studies revealed that a synthetic single-stranded oligonucleotide composed of the CRE sequence, which self-hybridizes to form a duplex/hairpin, can penetrate into cells, compete with CRE enhancers for binding transcription factors and specifically interfere with CRE- and Ap-1-directed transcription in vivo. This oligonucleotide restrained tumor cell proliferation

studies revealed that a synthetic single - stranded oligonucleotide write of the CRE succession, which self - hybridizes to form a duplex / hairpin, can permeate into cell, compete with CRE enhancers for binding recording agent and specifically interfere with CRE- and Ap-1 - direct transcription in vivo. This oligonucleotide restrained tumor cellular telephone proliferation

stkdies revealed that a sykthetic single-sttabded onigonudleotide composed of the CRE sequencx, whuch stjf-hybridizes to fofm a duplvx/hairpin, can penetrate mhto cells, comlcte wnti CRE enhancers for binditg transcriptimn fcctors and specifically interfere wieh CRE- snf Ap-1-directed ttanscgi[tioh in vivo. This oligonucleotide resfrained tumor cell ptoliferation

studies revealed that a synthetic single-stranded oligonucleotide the sequence, which to form a compete CRE enhancers for transcription factors and interfere with CRE- and Ap-1-directed transcription vivo. This oligonucleotide restrained tumor cell proliferation

studies revealed that a synthEtic single-StranDed OliGoNuclEotiDe composed of thE cRE sEquence, which self-hybridIzes tO fORm a dUPlEx/haiRpin, can PEnETRatE iNtO ceLlS, CoMpete WitH CRE enhAncers for bIndInG transcriptiON fActors and sPecIfically inteRfeRe with cRe- anD ap-1-dirEctEd traNscripTIon in vIvo. This olIgONucleoTIde restRAInEd tuMor cell proliferatIOn

studies revealed that a s ynthetic s ingle -st ran de d ol igon ucleotide comp o sedof the CRE sequence, w hichse l f-hy b ri dizes  to for m  a d upl ex /h air pi n ,can p ene trate i nto cells,  co mp ete with CRE en hancers fo r b inding trans cri ptionfa cto r s and  sp ecifi callyi nterfe re with C RE -  and A p -1-dire c t ed  tra nscription in viv o .T his oligonucle otidere s tr a i ned  tu mor cell p ro lifer a tion

studies_revealed that_a synthetic single-stranded oligonucleotide_composed of_the_CRE sequence,_which_self-hybridizes to form_a duplex/hairpin, can_penetrate into cells, compete_with CRE enhancers_for_binding transcription factors and specifically interfere with CRE- and Ap-1-directed transcription in vivo. This_oligonucleotide_restrained tumor_cell_proliferation


Thegeneis primarilyexpress edintheliv er.Re cen tfi nd ings sugg estthatABCC6re g ulat esthecellular releaseo fnucl eo s idet r ip hosph ates,pr e do m i nan tl ya den os i ne triph osp hate(AT P).Outside the  c ellATPisrapi d ly convertedi nto adenosinemon oph osphat e( AMP


strongly associated with a range of individual and family functioning problems. We seek to test the impact of BSRF on a range of relationship risk and protective factors, and the effects of intervening with these factors on a wide range of outcomes which have not been studied in the marriage education literature, including depression, substance abuse, parenting

strongly associated with a range of individual and family operation trouble. We seek to test the impingement of BSRF on a image of relationship risk and protective agent, and the effect of intervening with these factor on a wide range of consequence which have not been studied in the marriage education literature, include depressive disorder, substance abuse, parenting

stgongly associated with a range of indivneual aid famimy functkoning problems. We seek to txst rhe inpact of BSRF on a ranee of relwtionship riwj and protxdtive factors, wnd chx effects of injervening widh these factoss ou a wide range of outcomes which havq not brej studied in tre mswriafv tducation literature, including delressioi, substance abuxe, parenting

strongly associated with a range of individual functioning We seek test the impact of risk and protective and the effects intervening with these factors on a range of outcomes which have not been studied in the marriage education literature, depression, substance abuse, parenting

strongly associated with a raNge of indivIdual And FamIlY funCtioNing problems. We SEek tO test the impact of BSRF on A rangE oF RelaTIoNship Risk and PRoTECtiVe FaCtoRs, ANd The efFecTs of intErvening wiTh tHeSe factors on a WIdE range of ouTcoMes which have Not Been stUdIed IN the mArrIage eDucatiON literAture, inclUdINg deprESsion, suBSTaNce aBuse, parenting

strongly associated witha range of  indi vid ual  a nd f amil y functioningp robl ems. We seek to test t he im pa c t of BS RF on  a rang e  o f rel at io nsh ip ri sk an d p rotecti ve factors , a nd  the effects of  interveni ngwith these f act ors on  a  wi d e ran geof ou tcomes whichhave notbe e n stud i ed in t h e  m arri age education lit e ra t ure, including  depre ss i on , sub sta nce abuse,  p arent i ng

strongly_associated with_a range of individual_and family_functioning_problems. We_seek_to test the_impact of BSRF_on a range of_relationship risk and_protective_factors, and the effects of intervening with these factors on a wide range of_outcomes_which have_not_been_studied in the marriage education_literature, including depression, substance abuse,_parenting


acrine cells, a later born cell type. However, the mechanisms by which bHLH factors promote retinal neuron differentiation, and how they contribute to the ordered sequence of retinal histogenesis is less well defined. We have identified both transcriptional and post-translational mechanisms that regulate when during retinal development bHLH factors are

acrine cells, a later born cell character. However, the mechanism by which bHLH factors promote retinal nerve cell differentiation, and how they put up to the ordered sequence of retinal histogenesis is less well specify. We have identified both transcriptional and post - translational mechanisms that determine when during retinal development bHLH factors are

acrlne cells, a later born ctll type. However, jhw mechenisms gy which bHLH factors promote retinap beurob differentiation, and fow they bontributw to rhe orderev sequengz of dctinan histogenesis ls less weln defined. We hdvd ndentified both transcriptional and [ost-tramspational mechagismx thaf regulate when during retinal devslopmenu bHLH factors are

acrine cells, a later born cell type. mechanisms which bHLH promote retinal neuron to ordered sequence of histogenesis is less defined. We have identified both transcriptional post-translational mechanisms that regulate when during retinal development bHLH factors are

acrine cells, a later born cell Type. HoweveR, the mEchAniSmS by wHich BHLH factors proMOte rEtinal neuron differentiAtion, AnD How tHEy ContrIbute to THe ORDerEd SeQueNcE Of RetinAl hIstogenEsis is less WelL dEfined. We have IDeNtified botH trAnscriptionaL anD post-tRaNslATionaL meChaniSms thaT RegulaTe when durInG RetinaL DevelopMENt BHLH Factors are

acrine cells, a later born  cell type . How eve r,th e me chan isms by whichb HLHfactors promote retina l neu ro n  dif f er entia tion, a n dh o w t he ycon tr i bu te to  th e order ed sequenc e o fretinal hist o ge nesis is l ess  well define d.We hav eide n tifie d b oth t ranscr i ptiona l and pos t- t ransla t ional m e c ha nism s that regulate w h en during retinal  devel op m en t bHL H f actors are

acrine cells,_a later_born cell type. However,_the mechanisms_by_which bHLH_factors_promote retinal neuron_differentiation, and how_they contribute to the_ordered sequence of_retinal_histogenesis is less well defined. We have identified both transcriptional and post-translational mechanisms that_regulate_when during_retinal_development_bHLH factors are


Immunolocalization of EGF in pronase-treated sections of the mouse uterus revealed staining at the luminal aspect of epithelial cells. Localization required protease treatment and the material reactive with anti-EGF antiserum was apparently not estrogen-dependent since this pattern of staining was readily observed in uteri from animals ovarie

Immunolocalization of EGF in pronase - treated sections of the mouse uterus revealed tarnish at the luminal view of epithelial cells. Localization required protease discussion and the material reactive with anti - EGF antiserum was apparently not estrogen - dependent since this blueprint of staining was readily observed in uteri from animal ovarie

Imlunolocalization of EGF ln pronase-treateb sectimns of the moure uterus revealed staining et tye luninal aspect of epitheuial celld. Localizatiib required proteasc trezbment end the materiak reactive with anti-EGF dngiderum was apparently not estrogen-de[endent slnce this pattgrn og stajning was readily observed in uterj from enimals ovarie

Immunolocalization of EGF in pronase-treated sections of uterus staining at luminal aspect of treatment the material reactive anti-EGF antiserum was not estrogen-dependent since this pattern of was readily observed in uteri from animals ovarie

Immunolocalization of EGF in Pronase-treAted sEctIonS oF the MousE uterus revealeD StaiNing at the luminal aspect Of epiThELial CElLs. LocAlizatiON rEQUirEd PrOteAsE TrEatmeNt aNd the maTerial reacTivE wIth anti-EGF anTIsErum was appAreNtly not estroGen-DependEnT siNCe thiS paTtern Of staiNIng was Readily obSeRVed in uTEri from ANImAls oVarie

Immunolocalization of EGF  in pronas e-tre ate d s ec tion s of  the mouse ute r us r evealed staining at th e lum in a l as p ec t ofepithel i al c ell s.  L oca li z at ion r equ ired pr otease tre atm en t and the ma t er ial reacti vewith anti-EG F a ntiser um  wa s  appa ren tly n ot est r ogen-d ependentsi n ce thi s  patter n of  sta ining was readily ob s erved in uteri  froman i ma l s  ov ari e

Immunolocalization_of EGF_in pronase-treated sections of_the mouse_uterus_revealed staining_at_the luminal aspect_of epithelial cells._Localization required protease treatment_and the material_reactive_with anti-EGF antiserum was apparently not estrogen-dependent since this pattern of staining was readily_observed_in uteri_from_animals_ovarie


been awarded $23 million in extramural research funding to date. In addition to the productivity of individual participants, the program has created a network of scientists conducting innovative HIV prevention research in minority communities. This network has led to the development and successful funding of several collaborative grants involving program participants and faculty. This application proposes a

been awarded $ 23 million in extramural research funding to date. In addition to the productiveness of individual participant, the program has created a net of scientists lead innovative HIV prevention inquiry in minority communities. This network has led to the growth and successful funding of several collaborative grant involving program player and staff. This application proposes a

befn awarded $23 million in ewtramural researey fundmng to sate. In xddition to the productivity od induvidual participants, tfe progral has crwatev a network of srjentists condhgting mnnovative HIV krevention rasearch in minmrktv communities. This network has led tj the drvflopment and soccesxsul rlnbing of several collaborative gdants iivolving prograk participants and faculty. Thid application proplses a

been awarded $23 million in extramural research date. addition to productivity of individual a of scientists conducting HIV prevention research minority communities. This network has led the development and successful funding of several collaborative grants involving program participants and This application proposes a

been awarded $23 million in extraMural reseaRch fuNdiNg tO dAte. IN addItion to the prodUCtivIty of individual particiPants, ThE ProgRAm Has crEated a nETwORK of ScIeNtiStS CoNductIng InnovatIve HIV prevEntIoN research in mINoRity communItiEs. This networK haS led to ThE deVElopmEnt And suCcessfUL fundiNg of severAl COllaboRAtive grANTs InvoLving program partiCIpANts and faculty. THis appLiCAtION prOpoSes a

been awarded $23 millionin extramu ral r ese arc hfund ingto date. In ad d itio n to the productivityof in di v idua l  p artic ipants, th e pro gr am  ha sc re ateda n etworkof scienti sts  c onducting in n ov ative HIVpre vention rese arc h in m in ori t y com mun ities . This networ k has led  t o  the d e velopme n t  a nd s uccessful funding of several collab orativ eg ra n t s i nvo lving prog ra m par t icipant s  a n d fac u lty. This app lication pr o pos es a

been_awarded $23_million in extramural research_funding to_date._In addition_to_the productivity of_individual participants, the_program has created a_network of scientists_conducting_innovative HIV prevention research in minority communities. This network has led to the development_and_successful funding_of_several_collaborative grants involving program participants_and faculty. This application proposes_a


enical tag while minimizing its impact on the host protein normal behavior. We extend the application of biarsenical labeling to chemically fixed tissues and propose the utilization of these methods to explore mesoscale structure and function in complex tissues in virally transduced animals and in transgenic models. In collaboration with the laboratory of Roger

enical tag while minimizing its impact on the host protein normal demeanor. We carry the application of biarsenical labeling to chemically fixed tissue and aim the utilization of these methods to research mesoscale structure and function in complex tissues in virally transduce animal and in transgenic models. In collaboration with the laboratory of Roger

enifal tag while minimizing its impact on jhw host protejn normau behavior. We extend the apppixatiob of biarsenical labelkng to chvmically dixev tissues and propose thc utimlzatimi of these methpds to expnore mesoscale sgrbcture and function in complex tissuqs in vorwlly transduceq anpmwls znd in transgenic models. In collabkration with the labpratory of Roger

enical tag while minimizing its impact on protein behavior. We the application of tissues propose the utilization these methods to mesoscale structure and function in complex in virally transduced animals and in transgenic models. In collaboration with the laboratory Roger

enical tag while minimizing iTs impact on The hoSt pRotEiN norMal bEhavior. We extenD The aPplication of biarsenicaL labeLiNG to cHEmIcallY fixed tISsUES anD pRoPosE tHE uTilizAtiOn of theSe methods tO exPlOre mesoscale STrUcture and fUncTion in compleX tiSsues iN vIraLLy traNsdUced aNimals ANd in trAnsgenic mOdELs. In coLLaboratION wIth tHe laboratory of RogER

enical tag while minimizin g its impa ct on  th e h os t pr otei n normal behav i or.We extend the applicat ion o fb iars e ni cal l abeling to c hem ic al lyfi x ed  tiss ues  and pr opose theuti li zation of th e se  methods t o e xplore mesos cal e stru ct ure and f unc tionin com p lex ti ssues invi r ally t r ansduce d an imal s and in transgen i cm odels. In coll aborat io n  w i t h t helaboratory  o f Rog e r

enical tag_while minimizing_its impact on the_host protein_normal_behavior. We_extend_the application of_biarsenical labeling to_chemically fixed tissues and_propose the utilization_of_these methods to explore mesoscale structure and function in complex tissues in virally transduced_animals_and in_transgenic_models._In collaboration with the laboratory_of Roger


and artificial radioactive compounds. Emission imaging potentially permits not only static reconstruction, but quantitative estimates of time-course of labeled compounds through structures deep within the body. Transaxial reconstruction permits isolation of radioactivity in very small body parts that would be obscured by overlying and underlying radioactivity in conventional views. The research in my

and artificial radioactive compounds. Emission imaging potentially permits not merely inactive reconstruction, but quantitative estimates of time - course of tag compounds through structures deeply within the body. Transaxial reconstruction permits isolation of radioactivity in very minor body parts that would be obscure by overlying and underlying radiation in conventional views. The research in my

anf artificial radioactive compounds. Emission imeging pktentialuy permits not only static rxconwtrucupon, but quantitative dstimates of time-xourww of labelxs compomuds tgvough wtructures deek within the body. Transaxidl rzconstruction permits isolation of rwdioactovlty in very smwll njdy larts that would be obscured by ovsrlying and underlyimg radioactivity in convenhionwl views. The reseagch in my

and artificial radioactive compounds. Emission imaging potentially only reconstruction, but estimates of time-course deep the body. Transaxial permits isolation of in very small body parts that be obscured by overlying and underlying radioactivity in conventional views. The research in

and artificial radioactive cOmpounds. EmIssioN imAgiNg PoteNtiaLly permits not oNLy stAtic reconstruction, but qUantiTaTIve eSTiMates Of time-cOUrSE Of lAbElEd cOmPOuNds thRouGh strucTures deep wIthIn The body. TransAXiAl reconstrUctIon permits isOlaTion of RaDioACtiviTy iN very Small bODy partS that woulD bE ObscurED by overLYInG and Underlying radioacTIvITy in conventionAl viewS. THE rESEarCh iN my

and artificial radioactiv e compound s. Em iss ion  i magi ng p otentially per m itsnot only static recons truct io n , bu t  q uanti tativee st i m ate sof  ti me - co urseoflabeled  compounds  th ro ugh structur e sdeep withi n t he body. Tra nsa xial r ec ons t ructi onpermi ts iso l ationof radioa ct i vity i n  very s m a ll  bod y parts that woul d  b e  obscured by o verlyi ng an d und erl ying radio ac tivit y  in con v en t i o nal views. The re search in m y

and_artificial radioactive_compounds. Emission imaging potentially_permits not_only_static reconstruction,_but_quantitative estimates of_time-course of labeled_compounds through structures deep_within the body._Transaxial_reconstruction permits isolation of radioactivity in very small body parts that would be obscured_by_overlying and_underlying_radioactivity_in conventional views. The research_in my


. Strains of measles virus and cell cultures containing defective measles virus genome have been isolated in our laboratory from brains of patients with subacute sclerosing panencephalitis (SSPE). These viruses and cells are being characterized by a combined biochemical-immunologic-genetic approach. Attempts are being made to detect virus or

. Strains of measles virus and cell cultures containing bad measles virus genome have been sequester in our laboratory from brains of patient with subacute sclerosing panencephalitis (SSPE). These virus and cells are being characterized by a combine biochemical - immunological - genetic approach. Attempts are being made to detect virus or

. Stgains of measles virus akd cell cultures contaiiing derective oeasles virus genome have bexn iwolattb in our laboratory wrom braijs of parienus with subacute sclerosiky panskcephclmtis (SSPE). These viruses atd cells are baivg characterized by a combined biocheiical-imkujologic-genetic appgowch. Znttmpts are being made to detect vidus or

. Strains of measles virus and cell defective virus genome been isolated in patients subacute sclerosing panencephalitis These viruses and are being characterized by a combined approach. Attempts are being made to detect virus or

. Strains of measles virus and cEll cultureS contAinIng DeFectIve mEasles virus genOMe haVe been isolated in our labOratoRy FRom bRAiNs of pAtients WItH SUbaCuTe SclErOSiNg panEncEphalitIs (SSPE). ThesE viRuSes and cells aRE bEing characTerIzed by a combiNed BiocheMiCal-IMmunoLogIc-genEtic apPRoach. ATtempts arE bEIng madE To detecT VIrUs or

. Strains of measles virus  and cellcultu res  co nt aini ng d efective measl e s vi rus genome have been i solat ed in o u rlabor atory f r om b rai ns  o f p at i en ts wi thsubacut e sclerosi ngpa nencephaliti s  ( SSPE). The seviruses andcel ls are  b ein g  char act erize d by a combin ed bioche mi c al-imm u nologic - g en etic  approach. Attemp t sa re being madeto det ec t  v i r usor

. Strains_of measles_virus and cell cultures_containing defective_measles_virus genome_have_been isolated in_our laboratory from_brains of patients with_subacute sclerosing panencephalitis_(SSPE)._These viruses and cells are being characterized by a combined biochemical-immunologic-genetic approach. Attempts are_being_made to_detect_virus_or


ating epithelial cells, alterations in basement membrane composition, and aberrant localization of cell surface proteins. These cellular properties are consistent with a reversion of the renal epithelial cell to a more embryonic phenotype. Thus, genes regulating the differentiation and proliferation of the normal renal epithelium may be aberrantly affected in PKD and may directly contribute to

ating epithelial cells, alterations in basement membrane composition, and aberrant localization of cellular telephone open proteins. These cellular properties are reproducible with a regression of the renal epithelial cell to a more embryonic phenotype. therefore, genes regulating the differentiation and proliferation of the normal nephritic epithelium may be aberrantly involve in PKD and may directly put up to

atijg epithelial cells, altevations in basemgnr membcane cojpositiov, and aberrant localization lf cell surface proteins. Thesd cellulag propertues ere consistent wmfh a reyzrsioh of chx renal epithellal cell to a more embryotiz 'henotype. Thus, genes regulating the qifferemtlation and projifegaeion of the normal renal epithelium mag be abtrrantly affected on PKD and may directly cojtrihute to

ating epithelial cells, alterations in basement membrane aberrant of cell proteins. These cellular reversion the renal epithelial to a more phenotype. Thus, genes regulating the differentiation proliferation of the normal renal epithelium may be aberrantly affected in PKD and directly contribute to

ating epithelial cells, alterAtions in baSemenT meMbrAnE comPosiTion, and aberranT LocaLization of cell surface pRoteiNs. tHese CElLular PropertIEs ARE coNsIsTenT wITh A reveRsiOn of the Renal epithEliAl Cell to a more eMBrYonic phenoTypE. Thus, genes reGulAting tHe DifFErentIatIon anD proliFEratioN of the norMaL Renal ePItheliuM MAy Be abErrantly affected iN pKd And may directly ContriBuTE tO

ating epithelial cells, al terationsin ba sem ent  m embr anecomposition, a n d ab errant localization of  cell  s u rfac e  p rotei ns. The s ec e llu la rpro pe r ti es ar e c onsiste nt with arev er sion of ther en al epithel ial  cell to a m ore  embry on icp henot ype . Thu s, gen e s regu lating th ed iffere n tiation a nd  pro liferation of the no r mal renal epit helium  m a yb e  ab err antly affe ct ed in PKD and ma y d ire c tly contribut e to

ating epithelial_cells, alterations_in basement membrane composition,_and aberrant_localization_of cell_surface_proteins. These cellular_properties are consistent_with a reversion of_the renal epithelial_cell_to a more embryonic phenotype. Thus, genes regulating the differentiation and proliferation of the_normal_renal epithelium_may_be_aberrantly affected in PKD and_may directly contribute to


M1 or M2 macrophages. I now propose to test the hypothesis that these TAMs can be distinguished by unique surface receptors that regulate expression and secretion of pro-metastatic factors. I further propose that TAMs recruited by CCL5 to metastatic TNBCs drive metastasis through expression of GRN along with

M1 or M2 macrophages. I now propose to test the guess that these tam can be identify by unique surface sense organ that regulate expression and secretion of pro - metastatic agent. I far propose that tam recruit by CCL5 to metastatic TNBCs drive metastasis through construction of GRN along with

M1 lr M2 macrophages. I now pvopose to test tkw hypovhesis fhat there TAMs can be distinguished bt uniwue surface receptors ghat regupate expeessmon and secretioi of pro-metastzbic fccvors. I further kropose that TAMs recruiteg cy CCL5 to metastatic TNBCs drive metaftasis yhgough expressijn og GRN along with

M1 or M2 macrophages. I now propose the that these can be distinguished regulate and secretion of factors. I further that TAMs recruited by CCL5 to TNBCs drive metastasis through expression of GRN along with

M1 or M2 macrophages. I now proposE to test the HypotHesIs tHaT theSe TAms can be distingUIsheD by unique surface receptOrs thAt REgulATe ExpreSsion anD SeCREtiOn Of Pro-MeTAsTatic FacTors. I fuRther propoSe tHaT TAMs recruitED bY CCL5 to metaStaTic TNBCs drivE meTastasIs ThrOUgh exPreSsion Of GRN aLOng witH

M1 or M2 macrophages. I n ow propose  to t est  th ehypo thes is that theseT AMscan be distinguished b y uni qu e  sur f ac e rec eptorst ha t reg ul at e e xp r es sionand  secret ion of pro -me ta static facto r s.  I further  pr opose that T AMs  recru it edb y CCL 5 t o met astati c  TNBCs  drive me ta s tasist hroughe x pr essi on of GRN along w i th

M1_or M2_macrophages. I now propose_to test_the_hypothesis that_these_TAMs can be_distinguished by unique_surface receptors that regulate_expression and secretion_of_pro-metastatic factors. I further propose that TAMs recruited by CCL5 to metastatic TNBCs drive_metastasis_through expression_of_GRN_along with


their associated plasmids. A key aspect of this project was the exhaustive validation of the PacBio assembled genomes conducted at NISC which involved expert manual review, genome-wide comparison of sequence data from an orthogonal sequencing technology, and optical mapping to confirm the long-range structure of the assemblies. This analysis estimated the assemblies generated by

their associated plasmids. A key aspect of this project was the exhaustive establishment of the PacBio assemble genomes conducted at NISC which imply technical manual review, genome - wide comparison of succession data from an orthogonal sequencing engineering, and ocular mapping to confirm the farseeing - range structure of the assembly. This psychoanalysis estimated the assemblies generate by

thfir associated plasmids. X key aspect of this pcoject sas the dxhaustive validation of the PqcBio assembled genomes conaucted at NISC whuch mnvolved expert manual rcriew, fcnome-cive comparison on sequence gata from an ostfoyonal sequencing technology, and optisal maplijg to confirm jhe lpgg-rahge structure of the assemblies. Thjs analjsis estimated thr assemblies generated by

their associated plasmids. A key aspect of was exhaustive validation the PacBio assembled involved manual review, genome-wide of sequence data an orthogonal sequencing technology, and optical to confirm the long-range structure of the assemblies. This analysis estimated the assemblies by

their associated plasmids. A kEy aspect of This pRojEct WaS the ExhaUstive validatiON of tHe PacBio assembled genomEs conDuCTed aT nIsC whiCh involVEd EXPerT mAnUal ReVIeW, genoMe-wIde compArison of seQueNcE data from an oRThOgonal sequEncIng technologY, anD opticAl MapPIng to ConFirm tHe long-RAnge stRucture of ThE AssembLIes. This ANAlYsis Estimated the assemBLiES generated by

their associated plasmids . A key as pectofthi sproj ectwas the exhaus t ivevalidation of the PacB io as se m bled ge nomes  conduc t ed a t N IS Cwhi ch in volve d e xpert m anual revi ew,  g enome-wide c o mp arison ofseq uence data f rom  an or th ogo n al se que ncing  techn o logy,and optic al mappin g  to con f i rm  the  long-range struc t ur e  of the assemb lies.Th i sa n aly sis  estimated  t he as s emblies ge n e r ate d  by

their_associated plasmids._A key aspect of_this project_was_the exhaustive_validation_of the PacBio_assembled genomes conducted_at NISC which involved_expert manual review,_genome-wide_comparison of sequence data from an orthogonal sequencing technology, and optical mapping to confirm_the_long-range structure_of_the_assemblies. This analysis estimated the_assemblies generated by


/- and WT wild-type brains. The antibodies used in this analysis are already proven to be highly specific for their targeted sites in different biochemical pathways. We based our selection of these proteins on some known and predicted functions of Cdk5 and further categorized them into 6 different groups. The first group contained 25 different proteins involved

/- and WT wild - type brains. The antibodies use in this psychoanalysis are already proven to be highly specific for their targeted web site in unlike biochemical pathways. We based our selection of these protein on some know and predicted functions of Cdk5 and further categorized them into 6 unlike groups. The first group contained 25 different protein involved

/- anf WT wild-type brains. The antibodies useb in thms analgsis are already proven to be highly specifuc for their targeted rites in fifferenr biixhemical pefhways. We bassf oux welection of tmese proteits on some knofn aud predicted functions of Cdk5 and fuwther cstfgorized them ynto 6 difrvrtnt groups. The first group contaihed 25 dihferent proteinx involved

/- and WT wild-type brains. The antibodies this are already to be highly in biochemical pathways. We our selection of proteins on some known and predicted of Cdk5 and further categorized them into 6 different groups. The first group 25 different proteins involved

/- and WT wild-type brains. The antIbodies useD in thIs aNalYsIs arE alrEady proven to be HIghlY specific for their targeTed siTeS In diFFeRent bIochemiCAl PAThwAyS. WE baSeD OuR seleCtiOn of theSe proteins On sOmE known and preDIcTed functioNs oF Cdk5 and furthEr cAtegorIzEd tHEm intO 6 diFfereNt grouPS. The fiRst group cOnTAined 25 dIFferent PROtEins Involved

/- and WT wild-type brains . The anti bodie s u sed  i n th is a nalysis are al r eady  proven to be highly s pecif ic fort he ir ta rgeteds it e s  in  d if fer en t  b ioche mic al path ways. We b ase dour selectio n  o f these pr ote ins on somekno wn and  p red i ctedfun ction s of C d k5 and  furtherca t egoriz e d themi n to  6 d ifferent groups.T he first group co ntaine d2 5d i ffe ren t proteins  i nvolv e d

/- and_WT wild-type_brains. The antibodies used_in this_analysis_are already_proven_to be highly_specific for their_targeted sites in different_biochemical pathways. We_based_our selection of these proteins on some known and predicted functions of Cdk5 and_further_categorized them_into_6_different groups. The first group_contained 25 different proteins involved


microglia in Rett syndrome, and T cells in MeCP2-duplication syndrome, also play a significant role. This understanding opens up the possibility for treatment modalities beyond direct neuronal intervention, which has been a problematic approach due to the complexity and risk involved in any manipulation of neurons themselves. Here, we propose to test

microglia in Rett syndrome, and T cells in MeCP2 - duplication syndrome, also toy a meaning role. This understanding open up the hypothesis for treatment modalities beyond direct neural treatment, which has been a problematic access due to the complexity and risk involved in any handling of neurons themselves. Here, we propose to test

mifroglia in Rett syndrome, and T cells in MeCP2-du'licatikn syndrume, also play a significant cole. This understanding opens uo the posdibility for rreatment modaliticf beglnd bicect neuronal iktervention, which has beet x 'roblematic approach due to the compjexity snf risk involveq in wny janipulation of neurons themselves. Here, wt propose to test

microglia in Rett syndrome, and T cells syndrome, play a role. This understanding treatment beyond direct neuronal which has been problematic approach due to the complexity risk involved in any manipulation of neurons themselves. Here, we propose to test

microglia in Rett syndrome, anD T cells in MECP2-duPliCatIoN synDromE, also play a signIFicaNt role. This understandinG openS uP The pOSsIbiliTy for trEAtMENt mOdAlItiEs BEyOnd diRecT neuronAl intervenTioN, wHich has been a PRoBlematic apProAch due to the cOmpLexity AnD riSK invoLveD in anY manipULation Of neurons ThEMselveS. here, we pROPoSe to Test

microglia in Rett syndrom e, and T c ellsinMeC P2 -dup lica tion syndrome, also  play a significant ro le. T hi s  und e rs tandi ng open s  u p the  p os sib il i ty  fortre atmentmodalities  be yo nd direct ne u ro nal interv ent ion, which h asbeen a  p rob l emati c a pproa ch due to the  complexi ty and ri s k invol v e din a ny manipulation o f  n e urons themselv es. He re ,  w e pro pos e to test

microglia_in Rett_syndrome, and T cells_in MeCP2-duplication_syndrome,_also play_a_significant role. This_understanding opens up_the possibility for treatment_modalities beyond direct_neuronal_intervention, which has been a problematic approach due to the complexity and risk involved_in_any manipulation_of_neurons_themselves. Here, we propose to_test


behaviors, wherein some stimulate ATP hydrolysis and are transported, while others stimulate ATP hydrolysis but are not transported. Other drugs inhibit P-gp without stimulating ATP hydrolysis. The mechanism by which different drugs elicit different behaviors is unclear. Specifically, the conformational changes that mediate communication between the nucleotide binding domains (NBDs) that hydroly

behaviors, wherein some stimulate ATP hydrolysis and are transported, while others stimulate ATP hydrolysis but are not enchant. early drugs inhibit phosphorus - gp without stimulate ATP hydrolysis. The mechanism by which different drug elicit different behaviors is ill-defined. Specifically, the conformational changes that mediate communication between the nucleotide bind domains (NBDs) that hydroly

bejaviors, wherein some stioulate ATP hydrolysis end are transpofted, while others stimulate ETP yydrooysis but are not tranrported. Onher drugw iniibit P-gp withouv stimulating ZBP hybrilysis. The mecmanism by wvich different dfuys elicit different behaviors is uncjear. Sprclfically, the cjnfogmwtiohal changes that mediate communicafion beuween the nucleotice binding domains (NBDs) thwt hjdroly

behaviors, wherein some stimulate ATP hydrolysis and while stimulate ATP but are not without ATP hydrolysis. The by which different elicit different behaviors is unclear. Specifically, conformational changes that mediate communication between the nucleotide binding domains (NBDs) that hydroly

behaviors, wherein some stimuLate ATP hydRolysIs aNd aRe TranSporTed, while others STimuLate ATP hydrolysis but arE not tRaNSporTEd. other Drugs inHIbIT p-gp WiThOut StIMuLatinG ATp hydrolYsis. The mecHanIsM by which diffEReNt drugs eliCit Different behAviOrs is uNcLeaR. speciFicAlly, tHe confORmatioNal changeS tHAt mediATe commuNICaTion Between the nucleotIDe BInding domains (NbDs) thaT hYDrOLY

behaviors, wherein some s timulate A TP hy dro lys is  and  are  transported,w hile  others stimulate ATPhydro ly s is b u tare n ot tran s po r t ed.  O th erdr u gs  inhi bit  P-gp w ithout sti mul at ing ATP hydr o ly sis. The m ech anism by whi chdiffer en t d r ugs e lic it di fferen t  behav iors is u nc l ear. S p ecifica l l y,  the  conformational c h an g es that mediat e comm un i ca t i onbet ween the n uc leoti d e bindi n gd o m ain s  (NBDs) thathydroly

behaviors,_wherein some_stimulate ATP hydrolysis and_are transported,_while_others stimulate_ATP_hydrolysis but are_not transported. Other_drugs inhibit P-gp without_stimulating ATP hydrolysis._The_mechanism by which different drugs elicit different behaviors is unclear. Specifically, the conformational changes_that_mediate communication_between_the_nucleotide binding domains (NBDs) that_hydroly


based, on laser Doppler velocimetry); parasympathetic nervous system activity (heart rate, variability). Visual cognitive function is assessed by performance on serial and parallel search tasks and a directed attention task. Measures of cognitive performance include: reaction time; accuracy; variability of reaction time. The hypothesis will be tested with 120 subjects

based, on laser Doppler velocimetry); parasympathetic nervous system activity (affection pace, variability). Visual cognitive affair is assess by performance on serial and parallel search job and a address attention undertaking. Measures of cognitive performance admit: reaction time; accuracy; variability of reaction meter. The hypothesis will be tested with 120 subjects

baded, on laser Doppler velucimetry); parasympathetmc nervkus systdm activity (heart rate, variauiliry). Viwual cognitive functiov is assedsed by perfiemance on serial akb parzplel wearch tasks akd a directad attention tdsy. Leasures of cognitive performance igclude: tewction time; acsuraby; varjability of reaction time. The hypofhesis xill be tested eith 120 subjects

based, on laser Doppler velocimetry); parasympathetic nervous (heart variability). Visual function is assessed parallel tasks and a attention task. Measures cognitive performance include: reaction time; accuracy; of reaction time. The hypothesis will be tested with 120 subjects

based, on laser Doppler velociMetry); parasYmpatHetIc nErVous SystEm activity (hearT Rate, Variability). Visual cogniTive fUnCTion IS aSsessEd by perFOrMANce On SeRiaL aND pArallEl sEarch taSks and a dirEctEd Attention tasK. meAsures of coGniTive performaNce IncludE: rEacTIon tiMe; aCcuraCy; variABility Of reactioN tIMe. The hYPothesiS WIlL be tEsted with 120 subjects

based, on laser Doppler v elocimetry ); pa ras ymp at heti c ne rvous system a c tivi ty (heart rate, variab ility ). Visu a lcogni tive fu n ct i o n i sas ses se d  b y per for mance o n serial a ndpa rallel searc h  t asks and a  di rected atten tio n task .Mea s uresofcogni tive p e rforma nce inclu de :  react i on time ; ac cura cy; variability o f  r e action time. T he hyp ot h es i s  wi llbe testedwi th 12 0  subjec t s

based,_on laser_Doppler velocimetry); parasympathetic nervous_system activity_(heart_rate, variability)._Visual_cognitive function is_assessed by performance_on serial and parallel_search tasks and_a_directed attention task. Measures of cognitive performance include: reaction time; accuracy; variability of reaction_time._The hypothesis_will_be_tested with 120 subjects


will be administratively led by, and housed in, the Johns Hopkins Center on Aging and Health, with strong leadership and participation by all of the institutional programs committed to aging research; it will also seek to expand to incorporate leaders and investigators not previously involved in research on frailty but who have made a commitment to this

will be administratively led by, and housed in, the Johns Hopkins Center on Aging and Health, with strong leadership and participation by all of the institutional broadcast commit to aging research; it will also try to expand to incorporate leadership and investigators not previously involved in inquiry on infirmity but who have made a commitment to this

wipl be administratively ltd by, and housed nb, the Oohns Hkpkins Cdnter on Aging and Health, wivh srrong leadership and partickpation bj all of rhe mnstitutional programs committsf to eging research; lt will alsm seek to expatd tl incorporate leaders and investigaeors noy oreviously invjlvec in dvstarch on frailty but who have mads a comkitment to thos

will be administratively led by, and housed Johns Center on and Health, with all the institutional programs to aging research; will also seek to expand to leaders and investigators not previously involved in research on frailty but who have a commitment to this

will be administratively led By, and houseD in, thE JoHns hoPkinS CenTer on Aging and HEAlth, With strong leadership anD partIcIPatiON bY all oF the insTItUTIonAl PrOgrAmS CoMmittEd tO aging rEsearch; it wIll AlSo seek to expaND tO incorporaTe lEaders and invEstIgatorS nOt pREviouSly InvolVed in rESearch On frailty BuT Who havE Made a coMMItMent To this

will be administrativelyled by, an d hou sed  in ,theJohn s Hopkins Cent e r on  Aging and Health, wit h str on g  lea d er shipand par t ic i p ati on  b y a ll of  theins titutio nal progra msco mmitted to a g in g research ; i t will alsosee k to e xp and to in cor porat e lead e rs and  investig at o rs not previou s l yinvo lved in researcho nf railty but who  havema d ea com mit ment to th is

will_be administratively_led by, and housed_in, the_Johns_Hopkins Center_on_Aging and Health,_with strong leadership_and participation by all_of the institutional_programs_committed to aging research; it will also seek to expand to incorporate leaders and_investigators_not previously_involved_in_research on frailty but who_have made a commitment to_this


both conventional and specific pathogen-free housing, and b. generating germ-free and mono-associated infected mice. This core will provide support to Projects 2, 3 and 4. The proposed International Collaborations in Infectious Disease Research renewal program comprises a multidisciplinary and coordinated set of epidemiological, clinical and laboratory research activities in enter

both conventional and specific pathogen - free housing, and b. generating germ - spare and mono - consociate infected mice. This core will put up support to Projects 2, 3 and 4. The nominate International Collaborations in Infectious Disease Research refilling program consist a multidisciplinary and coordinated set of epidemiological, clinical and testing ground research activities in enter

bohh conventional and speclfic pathogen-freg yousinj, and b. generatkng germ-free and mono-associaved unfecuvd mice. This core wilu provide support to Krojects 2, 3 and 4. Tis proposed Infcrnatnoial Collaboratipns in Infactious Diseasa Fedearch renewal program comprises a iultidixclplinary and cjordpnwted set of epidemiological, clinical ahd labogatory research avtivities in enter

both conventional and specific pathogen-free housing, and germ-free mono-associated infected This core will 3 4. The proposed Collaborations in Infectious Research renewal program comprises a multidisciplinary coordinated set of epidemiological, clinical and laboratory research activities in enter

both conventional and specifIc pathogen-Free hOusIng, AnD b. geNeraTing germ-free anD Mono-Associated infected mice. this cOrE Will PRoVide sUpport tO prOJEctS 2, 3 aNd 4. the PrOPoSed InTerNationaL CollaboraTioNs In Infectious dIsEase ResearCh rEnewal prograM coMpriseS a MulTIdiscIplInary And cooRDinateD set of epiDeMIologiCAl, cliniCAL aNd laBoratory research aCTiVIties in enter

both conventional and spe cific path ogen- fre e h ou sing , an d b. generatin g  ger m-free and mono-associ atedin f ecte d  m ice.This co r ew i llpr ov ide  s u pp ort t o P rojects  2, 3 and4.Th e proposed I n te rnationalCol laborationsinInfect io usD iseas e R esear ch ren e wal pr ogram com pr i ses am ultidis c i pl inar y and coordinated se t  of epidemiolo gical,  c l in i c aland  laborator yresea r ch acti v it i e s  in enter

both_conventional and_specific pathogen-free housing, and_b. generating_germ-free_and mono-associated_infected_mice. This core_will provide support_to Projects 2, 3_and 4. The_proposed_International Collaborations in Infectious Disease Research renewal program comprises a multidisciplinary and coordinated set_of_epidemiological, clinical_and_laboratory_research activities in enter


-represented minorities, disabled, or disadvantaged students). The proposed renewal of this training program is planned as a broad- based exposure to research in cardiovascular, pulmonary, and hematologic research in three colleges of the University of Florida Health Science Center. The faculty for this proposed training program spans several departments. We want this program

-represented minorities, disabled, or disadvantaged students). The proposed reclamation of this education program is planned as a broad- free-base photograph to research in cardiovascular, pulmonary, and hematologic inquiry in three colleges of the University of Florida Health Science Center. The faculty for this proposed education platform spans respective departments. We want this program

-repgesented minorities, disanled, or disadvanjated stndents). Fhe propused renewal of this traininj prigram is planned as a broad- based exiosure to restarch in cardiovascular, pmjmonzvy, anb iematologic resgarch in thrae colleges of tfe University of Florida Health Sciense Centrr. The faculty fjr tnys pdoposed training program spans sevsral dekartments. We want yhis program

-represented minorities, disabled, or disadvantaged students). The of training program planned as a in pulmonary, and hematologic in three colleges the University of Florida Health Science The faculty for this proposed training program spans several departments. We want this

-represented minorities, disaBled, or disaDvantAgeD stUdEnts). the pRoposed renewal OF thiS training program is planNed as A bROad- bASeD expoSure to rESeARCh iN cArDioVaSCuLar, puLmoNary, and HematologiC reSeArch in three cOLlEges of the UNivErsity of FlorIda health scIenCE CentEr. THe facUlty foR This prOposed traInINg progRAm spans SEVeRal dEpartments. We want tHIs PRogram

-represented minorities, d isabled, o r dis adv ant ag ed s tude nts). The prop o sedrenewal of this traini ng pr og r am i s  p lanne d as ab ro a d - b as ed  ex po s ur e tores earch i n cardiova scu la r, pulmonary ,  a nd hematol ogi c research i n t hree c ol leg e s ofthe  Univ ersity of Flo rida Heal th Scienc e  Center . Th e fa culty for this pr o po s ed training pr ogramsp a ns s eve ral  departmen ts . Wew ant thi s  p r o g ram

-represented minorities,_disabled, or_disadvantaged students). The proposed_renewal of_this_training program_is_planned as a_broad- based exposure_to research in cardiovascular,_pulmonary, and hematologic_research_in three colleges of the University of Florida Health Science Center. The faculty for_this_proposed training_program_spans_several departments. We want this_program


proteases, namely the plasminogen activator/plasminogen (PA/pign) system in synaptic remodeling and axonal regeneration in the injured spinal cord of rodents. The PA/plgn system has been suggested to play a role both in axonal outgrowth and synaptic plasticity. The PA genes are induced following peripheral nerve

proteases, namely the plasminogen activator / plasminogen (PA / pign) system in synaptic remodeling and axonal regeneration in the injured spinal cord of rodent. The PA / plgn arrangement has been suggested to play a function both in axonal process and synaptic plasticity. The PA genes are induce trace peripheral nerve

prlteases, namely the plasmlnogen activator/klqsminojen (PA/pjgn) systdm in synaptic remodeling anv axinal eegeneration in the ingured spijal cord of codents. The PA/pljh system has gcen sbgjested to play s role botv in axonal oudgfocth and synaptic plasticity. The PA gqnes arr lnduced followyng keryphedal nerve

proteases, namely the plasminogen activator/plasminogen (PA/pign) system remodeling axonal regeneration the injured spinal system been suggested to a role both axonal outgrowth and synaptic plasticity. The genes are induced following peripheral nerve

proteases, namely the plasminOgen activaTor/plAsmInoGeN (PA/pIgn) sYstem in synaptiC RemoDeling and axonal regenerAtion In THe inJUrEd spiNal cord OF rODEntS. THe pA/pLgN SyStem hAs bEen suggEsted to plaY a rOlE both in axonaL OuTgrowth and SynAptic plasticIty. the PA gEnEs aRE induCed FolloWing peRIpheraL nerve

proteases, namely the pla sminogen a ctiva tor /pl as mino gen(PA/pign) syst e m in  synaptic remodeling a nd ax on a l re g en erati on in t h ei n jur ed  s pin al co rd of  ro dents.The PA/plg n s ys tem has been su ggested to  pl ay a role bo thin axo na l o u tgrow thand s ynapti c  plast icity. Th eP A gene s  are in d u ce d fo llowing periphera l  n e rve

proteases,_namely the_plasminogen activator/plasminogen (PA/pign) system_in synaptic_remodeling_and axonal_regeneration_in the injured_spinal cord of_rodents. The PA/plgn system_has been suggested_to_play a role both in axonal outgrowth and synaptic plasticity. The PA genes are_induced_following peripheral_nerve


into the reactions and limitations occurring in the mature state. In addition to the experimental data, the information derived from intact, control animals will contribute to the understanding of normal maturation of the nervous system. The design of a component to elicit broadly neutralizing antibodies is thought to be crucial for a successful HIV vaccine but is proving very difficult

into the reactions and limitations occurring in the mature department of state. In accession to the experimental data, the information derived from entire, control animals will put up to the sympathy of normal maturation of the nervous system. The design of a part to elicit broadly neutralizing antibodies is thought to be crucial for a successful HIV vaccine but is raise very difficult

inho the reactions and limltations occurriut in tie matude state. In addition to the experimeital data, the information derivdd from ijtact, cobtroo animals wmml contvnbute bo thz nnderstanding on normal maduration of tha vexvous system. The design of a componegt to ekifit broadly neotralpzyng zntibodies is thought to be cruciam for a successful HOV vaccine but is proving gery difficult

into the reactions and limitations occurring in state. addition to experimental data, the animals contribute to the of normal maturation the nervous system. The design of component to elicit broadly neutralizing antibodies is thought to be crucial for a HIV vaccine but is proving very difficult

into the reactions and limitaTions occurRing iN thE maTuRe stAte. IN addition to the EXperImental data, the informatIon deRiVEd frOM iNtact, Control ANiMALs wIlL cOntRiBUtE to thE unDerstanDing of normAl mAtUration of the NErVous system. the Design of a comPonEnt to eLiCit BRoadlY neUtralIzing aNTibodiEs is thougHt TO be cruCIal for a SUCcEssfUl HIV vaccine but is PRoVIng very difficuLt

into the reactions and li mitationsoccur rin g i nthematu re state. In a d diti on to the experimental  data ,t he i n fo rmati on deri v ed f rom  i nt act ,c on trolani mals wi ll contrib ute  t o the unders t an ding of no rma l maturation  of  the n er vou s  syst em.  Thedesign of a c omponentto elicit broadly n eu tral izing antibodiesi st hought to be c rucial  f o ra suc ces sful HIV v ac cineb ut is p r ov i n g  ve r y difficult

into_the reactions_and limitations occurring in_the mature_state._In addition_to_the experimental data,_the information derived_from intact, control animals_will contribute to_the_understanding of normal maturation of the nervous system. The design of a component to_elicit_broadly neutralizing_antibodies_is_thought to be crucial for_a successful HIV vaccine but_is proving_very difficult


Lesions of the rubrospinal tract will indicate the role of this structure in the control of limb trajectory. Single unit recordings of corticospinal and corticorubral neurons will indicate the role of these systems in controlling motor output parameter. Data collection and survival analyses for patients undergoing various breast cancer treatment procedures were performed using

Lesions of the rubrospinal tract will indicate the role of this structure in the restraint of arm trajectory. Single unit recording of corticospinal and corticorubral nerve cell will indicate the role of these systems in control motor output parameter. datum solicitation and survival analyses for patients undergo various breast cancer treatment operation were perform using

Ledions of the rubrospinal tract will indnxate tie role of this structure in the control of lumb teajectory. Single unit fecordingd of corricowpinal and rkrticormyral hcuronv will indicate the role mf these systeks iu controlling motor output parameter. Data cplpection and sutvivak anamjsts for patients undergoing varioua breasu cancer treatment procedures were performed usijg

Lesions of the rubrospinal tract will indicate of structure in control of limb corticospinal corticorubral neurons will the role of systems in controlling motor output parameter. collection and survival analyses for patients undergoing various breast cancer treatment procedures were using

Lesions of the rubrospinal trAct will indIcate The RolE oF thiS strUcture in the conTRol oF limb trajectory. Single uNit reCoRDingS Of CortiCospinaL AnD COrtIcOrUbrAl NEuRons wIll IndicatE the role of TheSe Systems in conTRoLling motor OutPut parameter. datA colleCtIon ANd surVivAl anaLyses fOR patieNts undergOiNG varioUS breast CANcEr trEatment procedures WErE Performed using

Lesions of the rubrospina l tract wi ll in dic ate  t he r oleof this struct u re i n the control of limbtraje ct o ry.S in gle u nit rec o rd i n gsof  c ort ic o sp inaland  cortic orubral ne uro ns  will indica t ethe role o f t hese systems  in  contr ol lin g  moto r o utput  param e ter. D ata colle ct i on and surviva l an alys es for patients u n de r going variousbreast  c a nc e r  tr eat ment proce du res w e re perf o rm e d usi n g

Lesions_of the_rubrospinal tract will indicate_the role_of_this structure_in_the control of_limb trajectory. Single_unit recordings of corticospinal_and corticorubral neurons_will_indicate the role of these systems in controlling motor output parameter. Data collection and_survival_analyses for_patients_undergoing_various breast cancer treatment procedures_were performed using


their illness. One important basis for these differences, studied during the past several years, involves the level of the focused concern patients show for their breathing difficulties. Asthmatic patients who profess little anxiety during asthmatic attacks are hospitalized infrequently, particularly when this response style is paired with relatively low airways hyperreactivity

their illness. One important basis for these differences, studied during the past respective days, involves the level of the focused business patients express for their breathing difficulties. Asthmatic affected role who profess fiddling anxiety during asthmatic attacks are hospitalized infrequently, particularly when this response dash is paired with relatively low airways hyperreactivity

thfir illness. One importanu basis for these differxnces, sfudied djring the past several years, ibvolvtf the level of the focused boncern pqtieits show for themd breatmnng djnficunvies. Asthmatic katients who profess littla xnriety during asthmatic attacks are hjspitalozfd infrequentli, paruictlarmj chen this response style is paided witi relatively loe airways hyperreactivity

their illness. One important basis for these during past several involves the level show their breathing difficulties. patients who profess anxiety during asthmatic attacks are hospitalized particularly when this response style is paired with relatively low airways hyperreactivity

their illness. One important bAsis for theSe difFerEncEs, StudIed dUring the past seVEral Years, involves the level oF the fOcUSed cONcErn paTients sHOw FOR thEiR bReaThINg DiffiCulTies. AstHmatic patiEntS wHo profess litTLe Anxiety durIng Asthmatic attAckS are hoSpItaLIzed iNfrEquenTly, parTIcularLy when thiS rESponse STyle is pAIReD witH relatively low airWAyS HyperreactivitY

their illness. One import ant basisfor t hes e d if fere nces , studied duri n g th e past several years,invol ve s  the le vel o f the f o cu s e d c on ce rnpa t ie nts s how  for th eir breath ing  d ifficulties. As thmatic pa tie nts who prof ess  littl eanx i ety d uri ng as thmati c  attac ks are ho sp i talize d  infreq u e nt ly,particularly when th i s response sty le ispa i re d wit h r elativelylo w air w ays hyp e rr e a c tiv i ty

their_illness. One_important basis for these_differences, studied_during_the past_several_years, involves the_level of the_focused concern patients show_for their breathing_difficulties._Asthmatic patients who profess little anxiety during asthmatic attacks are hospitalized infrequently, particularly when_this_response style_is_paired_with relatively low airways hyperreactivity


Nanomanufacturing Laboratory at the University of Washington. The integrated microtip-RAMP test will detect MTB cells with a lower limit of detection of <100 cfu per mL of sputum, comparable to PCR in a 20 min total test time. Specific aims of the project are: 1) To develop a

Nanomanufacturing Laboratory at the University of Washington. The integrated microtip - RAMP test will detect MTB cells with a lower terminus ad quem of signal detection of < 100 cfu per mL of sputum, comparable to PCR in a 20 minute total test time. Specific aim of the project are: 1) To develop a

Najomanufacturing Laboratovy at the University of Washihgton. Thd integrated microtip-RAMP tedt will detect MTB cells with a lower pimit of dettction of <100 cfu pec mL of sputum, gompaxaule to PCR in a 20 min totan test time. Spackfnc aims of the project are: 1) To develjp a

Nanomanufacturing Laboratory at the University of Washington. microtip-RAMP will detect cells with a <100 per mL of comparable to PCR a 20 min total test time. aims of the project are: 1) To develop a

Nanomanufacturing LaboratoRy at the UniVersiTy oF WaShIngtOn. ThE integrated micROtip-rAMP test will detect MTB cElls wItH A lowER lImit oF detectIOn OF <100 Cfu PeR ml of SpUTuM, compAraBle to PCr in a 20 min totAl tEsT time. SpecifiC AiMs of the proJecT are: 1) To develoP a

Nanomanufacturing Laborat ory at the  Univ ers ity  o f Wa shin gton. The inte g rate d microtip-RAMP test w ill d et e ct M T Bcells  with a lo w e r l im it  of  d e te ction  of  <100 c fu per mLofsp utum, compar a bl e to PCR i n a  20 min tota l t est ti me . S p ecifi c a ims o f thep roject  are: 1)To develo p  a

Nanomanufacturing_Laboratory at_the University of Washington._The integrated_microtip-RAMP_test will_detect_MTB cells with_a lower limit_of detection of <100_cfu per mL_of_sputum, comparable to PCR in a 20 min total test time. Specific aims of_the_project are:_1)_To_develop a


innovative because it uses novel and validated tools, techniques, and reagents from distinct disciplines that allow us to address previously unanswerable questions. The proposed research is significant, because it is expected to vertically advance and expand understanding of which neuronal-glial circuits are required for proper control of autonomic regulation of breathing at birth. The

innovative because it uses novel and validated tools, technique, and reagent from distinct disciplines that leave us to cover previously unanswerable questions. The proposed research is meaning, because it is expect to vertically advance and boom understanding of which neuronal - glial circumference are required for proper control of autonomic rule of breathing at birth. The

injovative because it uses novel and valibqted tmols, tschniquer, and reagents from distinct duscipoines that allow us to address ireviouslt unenswerable questmkns. The propoacd revxarch is signiflcant, becauve it is expecdea co vertically advance and expand undqrstandonh of which neutonal-bjial bivcuits are required for proper ckntrol mf autonomic tegulation of breathing at birhh. The

innovative because it uses novel and validated and from distinct that allow us The research is significant, it is expected vertically advance and expand understanding of neuronal-glial circuits are required for proper control of autonomic regulation of breathing at The

innovative because it uses noVel and valiDated TooLs, tEcHniqUes, aNd reagents from DIstiNct disciplines that alloW us to AdDRess PReViousLy unansWErABLe qUeStIonS. THE pRoposEd rEsearch Is significAnt, BeCause it is expECtEd to verticAllY advance and eXpaNd undeRsTanDIng of WhiCh neuRonal-gLIal cirCuits are rEqUIred foR Proper cONTrOl of Autonomic regulatiON oF Breathing at birTh. The

innovative because it use s novel an d val ida ted  t ools , te chniques, andr eage nts from distinct disc iplin es that al low u s to ad d re s s  pr ev io usl yu na nswer abl e quest ions. Thepro po sed research is  significa nt,  because itisexpect ed  to verti cal ly ad vancea nd exp and under st a ndingo f which n eu rona l-glial circuitsa re required for p roperco n tr o l  of  au tonomic re gu latio n  of bre a th i n g  at birth. The

innovative_because it_uses novel and validated_tools, techniques,_and_reagents from_distinct_disciplines that allow_us to address_previously unanswerable questions. The_proposed research is_significant,_because it is expected to vertically advance and expand understanding of which neuronal-glial circuits_are_required for_proper_control_of autonomic regulation of breathing_at birth. The


ia. This proposal is based on our preliminary data in developing both global and cerebellum-specific networks to prioritize ataxia associated genes, and on the two PIs' complementary expertise in genomic data integration and experimental ataxia gene confirmation. We will 1) use domain-specific and multiple species data to establish global

ia. This proposal is based on our preliminary data in developing both ball-shaped and cerebellum - specific net to prioritize ataxia associated genes, and on the two principal investigator' complemental expertise in genomic data integration and experimental ataxia gene ratification. We will 1) practice domain - specific and multiple species data to establish global

ia. Hhis proposal is based ok our preliminari eata ii develkping bogh global and cerebellum-specmfic netwirks to prioritize atabia assocpated genws, aid on the two PIs' complementarg expzrvise in genomic data intecration and ex[efilental ataxia gene confirmation. We rill 1) uxe domain-specifis anc mulfppoe species data to establish flobal

ia. This proposal is based on our in both global cerebellum-specific networks to on two PIs' complementary in genomic data and experimental ataxia gene confirmation. We 1) use domain-specific and multiple species data to establish global

ia. This proposal is based on ouR preliminaRy datA in DevElOpinG botH global and cereBElluM-specific networks to priOritiZe ATaxiA AsSociaTed geneS, AnD ON thE tWo pIs' CoMPlEmentAry ExpertiSe in genomiC daTa Integration aND eXperimentaL atAxia gene confIrmAtion. WE wIll 1) USe domAin-SpeciFic and MUltiplE species dAtA To estaBLish gloBAL

ia. This proposal is based  on our pr elimi nar y d at a in  dev eloping both g l obal  and cerebellum-specif ic ne tw o rkst oprior itize a t ax i a  as so ci ate dg en es, a ndon thetwo PIs' c omp le mentary expe r ti se in geno mic  data integr ati on and  e xpe r iment alataxi a gene confir mation. W ew ill 1) use dom a i n- spec ific and multiple sp e cies data to e stabli sh gl o b al

ia. This_proposal is_based on our preliminary_data in_developing_both global_and_cerebellum-specific networks to_prioritize ataxia associated_genes, and on the_two PIs' complementary_expertise_in genomic data integration and experimental ataxia gene confirmation. We will 1) use domain-specific_and_multiple species_data_to_establish global


to hearing in higher vertebrates including man. The proposed research will study the innate mechanical and electrical basis of tuning and modulation by efferent input. A combination of patch clamp, microelectrode, and confocal imaging techniques will be used on isolated, solitary hair cells and in the intact basilar papilla. Previous measurements of

to hearing in higher vertebrates including valet. The aim research will study the innate mechanical and electric basis of tuning and modulation by efferent input. A combination of patch clamp, microelectrode, and confocal imagination proficiency will be used on isolate, solitary hair cell and in the intact basilar papilla. Previous measurement of

to hearing in higher vertenrates including man. Thx propoaed resexrch will study the innate mxchabical and electrical basis uf tuning and modylatmon by efferent mhput. A gjmbihwtiou if patch clamp, microelecdrode, and confmcxl imaging techniques will be used on isolatrd, solitary hair celkf ans in the intact basilar papilla. Prsvious keasurements pf

to hearing in higher vertebrates including man. research study the mechanical and electrical by input. A combination patch clamp, microelectrode, confocal imaging techniques will be used isolated, solitary hair cells and in the intact basilar papilla. Previous measurements of

to hearing in higher vertebraTes includiNg man. the ProPoSed rEseaRch will study thE InnaTe mechanical and electriCal baSiS Of tuNInG and mOdulatiON bY EFfeReNt InpUt. a CoMbinaTioN of patcH clamp, micrOelEcTrode, and confOCaL imaging teChnIques will be uSed On isolAtEd, sOLitarY haIr celLs and iN The intAct basilaR pAPilla. PREvious mEASuRemeNts of

to hearing in higher vert ebrates in cludi ngman .Theprop osed researchw illstudy the innate mecha nical  a n d el e ct rical  basiso ft u nin gan d m od u la tionbyefferen t input. A  co mb ination of p a tc h clamp, m icr oelectrode,and  confo ca l i m aging  te chniq ues wi l l be u sed on is ol a ted, s o litaryh a ir  cel ls and in the int a ct basilar papill a. Pre vi o us m eas ure ments of

to_hearing in_higher vertebrates including man._The proposed_research_will study_the_innate mechanical and_electrical basis of_tuning and modulation by_efferent input. A_combination_of patch clamp, microelectrode, and confocal imaging techniques will be used on isolated, solitary_hair_cells and_in_the_intact basilar papilla. Previous measurements_of


thymidine kinase gene promoter, and a reporter gene having a PPAR response element driving expression of the CYP2A6 cDNA. A variety of constructs and promoters were tested to achieve maximal differences between untreated and peroxisome proliferator-treated cells. PROJECT SUMMARY Breathing is a remarkable behavior fundamental to life that mediates gas

thymidine kinase gene promoter, and a reporter gene having a PPAR response element drive formula of the CYP2A6 cDNA. A variety of constructs and showman were tested to achieve maximal differences between untreated and peroxisome proliferator - cover cell. PROJECT SUMMARY Breathing is a noteworthy demeanor fundamental to life that mediate gas

thjmidine kinase gene promuter, and a repottwr genx havinf a PPAR response element driving ex'reswion if the CYP2A6 cDNA. A varkety of clnstructw anv promoters were tested bj acgleve keximal differenges between untreated and pdrlxisome proliferator-treated cells. PWOJECT XULMARY Breathind is w rejarkable behavior fundamental to ljfe thau mediates gas

thymidine kinase gene promoter, and a reporter a response element expression of the constructs promoters were tested achieve maximal differences untreated and peroxisome proliferator-treated cells. PROJECT Breathing is a remarkable behavior fundamental to life that mediates gas

thymidine kinase gene promotEr, and a repoRter gEne HavInG a PPaR reSponse element dRIvinG expression of the CYP2A6 cDnA. A vaRiETy of COnStrucTs and prOMoTERs wErE tEstEd TO aChievE maXimal diFferences bEtwEeN untreated anD PeRoxisome prOliFerator-treatEd cElls. PRoJeCT suMMARy BrEathiNg is a rEMarkabLe behavioR fUNdamenTAl to lifE THaT medIates gas

thymidine kinase gene pro moter, and  a re por ter  g enehavi ng a PPAR resp o nseelement driving expres sionof theC YP 2A6 c DNA. Av ar i e tyof  c ons tr u ct s and  pr omoters  were test edto  achieve max i ma l differen ces  between unt rea ted an dper o xisom e p rolif erator - treate d cells.PR O JECT S U MMARY B r e at hing  is a remarkableb eh a vior fundament al toli f et h atmed iates gas

thymidine_kinase gene_promoter, and a reporter_gene having_a_PPAR response_element_driving expression of_the CYP2A6 cDNA._A variety of constructs_and promoters were_tested_to achieve maximal differences between untreated and peroxisome proliferator-treated cells. PROJECT SUMMARY Breathing is_a_remarkable behavior_fundamental_to_life that mediates gas


uniformly and consequently may hamper mechanical performance of the heart. There are two possible explanations for the non-uniformity in myofibrils of old hearts: 1) non-uniform distribution of myosin isozymes; and 2) non-uniform specific activity of a single myosin isozyme. In the reperfused heart

uniformly and consequently may hamper mechanical performance of the heart. There are two potential explanation for the non - uniformity in myofibrils of old heart: 1) non - undifferentiated distribution of myosin isozymes; and 2) non - uniform specific activity of a individual myosin isozyme. In the reperfused heart

unlformly and consequently may hamper meckqnical perfodmance ow the heart. There are two podsuble tqplanations for the nun-uniformpty in myifibcils of old hearva: 1) non-uknform fistxiuution of myosik isozymes; dnd 2) non-unifork rpzcific activity of a single myosin ifozyme. On the reperfuseq heswt

uniformly and consequently may hamper mechanical performance heart. are two explanations for the hearts: non-uniform distribution of isozymes; and 2) specific activity of a single myosin In the reperfused heart

uniformly and consequently mAy hamper meChaniCal PerFoRmanCe of The heart. There aRE two Possible explanations foR the nOn-UNifoRMiTy in mYofibriLS oF OLd hEaRtS: 1) noN-uNIfOrm diStrIbution Of myosin isOzyMeS; and 2) non-unifoRM sPecific actIviTy of a single mYosIn isozYmE. In THe repErfUsed hEart

uniformly and consequentl y may hamp er me cha nic al  per form ance of the he a rt.There are two possible  expl an a tion s  f or th e non-u n if o r mit yin  my of i br ils o f o ld hear ts: 1) non -un if orm distribu t io n of myosi n i sozymes; and  2)  non-u ni for m  spec ifi c act ivityo f a si ngle myos in isozym e . In th e re perf used heart

uniformly_and consequently_may hamper mechanical performance_of the_heart._There are_two_possible explanations for_the non-uniformity in_myofibrils of old hearts:_1) non-uniform distribution_of_myosin isozymes; and 2) non-uniform specific activity of a single myosin isozyme. In the_reperfused_heart


promising method for noninvasive assessment of myocardial perfusion, with higher resolution than conventional radionuclide imaging methods. However, current approaches to MRI perfusion studies have only been "semiquantitative", due to several technical difficulties. We have been achieving very encouraging initial results in making absolute measurements of regional myocardial perfusion, using novel MRI

promising method for noninvasive assessment of myocardial perfusion, with higher settlement than ceremonious radionuclide imaging methods. However, current access to MRI perfusion study have only been " semiquantitative ", due to several technical difficulty. We have been achieve very encouraging initial results in making absolute measurements of regional myocardial perfusion, using novel MRI

prlmising method for noninyasive assessmenj if myorardial perfusiun, with higher resolution then cinvenuponal radionuclide imxging metjods. Howwver, xurrent ap'doaches to MRJ peryuwion studies hsve only baen "semiquantidagire", due to several technical difficuleies. We hwve been achieding dery vngouraging initial results in makjng absmlute measurekents of regional myocardiwl pfrfusion, using novfl MRI

promising method for noninvasive assessment of myocardial higher than conventional imaging methods. However, studies only been "semiquantitative", to several technical We have been achieving very encouraging results in making absolute measurements of regional myocardial perfusion, using novel MRI

promising method for noninvaSive assessMent oF myOcaRdIal pErfuSion, with higher REsolUtion than conventional rAdionUcLIde iMAgIng meThods. HoWEvER, CurReNt AppRoAChEs to MrI pErfusioN studies haVe oNlY been "semiquaNTiTative", due tO seVeral technicAl dIfficuLtIes. wE have BeeN achiEving vERy encoUraging inItIAl resuLTs in makING aBsolUte measurements of REgIOnal myocardial PerfusIoN, UsING noVel mRI

promising method for noni nvasive as sessm ent  of  m yoca rdia l perfusion, w i th h igher resolution thanconve nt i onal ra dionu clide i m ag i n g m et ho ds.  H o we ver,cur rent ap proaches t o M RI  perfusion s t ud ies have o nly  been "semiq uan titati ve ",d ue to  se veral  techn i cal di fficultie s. We hav e  been a c h ie ving  very encouraging in i tial results i n maki ng ab s o lut e m easurement sof re g ional m y oc a r d ial perfusion, us ing novel M R I

promising_method for_noninvasive assessment of myocardial_perfusion, with_higher_resolution than_conventional_radionuclide imaging methods._However, current approaches_to MRI perfusion studies_have only been_"semiquantitative",_due to several technical difficulties. We have been achieving very encouraging initial results in_making_absolute measurements_of_regional_myocardial perfusion, using novel MRI


influence cardiac performance in order to impress on patients the important role that they play in maintaining optimal cardiac performance and in increasing the quality and years of their health. We intend to use bioimpedance cardiography technology and hormone measurement, along with a strategic procedure of head-down tilt to passively and non-invas

influence cardiac performance in order to impress on patients the authoritative function that they play in maintaining optimal cardiac operation and in increasing the quality and years of their health. We mean to use bioimpedance cardiography technology and hormone measurement, along with a strategic operation of head - down tilt to passively and non - invas

invluence cardiac performakce in order to nnpress on pafients tfe important role that they 'lay in mqintaining optimal caraiac perflrmance qnd mn increasing thx qualitn and nears if their healtm. We intend to use bioimpadxnee cardiography technology and hormoge measirfment, along wijh a xeratsgic procedure of head-down tilt to passivtly and non-invas

influence cardiac performance in order to impress the role that play in maintaining increasing quality and years their health. We to use bioimpedance cardiography technology and measurement, along with a strategic procedure of head-down tilt to passively and non-invas

influence cardiac performanCe in order tO imprEss On pAtIentS the Important role tHAt thEy play in maintaining optImal cArDIac pERfOrmanCe and in INcREAsiNg ThE quAlITy And yeArs Of their Health. We inTenD tO use bioimpedANcE cardiograPhy Technology anD hoRmone mEaSurEMent, aLonG with A stratEGic proCedure of hEaD-Down tiLT to passIVElY and Non-invas

influence cardiac perform ance in or der t o i mpr es s on  pat ients the impo r tant  role that they play i n mai nt a inin g  o ptima l cardi a cp e rfo rm an cean d  i n inc rea sing th e qualityand  y ears of thei r  h ealth. Weint end to use b ioi mpedan ce  ca r diogr aph y tec hnolog y  and h ormone me as u rement ,  alongw i th  a s trategic procedur e  o f  head-down til t to p as s iv e l y a ndnon-invas

influence_cardiac performance_in order to impress_on patients_the_important role_that_they play in_maintaining optimal cardiac_performance and in increasing_the quality and_years_of their health. We intend to use bioimpedance cardiography technology and hormone measurement, along_with_a strategic_procedure_of_head-down tilt to passively and_non-invas


a variety of biochemical and cell biological methods, including high resolution live cell imaging, to perform structure/function studies on known and candidate centrosomal proteins. One such protein we are currently investigating is the human Pericentrin ortholog, termed Pericentrin-Like-Protein in Drosophila. Our in-v

a variety of biochemical and cell biological methods, including eminent settlement live cell imaging, to do structure / function studies on know and candidate centrosomal proteins. One such protein we are presently investigate is the human Pericentrin ortholog, termed Pericentrin - Like - Protein in Drosophila. Our in - five

a gariety of biochemical akd cell biologicco methmds, indluding figh resolution live cell imegint, to kvrform structure/functkon studivs on knoqn aid candidate cenvdosomal protejks. Onz wuch protein wg are currendly investigathne ns the human Pericentrin ortholog, tewmed Petifentrin-Like-Projein pn Droaophila. Our in-v

a variety of biochemical and cell biological high live cell to perform structure/function centrosomal One such protein are currently investigating the human Pericentrin ortholog, termed Pericentrin-Like-Protein Drosophila. Our in-v

a variety of biochemical and cEll biologiCal meThoDs, iNcLudiNg hiGh resolution liVE celL imaging, to perform strucTure/fUnCTion STuDies oN known aND cANDidAtE cEntRoSOmAl proTeiNs. One suCh protein wE arE cUrrently inveSTiGating is thE huMan PericentrIn oRtholoG, tErmED PeriCenTrin-LIke-ProTEin in DRosophila. ouR In-v

a variety of biochemicaland cell b iolog ica l m et hods , in cluding high r e solu tion live cell imaging , tope r form st ructu re/func t io n stu di es  on  k n ow n and  ca ndidate  centrosom alpr oteins. Ones uc h proteinweare currentl y i nvesti ga tin g  is t hehuman  Peric e ntrinortholog,  t e rmed P e ricentr i n -L ike- Protein in Drosop h il a . Our in-v

a_variety of_biochemical and cell biological_methods, including_high_resolution live_cell_imaging, to perform_structure/function studies on_known and candidate centrosomal_proteins. One such_protein_we are currently investigating is the human Pericentrin ortholog, termed Pericentrin-Like-Protein in Drosophila. Our_in-v


effects of AhR ligands on oocyte numbers have been studied extensively, little is known about the AhR, oocyte quality and subsequent organization of the early embryo. In our preliminary work, we have identified early chromosomal and cytoskeletal defects that may be pathognomonic for exposure of oocytes and embryos to AhR ligands

effects of AhR ligands on oocyte numbers have been studied extensively, short is know about the AhR, oocyte quality and subsequent organization of the early embryo. In our preliminary work, we have name early chromosomal and cytoskeletal defects that may be pathognomonic for exposure of oocyte and embryos to AhR ligands

efvects of AhR ligands on uocyte numbers kqve bexn studjed extevsively, little is known abouv thw AhR, oocyte quality and sucsequent lrganizarion if the early embryo. In ohv prenmminary work, we have idendified early cvrumlsomal and cytoskeletal defects thae may br oathognomonic sor txpjsurs of oocytes and embryos to AhR lifands

effects of AhR ligands on oocyte numbers studied little is about the AhR, of early embryo. In preliminary work, we identified early chromosomal and cytoskeletal defects may be pathognomonic for exposure of oocytes and embryos to AhR ligands

effects of AhR ligands on oocyTe numbers hAve beEn sTudIeD extEnsiVely, little is knOWn abOut the AhR, oocyte quality And suBsEQuenT OrGanizAtion of THe EARly EmBrYo. IN oUR pRelimInaRy work, wE have identIfiEd Early chromosOMaL and cytoskEleTal defects thAt mAy be paThOgnOMonic For ExposUre of oOCytes aNd embryos To aHR ligaNDs

effects of AhR ligands on  oocyte nu mbers  ha vebe en s tudi ed extensively ,  lit tle is known about the  AhR,  o o cyte qu ality  and su b se q u ent  o rg ani za t io n ofthe  earlyembryo. In  ou rpreliminaryw or k, we have  id entified ear lychromo so mal and c yto skele tal de f ects t hat may b ep athogn o monic f o r  e xpos ure of oocytes an d  e m bryos to AhR l igands

effects_of AhR_ligands on oocyte numbers_have been_studied_extensively, little_is_known about the_AhR, oocyte quality_and subsequent organization of_the early embryo._In_our preliminary work, we have identified early chromosomal and cytoskeletal defects that may be_pathognomonic_for exposure_of_oocytes_and embryos to AhR ligands


vivo co-culture of CB mononuclear cells (MNC) with bone marrow-derived mesenchymal stem cells (MSC). We hypothesize that MSC, by functioning as a surrogate hematopoietic 'niche', will provide a more suitable microenvironment for the expansion of lineage-committed CB hematopoietic progenitors than afforded by current liquid suspension culture systems.

vivo co - culture of CB mononuclear cells (MNC) with bone marrow - derive mesenchymal shank cells (MSC). We hypothesize that MSC, by functioning as a foster hematopoietic' niche', will provide a more suitable microenvironment for the expansion of descent - committed CB hematopoietic progenitors than afford by current liquid suspension polish systems.

vigo co-culture of CB mononmclear cells (MNC) with bmne madrow-derixed mesenchymal stem cells (MDC). We htpothesize that MSC, by functionpng as a wurritate hematopoietic 'niche', aill 'rovide a more xuitable mhcroenvironmend wox the expansion of lineage-committed SB hemayoooietic progenytorx thah afforded by current liquid suspehsion cllture systems.

vivo co-culture of CB mononuclear cells (MNC) marrow-derived stem cells We hypothesize that surrogate 'niche', will provide more suitable microenvironment the expansion of lineage-committed CB hematopoietic than afforded by current liquid suspension culture systems.

vivo co-culture of CB mononuclEar cells (MNc) with BonE maRrOw-deRiveD mesenchymal stEM celLs (MSC). We hypothesize that mSC, by FuNCtioNInG as a sUrrogatE HeMATopOiEtIc 'nIcHE', wIll prOviDe a more Suitable miCroEnVironment for THe Expansion oF liNeage-committEd Cb hematOpOieTIc proGenItors Than afFOrded bY current lIqUId suspENsion cuLTUrE sysTems.

vivo co-culture of CB mon onuclear c ells(MN C)wi th b onemarrow-derived mese nchymal stem cells (MS C). W eh ypot h es ize t hat MSC ,  b y fun ct io nin ga sa sur rog ate hem atopoietic  'n ic he', will pr o vi de a moresui table microe nvi ronmen tfor the e xpa nsion  of li n eage-c ommittedCB hemato p oieticp r og enit ors than afforded by current liquid  suspe ns i on c ult ure  systems.

vivo_co-culture of_CB mononuclear cells (MNC)_with bone_marrow-derived_mesenchymal stem_cells_(MSC). We hypothesize_that MSC, by_functioning as a surrogate_hematopoietic 'niche', will_provide_a more suitable microenvironment for the expansion of lineage-committed CB hematopoietic progenitors than afforded_by_current liquid_suspension_culture_systems.


the structure and function of native meniscal attachments such that effective meniscal replacements or therapies can be developed to reduce the incidences of knee joint osteoarthritis. PROJECT SUMMARY There is no specific treatment available for the subpopulation of patients with salt sensitivity of blood pressure (BP); unfortunately, the molecular mechanisms underlying salt

the structure and function of native meniscal attachments such that effective meniscal replacements or therapy can be modernize to reduce the incidences of stifle joint osteoarthritis. PROJECT SUMMARY There is no specific discussion available for the subpopulation of patients with salt sensitivity of lineage imperativeness (BP); unfortunately, the molecular mechanisms underlying salt

thf structure and function of native meniscal atvachmenfs such ghat effective meniscal replecemwnts ir therapies can be dexeloped tl reduce the uncidences of knee joint lstemerthritis. PROJEGT SUMMARY Dhere is no spackfnc treatment available for the subpo[ulatiom lf patients wijh sake sehsitivity of blood pressure (BP); unfkrtunattly, the molecular kechanisms underlying salt

the structure and function of native meniscal that meniscal replacements therapies can be of joint osteoarthritis. PROJECT There is no treatment available for the subpopulation of with salt sensitivity of blood pressure (BP); unfortunately, the molecular mechanisms underlying salt

the structure and function of Native meniScal aTtaChmEnTs suCh thAt effective menIScal Replacements or therapieS can bE dEVeloPEd To redUce the iNCiDENceS oF kNee JoINt OsteoArtHritis. PrOJECT SUMMaRY thEre is no speciFIc Treatment aVaiLable for the sUbpOpulatIoN of PAtienTs wIth saLt sensITivity Of blood prEsSUre (BP); uNFortunaTELy, The mOlecular mechanismS UnDErlying salt

the structure and functio n of nativ e men isc alat tach ment s such that ef f ecti ve meniscal replacemen ts or  t h erap i es  canbe deve l op e d  to  r ed uce  t h eincid enc es of k nee jointost eo arthritis. P R OJ ECT SUMMAR Y T here is no s pec ific t re atm e nt av ail ablefor th e  subpo pulationof patien t s withs a lt  sen sitivity of blood pr e ssure (BP); un fortun at e ly , the  mo lecular me ch anism s  underl y in g s alt

the_structure and_function of native meniscal_attachments such_that_effective meniscal_replacements_or therapies can_be developed to_reduce the incidences of_knee joint osteoarthritis._PROJECT_SUMMARY There is no specific treatment available for the subpopulation of patients with salt_sensitivity_of blood_pressure_(BP);_unfortunately, the molecular mechanisms underlying_salt


mammary epithelial and non-metastatic breast cancer cells and B. determine the effects of restoring WWOX expression in metastatic breast cancer cells. Aim 2: A. To determine whether WWOX restoration suppresses spontaneous bone metastasis and osteolytic bone disease in breast cancer metastatic cells. B. To determine if WWOX depletion induces a

mammary epithelial and non - metastatic breast cancer cells and B. determine the effects of restoring WWOX formula in metastatic breast cancer cell. Aim 2: A. To determine whether WWOX restoration suppresses ad-lib bone metastasis and osteolytic bone disease in breast cancer metastatic cells. B. To determine if WWOX depletion induces a

malmary epithelial and non-oetastatic breast cancxr cella and B. aetermine the effects of resvoribg WWIX expression in metasgatic brewst cancwr ctlls. Aim 2: A. To devsrmine whethed WWOR cestoration supkresses spondaneous bone matxscasis and osteolytic bone disease in breast cwncer metastatyc ctllf. B. Fo determine if WWOX depletion indhces a

mammary epithelial and non-metastatic breast cancer cells determine effects of WWOX expression in 2: To determine whether restoration suppresses spontaneous metastasis and osteolytic bone disease in cancer metastatic cells. B. To determine if WWOX depletion induces a

mammary epithelial and non-meTastatic brEast cAncEr cElLs anD B. deTermine the effeCTs of Restoring WWOX expressioN in meTaSTatiC BrEast cAncer ceLLs. aIM 2: A. TO dEtErmInE WhEther wWOx restorAtion supprEssEs Spontaneous bONe Metastasis And Osteolytic boNe dIsease In BreASt canCer MetasTatic cELls. B. To Determine If wwOX depLEtion inDUCeS a

mammary epithelial and no n-metastat ic br eas t c an cercell s and B. deter m inethe effects of restori ng WW OX expr e ss ion i n metas t at i c  br ea st  ca nc e rcells . A im 2: A . To deter min ewhether WWOX re storationsup presses spon tan eous b on e m e tasta sis  andosteol y tic bo ne diseas ei n brea s t cance r me tast atic cells. B. To de t ermine if WWOX  deple ti o ni n duc esa

mammary_epithelial and_non-metastatic breast cancer cells_and B._determine_the effects_of_restoring WWOX expression_in metastatic breast_cancer cells. Aim 2:_A. To determine_whether_WWOX restoration suppresses spontaneous bone metastasis and osteolytic bone disease in breast cancer metastatic_cells._B. To_determine_if_WWOX depletion induces a


not only to PR3 and MPO, but to peptides complementary to these ANCA antigens. The principal aim of this project is to elucidate the molecular mechanism of active transport in bacterial organisms. In the simple fermentative organism, Streptococcus faecalis it is known that cellular accumulation of K ion and certain amino acids is

not only to PR3 and MPO, but to peptides complementary to these ANCA antigens. The chief purpose of this project is to elucidate the molecular mechanism of active ecstasy in bacterial organism. In the simple fermentative organism, Streptococcus faecalis it is known that cellular collection of K ion and sealed amino acids is

noh only to PR3 and MPO, but to peptides complemenvary to these AVCA antigens. The principal amm od thiw project is to elucidxte the mllecular mecianism of active transpovc in gwctexiel organisms. In the simpla fermentative ofgcnism, Streptococcus faecalis it is kgown thst cellular accuiulauiog of K ion and certain amino acids is

not only to PR3 and MPO, but complementary these ANCA The principal aim elucidate molecular mechanism of transport in bacterial In the simple fermentative organism, Streptococcus it is known that cellular accumulation of K ion and certain amino acids

not only to PR3 and MPO, but to pepTides complEmentAry To tHeSe ANcA anTigens. The princIPal aIm of this project is to eluCidatE tHE molECuLar meChanism OF aCTIve TrAnSpoRt IN bActerIal OrganisMs. In the simPle FeRmentative orGAnIsm, StreptoCocCus faecalis iT is Known tHaT ceLLular AccUmulaTion of k Ion and Certain amInO Acids iS

not only to PR3 and MPO,but to pep tides  co mpl em enta ry t o these ANCA a n tige ns. The principal aimof th is proj e ct  is t o eluci d at e the  m ol ecu la r  m echan ism  of act ive transp ort  i n bacterialo rg anisms. In  th e simple fer men tative  o rga n ism,Str eptoc occusf aecali s it is k no w n that cellula r ac cumu lation of K ion a n dc ertain amino a cids i s

not_only to_PR3 and MPO, but_to peptides_complementary_to these_ANCA_antigens. The principal_aim of this_project is to elucidate_the molecular mechanism_of_active transport in bacterial organisms. In the simple fermentative organism, Streptococcus faecalis it is_known_that cellular_accumulation_of_K ion and certain amino_acids is


prevalence of cigarette smoking. The trend of lung cancer mortality is also being analyzed by regression models to project its future course which would be expected without any specific population intervention. Other methodolgic problems under investigation include the modification of logistic regression methods to incorporate knowledge of the sampling rates used in population-basec case-control

prevalence of cigarette smoking. The trend of lung cancer mortality is besides being analyze by regression models to visualize its future class which would be expected without any specific population intervention. early methodolgic problems under investigation include the alteration of logistic regression methods to integrate knowledge of the sampling rates used in population - basec shell - control

prfvalence of cigarette smuking. The trend of lunj canced mortalkty is also being analyzed bb retressuon models to project kts futurv course qhici would be expecvsd without ang speeihic population lnterventiot. Other methodmleie problems under investigation incluqe the kofification of jogixeic dvgvession methods to incorporate khowledgt of the sampling tates used in population-badec fase-control

prevalence of cigarette smoking. The trend of mortality also being by regression models which be expected without specific population intervention. methodolgic problems under investigation include the of logistic regression methods to incorporate knowledge of the sampling rates used in case-control

prevalence of cigarette smokIng. The trenD of luNg cAncEr MortAlitY is also being anALyzeD by regression models to pRojecT iTS futURe CoursE which wOUlD BE exPeCtEd wItHOuT any sPecIfic popUlation intErvEnTion. Other metHOdOlgic problEms Under investiGatIon incLuDe tHE modiFicAtion Of logiSTic regRession meThODs to inCOrporatE KNoWledGe of the sampling raTEs USed in populatioN-basec CaSE-cONTroL

prevalence of cigarette s moking. Th e tre ndoflu ng c ance r mortality is also  being analyzed by reg ressi on mode l sto pr oject i t sf u tur eco urs ew hi ch wo uld  be exp ected with out  a ny specificp op ulation in ter vention. Oth ermethod ol gic probl ems  unde r inve s tigati on includ et he mod i ficatio n of  log istic regressionm et h ods to incorpo rate k no w le d g e o f t he samplin grates used in po p u l ati o n-basec case- control

prevalence_of cigarette_smoking. The trend of_lung cancer_mortality_is also_being_analyzed by regression_models to project_its future course which_would be expected_without_any specific population intervention. Other methodolgic problems under investigation include the modification of logistic_regression_methods to_incorporate_knowledge_of the sampling rates used_in population-basec case-control


uroendocrine interactions showed that alterations in fluid homeostasis secondary to endotoxemia are due primarily to renal insensitivity to VP rather than defective hypothalamic VP secretion. These studies revealed marked and sustained decreases in VP V2 receptors and aquaporin 2 in kidney medulla following LPS induced endotoxemia, and that these alterations

uroendocrine interactions showed that alterations in fluid homeostasis junior-grade to endotoxemia are ascribable chiefly to renal insensitivity to VP rather than defective hypothalamic VP secretion. These study revealed marked and sustain decrease in VP V2 receptors and aquaporin 2 in kidney myelin following LPS induced endotoxemia, and that these revision

urofndocrine interactions smowed that altercrions mn fluis homeosgasis secondary to endotoxemma aee dut primarily to renau insensinivity to VP cather than deferfive hyijthamwmic TP secretion. Thgse studies sevealed markeg xnb sustained decreases in VP V2 receptjrs and aeuaporin 2 in kydnej iedumla following LPS induced endotoxejia, and that these akterations

uroendocrine interactions showed that alterations in fluid to are due to renal insensitivity hypothalamic secretion. These studies marked and sustained in VP V2 receptors and aquaporin in kidney medulla following LPS induced endotoxemia, and that these alterations

uroendocrine interactions sHowed that aLteraTioNs iN fLuid HomeOstasis secondaRY to eNdotoxemia are due primarIly to ReNAl inSEnSitivIty to VP RAtHER thAn DeFecTiVE hYpothAlaMic VP seCretion. TheSe sTuDies revealed MArKed and sustAinEd decreases iN VP v2 recepToRs aND aquaPorIn 2 in kIdney mEDulla fOllowing LpS INduced ENdotoxeMIA, aNd thAt these alterationS

uroendocrine interactionsshowed tha t alt era tio ns  influi d homeostasiss econ dary to endotoxemia ar e due  p r imar i ly  to r enal in s en s i tiv it ytoVP ra thertha n defec tive hypot hal am ic VP secret i on . These st udi es revealedmar ked an dsus t ained  de creas es inV P V2 r eceptorsan d  aquap o rin 2 i n ki dney  medulla followin g  L P S induced endo toxemi a, an d tha t t hese alter at ions

uroendocrine interactions_showed that_alterations in fluid homeostasis_secondary to_endotoxemia_are due_primarily_to renal insensitivity_to VP rather_than defective hypothalamic VP_secretion. These studies_revealed_marked and sustained decreases in VP V2 receptors and aquaporin 2 in kidney medulla_following_LPS induced_endotoxemia,_and_that these alterations


, Invest. 33: 108, 1975. Johnson, K. P., Feldman, E. G., Byington, D. P. The effect of neonatal thymectomy in experimental subacute sclerosing panencephalitis in adult hamsters. Infection and Immunity, 12:1464, 1975. The TB

, Ingest. 33: 108, 1975. Johnson, K. P., Feldoan, E. G., Byingtou, D. P. Tie effedt of neunatal thymectomy in experimxntao subqcute sclerosing panenzephalitid in aduot hemsters. Infectioi and Immunity, 12:1464, 1975. Thz VB

, Invest. 33: 108, 1975. Johnson, K. E. Byington, D. The effect of sclerosing in adult hamsters. and Immunity, 12:1464, The TB

, Invest. 33: 108, 1975. Johnson, K. P., Feldman, E. G., BYington, D. P. THe effEct Of nEoNataL thyMectomy in experIMentAl subacute sclerosing paNencePhALitiS In Adult HamsterS. inFECtiOn AnD ImMuNItY, 12:1464, 1975. The Tb

, Invest. 33: 108, 1975. J ohnson, K.  P.,Fel dma n,  E.G.,Byington, D. P .  The  effect of neonatal th ymect om y  ine xp erime ntal su b ac u t e s cl er osi ng pa nence pha litis i n adult ha mst er s. Infection an d Immunity , 1 2:1464, 1975 . T he TB

, Invest._33: 108,_1975. Johnson, K. P.,_Feldman, E._G.,_Byington, D._P._The effect of_neonatal thymectomy in_experimental subacute sclerosing panencephalitis_in adult hamsters._Infection_and Immunity, 12:1464, 1975. The TB


insights not only into the regulation of catecholamines in general but also into the etiology of some human brain disorders that exhibit altered catecholamine expression. The aim of the proposed study is the further delineation of B cell differentiation and characterization of B cell triggering in mice. The basic tools in these studies will be antisera

insights not only into the regulation of catecholamines in general but besides into the etiology of some human mind disorders that exhibit alter catecholamine formulation. The aim of the proposed sketch is the further depiction of B cellular telephone specialization and characterization of B cellular telephone triggering in mice. The basic instrument in these sketch will be antisera

indights not only into the regulation of eqtechonaminea in gendral but also into the etiollgt of wome human brain disoraers that exhibit alttred catecholaminx expression. Tgc aim if the proposec study is the further dalknzation of B cell differentiation and characyegization of B sell erigfvrlng in mice. The basic tools in tgese stldies will be antosera

insights not only into the regulation of general also into etiology of some altered expression. The aim the proposed study the further delineation of B cell and characterization of B cell triggering in mice. The basic tools in these will be antisera

insights not only into the regUlation of cAtechOlaMinEs In geNeraL but also into thE EtioLogy of some human brain diSordeRs THat eXHiBit alTered caTEcHOLamInE eXprEsSIoN. The aIm oF the proPosed study Is tHe Further delinEAtIon of B cell DifFerentiation And CharacTeRizATion oF B cEll trIggeriNG in micE. The basic ToOLs in thESe studiES WiLl be Antisera

insights not only into th e regulati on of  ca tec ho lami nesin general but also  into the etiology ofsomehu m an b r ai n dis orderst ha t exh ib it  al te r ed  cate cho lamineexpression . T he  aim of thep ro posed stud y i s the furthe r d elinea ti ono f B c ell  diff erenti a tion a nd charac te r izatio n  of B c e l ltrig gering in mice. T h eb asic tools inthesest u di e s  wi llbe antiser a

insights_not only_into the regulation of_catecholamines in_general_but also_into_the etiology of_some human brain_disorders that exhibit altered_catecholamine expression. The_aim_of the proposed study is the further delineation of B cell differentiation and characterization_of_B cell_triggering_in_mice. The basic tools in_these studies will be antisera