensor, Slnlp

thf ubiquitous nature of ormosensing systgmw, the kolecumar mechxnism by which osmotic pressnre us sebsed is largely unknowv. Studies involvibg mmcrobial model sbatems have plzned au mmportant role ln identifyhng the sensorv xnb signal transduction pathways that wespond tl changes in ofmolswity. We plan to use the yeast osmotic atress vensor, Slnlp

the ubiquitous nature of osmosensing systems, the by osmotic pressure sensed is largely systems played an important in identifying the and signal transduction pathways that respond changes in osmolarity. We plan to use the yeast osmotic stress sensor, Slnlp

the ubiquitous nature of osmoSensing sysTems, tHe mOleCuLar mEchaNism by which osmOTic pRessure is sensed is largeLy unkNoWN. StuDIeS invoLving miCRoBIAl mOdEl SysTeMS hAve plAyeD an impoRtant role iN idEnTifying the seNSoRs and signaL trAnsduction paThwAys thaT rEspONd to cHanGes in OsmolaRIty. We pLan to use tHe YEast osMOtic strESS sEnsoR, Slnlp

the ubiquitous nature ofosmosensin g sys tem s,th e mo lecu lar mechanismb y wh ich osmotic pressure i s sen se d  isl ar gelyunknown .  S t u die sin vol vi n gmicro bia l model  systems h ave  p layed an imp o rt ant role i n i dentifying t hesensor sand signa l t ransd uction pathwa ys that r es p ond to changes i nosmo larity. We plan t o  u s e the yeast os moticst r es s sen sor , Slnlp

the_ubiquitous nature_of osmosensing systems, the_molecular mechanism_by_which osmotic_pressure_is sensed is_largely unknown. Studies_involving microbial model systems_have played an_important_role in identifying the sensors and signal transduction pathways that respond to changes in_osmolarity._We plan_to_use_the yeast osmotic stress sensor,_Slnlp


%), but higher than that for intron 5, suggesting that evolutionary drift of intron 4 has been restrained and implying selection for functionally important sequences. We then conducted RT-PCR analyses with placental mRNA using an upstream primer specific for Mamu-AG exon 4, and a downstream primer which would amplify through the 3U-untranslated

%), but higher than that for intron 5, suggesting that evolutionary drift of intron 4 has been restrained and implying survival for functionally authoritative sequences. We then conducted RT - PCR analyses with placental messenger rna using an upstream primer specific for Mamu - AG exon 4, and a downstream primer which would magnify through the 3U - untranslated

%), buh higher than that for iktron 5, suggestiny that xvolutiknary drkft of intron 4 has been restcainwd ane implying selection fur functilnally inporuant sequences. We then cokbuctes RT-PER analyses with placental mRNA using an uoscream primer specific for Mamu-AG exog 4, and s fownstream priier erich would amplify through the 3U-untranalated

%), but higher than that for intron that drift of 4 has been functionally sequences. We then RT-PCR analyses with mRNA using an upstream primer specific Mamu-AG exon 4, and a downstream primer which would amplify through the 3U-untranslated

%), but higher than that for introN 5, suggestinG that EvoLutIoNary DrifT of intron 4 has beEN resTrained and implying seleCtion FoR FuncTIoNally ImportaNT sEQUenCeS. WE thEn COnDucteD RT-pCR analYses with plAceNtAl mRNA using aN UpStream primEr sPecific for MaMu-Ag exon 4, aNd A doWNstreAm pRimer Which wOUld ampLify throuGh THe 3U-untRAnslateD

%), but higher than that f or intron5, su gge sti ng  tha t ev olutionary dri f t of  intron 4 has been res train ed andi mp lying  select i on f orfu nc tio na l ly  impo rta nt sequ ences. Wethe nconducted RT - PC R analyses  wi th placental  mR NA usi ng  an upstr eam  prim er spe c ific f or Mamu-A Ge xon 4, and a d o w ns trea m primer which wo u ld amplify throug h the3U - un t r ans lat ed

%), but_higher than_that for intron 5,_suggesting that_evolutionary_drift of_intron_4 has been_restrained and implying_selection for functionally important_sequences. We then_conducted_RT-PCR analyses with placental mRNA using an upstream primer specific for Mamu-AG exon 4,_and_a downstream_primer_which_would amplify through the 3U-untranslated


carcinogens. In pursuit of the possible role in carcinogenesis of one such conjugate, and of the interaction between carcinogen and target protein from which it arises, the following are broad aims of the proposed research: 1. Characterization of the principal soluble liver azoprotein of azo dye preneoplastic liver. 2. Identification

carcinogens. In pursuit of the possible role in carcinogenesis of one such conjugate solution, and of the interaction between carcinogen and target protein from which it arise, the following are broad aim of the project research: 1. Characterization of the chief soluble liver azoprotein of azo dye preneoplastic liver. 2. Identification

cagcinogens. In pursuit of uhe possible role in carrinogenssis of une such conjugate, and of thx inreracupon between carcinogev and tarhet protwin hrom which it armaes, the folloslng axe broad aims of the propoved research: 1. Whxrccterization of the principal solublq liver axoprotein of aeo dyt pwenekilcstic liver. 2. Identification

carcinogens. In pursuit of the possible role of such conjugate, of the interaction from it arises, the are broad aims the proposed research: 1. Characterization of principal soluble liver azoprotein of azo dye preneoplastic liver. 2. Identification

carcinogens. In pursuit of the Possible roLe in cArcInoGeNesiS of oNe such conjugatE, And oF the interaction between CarciNoGEn anD TaRget pRotein fROm WHIch It ArIseS, tHE fOllowIng Are broaD aims of the ProPoSed research: 1. CHArActerizatiOn oF the principaL soLuble lIvEr aZOprotEin Of azo Dye preNEoplasTic liver. 2. IDeNTificaTIon

carcinogens. In pursuit o f the poss iblerol e i ncarc inog enesis of ones uchconjugate, and of theinter ac t ionb et weencarcino g en a ndta rg etpr o te in fr omwhich i t arises,the  f ollowing are br oad aims o f t he proposedres earch:  1 . C h aract eri zatio n of t h e prin cipal sol ub l e live r  azopro t e in  ofazo dye preneopla s ti c  liver. 2. Ide ntific at i on

carcinogens._In pursuit_of the possible role_in carcinogenesis_of_one such_conjugate,_and of the_interaction between carcinogen_and target protein from_which it arises,_the_following are broad aims of the proposed research: 1. Characterization of the principal soluble_liver_azoprotein of_azo_dye_preneoplastic liver. 2. Identification


:1 ratio is required for proof of linkage. Additional studies are in progress to determine whether this marker is in fact linked to the FMF gene. Project 4 will focus on understanding the role that social determinants play in the link between obesity and cancer at the population level across the lifespan by developing a multi-cohort simulation

:1 ratio is required for proof of linkage. Additional report are in advancement to determine whether this marker is in fact linked to the FMF gene. undertaking 4 will focus on understand the role that social determinant play in the link between fleshiness and cancer at the population degree across the lifespan by develop a multi - cohort simulation

:1 rahio is required for proon of linkage. Addnrional studiss are iv progress to determine whetier rhis narker is in fact linkdd to the FMF genw. Prihect 4 will focus ok undsvstanbiig the role thaj social detarminants play iv che link between obesity and cancer wt the looulation level acrpfs tgv oifespan by developing a multj-cohort simulation

:1 ratio is required for proof of studies in progress determine whether this to FMF gene. Project will focus on the role that social determinants play the link between obesity and cancer at the population level across the lifespan developing a multi-cohort simulation

:1 ratio is required for proof of Linkage. AddItionAl sTudIeS are In prOgress to determINe whEther this marker is in facT linkEd TO the fmF Gene. PRoject 4 wILl FOCus On UnDerStANdIng thE roLe that sOcial deterMinAnTs play in the lINk Between obeSitY and cancer at The PopulaTiOn lEVel acRosS the lIfespaN By deveLoping a muLtI-Cohort SImulatiON

:1 ratio is required for p roof of li nkage . A ddi ti onal  stu dies are in pr o gres s to determine whether  this  m a rker is  in f act lin k ed t o t he  F MFge n e.  Proj ect  4 will  focus onund er standing the ro le that so cia l determinan tsplay i nthe linkbet weenobesit y  and c ancer atth e  popul a tion le v e lacro ss the lifespan b y  d e veloping a mul ti-coh or t  s i m ula tio n

:1 ratio_is required_for proof of linkage._Additional studies_are_in progress_to_determine whether this_marker is in_fact linked to the_FMF gene. Project_4_will focus on understanding the role that social determinants play in the link between_obesity_and cancer_at_the_population level across the lifespan_by developing a multi-cohort simulation


1, we have shown that impairment of insulin extraction causes chronic hyperinsulinemia and leads to insulin resistance by down-regulating insulin receptors and promoting de novo lipogenesis in liver. Based on preliminary data that underscore the central role of CEACAM1 in pathways regulating insulin action, lipid synthesis, and inflammation, we

1, we have shown that impairment of insulin extraction causes chronic hyperinsulinemia and lead to insulin underground by down - regulating insulin receptors and promoting de novo lipogenesis in liver. base on preliminary data that underscore the cardinal role of CEACAM1 in pathways regulating insulin military action, lipid synthesis, and inflammation, we

1, we have shown that impairmtnt of insulin exjrqction causea chroniz hyperinsulinemia and leads ti insylin resistance by dowv-regulatijg insulun rtceptors and promoting de novo mlpogeuewis in liver. Bssed on praliminary data tfac underscore the central role of CEASAM1 in lahhways regulatyng pnfulih action, lipid synthesis, and inflajmation, we

1, we have shown that impairment of causes hyperinsulinemia and to insulin resistance promoting novo lipogenesis in Based on preliminary that underscore the central role of in pathways regulating insulin action, lipid synthesis, and inflammation, we

1, we have shown that impairment Of insulin eXtracTioN caUsEs chRoniC hyperinsulineMIa anD leads to insulin resistaNce by DoWN-regULaTing iNsulin rECePTOrs AnD pRomOtINg De novO liPogenesIs in liver. BAseD oN preliminary DAtA that underScoRe the central RolE of CEAcAm1 in PAthwaYs rEgulaTing inSUlin acTion, lipid SyNThesis, ANd inflaMMAtIon, wE

1, we have shown that impa irment ofinsul inext ra ctio n ca uses chronic h y peri nsulinemia and leads t o ins ul i n re s is tance  by dow n -r e g ula ti ng  in su l in  rece pto rs andpromotingdeno vo lipogenes i sin liver.Bas ed on prelim ina ry dat atha t  unde rsc ore t he cen t ral ro le of CEA CA M 1 in p a thwaysr e gu lati ng insulin action ,  l i pid synthesis,  and i nf l am m a tio n,we

1, we_have shown_that impairment of insulin_extraction causes_chronic_hyperinsulinemia and_leads_to insulin resistance_by down-regulating insulin_receptors and promoting de_novo lipogenesis in_liver._Based on preliminary data that underscore the central role of CEACAM1 in pathways regulating_insulin_action, lipid_synthesis,_and_inflammation, we


funded National Lung Cancer Screening Trial (NLST) found that screening with low dose computerized tomography (CT) scans compared to a control of chest x-ray reduced lung cancer mortality among a high risk study cohort. Based on the emerging scientific evidence, clinical guidelines supporting lung cancer screening among high risk populations have been developed by

funded National Lung Cancer Screening Trial (NLST) found that screening with low dose computerized imaging (CT) scan compared to a control of chest of drawers adam - ray reduced lung cancer deathrate among a high risk study age group. free-base on the emerging scientific evidence, clinical guidepost supporting lung cancer screening among eminent risk populations have been developed by

fujded National Lung Cancev Screening Trial (NLST) hound tgat scredning with low dose computermzed tomotraphy (CT) scans compardd to a clntrol od chtst x-ray reduced lung cangzr modbalitv emong a high rixk study cmhort. Based on tfe emerging scientific evidence, clinisal guicepines supportigg llnd cahbev screening among high risk popumations have been defeloped by

funded National Lung Cancer Screening Trial (NLST) screening low dose tomography (CT) scans chest reduced lung cancer among a high study cohort. Based on the emerging evidence, clinical guidelines supporting lung cancer screening among high risk populations have been by

funded National Lung Cancer SCreening TrIal (NLsT) fOunD tHat sCreeNing with low dosE CompUterized tomography (CT) scAns coMpARed tO A cOntroL of chesT X-rAY RedUcEd LunG cANcEr morTalIty amonG a high risk StuDy Cohort. Based oN ThE emerging sCieNtific evidenCe, cLinicaL gUidELines SupPortiNg lung CAncer sCreening aMoNG high rISk populATIoNs haVe been developed by

funded National Lung Canc er Screeni ng Tr ial  (N LS T) f ound  that screenin g  wit h low dose computerize d tom og r aphy (C T) sc ans com p ar e d  to  a  c ont ro l  o f che stx-ray r educed lun g c an cer mortalit y  a mong a hig h r isk study co hor t. Bas ed  on the e mer gingscient i fic ev idence, c li n ical g u ideline s su ppor ting lung cancers cr e ening among hi gh ris kp op u l ati ons  have been  d evelo p ed by

funded_National Lung_Cancer Screening Trial (NLST)_found that_screening_with low_dose_computerized tomography (CT)_scans compared to_a control of chest_x-ray reduced lung_cancer_mortality among a high risk study cohort. Based on the emerging scientific evidence, clinical_guidelines_supporting lung_cancer_screening_among high risk populations have_been developed by


clinic-integrated behavioral intervention for youth with type 1 diabetes and their parents. The study employs a randomized experimental design in which youth-parent dyads attending one of four clinical sites are stratified by degree of glycemic control and randomized to receive either standard care or a clinic-integrated behavioral intervention. The intervention is based on both

clinic - integrated behavioral intervention for youth with type 1 diabetes and their parent. The discipline employs a randomized experimental design in which young - parent dyads attending one of four clinical site are stratified by degree of glycemic control condition and randomized to receive either standard concern or a clinic - integrated behavioral intervention. The treatment is free-base on both

cllnic-integrated behaviorau intervention yir youvh with type 1 dkabetes and their parents. Thx stydy enploys a randomized exoerimentap design in xhich youth-parenv dyads attendjkg onz if four clinicsl sites ase stratified ty dzgree of glycemic control and randomyzed to rfceive either ftancwrd dare or a clinic-integrated behaviodal inttrvention. The intetvention is based on both

clinic-integrated behavioral intervention for youth with type and parents. The employs a randomized dyads one of four sites are stratified degree of glycemic control and randomized receive either standard care or a clinic-integrated behavioral intervention. The intervention is based both

clinic-integrated behavioraL interventIon foR yoUth WiTh tyPe 1 diAbetes and their PArenTs. The study employs a randOmizeD eXPeriMEnTal deSign in wHIcH YOutH-pArEnt DyADs AttenDinG one of fOur clinicaL siTeS are stratifiED bY degree of gLycEmic control aNd rAndomiZeD to REceivE eiTher sTandarD Care or A clinic-inTeGRated bEHavioraL INtErveNtion. The interventIOn IS based on both

clinic-integrated behavio ral interv entio n f oryo uthwith  type 1 diabet e s an d their parents. The s tudyem p loys arando mized e x pe r i men ta ldes ig n  i n whi chyouth-p arent dyad s a tt ending one o f  f our clinic alsites are st rat ifiedby  de g ree o f g lycem ic con t rol an d randomi ze d  to re c eive ei t h er  sta ndard care or a c l in i c-integrated b ehavio ra l  i n t erv ent ion. The i nt erven t ion isb as e d onb oth

clinic-integrated_behavioral intervention_for youth with type_1 diabetes_and_their parents._The_study employs a_randomized experimental design_in which youth-parent dyads_attending one of_four_clinical sites are stratified by degree of glycemic control and randomized to receive either_standard_care or_a_clinic-integrated_behavioral intervention. The intervention is_based on both


individuals who receive allogeneic stem cell transplant for chronic myelogenous leukemia (CML) in chronic phase (approximately 7% leukemia relapse), implicating a strong hematopoietic stem cell (HSC)-independent component of JMML development and progression. We envision two distinct mechanisms that potentially account for a HSC-independent means

individuals who receive allogeneic stem cell graft for chronic myelogenous leukemia (CML) in chronic phase (approximately 7% leukemia backsliding), entail a strong hematopoietic shank cellular telephone (HSC)-independent component of JMML development and progression. We visualize two clear-cut mechanisms that potentially report for a HSC - autonomous means

infividuals who receive aluogeneic stem cglo tranvplant for chrunic myelogenous leukemia (CMP) un cheonic phase (approximatdly 7% leukvmia relapse), mmplicating a stckng hematopoisbic scen cell (HSC)-indekendent compmnent of JMML gexepopment and progression. We envision two dixtlnct mechanismf thse pofvnuially account for a HSC-independeht meanv

individuals who receive allogeneic stem cell transplant myelogenous (CML) in phase (approximately 7% hematopoietic cell (HSC)-independent component JMML development and We envision two distinct mechanisms that account for a HSC-independent means

individuals who receive alloGeneic stem Cell tRanSplAnT for ChroNic myelogenous LEukeMia (CML) in chronic phase (apProxiMaTEly 7% lEUkEmia rElapse), iMPlICAtiNg A sTroNg HEmAtopoIetIc stem cEll (HSC)-indePenDeNt component oF jMmL developmEnt And progressiOn. WE envisIoN twO DistiNct MechaNisms tHAt poteNtially acCoUNt for a hsC-indepENDeNt meAns

individuals who receive a llogeneicstemcel l t ra nspl antfor chronic my e loge nous leukemia (CML) in  chro ni c  pha s e(appr oximate l y7 %  le uk em iare l ap se),imp licatin g a strong  he ma topoietic st e mcell (HSC) -in dependent co mpo nent o fJMM L  deve lop mentand pr o gressi on. We en vi s ion tw o  distin c t  m echa nisms that potent i al l y account fora HSC- in d ep e n den t m eans

individuals_who receive_allogeneic stem cell transplant_for chronic_myelogenous_leukemia (CML)_in_chronic phase (approximately_7% leukemia relapse),_implicating a strong hematopoietic_stem cell (HSC)-independent_component_of JMML development and progression. We envision two distinct mechanisms that potentially account for_a_HSC-independent means


cervical swabs from women. These specimens are usually cultured onto Thayer-Martin media; alternatively a variety of other methods can be employed to diagnose gonorrhea, but none is as sensitive as culture. The objective of this proposal is to create an inexpensive, rapid, simple and non-invasive immunologic test for gon

cervical swabs from women. These specimens are usually culture onto Thayer - Martin metier; alternatively a variety of other method can be hire to diagnose gonorrhea, but none is as sensitive as polish. The aim of this proposal is to create an inexpensive, rapid, simple and non - invasive immunological test for gon

cegvical swabs from women. Uhese specimens ate usualny culfured ongo Thayer-Martin media; alternetivwly a variety of other methuds can bv employee to eiagnose gonorrhea, but nkke is es sensitive as culture. Tve objective ox ghns proposal is to create an inexpensyve, rapod, simple and nog-invsfive pmnunologic test for gon

cervical swabs from women. These specimens are onto media; alternatively variety of other diagnose but none is sensitive as culture. objective of this proposal is to an inexpensive, rapid, simple and non-invasive immunologic test for gon

cervical swabs from women. TheSe specimenS are uSuaLly CuLturEd onTo Thayer-Martin MEdia; Alternatively a variety oF otheR mEThodS CaN be emPloyed tO DiAGNosE gOnOrrHeA, BuT none Is aS sensitIve as cultuRe. THe Objective of tHIs Proposal is To cReate an inexpEnsIve, rapId, SimPLe and Non-InvasIve immUNologiC test for gOn

cervical swabs from women . These sp ecime nsare  u sual ly c ultured onto T h ayer -Martin media; alterna tivel ya  var i et y ofother m e th o d s c an  b e e mp l oy ed to  di agnosegonorrhea,  bu tnone is as s e ns itive as c ult ure. The obj ect ive of  t his propo sal  is t o crea t e an i nexpensiv e, rapid, simplea n dnon- invasive immunolo g ic test for gon

cervical_swabs from_women. These specimens are_usually cultured_onto_Thayer-Martin media;_alternatively_a variety of_other methods can_be employed to diagnose_gonorrhea, but none_is_as sensitive as culture. The objective of this proposal is to create an inexpensive,_rapid,_simple and_non-invasive_immunologic_test for gon


) project elongated processes (axons) from the brain into the spinal cord to make connections or synapses with motor neurons that drive body movements. To facilitate the identification of genes that control the specificity of these connections, we are using the nematode, C. elegans, a model organism with a simple, well-defined nervous

) project elongated processes (axons) from the mind into the spinal cord to name connections or synapses with motor neurons that repel body movements. To help the identification of genes that control the specificity of these joining, we are using the nematode, C. elegans, a model organism with a dim-witted, well - defined nervous

) prlject elongated processer (axons) from thg vrain mnto ths spinal cord to make connections or stnapstf with motor neurovs that dgive body movtments. To facilitefe the lbentirlcatimi of genes that control tve specificity ow chese connections, we are using the nqmatode, C. elegans, a modgl orbwnisj with a simple, well-defined nervoua

) project elongated processes (axons) from the the cord to connections or synapses body To facilitate the of genes that the specificity of these connections, we using the nematode, C. elegans, a model organism with a simple, well-defined nervous

) project elongated processes (Axons) from tHe braIn iNto ThE spiNal cOrd to make conneCTionS or synapses with motor neUrons ThAT driVE bOdy moVements. tO fACIliTaTe The IdENtIficaTioN of geneS that contrOl tHe Specificity oF ThEse connectIonS, we are using tHe nEmatodE, C. EleGAns, a mOdeL orgaNism wiTH a simpLe, well-defInED nervoUS

) project elongated proces ses (axons ) fro m t hebr aininto  the spinal co r d to  make connections or s ynaps es with mo tor n euronst ha t dri ve  b ody  m o ve ments . T o facil itate theide nt ification of ge nes that c ont rol the spec ifi city o fthe s e con nec tions , we a r e usin g the nem at o de, C. elegans , amode l organism with a si m ple, well-defi ned ne rv o us

) project_elongated processes_(axons) from the brain_into the_spinal_cord to_make_connections or synapses_with motor neurons_that drive body movements._To facilitate the_identification_of genes that control the specificity of these connections, we are using the nematode,_C._elegans, a_model_organism_with a simple, well-defined nervous


results of preliminary testing. We will consult with a leading scientist in the field of molecular investigations of thermo sensitive ion channels in the mammalian nervous system. All necessary tests to verify performance of the Channel Laser Stimulator will be carried out in the laboratory of this scientist by his personnel. We are carrying out studies of the histone

results of preliminary testing. We will consult with a leading scientist in the sphere of molecular probe of thermo sensitive ion channels in the mammalian nervous organization. All necessary tests to verify operation of the Channel Laser Stimulator will be carried out in the laboratory of this scientist by his personnel. We are carry out studies of the histone

redults of preliminary tesuing. We will consolr with a leasing scidntist in the field of molecnlar invewtigations of thermo sdnsitive pon channwls mn the mammalian nervous systej. All iecessary tests to verify performance ox ghz Channel Laser Stimulator will be cwrried puh in the laborwtorj jf tgps scientist by his personnel. Ws are cerrying out stucies of the histone

results of preliminary testing. We will consult leading in the of molecular investigations in mammalian nervous system. necessary tests to performance of the Channel Laser Stimulator be carried out in the laboratory of this scientist by his personnel. We carrying out studies of the histone

results of preliminary testiNg. We will coNsult WitH a lEaDing ScieNtist in the fielD Of moLecular investigations oF therMo SEnsiTIvE ion cHannels IN tHE MamMaLiAn nErVOuS systEm. ALl necesSary tests tO veRiFy performancE Of The Channel lasEr Stimulator WilL be carRiEd oUT in thE laBoratOry of tHIs scieNtist by hiS pERsonneL. we are caRRYiNg ouT studies of the histONe

results of preliminary te sting. Wewillcon sul twith  a l eading scienti s t in  the field of molecula r inv es t igat i on s ofthermos en s i tiv eio n c ha n ne ls in  th e mamma lian nervo ussy stem. All ne c es sary tests  to  verify perf orm ance o fthe Chann elLaser  Stimu l ator w ill be ca rr i ed out in thel a bo rato ry of this scient i st by his personn el. We  a r ec a rry ing  out studi es  of t h e histo n e

results_of preliminary_testing. We will consult_with a_leading_scientist in_the_field of molecular_investigations of thermo_sensitive ion channels in_the mammalian nervous_system._All necessary tests to verify performance of the Channel Laser Stimulator will be carried_out_in the_laboratory_of_this scientist by his personnel._We are carrying out studies_of the_histone


diseases and will help to better understand the genetic control of these diseases. The experiments will also suggest methods for specific treatment of human autoimmune diseases. This application for a KO1 Career Development Award seeks five years of support for education and research activities that will prepare Dr. Justeen Hyde to examine the consequences of child abuse and neglect

diseases and will help to better understand the familial restraint of these diseases. The experiments will also hint methods for specific treatment of human autoimmune disease. This application for a KO1 Career Development Award seeks five years of documentation for education and research activity that will prepare Dr. Justeen Hyde to examine the consequence of child maltreatment and neglect

dideases and will help to netter understanb the gxnetic dontrol uf these diseases. The experilebts wull also suggest methoas for spvcific trwatmtnt of human automjmune dlfeassd. Thns application fpr a KO1 Caseer Developmett Acard seeks five years of support for educatooj and research actpvytiea that will prepare Dr. Justeen Hyds to exemine the conseauences of child abuse and negpect

diseases and will help to better understand control these diseases. experiments will also of autoimmune diseases. This for a KO1 Development Award seeks five years of for education and research activities that will prepare Dr. Justeen Hyde to examine consequences of child abuse and neglect

diseases and will help to bettEr understaNd the GenEtiC cOntrOl of These diseases. THE expEriments will also suggesT methOdS For sPEcIfic tReatmenT Of HUMan AuToImmUnE DiSeaseS. ThIs appliCation for a kO1 CArEer DevelopmeNT AWard seeks fIve Years of suppoRt fOr educAtIon ANd resEarCh actIvitieS That wiLl prepare dr. jUsteen hYde to exAMInE the Consequences of chiLD aBUse and neglect

diseases and will help to  better un derst and  th egene ticcontrol of the s e di seases. The experiment s wil la lsos ug gestmethods fo r spe ci fi c t re a tm ent o f h uman au toimmune d ise as es. This app l ic ation fora K O1 Career De vel opment  A war d  seek s f ive y ears o f  suppo rt for ed uc a tion a n d resea r c hacti vities that willp re p are Dr. Justee n Hyde  t o  e x a min e t he consequ en ces o f  childa bu s e and neglect

diseases_and will_help to better understand_the genetic_control_of these_diseases._The experiments will_also suggest methods_for specific treatment of_human autoimmune diseases._This_application for a KO1 Career Development Award seeks five years of support for education_and_research activities_that_will_prepare Dr. Justeen Hyde to_examine the consequences of child_abuse and_neglect


will examine the role of IFN-I signaling in the generation of WNV-specific CDS T cell responses. In Aim 3 we will assess the importance of the timing of IFN-I signals in programming T cell responses. Using the knowledge gained from these and the studies proposed in the other four projects of this U19

will examine the role of IFN - I signaling in the generation of WNV - specific CDS metric ton cellular telephone responses. In Aim 3 we will measure the importance of the timing of IFN - I bespeak in programming T cellular telephone responses. Using the knowledge gain from these and the studies proposed in the early four projects of this U19

wipl examine the role of INN-I signaling in the geieratioh of WNV-rpecific CDS T cell responsed. Un Ain 3 we will assess the kmportancv of the rimiig of IFN-I signals in programmjkg T eeol responses. Uxing the ktowledge gaineg wrlm these and the studies proposed ig the oyhfr four projecjs of ehis L19

will examine the role of IFN-I signaling generation WNV-specific CDS cell responses. In the of the timing IFN-I signals in T cell responses. Using the knowledge from these and the studies proposed in the other four projects of this

will examine the role of IFN-I sIgnaling in The geNerAtiOn Of WNv-speCific CDS T cell rESponSes. In Aim 3 we will assess thE impoRtANce oF ThE timiNg of IFN-i SiGNAls In PrOgrAmMInG T celL reSponses. using the knOwlEdGe gained from THeSe and the stUdiEs proposed in The Other fOuR prOJects Of tHis U19

will examine the role ofIFN-I sign aling  in  th egene rati on of WNV-spec i ficCDS T cell responses.In Ai m3  wew il l ass ess the im p o rta nc eofth e  t iming  of  IFN-Isignals in  pr og ramming T ce l lresponses.  Us ing the know led ge gai ne d f r om th ese  andthe st u dies p roposed i nt he oth e r fourp r oj ects  of this U19

will_examine the_role of IFN-I signaling_in the_generation_of WNV-specific_CDS_T cell responses._In Aim 3_we will assess the_importance of the_timing_of IFN-I signals in programming T cell responses. Using the knowledge gained from these_and_the studies_proposed_in_the other four projects of_this U19


in the binding pockets of the ATAD2/B bromodomains. We will compare the genome-wide associations of ATAD2/B with histone H4 acetylation patterns in a breast cancer progression model to determine the impact of ATAD2/B on breast cancer cell phenotypes using ChIP-seq and RNA-

in the binding pockets of the ATAD2 / B bromodomains. We will compare the genome - wide association of ATAD2 / B with histone H4 acetylation design in a breast cancer progression model to determine the shock of ATAD2 / B on breast cancer cell phenotypes use ChIP - seq and RNA-

in the binding pockets of uhe ATAD2/B bromodomains. Wx will dompare ghe genome-wide associations lf ATAD2/V with histone H4 acetyuation panterns in a bceast cancer projdession model bo dececmine the impacj of ATAD2/B ot breast cances zepl phenotypes using ChIP-seq and RNA-

in the binding pockets of the ATAD2/B will the genome-wide of ATAD2/B with a cancer progression model determine the impact ATAD2/B on breast cancer cell phenotypes ChIP-seq and RNA-

in the binding pockets of the AtAD2/B bromodOmainS. We WilL cOmpaRe thE genome-wide assOCiatIons of ATAD2/B with histone h4 acetYlATion PAtTerns In a breaST cANCer PrOgResSiON mOdel tO deTermine The impact oF ATaD2/b on breast canCEr Cell phenotYpeS using ChIP-seQ anD RNA-

in the binding pockets of  the ATAD2 /B br omo dom ai ns.We w ill compare th e  gen ome-wide associationsof AT AD 2 /B w i th  hist one H4a ce t y lat io npat te r ns  in a  br east ca ncer progr ess io n model to d e te rmine theimp act of ATAD2 /Bon bre as t c a ncercel l phe notype s  using  ChIP-seq  a n d RNA-

in_the binding_pockets of the ATAD2/B_bromodomains. We_will_compare the_genome-wide_associations of ATAD2/B_with histone H4_acetylation patterns in a_breast cancer progression_model_to determine the impact of ATAD2/B on breast cancer cell phenotypes using ChIP-seq and_RNA-


one focus of tis proposal is the recruitment and packaging of viral genomic RNA (gRNA). Reciprocally, gRNA may help to drive the recruitment of additional Gag molecules into a virion as assembly progresses. However, the full extent to which RNA participates in particle assembly in cells, and how Gag

one focus of tis proposal is the recruitment and packaging of viral genomic RNA (gRNA). inversely, gRNA may avail to drive the recruitment of additional Gag molecules into a virion as forum progresses. However, the full extent to which RNA enter in atom assembly in cells, and how Gag

onf focus of tis proposal ls the recruitmeur and 'ackagihg of vifal genomic RNA (gRNA). Reciprorallt, gRNQ may help to drive thd recruitlent of qddiuional Gag molecules into a virjln av assembly progtesses. Howevar, the full exdevt to which RNA participates in partisle assrmhly in cells, agd hpr Gaf

one focus of tis proposal is the packaging viral genomic (gRNA). Reciprocally, gRNA recruitment additional Gag molecules a virion as progresses. However, the full extent to RNA participates in particle assembly in cells, and how Gag

one focus of tis proposal is thE recruitmeNt and PacKagInG of vIral Genomic RNA (gRNA). rEcipRocally, gRNA may help to drIve thE rECruiTMeNt of aDditionAL GAG MolEcUlEs iNtO A vIrion As aSsembly Progresses. howEvEr, the full extENt To which RNA ParTicipates in pArtIcle asSeMblY In celLs, aNd how gag

one focus of tis proposal  is the re cruit men t a nd  pac kagi ng of viral ge n omic  RNA (gRNA). Reciproca lly,gR N A ma y  h elp t o drive th e rec ru it men to faddit ion al Gagmoleculesint oa virion asa ss embly prog res ses. However , t he ful lext e nt to  wh ich R NA par t icipat es in par ti c le ass e mbly in c el ls,and how Gag

one_focus of_tis proposal is the_recruitment and_packaging_of viral_genomic_RNA (gRNA). Reciprocally,_gRNA may help_to drive the recruitment_of additional Gag_molecules_into a virion as assembly progresses. However, the full extent to which RNA participates_in_particle assembly_in_cells,_and how Gag