into mechanisms and signaling pathways involved in the malignant transformation of cells. The goals are to advance basic understanding of cancer pathogenesis and to translate basic science discoveries into the clinical arena to improve the outcome of patients with cancer. The Program encompasses three major thematic groups: 1) Mechanisms and Pathways of Oncogenesis;2

into mechanisms and signaling pathways involved in the malignant transformation of cell. The goal are to advance basic understanding of cancer pathogenesis and to translate basic skill discoveries into the clinical arena to improve the result of patients with cancer. The Program encompasses three major thematic group: 1) Mechanisms and Pathways of Oncogenesis;2

inho mechanisms and signallng pathways involved ii the mzlignant transformation of cells. The gials qre to advance basic uvderstandpng of cabcer pathogenesma and to tranapate uasic science dlscoveries hnto the cliniwau crena to improve the outcome of patiqnts wiyh cancer. The Prjgrak enckmpasses three major thematic grouls: 1) Mecianisms and Patnways of Oncogenesis;2

into mechanisms and signaling pathways involved in transformation cells. The are to advance and translate basic science into the clinical to improve the outcome of patients cancer. The Program encompasses three major thematic groups: 1) Mechanisms and Pathways of

into mechanisms and signalinG pathways iNvolvEd iN thE mAligNant Transformation OF celLs. The goals are to advance Basic UnDErstANdIng of Cancer pAThOGEneSiS aNd tO tRAnSlate BasIc scienCe discoverIes InTo the clinicaL ArEna to improVe tHe outcome of pAtiEnts wiTh CanCEr. The proGram eNcompaSSes thrEe major thEmATic groUPs: 1) MechaNISmS and pathways of OncogenESiS;2

into mechanisms and signa ling pathw ays i nvo lve din t he m alignant trans f orma tion of cells. The goa ls ar et o ad v an ce ba sic und e rs t a ndi ng  o f c an c er  path oge nesis a nd to tran sla te  basic scien c ediscoverie s i nto the clin ica l aren atoi mprov e t he ou tcomeo f pati ents with  c a ncer.T he Prog r a menco mpasses three maj o rt hematic groups : 1) M ec h an i s msand  Pathwaysof  Onco g enesis; 2

into_mechanisms and_signaling pathways involved in_the malignant_transformation_of cells._The_goals are to_advance basic understanding_of cancer pathogenesis and_to translate basic_science_discoveries into the clinical arena to improve the outcome of patients with cancer. The_Program_encompasses three_major_thematic_groups: 1) Mechanisms and Pathways_of Oncogenesis;2


that Gbx2 is required at certain threshold levels for different parts of the brain. Compared to Gbx2 relatively little has been reported about Gbx1. We recently described the cloning and embryonic expression pattern of Gbx1 and defined regions of potential molecular redundancy with Gbx2. (Waters et al 2003 Gene

that Gbx2 is required at certain threshold levels for unlike part of the brain. Compared to Gbx2 relatively short has been report about Gbx1. We recently described the cloning and embryonic expression convention of Gbx1 and define regions of likely molecular redundancy with Gbx2. (body of water et al 2003 Gene

thwt Gbx2 is required at cevtain threshold levels hor difrerent pxrts of the brain. Compared tl Tbx2 rtjatively little har been reiorted abiut Jbx1. We recently vsscribed the dponiug and embryonic expressiot pattern of Gtx1 aud defined regions of potential molesular rrdkndancy with Gfx2. (Wseers vt al 2003 Gene

that Gbx2 is required at certain threshold different of the Compared to Gbx2 about We recently described cloning and embryonic pattern of Gbx1 and defined regions potential molecular redundancy with Gbx2. (Waters et al 2003 Gene

that Gbx2 is required at certaiN threshold LevelS foR diFfErenT parTs of the brain. CoMPareD to Gbx2 relatively little Has beEn REporTEd About gbx1. We reCEnTLY deScRiBed ThE ClOning And EmbryonIc expressiOn pAtTern of Gbx1 and DEfIned regionS of Potential molEcuLar redUnDanCY with gbx2. (waterS et al 2003 GENe

that Gbx2 is required atcertain th resho ldlev el s fo r di fferent partso f th e brain. Compared to G bx2 r el a tive l ylittl e has b e en r epo rt ed  ab ou t  G bx1.Werecentl y describe d t he  cloning and em bryonic ex pre ssion patter n o f Gbx1  a ndd efine d r egion s of p o tentia l molecul ar redund a ncy wit h Gb x2.(Waters et al 200 3  G e ne

that_Gbx2 is_required at certain threshold_levels for_different_parts of_the_brain. Compared to_Gbx2 relatively little_has been reported about_Gbx1. We recently_described_the cloning and embryonic expression pattern of Gbx1 and defined regions of potential molecular_redundancy_with Gbx2._(Waters_et_al 2003 Gene


role of pregnancy and parturition in the etiology and prevention of pelvic floor disorders (PFDs). Magee-Womens Hospital (MWH) is the central resource for gynecologic specialty care for the 19 hospital University of Pittsburgh Health System serving a very large aging population. Our site brings expertise in u

role of pregnancy and parturition in the etiology and prevention of pelvic floor disorders (PFDs). Magee - Womens Hospital (MWH) is the central resource for gynecologic specialization caution for the 19 hospital University of Pittsburgh Health System serving a very large aging population. Our web site brings expertise in u

rope of pregnancy and partmrition in the ejiilogy end prebention uf pelvic floor disorders (PFVs). Mqgee-Wimens Hospital (MWH) is ghe centrwl resouece hor gynecologic specialtn cars for vhe 19 hospital Ukiversity ox Pittsburgh Haautk System serving a very large aging [opulatooj. Our site briggs txpqrtiav ln u

role of pregnancy and parturition in the prevention pelvic floor (PFDs). Magee-Womens Hospital for specialty care for 19 hospital University Pittsburgh Health System serving a very aging population. Our site brings expertise in u

role of pregnancy and parturiTion in the eTioloGy aNd pReVentIon oF pelvic floor diSOrdeRs (PFDs). Magee-Womens HospiTal (MWh) iS The cENtRal reSource fOR gYNEcoLoGiC spEcIAlTy carE foR the 19 hosPital UniveRsiTy Of Pittsburgh hEaLth System sErvIng a very largE agIng popUlAtiON. Our sIte BringS experTIse in u

role of pregnancy and par turition i n the  et iol og y an d pr evention of pe l vicfloor disorders (PFDs) . Mag ee - Wome n sHospi tal (MW H )i s  th ece ntr al re sourc e f or gyne cologic sp eci al ty care fort he  19 hospit alUniversity o f P ittsbu rg h H e althSys tem s erving a very  large ag in g  popul a tion. O u r  s itebrings expertisei nu

role_of pregnancy_and parturition in the_etiology and_prevention_of pelvic_floor_disorders (PFDs). Magee-Womens_Hospital (MWH) is_the central resource for_gynecologic specialty care_for_the 19 hospital University of Pittsburgh Health System serving a very large aging population._Our_site brings_expertise_in_u


3) provide Core resources to investigators in the center in order to facilitate research design, diagnostic and behavioral assessment, statistical analysis and access to a computer facility, (4) provide Core laboratories to investigators in the Center so that specialized tests and procedures can be carried out in conjunction with clinical and basic science studies, (5)

3) provide Core resources to investigators in the center in decree to help research design, diagnostic and behavioral appraisal, statistical psychoanalysis and access to a computer facility, (4) supply Core laboratories to investigators in the Center so that specialized trial and procedures can be carried out in junction with clinical and basic science studies, (5 )

3) prlvide Core resources to lnvestigators in the ceiter in order tu facilitate research design, duagnowtic and behavioral asressment, dtatistixal enalysis and accxas to a compufcr faeioity, (4) provide Gore laboradories to invevtkgctors in the Center so that specialised tesys and proceduref cam be darried out in conjunction with cljnical end basic scienve studies, (5)

3) provide Core resources to investigators in in to facilitate design, diagnostic and access a computer facility, provide Core laboratories investigators in the Center so that tests and procedures can be carried out in conjunction with clinical and basic studies, (5)

3) provide Core resources to invEstigators In the CenTer In OrdeR to fAcilitate reseaRCh deSign, diagnostic and behavIoral AsSEssmENt, StatiStical aNAlYSIs aNd AcCesS tO A cOmputEr fAcility, (4) Provide CorE laBoRatories to inVEsTigators in The center so that SpeCializEd TesTS and pRocEdureS can be CArried Out in conjUnCTion wiTH clinicAL AnD basIc science studies, (5)

3) provide Core resourcesto investi gator s i n t he  cen terin order to fa c ilit ate research design, d iagno st i c an d  b ehavi oral as s es s m ent ,st ati st i ca l ana lys is andaccess toa c om puter facili t y,  (4) provi deCore laborat ori es toin ves t igato rsin th e Cent e r so t hat speci al i zed te s ts andp r oc edur es can be carried ou t  in conjunctio n with  c l in i c aland  basic sci en ce st u dies, ( 5 )

3) provide_Core resources_to investigators in the_center in_order_to facilitate_research_design, diagnostic and_behavioral assessment, statistical_analysis and access to_a computer facility,_(4)_provide Core laboratories to investigators in the Center so that specialized tests and procedures_can_be carried_out_in_conjunction with clinical and basic_science studies, (5)


ial cells cultured from the ureter, this novel concept has broad implications in the pathophysiology of the urinary tract. The goal of this project is to identify cellular pathways of stretch-induced COX-2 expression and thereby provide several potential targets for drug therapy. Based on titerature reports in other cells, and preliminary data,

ial cells cultured from the ureter, this novel concept has broad implication in the pathophysiology of the urinary nerve pathway. The goal of this project is to name cellular pathways of reach - induced COX-2 expression and thereby supply several potential target for drug therapy. Based on titerature reports in early cells, and preliminary data,

ial cells cultured from the ureter, this norwl conrept haa broad kmplications in the pathophydiilogy of the urinary tract. Ghe goal lf this projtct is to identifb cellular patgaays if stretch-induged COX-2 expsession and thardbv provide several potential targets sor drub hherapy. Based jn tptqrathge reports in other cells, and pdeliminery data,

ial cells cultured from the ureter, this has implications in pathophysiology of the this is to identify pathways of stretch-induced expression and thereby provide several potential for drug therapy. Based on titerature reports in other cells, and preliminary data,

ial cells cultured from the urEter, this noVel coNcePt hAs BroaD impLications in the PAthoPhysiology of the urinary Tract. thE Goal OF tHis prOject is TO iDENtiFy CeLluLaR PaThwayS of Stretch-Induced COX-2 ExpReSsion and therEBy Provide sevEraL potential taRgeTs for dRuG thERapy. BAseD on tiTeratuRE reporTs in other CeLLs, and pREliminaRY DaTa,

ial cells cultured from th e ureter,thisnov elco ncep t ha s broad implic a tion s in the pathophysiolo gy of  t h e ur i na ry tr act. Th e  g o a l o fth ispr o je ct is  to  identi fy cellula r p at hways of str e tc h-inducedCOX -2 expressio n a nd the re byp rovid e s evera l pote n tial t argets fo rd rug th e rapy. B a s ed  ontiterature report s  i n  other cells,and pr el i mi n a rydat a,

ial cells_cultured from_the ureter, this novel_concept has_broad_implications in_the_pathophysiology of the_urinary tract. The_goal of this project_is to identify_cellular_pathways of stretch-induced COX-2 expression and thereby provide several potential targets for drug therapy._Based_on titerature_reports_in_other cells, and preliminary data,


with ET none of these treatments has changed the natural history of the MPN. We have established the Myeloproliferative Disorders Research Consortium (MPD-RC) an intemationai group of 24 academic centers in the US and Europe to conduct translational clinical trials in MPN. The goals of this project

with ET none of these treatments has changed the natural history of the MPN. We have established the Myeloproliferative Disorders Research Consortium (MPD - RC) an intemationai group of 24 academic center in the US and Europe to conduct translational clinical trials in MPN. The goal of this undertaking

wihh ET none of these treauments has changeb the netural gistory uf the MPN. We have establishxd tye Mytjoproliferative Dirorders Rvsearch Cinsoctium (MPD-RC) an iifematiokci grkmp of 24 academic centgrs in the UV and Europe tm zouduct translational clinical trials yn MPN. Yhf goals of thif prptect

with ET none of these treatments has natural of the We have established (MPD-RC) intemationai group of academic centers in US and Europe to conduct translational trials in MPN. The goals of this project

with ET none of these treatmenTs has changEd the NatUraL hIstoRy of The MPN. We have esTAbliShed the MyeloproliferatIve DiSoRDers rEsEarch consortIUm (mpd-RC) An InTemAtIOnAi groUp oF 24 academIc centers iN thE Us and Europe to COnDuct translAtiOnal clinical TriAls in MpN. the GOals oF thIs proJect

with ET none of these tre atments ha s cha nge d t he  nat ural  history of th e  MPN . We have establishedthe M ye l opro l if erati ve Diso r de r s  Re se ar chCo n so rtium  (M PD-RC)an intemat ion ai  group of 24 ac ademic cen ter s in the USand  Europ etoc onduc t t ransl ationa l  clini cal trial si n MPN. The goa l s  o f th is project

with_ET none_of these treatments has_changed the_natural_history of_the_MPN. We have_established the Myeloproliferative_Disorders Research Consortium (MPD-RC)_an intemationai group_of_24 academic centers in the US and Europe to conduct translational clinical trials in_MPN._The goals_of_this_project


disease in young hyperlipidemic subjects remains a major unsolved health problem in terms of pethogenesis and treatment. Recent research has made available reference values for diagnosing hyperlipidemia, markers for genetic analysis, and methods for studying lipoprotein metabolism and arteriosclerotic disease progression. With these advances, the opportunity now exists for in

disease in young hyperlipidemic subjects remains a major unsolved health problem in term of pethogenesis and discussion. Recent research has make available citation values for diagnosing lipemia, markers for genetic analysis, and method for studying lipoprotein metabolism and arteriosclerotic disease progress. With these advances, the opportunity now exist for in

didease in young hyperlipiaemic subjects tenains e major unsolvea health problem in terms of pwthogtuesis and treatment. Fecent redearch hqs mede available rehsrence yclues nor dnajnosing hyperlikidemia, markars for genetiw xnclysis, and methods for studying lipo[rotein mftabolism and wrtegijsclsgouic disease progression. With thess advanbes, the opportuniyy now exists for in

disease in young hyperlipidemic subjects remains a health in terms pethogenesis and treatment. reference for diagnosing hyperlipidemia, for genetic analysis, methods for studying lipoprotein metabolism and disease progression. With these advances, the opportunity now exists for in

disease in young hyperlipideMic subjectS remaIns A maJoR unsOlveD health problem IN terMs of pethogenesis and treAtmenT. RECent REsEarch Has made AVaILAblE rEfEreNcE VaLues fOr dIagnosiNg hyperlipIdeMiA, markers for gENeTic analysiS, anD methods for sTudYing liPoProTEin meTabOlism And artERiosclErotic disEaSE progrESsion. WiTH ThEse aDvances, the opportuNItY Now exists for in

disease in young hyperlip idemic sub jects  re mai ns  a m ajor  unsolved heal t h pr oblem in terms of peth ogene si s  and tr eatme nt. Rec e nt r ese ar ch  ha sm ad e ava ila ble ref erence val ues  f or diagnosin g  h yperlipide mia , markers fo r g enetic  a nal y sis,and  meth ods fo r  study ing lipop ro t ein me t abolism a nd  art eriosclerotic dis e as e  progression.With t he s ea d van ces , the oppo rt unity now exi s ts f o r i n

disease_in young_hyperlipidemic subjects remains a_major unsolved_health_problem in_terms_of pethogenesis and_treatment. Recent research_has made available reference_values for diagnosing_hyperlipidemia,_markers for genetic analysis, and methods for studying lipoprotein metabolism and arteriosclerotic disease progression._With_these advances,_the_opportunity_now exists for in


achieve optimum integration of the auditory and visual signals. Third, we will determine whether or not the presence of hearing loss may affect integration performance for both older and younger adults, and whether the type of speech material interacts with one's ability to integrate. The results may affect several stages of the geriatric audiological rehabilitation plan,

achieve optimum integration of the auditory and visual signals. Third, we will determine whether or not the bearing of hear loss may affect consolidation performance for both erstwhile and younger adults, and whether the character of actor's line material interact with one's ability to desegregate. The results may affect respective stages of the geriatric audiological rehabilitation design,

acjieve optimum integratiok of the auditori qnd vivual sjgnals. Tfird, we will determine whethxr oe not the presence of hearivg loss mwy affecr inuegration performehce for both kpder end younger adukts, and whather the type ow dpeech material interacts with one's abilitu ho integrate. Tre rtsujts jay affect several stages of the gsriatrib audiological renabilitation plan,

achieve optimum integration of the auditory and Third, will determine or not the affect performance for both and younger adults, whether the type of speech material with one's ability to integrate. The results may affect several stages of the audiological rehabilitation plan,

achieve optimum integration Of the auditOry anD viSuaL sIgnaLs. ThIrd, we will deterMIne wHether or not the presence Of heaRiNG losS MaY affeCt integRAtION peRfOrManCe FOr Both oLdeR and youNger adults, And WhEther the type OF sPeech materIal Interacts witH onE's abilItY to INtegrAte. the reSults mAY affecT several sTaGEs of thE GeriatrIC AuDiolOgical rehabilitatIOn PLan,

achieve optimum integrati on of theaudit ory  an dvisu al s ignals. Third, we w ill determine whetheror no tt he p r es enceof hear i ng l oss  m ay  af fe c tinteg rat ion per formance f orbo th older and yo unger adul ts,  and whether  th e type  o f s p eechmat erial  inter a cts wi th one'sab i lity t o  integr a t e.  The  results may affe c ts everal stagesof the  g e ri a t ric  au diological  r ehabi l itation pl a n ,

achieve_optimum integration_of the auditory and_visual signals._Third,_we will_determine_whether or not_the presence of_hearing loss may affect_integration performance for_both_older and younger adults, and whether the type of speech material interacts with one's_ability_to integrate._The_results_may affect several stages of_the geriatric audiological rehabilitation plan,


of early events in murine TB, and will be the first to fully characterize lung Mphi apoptosis in vivo and to define it's contribution to the integrated host response to infection. Our model may reflect a mechanism broadly involved in the defense against a variety of other intracellular pathogens (such as Legionella) of immediate relevance to the

of early events in murine TB, and will be the first to fully characterize lung Mphi apoptosis in vivo and to specify it's contribution to the integrate host response to infection. Our mannequin may reflect a mechanism broadly involved in the defensive structure against a kind of other intracellular pathogen (such as Legionella) of contiguous relevance to the

of early events in murine UB, and will be thg dirst vo fullg characgerize lung Mphi apoptosis ii vico ane to define it's contricution to the intwgraued host response to infegcion. Kmr mobeo may reflect s mechanisk broadly invonvdd in the defense against a variety os other ijtracellular pwthobqns (alcm as Legionella) of immediate relsvance uo the

of early events in murine TB, and the to fully lung Mphi apoptosis it's to the integrated response to infection. model may reflect a mechanism broadly in the defense against a variety of other intracellular pathogens (such as Legionella) immediate relevance to the

of early events in murine TB, anD will be the First To fUllY cHaraCterIze lung Mphi apoPTosiS in vivo and to define it's cOntriBuTIon tO ThE inteGrated hOSt RESpoNsE tO inFeCTiOn. Our ModEl may reFlect a mechAniSm Broadly involVEd In the defenSe aGainst a varieTy oF other InTraCEllulAr pAthogEns (sucH As LegiOnella) of iMmEDiate rELevance TO ThE

of early events in murine  TB, and w ill b e t hefi rstto f ully character i ze l ung Mphi apoptosis invivoan d  tod ef ine i t's con t ri b u tio nto  th ei nt egrat edhost re sponse toinf ec tion. Our mo d el  may refle cta mechanismbro adly i nv olv e d inthe  defe nse ag a inst a  varietyof otheri ntracel l u la r pa thogens (such asL eg i onella) of imm ediate  r e le v a nce  to  the

of_early events_in murine TB, and_will be_the_first to_fully_characterize lung Mphi_apoptosis in vivo_and to define it's_contribution to the_integrated_host response to infection. Our model may reflect a mechanism broadly involved in the_defense_against a_variety_of_other intracellular pathogens (such as_Legionella) of immediate relevance to_the


-term depression (LTD) at the commissural-CA1 synapse in the hippocampus in vivo. Homosynaptic LTD is a lasting decrease in synaptic transmission that results from activity in the afferent pathway. Research with formal models of learning and memory has shown that synaptic strength must have the capacity to both decrease and

-term depression (LTD) at the commissural - CA1 synapse in the hippocampus in vivo. Homosynaptic LTD is a lasting decrease in synaptic transmission that results from natural process in the sensory nerve pathway. Research with conventional model of learning and memory has shown that synaptic persuasiveness must give birth the capacity to both decrease and

-terl depression (LTD) at the gommissural-CA1 syuqpse ii the hjppocampjs in vivo. Homosynaptic LTD ms a lastung decrease in synaptkc transmpssion thqt rtsults from activmfy in tmz affsvent 'avhway. Research eith forman models of ledrviug and memory has shown that synaptis strenbtj must have thg capssity no both decrease and

-term depression (LTD) at the commissural-CA1 synapse hippocampus vivo. Homosynaptic is a lasting results activity in the pathway. Research with models of learning and memory has that synaptic strength must have the capacity to both decrease and

-term depression (LTD) at the comMissural-CA1 SynapSe iN thE hIppoCampUs in vivo. HomosyNAptiC LTD is a lasting decrease In synApTIc trANsMissiOn that rESuLTS frOm AcTivItY In The afFerEnt pathWay. ResearcH wiTh Formal models OF lEarning and MemOry has shown tHat SynaptIc StrENgth mUst Have tHe capaCIty to bOth decreaSe ANd

-term depression (LTD) atthe commis sural -CA 1 s yn apse  inthe hippocampu s  invivo. Homosynaptic LTD  is a  l a stin g  d ecrea se in s y na p t ictr an smi ss i on  that  re sults f rom activi tyin  the afferen t  p athway. Re sea rch with for mal  model sofl earni ngand m emoryh as sho wn that s yn a ptic s t rengthm u st  hav e the capacity to bo t h decrease and

-term depression_(LTD) at_the commissural-CA1 synapse in_the hippocampus_in_vivo. Homosynaptic_LTD_is a lasting_decrease in synaptic_transmission that results from_activity in the_afferent_pathway. Research with formal models of learning and memory has shown that synaptic strength_must_have the_capacity_to_both decrease and


will be recorded from patients undergoing surgical/invasive monitoring as part of the clinical treatment of medically refractory epilepsy. By performing cognitive tasks that pose no health risks whatsoever, these patients can provide exquisite data on the involvement of brain waves in memory formation. The proposed research aims to determine: (1) the relative roles of oscillations in

will be recorded from patients undergoing surgical / invasive monitoring as character of the clinical discussion of medically refractory epilepsy. By performing cognitive undertaking that model no health risks whatsoever, these patients can supply exquisite data on the engagement of brain waves in memory geological formation. The proposed research aim to settle: (1) the relative roles of oscillations in

wipl be recorded from patitnts undergoing sortical/iivasive monitorkng as part of the clinical vrearment of medically refractofy epilepdy. By peefornung cognitmbe tasks that iose uo health risks ehatsoever, these patientv zau provide exquisite data on the invojvement ov brain waves yn mtmowy fkgmction. The proposed research aima to deuermine: (1) the relatove roles of oscillations ln

will be recorded from patients undergoing surgical/invasive part the clinical of medically refractory that no health risks these patients can exquisite data on the involvement of waves in memory formation. The proposed research aims to determine: (1) the relative of oscillations in

will be recorded from patientS undergoinG surgIcaL/inVaSive MoniToring as part of THe clInical treatment of medicAlly rEfRActoRY ePilepSy. By perFOrMINg cOgNiTivE tASkS that PosE no healTh risks whaTsoEvEr, these patieNTs Can provide ExqUisite data on The InvolvEmEnt OF braiN waVes in Memory FOrmatiOn. The propOsED reseaRCh aims tO DEtErmiNe: (1) the relative roleS Of OScillations in

will be recorded from pat ients unde rgoin g s urg ic al/i nvas ive monitoring as p art of the clinical tr eatme nt of m e di cally  refrac t or y epi le ps y.By pe rform ing  cognit ive taskstha tpose no heal t hrisks what soe ver, these p ati ents c an  pr o videexq uisit e data on the  involvem en t  of br a in wave s in  mem ory formation. Th e  p r oposed researc h aims  t o  d e t erm ine : (1) there lativ e  roleso fo s c ill a tions in

will_be recorded_from patients undergoing surgical/invasive_monitoring as_part_of the_clinical_treatment of medically_refractory epilepsy. By_performing cognitive tasks that_pose no health_risks_whatsoever, these patients can provide exquisite data on the involvement of brain waves in_memory_formation. The_proposed_research_aims to determine: (1) the_relative roles of oscillations in


100 cells/injection site), the LDZ cells generated tumors more rapidly and with higher penetrance, and showed more frequent brain and lung metastasis. Both gene reactivation and tumorigenicity progressively increased G1 to G4. Tumors derived from G1-G4 LDZ cells were also increasingly more vascular. Global transcriptome

100 cells / injection site), the LDZ cells generated tumor more quickly and with high penetrance, and showed more frequent brain and lung metastasis. Both gene reactivation and tumorigenicity increasingly increased G1 to G4. Tumors derived from G1 - G4 LDZ cellular telephone were also increasingly more vascular. Global transcriptome

100 cepls/injection site), the LDE cells generated tumors more dapidly xnd with higher penetrance, aid syowed more frequent brain avd lung mvtastasis. Boti gene reactivatmkn and bbmorifcnicicy progressively increased G1 to G4. Tumors ddrnved from G1-G4 LDZ cells were also incweasingky more vascular. Glonwl tdanscriptome

100 cells/injection site), the LDZ cells generated rapidly with higher and showed more Both reactivation and tumorigenicity increased G1 to Tumors derived from G1-G4 LDZ cells also increasingly more vascular. Global transcriptome

100 cells/injection site), the LDZ cElls generaTed tuMorS moRe RapiDly aNd with higher peNEtraNce, and showed more frequeNt braIn ANd luNG mEtastAsis. BotH GeNE ReaCtIvAtiOn ANd TumorIgeNicity pRogressiveLy iNcReased G1 to G4. TuMOrS derived frOm G1-g4 LDZ cells werE alSo incrEaSinGLy morE vaSculaR. GlobaL TranscRiptome

100 cells/injection site),  the LDZ c ellsgen era te d tu mors  more rapidlya nd w ith higher penetrance,  andsh o wedm or e fre quent b r ai n and  l un g m et a st asis.  Bo th gene  reactivat ion  a nd tumorigen i ci ty progres siv ely increase d G 1 to G 4.  Tu m ors d eri ved f rom G1 - G4 LDZ  cells we re also i n creasin g l ymore  vascular. Global tr a nscriptome

100 cells/injection_site), the_LDZ cells generated tumors_more rapidly_and_with higher_penetrance,_and showed more_frequent brain and_lung metastasis. Both gene_reactivation and tumorigenicity_progressively_increased G1 to G4. Tumors derived from G1-G4 LDZ cells were also increasingly more_vascular._Global transcriptome


(1) to characterize expression of Sfswap gene in the mouse cortex during early development; (2) to examine if Sfswap expression in the cortex is regulated by perinatal exposure to elevated testosterone via androgen receptor; and (3) to investigate the physiological roles of Sfswap in the development of sexually dim

(1) to characterize expression of Sfswap gene in the mouse cortex during early growth; (2) to test if Sfswap expression in the cortex is regulated by perinatal photograph to elevated testosterone via androgen receptor; and (3) to investigate the physiologic roles of Sfswap in the development of sexually dim

(1) tl characterize expressiok of Sfswap gene in the mouse cortex auring early development; (2) to ezamint if Sfswap expresskon in thv cortex us rtgulated by perinefal exposure fl elzveted testosteroke via andrmgen receptor; dna (3) to investigate the physiological rjles of Svswap in the dgvelokmegt or sexually dim

(1) to characterize expression of Sfswap gene mouse during early (2) to examine cortex regulated by perinatal to elevated testosterone androgen receptor; and (3) to investigate physiological roles of Sfswap in the development of sexually dim

(1) to characterize expression oF Sfswap genE in thE moUse CoRtex DuriNg early developMEnt; (2) tO examine if Sfswap expresSion iN tHE corTEx Is regUlated bY PeRINatAl ExPosUrE To ElevaTed TestostErone via anDroGeN receptor; and (3) TO iNvestigate The PhysiologicaL roLes of SFsWap IN the dEveLopmeNt of seXUally dIm

(1) to characterize expre ssion of S fswap  ge nein  the  mou se cortex duri n g ea rly development; (2) t o exa mi n e if Sf swapexpress i on i n t he  c ort ex is  regu lat ed by p erinatal e xpo su re to elevat e dtestostero nevia androgen  re ceptor ;and (3) t o i nvest igatet he phy siologica lr oles o f  Sfswap i nthedevelopment of se x ua l ly dim

(1)_to characterize_expression of Sfswap gene_in the_mouse_cortex during_early_development; (2) to_examine if Sfswap_expression in the cortex_is regulated by_perinatal_exposure to elevated testosterone via androgen receptor; and (3) to investigate the physiological roles_of_Sfswap in_the_development_of sexually dim


2-day conference to bring together program participants, prospective participants, faculty and representatives of funding agencies. The conference will provide a structured environment to disseminate innovative research, promote the development of mentoring and collaborative research relationships, and to explore the current state of science and community practice regarding HIV prevention in disproportionately impacted minority communities

2 - day conference to bring together program participant, prospective participant, faculty and representatives of funding agency. The conference will provide a integrated environment to disseminate innovative research, advertise the growth of mentoring and collaborative inquiry relationships, and to explore the current state of science and residential district practice regarding HIV prevention in disproportionately impact minority communities

2-daj conference to bring tonether program pceticipents, prkspectivd participants, faculty and rxprewentaupves of funding agenckes. The clnferencw wioo provide e structmxed ehyironkxnt to disseminste innovadive research, [rumlte the development of mentoring anq collanogative researcr rekwtiohships, and to explore the current atate oh science and cpmmunity practice regardinh HIG prevention in didproportionqtelr impacted mivority communities

2-day conference to bring together program participants, faculty representatives of agencies. The conference to innovative research, promote development of mentoring collaborative research relationships, and to explore current state of science and community practice regarding HIV prevention in disproportionately impacted communities

2-day conference to bring togetHer program PartiCipAntS, pRospEctiVe participants, FAculTy and representatives of FundiNg AGencIEs. the coNferencE WiLL ProViDe A stRuCTuRed enVirOnment tO disseminaTe iNnOvative reseaRCh, Promote the DevElopment of meNtoRing anD cOllABoratIve ReseaRch relATionshIps, and to eXpLOre the CUrrent sTATe Of scIence and community PRaCTice regarding HiV prevEnTIoN IN diSprOportionatElY impaCTed minoRItY COMmuNIties

2-day conference to bring  togetherprogr ampar ti cipa nts,  prospective p a rtic ipants, faculty and re prese nt a tive s  o f fun ding ag e nc i e s.Th econ fe r en ce wi llprovide  a structu red  e nvironment t o  d isseminate  in novative res ear ch, pr om ote the d eve lopme nt ofm entori ng and co ll a borati v e resea r c hrela tionships, and to ex p lore the curre nt sta te of s cie nce  and commu ni ty pr a ctice r e ga r d i ngH IV prevention  in disprop o rti onatel yimp a cted m inori ty com munities

2-day_conference to_bring together program participants,_prospective participants,_faculty_and representatives_of_funding agencies. The_conference will provide_a structured environment to_disseminate innovative research,_promote_the development of mentoring and collaborative research relationships, and to explore the current state_of_science and_community_practice_regarding HIV prevention in disproportionately_impacted minority communities


, and researchers on the impact of unconscious bias on health outcomes to further build upon the exchange of ideas which began recently among research and practice professionals in cultural competency and health literacy. Specific aims include: 1) create a network of experts in cultural competency and health literacy curriculum development and research, 2) identify common competencies,

, and researchers on the impact of unconscious bias on health outcomes to far build up upon the exchange of ideas which began recently among inquiry and practice professionals in cultural competency and health literacy. Specific purpose include: 1) create a net of expert in cultural competency and health literacy curriculum exploitation and research, 2) identify common competence,

, anf researchers on the impxct of unconscious biav on hsalth ougcomes to further build upon tye exxhange of ideas which cegan recvntly amobg rtsearch and practmde profcfsiohwls nn cultural compgtency and haalth literacy. Soeeific aims include: 1) create a network of exprrhs in cultural comketqncy and health literacy curriculum debelopmeit and research, 2) identify common competenfies,

, and researchers on the impact of on outcomes to build upon the recently research and practice in cultural competency health literacy. Specific aims include: 1) a network of experts in cultural competency and health literacy curriculum development and 2) identify common competencies,

, and researchers on the impact Of unconsciOus biAs oN heAlTh ouTcomEs to further buiLD upoN the exchange of ideas whiCh begAn REcenTLy Among ResearcH AnD PRacTiCe ProFeSSiOnals In cUltural Competency And HeAlth literacy. sPeCific aims iNclUde: 1) create a neTwoRk of exPeRts IN cultUraL compEtency ANd healTh literacY cURriculUM develoPMEnT and Research, 2) identify cOMmON competencies,

, and researchers on the i mpact of u ncons cio usbi as o n he alth outcomest o fu rther build upon the e xchan ge of i d ea s whi ch bega n  r e c ent ly  a mon gr es earch  an d pract ice profes sio na ls in cultur a lcompetency  an d health lit era cy. Sp ec ifi c  aims  in clude : 1) c r eate a  networkof expert s  in cul t u ra l co mpetency and heal t hl iteracy curric ulum d ev e lo p m ent  an d research ,2) id e ntify c o mm o n com p etencies,

, and_researchers on_the impact of unconscious_bias on_health_outcomes to_further_build upon the_exchange of ideas_which began recently among_research and practice_professionals_in cultural competency and health literacy. Specific aims include: 1) create a network of_experts_in cultural_competency_and_health literacy curriculum development and_research, 2) identify common competencies,


constructed a replication-defective adenovirus encoding this protein (ADV-D1). Our preliminary studies indicate that ADV-D1 but not a control adenovirus, promotes cell cycle progression in primary hepatocytes in the absence of growth factor, and induces hepatocyte proliferation on extracellular matrices that are normally growth-inhib

constructed a replication - defective adenovirus encoding this protein (ADV - D1). Our preliminary report bespeak that ADV - D1 but not a control adenovirus, promotes cell bicycle progression in primary hepatocytes in the absence of emergence gene, and induces hepatocyte proliferation on extracellular matrix that are normally growth - inhib

cojstructed a replication-dtfective adenoviros encodmng thia proteiv (ADV-D1). Our preliminary studixs ibdicauv that ADV-D1 but not a control wdenovirys, pcomotes cell cycle progrcfsioh in 'rmmary hepatocytgs in the abvence of growtv waetor, and induces hepatocyte proliferwtion om fxtracellular iatrpcqs tgat are normally growth-inhib

constructed a replication-defective adenovirus encoding this protein preliminary indicate that but not a progression primary hepatocytes in absence of growth and induces hepatocyte proliferation on extracellular that are normally growth-inhib

constructed a replication-deFective adeNovirUs eNcoDiNg thIs prOtein (ADV-D1). Our prELimiNary studies indicate thaT ADV-D1 BuT Not a COnTrol aDenovirUS, pROMotEs CeLl cYcLE pRogreSsiOn in priMary hepatoCytEs In the absence OF gRowth factoR, anD induces hepaTocYte proLiFerATion oN exTraceLlular MAtriceS that are nOrMAlly grOWth-inhiB

constructed a replication -defective  aden ovi rus  e ncod ingthis protein ( A DV-D 1). Our preliminary st udies  i n dica t ethatADV-D1b ut n otaco ntr ol ad enovi rus , promo tes cell c ycl eprogressioni nprimary he pat ocytes in th e a bsence  o f g r owthfac tor,and in d uces h epatocyte  p r olifer a tion on e xt race llular matrices t h at are normally g rowth- in h ib

constructed_a replication-defective_adenovirus encoding this protein_(ADV-D1). Our_preliminary_studies indicate_that_ADV-D1 but not_a control adenovirus,_promotes cell cycle progression_in primary hepatocytes_in_the absence of growth factor, and induces hepatocyte proliferation on extracellular matrices that are_normally_growth-inhib


reactivity screening of the unknown cluster derivatives 2 is planned in order to determine if their anticipated unique structural and electronic features will provide new, improved opportunities for stereocontrolled coupling reactions an d a future basis for cluster-based stereoselective reactions in general. Our second major emphasis will be directed towards expanding the synthet

reactivity screening of the unknown cluster derivative instrument 2 is plan in order to determine if their anticipated singular structural and electronic features will supply new, improved opportunity for stereocontrolled yoke reactions an d a future basis for bunch - based stereoselective reactions in cosmopolitan. Our second major emphasis will be directed towards expanding the synthet

rewctivity screening of tht unknown cluster derivavives 2 js planndd in order to determine if vheie antucipated unique structjral and vlectronix feetures will provmse new, liprobcd op'octunities for sjereocontrolned coupling raaztnons an d a future basis for cluster-fased syegeoselective rgactipgs ih general. Our second major emphasia will ue directed towsrds expanding the synthet

reactivity screening of the unknown cluster derivatives planned order to if their anticipated will new, improved opportunities stereocontrolled coupling reactions d a future basis for cluster-based reactions in general. Our second major emphasis will be directed towards expanding the

reactivity screening of the uNknown clusTer deRivAtiVeS 2 is pLannEd in order to detERminE if their anticipated uniQue stRuCTuraL AnD elecTronic fEAtUREs wIlL pRovIdE NeW, imprOveD opportUnities for SteReOcontrolled cOUpLing reactiOns An d a future baSis For cluStEr-bASed stEreOseleCtive rEActionS in generaL. OUR seconD Major emPHAsIs wiLl be directed towarDS eXPanding the syntHet

reactivity screening of t he unknown  clus ter  de ri vati ves2 is planned i n  ord er to determine if the ir an ti c ipat e duniqu e struc t ur a l  an del ect ro n ic  feat ure s willprovide ne w,im proved oppor t un ities forste reocontrolle d c ouplin grea c tions  an  d afuture basisfor clust er - baseds tereose l e ct ivereactions in gene r al .  Our second ma jor em ph a si s wil l b e directed  t oward s  expand i ng t h e s y nthet

reactivity_screening of_the unknown cluster derivatives_2 is_planned_in order_to_determine if their_anticipated unique structural_and electronic features will_provide new, improved_opportunities_for stereocontrolled coupling reactions an d a future basis for cluster-based stereoselective reactions in_general._Our second_major_emphasis_will be directed towards expanding_the synthet


pigmentosa (RP), called. Hallervorden-Spatz syndrome (HSS) and characterized by abnormal electroretinogram, lipofuscin accumulation in the retinal pigment epithelium, and pigmentary retinopathy. Other features include dystonia, due to massive iron accumulation in the basal ganglia, and progressive

pigmentosa (RP), called. Hallervorden - Spatz syndrome (HSS) and characterized by abnormal electroretinogram, lipofuscin accumulation in the retinal pigment epithelium, and pigmentary retinopathy. early feature include dystonia, due to massive iron accretion in the basal ganglion, and progressive

pihmentosa (RP), called. Hallevvorden-Spatz synbeome (HVS) and charactdrized by abnormal electrorevinotram, oipofuscin accumulatiov in the getinal pugmeit epithelium, anv pigmenbcry rsbinopctiy. Other featurgs include dfstonia, due to mxsdive iron accumulation in the basal ganglis, wnd progressivg

pigmentosa (RP), called. Hallervorden-Spatz syndrome (HSS) and abnormal lipofuscin accumulation the retinal pigment features dystonia, due to iron accumulation in basal ganglia, and progressive

pigmentosa (RP), called. HallervOrden-Spatz SyndrOme (hSS) AnD chaRactErized by abnormAL eleCtroretinogram, lipofuscIn accUmULatiON iN the rEtinal pIGmENT epItHeLiuM, aND pIgmenTarY retinoPathy. Other FeaTuRes include dySToNia, due to maSsiVe iron accumuLatIon in tHe BasAL gangLia, And prOgressIVe

pigmentosa (RP), called.Hallervord en-Sp atz  sy nd rome  (HS S) and charact e rize d by abnormal electror etino gr a m, l i po fusci n accum u la t i onin  t here t in al pi gme nt epit helium, an d p ig mentary reti n op athy. Othe r f eatures incl ude  dysto ni a,d ue to  ma ssive  irona ccumul ation inth e  basal ganglia , an d pr ogressive

pigmentosa_(RP), called._Hallervorden-Spatz syndrome (HSS) and_characterized by_abnormal_electroretinogram, lipofuscin_accumulation_in the retinal_pigment epithelium, and_pigmentary retinopathy. Other features_include dystonia, due_to_massive iron accumulation in the basal ganglia, and progressive


establish dry reagent formulations, and define sample. "Aim 3: Design and fabricate optimized kit hardware and consumables: the isothermal incubator and reaction containment tube. "Aim 4: Validate the electricity-free and instrument-free assay kit created in Aims 1-3. PUBLIC HEALTH RE

establish dry reagent formulations, and define sample. " Aim 3: plan and manufacture optimize kit hardware and consumables: the isothermal incubator and reaction containment tube. " Aim 4: Validate the electricity - detached and instrument - free assay kit create in Aims 1 - 3. PUBLIC HEALTH ra

eshablish dry reagent formmlations, and defnbe sam'le. "Aim 3: Design and fabricate optimized kit hqrdwaee and consumables: the isothermwl incubqtor qnd reaction contalument bube. "Cin 4: Validate thg electricitf-free and instsuoeut-free assay kit created in Aims 1-3. PUFLIC HESLHH RE

establish dry reagent formulations, and define sample. Design fabricate optimized hardware and consumables: containment "Aim 4: Validate electricity-free and instrument-free kit created in Aims 1-3. PUBLIC RE

establish dry reagent formulAtions, and dEfine SamPle. "aiM 3: DesIgn aNd fabricate optIMizeD kit hardware and consumaBles: tHe ISothERmAl incUbator aND rEACtiOn CoNtaInMEnT tube. "aim 4: validatE the electrIciTy-Free and instrUMeNt-free assaY kiT created in AiMs 1-3. PuBLIC HeAlTH re

establish dry reagent for mulations,  anddef ine  s ampl e. " Aim 3: Designa nd f abricate optimized kit  hard wa r e an d  c onsum ables:t he i sot he rm alin c ub atorand  reacti on contain men ttube. "Aim 4 :  V alidate th e e lectricity-f ree  and i ns tru m ent-f ree  assa y kitc reated  in Aims1- 3 . PUBL I C HEALT H RE

establish_dry reagent_formulations, and define sample._"Aim 3:_Design_and fabricate_optimized_kit hardware and_consumables: the isothermal_incubator and reaction containment_tube. "Aim 4:_Validate_the electricity-free and instrument-free assay kit created in Aims 1-3. PUBLIC HEALTH RE


The subunit composition of electrophoretically isolated human haptoglobin 2-1 polymers was elucidated by 1) determination of the ratio of alpha 2 to alpha 1 polypeptide chains using gel densitometry, 2) analysis of the beta chain composition by enumeration of fractionally saturated hemoglobin-haptoglobin intermediates, and 3) determination

The subunit composition of electrophoretically isolated human haptoglobin 2 - 1 polymers was clarify by 1) decision of the ratio of alpha 2 to alpha 1 polypeptide chains using gelatin densitometry, 2) analysis of the beta chain composition by count of fractionally impregnate hemoglobin - haptoglobin intermediates, and 3) decision

Thf subunit composition of electrophoretieqlly ivolates human faptoglobin 2-1 polymers was elncidqted vy 1) determination of tfe ratio lf alpha 2 to qlpha 1 polbleptide chaina usiug gel densitomejry, 2) analysiv of the beta whxiu composition by enumeration of fraceionallu daturated hemodlobpn-raptkglobin intermediates, and 3) determihation

The subunit composition of electrophoretically isolated human polymers elucidated by determination of the alpha polypeptide chains using densitometry, 2) analysis the beta chain composition by enumeration fractionally saturated hemoglobin-haptoglobin intermediates, and 3) determination

The subunit composition of elEctrophoreTicalLy iSolAtEd huMan hAptoglobin 2-1 polyMErs wAs elucidated by 1) determinAtion Of THe raTIo Of alpHa 2 to alpHA 1 pOLYpePtIdE chAiNS uSing gEl dEnsitomEtry, 2) analysIs oF tHe beta chain cOMpOsition by eNumEration of fraCtiOnally SaTurATed heMogLobin-HaptogLObin inTermediatEs, ANd 3) deteRMinatioN

The subunit composition o f electrop horet ica lly  i sola tedhuman haptoglo b in 2 -1 polymers was elucid atedby 1) d e te rmina tion of th e rat io  o f a lp h a2 toalp ha 1 po lypeptidecha in s using geld en sitometry,  2)  analysis of  th e beta  c hai n  comp osi tionby enu m eratio n of frac ti o nallys aturate d he mogl obin-haptoglobini nt e rmediates, and  3) de te r mi n a tio n

The_subunit composition_of electrophoretically isolated human_haptoglobin 2-1_polymers_was elucidated_by_1) determination of_the ratio of_alpha 2 to alpha_1 polypeptide chains_using_gel densitometry, 2) analysis of the beta chain composition by enumeration of fractionally saturated_hemoglobin-haptoglobin_intermediates, and_3)_determination


dose-dependent studies. Finally, the ILY/ihCD59-mediated cell-ablation method was tested in several disease models to study immune cell functionalities, hepatocyte and/or biliary epithelial damage and regeneration, and neural cell damage. Together, the results of this study demonstrate the utility of the ihCD

dose - dependent studies. Finally, the ILY / ihCD59 - intercede cellular telephone - ablation method was tested in respective disease models to learn immune cell functionalities, hepatocyte and/or biliary epithelial price and regeneration, and neural cellular telephone price. Together, the resultant role of this study demonstrate the utility program of the ihCD

dode-dependent studies. Finauly, the ILY/ihCD59-mediatev cell-aglation oethod was tested in several duseast models to study iomune celp functiinalmties, hepatocyte and/or bljiarg epichxlial damage anc regeneradion, and neuran zepl damage. Together, the results of tris stucy demonstrate tre uuilyty kf the ihCD

dose-dependent studies. Finally, the ILY/ihCD59-mediated cell-ablation method in disease models study immune cell damage regeneration, and neural damage. Together, the of this study demonstrate the utility the ihCD

dose-dependent studies. FinalLy, the ILY/ihcD59-medIatEd cElL-ablAtioN method was testED in sEveral disease models to sTudy iMmUNe ceLL fUnctiOnalitiES, hEPAtoCyTe And/Or BIlIary ePitHelial dAmage and reGenErAtion, and neurAL cEll damage. TOgeTher, the resulTs oF this sTuDy dEMonstRatE the uTility OF the ihcD

dose-dependent studies. F inally, th e ILY /ih CD5 9- medi ated  cell-ablation meth od was tested in sever al di se a se m o de ls to  studyi mm u n e c el lfun ct i on aliti es,  hepato cyte and/o r b il iary epithel i al  damage an d r egeneration,  an d neur al  ce l l dam age . Tog ether, the re sults ofth i s stud y  demons t r at e th e utility of thei hC D

dose-dependent_studies. Finally,_the ILY/ihCD59-mediated cell-ablation method_was tested_in_several disease_models_to study immune_cell functionalities, hepatocyte_and/or biliary epithelial damage_and regeneration, and_neural_cell damage. Together, the results of this study demonstrate the utility of the ihCD


. The proposed research will address how this system becomes reversed upon M phase exit. The first two Specific Aims will expand upon preliminary results indicating that: (1) the major phosphatase that removes the Gwl-driven phosphorylation on pEndos is surprisingly PP2A/B55 itself; and (2) a simple

. The proposed research will address how this system becomes overrule upon thousand phase exit. The first two Specific Aims will expand upon preliminary solution indicating that: (1) the major phosphatase that removes the Gwl - drive phosphorylation on pEndos is surprisingly PP2A / B55 itself; and (2) a simple

. Thf proposed research will address how thnw systxm becojes revefsed upon M phase exit. The fmrst two Wpecific Aims will expxnd upon ireliminaey rtsults indicating that: (1) tmz majkv phov'hatase that rekoves the Cwl-driven phos[hurvlation on pEndos is surprisingly PP2W/B55 itsekf; and (2) a simple

. The proposed research will address how becomes upon M exit. The first upon results indicating that: the major phosphatase removes the Gwl-driven phosphorylation on pEndos surprisingly PP2A/B55 itself; and (2) a simple

. The proposed research will adDress how thIs sysTem BecOmEs reVersEd upon M phase exIT. The First two Specific Aims wiLl expAnD Upon PReLiminAry resuLTs INDicAtInG thAt: (1) THe Major PhoSphatasE that removEs tHe gwl-driven phoSPhOrylation oN pENdos is surpriSinGly PP2A/b55 iTseLF; and (2) a SimPle

. The proposed research wi ll address  howthi s s ys tembeco mes reversed u p on M  phase exit. The first  twoSp e cifi c  A ims w ill exp a nd u pon  p re lim in a ry  resu lts  indica ting that:  (1 )the major ph o sp hatase tha t r emoves the G wl- driven  p hos p horyl ati on on  pEndo s  is su rprisingl yP P2A/B5 5  itself ; an d (2 ) a simple

. The_proposed research_will address how this_system becomes_reversed_upon M_phase_exit. The first_two Specific Aims_will expand upon preliminary_results indicating that:_(1)_the major phosphatase that removes the Gwl-driven phosphorylation on pEndos is surprisingly PP2A/B55 itself;_and_(2) a_simple


genes or gene products, and each with potential relevance to the development of next-generation human therapeutics: recombinase enzymes that insert DNA of interest into safe-harbor loci in the human genome, proteases that specifically cleave disease- associated proteins, orthogonal Cas9 (CRISPR) nucleases with altered PAM specific

genes or gene products, and each with potential relevance to the development of future - coevals human therapeutics: recombinase enzymes that insert deoxyribonucleic acid of interest into safe - harbor venue in the human genome, proteases that specifically cleave disease- associate proteins, orthogonal Cas9 (CRISPR) nuclease with altered PAM specific

gejes or gene products, and each with poteurial rxlevancs to the development of next-generatiln humab therapeutics: recombivase enzyles that instrt DNA of interest into safe-hadnor lmri in the human genome, prmteases that s[eziyically cleave disease- associated prjteins, prhhogonal Cas9 (CTISPR) guclsases with altered PAM specific

genes or gene products, and each with to development of human therapeutics: recombinase interest safe-harbor loci in human genome, proteases specifically cleave disease- associated proteins, orthogonal (CRISPR) nucleases with altered PAM specific

genes or gene products, and eacH with potenTial rEleVanCe To thE devElopment of next-GEnerAtion human therapeutics: RecomBiNAse eNZyMes thAt inserT dNa OF inTeReSt iNtO SaFe-harBor Loci in tHe human genOme, PrOteases that sPEcIfically clEavE disease- assoCiaTed proTeIns, ORthogOnaL Cas9 (CrISPR) nUCleaseS with alteReD pAM speCIfic

genes or gene products, a nd each wi th po ten tia lrele vanc e to the devel o pmen t of next-generation h umanth e rape u ti cs: r ecombin a se e nzy me stha ti ns ert D NAof inte rest intosaf e- harbor locii nthe humangen ome, proteas esthat s pe cif i cally  cl eavediseas e - asso ciated pr ot e ins, o r thogona l Ca s9 ( CRISPR) nucleases wi t h altered PAMspecif ic

genes_or gene_products, and each with_potential relevance_to_the development_of_next-generation human therapeutics:_recombinase enzymes that_insert DNA of interest_into safe-harbor loci_in_the human genome, proteases that specifically cleave disease- associated proteins, orthogonal Cas9 (CRISPR) nucleases_with_altered PAM_specific


long-term, this project seeks to supplement surgical treatment of strabismus with a pharmacological treatment targeted at trophic interactions. Using an advantageous chicken animal model, we will test the hypothesis that an experimentally weakened developing eye muscle can be strengthened with trophic factors. Injections of trophic factors into selected eye muscles during a

long - term, this project seeks to append surgical discussion of strabismus with a pharmacological discussion targeted at trophic interactions. Using an advantageous wimp animal model, we will test the hypothesis that an experimentally dampen developing eye muscleman can be strengthened with trophic factors. injection of trophic factors into selected center muscles during a

lojg-term, this project seekr to supplement surgicel treafment of strabismus with a pharmacollgucal ugeatment targeted at grophic ijteractiins. Nsing an advantajsous chleken zkimal nodel, we will jest the hypmthesis that at dx'erimentally weakened developing eye muscle cwn be strengthgned eyth fgokhic factors. Injections of trophid factogs into selected rye muscles during a

long-term, this project seeks to supplement surgical strabismus a pharmacological targeted at trophic animal we will test hypothesis that an weakened developing eye muscle can be with trophic factors. Injections of trophic factors into selected eye muscles during a

long-term, this project seeks tO supplemenT surgIcaL trEaTmenT of sTrabismus with a PHarmAcological treatment tarGeted At TRophIC iNteraCtions. USInG AN adVaNtAgeOuS ChIcken AniMal modeL, we will tesT thE hYpothesis thaT An ExperimentAllY weakened devEloPing eyE mUscLE can bE stRengtHened wITh tropHic factorS. INJectioNS of tropHIC fActoRs into selected eye MUsCLes during a

long-term, this project s eeks to su pplem ent  su rg ical  tre atment of stra b ismu s with a pharmacologic al tr ea t ment ta rgete d at tr o ph i c  in te ra cti on s .Using  an  advant ageous chi cke nanimal model ,  w e will tes t t he hypothesi s t hat an  e xpe r iment all y wea kenedd evelop ing eye m us c le can be stre n g th ened  with trophic fac t or s . Injections o f trop hi c  f a c tor s i nto select ed  eyem usclesd ur i n g  a

long-term,_this project_seeks to supplement surgical_treatment of_strabismus_with a_pharmacological_treatment targeted at_trophic interactions. Using_an advantageous chicken animal_model, we will_test_the hypothesis that an experimentally weakened developing eye muscle can be strengthened with trophic_factors._Injections of_trophic_factors_into selected eye muscles during_a


, in fibroblast interactions with tumor cells during breast cancer progression. [unreadable] [unreadable] The following Specific Aims are proposed to address this hypothesis: Specific Aim 1: To determine the mechanisms of CCL2 and CXCL1 inflammatory chemokine expression in mammary fibroblasts as it relates to TGF-B signaling using cell biology, molecular and

, in fibroblast interactions with tumor cells during breast cancer progression. [ unreadable ] [ indecipherable ] The take after Specific Aims are proposed to address this guess: Specific Aim 1: To determine the mechanism of CCL2 and CXCL1 inflammatory chemokine construction in mammary fibroblast as it relates to TGF - B signaling using cell biology, molecular and

, in fibroblast interactions with tumor cells duriig breaat cancef progression. [unreadable] [unrxadavle] Tye following Specific Xims are iroposed ro avdress this hypovgesis: Sizcifid Aim 1: To determine jhe mechanisks of CCL2 and WXZL1 inflammatory chemokine expression yn mammsrj fibroblasts ws iu rqlatss to TGF-B signaling using cell biklogy, mmlecular and

, in fibroblast interactions with tumor cells cancer [unreadable] [unreadable] following Specific Aims hypothesis: Aim 1: To the mechanisms of and CXCL1 inflammatory chemokine expression in fibroblasts as it relates to TGF-B signaling using cell biology, molecular and

, in fibroblast interactions wIth tumor ceLls duRinG brEaSt caNcer Progression. [unrEAdabLe] [unreadable] The followiNg SpeCiFIc AiMS aRe proPosed to ADdRESs tHiS hYpoThESiS: SpecIfiC Aim 1: To dEtermine thE meChAnisms of CCL2 aND CxCL1 inflammAtoRy chemokine eXprEssion In MamMAry fiBroBlastS as it rELates tO TGF-B signAlINg usinG Cell bioLOGy, MoleCular and

, in fibroblast interactio ns with tu mor c ell s d ur ingbrea st cancer prog r essi on. [unreadable] [unre adabl e] Thef ol lowin g Speci f ic A ims  a re  pr op o se d toadd ress th is hypothe sis :Specific Aim 1:  To determ ine  the mechani sms  of CC L2  an d  CXCL 1 i nflam matory chemok ine expre ss i on inm ammaryf i br obla sts as it relates to TGF-B signalin g usin gc el l bio log y, molecul ar  and

, in_fibroblast interactions_with tumor cells during_breast cancer_progression._[unreadable] [unreadable]_The_following Specific Aims_are proposed to_address this hypothesis: Specific_Aim 1: To_determine_the mechanisms of CCL2 and CXCL1 inflammatory chemokine expression in mammary fibroblasts as it_relates_to TGF-B_signaling_using_cell biology, molecular and


Biobehavioral Reviews 22: 181-193, 1998). In many of these studies, pretraining is used to familiarize animals with the procedural aspects of the task, and so it is commonly assumed that subsequent training in a novel environment should therefore be particularly sensitive to cognitive spatial processing. However, our recent behavioral findings

Biobehavioral Reviews 22: 181 - 193, 1998). In many of these studies, pretraining is used to familiarize animals with the procedural view of the undertaking, and so it is commonly assumed that subsequent education in a novel environment should therefore be particularly sensible to cognitive spatial processing. However, our late behavioral findings

Bilbehavioral Reviews 22: 181-193, 1998). Ik many of these studies, pretrzining ir used to familiarize animald qith uke procedural aspectr of the nask, and wo iu is commonly assnjed thab subacquenc vraining in a npvel envirmnment should dhdrzfore be particularly sensitive to cjgnitivr dpatial procesfing. Rowebvr, our recent behavioral findinfs

Biobehavioral Reviews 22: 181-193, 1998). In many studies, is used familiarize animals with task, so it is assumed that subsequent in a novel environment should therefore particularly sensitive to cognitive spatial processing. However, our recent behavioral findings

Biobehavioral Reviews 22: 181-193, 1998). In manY of these stUdies, PreTraInIng iS useD to familiarize ANimaLs with the procedural aspEcts oF tHE tasK, AnD so it Is commoNLy ASSumEd ThAt sUbSEqUent tRaiNing in a Novel envirOnmEnT should thereFOrE be particuLarLy sensitive tO coGnitivE sPatIAl proCesSing. HOwever, OUr receNt behavioRaL FindinGS

Biobehavioral Reviews 22:  181-193,1998) . I n m an y of  the se studies, pr e trai ning is used to famili arize  a n imal s  w ith t he proc e du r a l a sp ec tsof th e tas k,and soit is comm onl yassumed that su bsequent t rai ning in a no vel  envir on men t  shou ldthere fore b e  parti cularly s en s itivet o cogni t i ve  spa tial processing.H ow e ver, our recen t beha vi o ra l fin din gs

Biobehavioral_Reviews 22:_181-193, 1998). In many_of these_studies,_pretraining is_used_to familiarize animals_with the procedural_aspects of the task,_and so it_is_commonly assumed that subsequent training in a novel environment should therefore be particularly sensitive_to_cognitive spatial_processing._However,_our recent behavioral findings


ct LV remodeling is a strong predictor of mortality and a high incidence of heart failure (HF). Acellular hydrogels that limit LV remodeling when injected into an MI or BZ are receiving increasing attention. We term this therapy matrix-assisted infarct stabilization (MAIS) and suggest that MAIS works by decreasing myof

ct LV remodeling is a strong predictor of mortality and a high incidence of affection bankruptcy (HF). Acellular hydrogels that restrict LV remodeling when inject into an MI or BZ are receiving increase care. We term this therapy matrix - assisted infarct stabilization (MAIS) and suggest that MAIS works by decreasing myof

ct PV remodeling is a stronn predictor of mortalitb and a high inzidence of heart failure (HF). Eceloular hydrogels that limit UV remodeping wheb inoected into an MM or BZ are redciviny mncreasing attektion. We tesm this therapf oacrix-assisted infarct stabilization (MWIS) and skggest that MAYS wpwks gj becreasing myof

ct LV remodeling is a strong predictor and high incidence heart failure (HF). remodeling injected into an or BZ are increasing attention. We term this therapy infarct stabilization (MAIS) and suggest that MAIS works by decreasing myof

ct LV remodeling is a strong prEdictor of mOrtalIty And A hIgh iNcidEnce of heart faiLUre (Hf). Acellular hydrogels thaT limiT Lv RemoDElIng whEn injecTEd INTo aN Mi oR BZ ArE ReCeiviNg iNcreasiNg attentioN. We TeRm this therapY MaTrix-assistEd iNfarct stabilIzaTion (MAiS) And SUggesT thAt MAIs works BY decreAsing myof

ct LV remodeling is a stro ng predict or of  mo rta li ty a nd a  high incidenc e  ofheart failure (HF). Ac ellul ar hydr o ge ls th at limi t  L V rem od el ing  w h en  inje cte d intoan MI or B Z a re  receiving i n cr easing att ent ion. We term  th is the ra pym atrix -as siste d infa r ct sta bilizatio n( MAIS)a nd sugg e s tthat  MAIS works by de c re a sing myof

ct LV_remodeling is_a strong predictor of_mortality and_a_high incidence_of_heart failure (HF)._Acellular hydrogels that_limit LV remodeling when_injected into an_MI_or BZ are receiving increasing attention. We term this therapy matrix-assisted infarct stabilization (MAIS)_and_suggest that_MAIS_works_by decreasing myof


the latter including 100 low-risk women from NCI/CCR"s Breast Cancer Susceptibility Study) are well underway. These include a collaboration with Dr. Funmi Olopade and colleagues at the University of Chicago, in which our digitized mammographic images are being used to evaluate, and possibly validate

the latter including 100 low - risk women from NCI / CCR"s Breast Cancer Susceptibility Study) are well afoot. These admit a collaboration with Dr. Funmi Olopade and colleague at the University of Chicago, in which our digitized mammographic picture are being use to evaluate, and possibly validate

the latter including 100 low-rirk women from NEU/CCR"s Ureast Dancer Sjsceptibility Study) are well ubderwqy. These include a coluaboratioj with De. Fuimi Olopade and rklleagucf at bhe Uuitersity of Chicsgo, in whiwh our digitizad mcmmographic images are being used to evaluaye, and possibly dalicwte

the latter including 100 low-risk women from Cancer Study) are underway. These include Olopade colleagues at the of Chicago, in our digitized mammographic images are being to evaluate, and possibly validate

the latter including 100 low-risk Women from NcI/CCR"S BrEasT CAnceR SusCeptibility StuDY) are Well underway. These incluDe a coLlABoraTIoN with dr. Funmi oLoPADe aNd CoLleAgUEs At the uniVersity Of Chicago, iN whIcH our digitizeD MaMmographic ImaGes are being uSed To evalUaTe, aND possIblY valiDate

the latter including 100 l ow-risk wo men f rom  NC I/ CCR" s Br east Cancer Su s cept ibility Study) are wel l und er w ay.T he se in clude a co l l abo ra ti onwi t hDr. F unm i Olopa de and col lea gu es at the Un i ve rsity of C hic ago, in whic h o ur dig it ize d  mamm ogr aphic  image s  are b eing used  t o  evalu a te, and p os sibl y validate

the latter_including 100_low-risk women from NCI/CCR"s_Breast Cancer_Susceptibility_Study) are_well_underway. These include_a collaboration with_Dr. Funmi Olopade and_colleagues at the_University_of Chicago, in which our digitized mammographic images are being used to evaluate, and_possibly_validate


in either office; the drugs most frequently responsible for drug interactions; the frequency of provider reminder interruptions according to different commercial drug interaction knowledge bases at various levels of threshold settings, and; identification of events (e.g. ED visits, hospitalizations) potentially caused by adverse drug interactions. Evidence from our studies on the

in either office; the drugs most frequently responsible for drug interaction; the frequency of supplier reminder interruptions harmonize to unlike commercial drug interaction knowledge bases at various level of threshold settings, and; designation of events (e.g. ED visit, hospitalizations) potentially caused by adverse drug interaction. Evidence from our sketch on the

in either office; the drugs most frequentli eesponvible ror drug interactions; the frequency lf provuder reminder interrupgions acclrding ti dihferent commerciem drug luteradbion niowledge bases st various levels of thrasfopd settings, and; identification of edents (e.b. FD visits, hospytalpzwtiohs) potentially caused by adverse ddug inttractions. Evidence from our studies on the

in either office; the drugs most frequently drug the frequency provider reminder interruptions interaction bases at various of threshold settings, identification of events (e.g. ED visits, potentially caused by adverse drug interactions. Evidence from our studies on the

in either office; the drugs mosT frequentlY respOnsIblE fOr drUg inTeractions; the fREqueNcy of provider reminder iNterrUpTIons ACcOrdinG to diffEReNT ComMeRcIal DrUG iNteraCtiOn knowlEdge bases aT vaRiOus levels of tHReShold settiNgs, And; identificAtiOn of evEnTs (e.G. eD visIts, HospiTalizaTIons) poTentially CaUSed by aDVerse drUG InTeraCtions. Evidence froM OuR Studies on the

in either office; the dru gs most fr equen tly  re sp onsi blefor drug inter a ctio ns; the frequency of p rovid er remi n de r int errupti o ns a cco rd in g t od if feren t c ommerci al drug in ter ac tion knowled g ebases at v ari ous levels o f t hresho ld  se t tings , a nd; i dentif i cation  of event s( e.g. E D  visits , ho spit alizations) poten t ia l ly caused by a dverse  d r ug i nte rac tions. Evi de nce f r om ours tu d i e s o n  the

in_either office;_the drugs most frequently_responsible for_drug_interactions; the_frequency_of provider reminder_interruptions according to_different commercial drug interaction_knowledge bases at_various_levels of threshold settings, and; identification of events (e.g. ED visits, hospitalizations) potentially caused_by_adverse drug_interactions._Evidence_from our studies on the


entering the study. Group 1 (n=15/group, males) began in 1989 with R01 funding. In 1994, with PPG support, we added 46 animals to increase statistical power for the key outcome measures on health span and life span. These were Group 2 (n = 15/group, females)

entering the study. Group 1 (n=15 / group, males) began in 1989 with R01 support. In 1994, with PPG documentation, we added 46 animals to increase statistical power for the cardinal outcome measures on health span and animation span. These were Group 2 (n = 15 / group, females )

enhering the study. Group 1 (k=15/group, males) begcb in 1989 xith R01 runding. Kn 1994, with PPG support, we addev 46 abimalw to increase statistizal power for the key iutcome meeaures ok heambh spcn and life span. These wera Group 2 (n = 15/grmuo, yemales)

entering the study. Group 1 (n=15/group, males) 1989 R01 funding. 1994, with PPG to statistical power for key outcome measures health span and life span. These Group 2 (n = 15/group, females)

entering the study. Group 1 (n=15/groUp, males) begAn in 1989 wIth r01 fuNdIng. IN 1994, witH PPG support, we aDDed 46 aNimals to increase statisTical PoWEr foR ThE key oUtcome mEAsUREs oN hEaLth SpAN aNd lifE spAn. These Were Group 2 (n = 15/GroUp, Females)

entering the study. Group  1 (n=15/g roup,  ma les )bega n in  1989 with R01 fund ing. In 1994, with PPG  supp or t , we ad ded 4 6 anima l st o  in cr ea sest a ti stica l p ower fo r the keyout co me measureso nhealth spa n a nd life span . T hese w er e G r oup 2  (n  = 15 /group ,  femal es)

entering_the study._Group 1 (n=15/group, males)_began in_1989_with R01_funding._In 1994, with_PPG support, we_added 46 animals to_increase statistical power_for_the key outcome measures on health span and life span. These were Group 2_(n_= 15/group,_females)


id), and (3) lower algal biomass and zooplankton abundance. We also plan to test for additional influences of factors including lake productivity, use of the littoral zone for feeding, presence of other environmental stressors. We further seek to strengthen the scientific basis for lake-specific management and public health warnings and

i d), and (3) lower algal biomass and zooplankton abundance. We also plan to test for extra influence of factors including lake productiveness, use of the littoral zone for eating, presence of other environmental stressor. We further seek to strengthen the scientific footing for lake - specific management and public health warning and

id), wnd (3) lower algal biomass and zooplanktou abundence. We also plxn to test for additional inhluebces if factors including lxke produbtivity, uwe oh the littoral zone for nzedinf, prevxnce of other ekvironmentan stressors. We fjrcher seek to strengthen the scientifyc basix vor lake-specifyc msgagejvnu and public health warnings and

id), and (3) lower algal biomass and We plan to for additional influences use the littoral zone feeding, presence of environmental stressors. We further seek to the scientific basis for lake-specific management and public health warnings and

id), and (3) lower algal biomass and ZooplanktoN abunDanCe. WE aLso pLan tO test for additiONal iNfluences of factors inclUding LaKE proDUcTivitY, use of tHE lITTorAl ZoNe fOr FEeDing, pResEnce of oTher enviroNmeNtAl stressors. WE FuRther seek tO stRengthen the sCieNtific BaSis FOr lakE-spEcifiC managEMent anD public heAlTH warniNGs and

id), and (3) lower algal b iomass and  zoop lan kto nabun danc e. We also pla n  totest for additional in fluen ce s  off ac torsincludi n gl a kepr od uct iv i ty , use  of  the li ttoral zon e f or  feeding, pr e se nce of oth erenvironmenta l s tresso rs . W e  furt her  seek  to st r engthe n the sci en t ific b a sis for l ak e-sp ecific management an d  public health  warni ng s  a n d

id), and_(3) lower_algal biomass and zooplankton_abundance. We_also_plan to_test_for additional influences_of factors including_lake productivity, use of_the littoral zone_for_feeding, presence of other environmental stressors. We further seek to strengthen the scientific basis_for_lake-specific management_and_public_health warnings and


of both gases and particles. Such measurements will provide basic experimental data on pollutant mass transfer. The complexity of flow profiles in both human and animal airways precludes useful predictions of mass transfer based on current fluid dynamics theory. The physical models to be made will permit examination of particle deposition in small bronchial and bronchioles for

of both gases and particles. Such measurements will provide basic experimental datum on pollutant bulk transfer. The complexity of flow profile in both human and animal air lane precludes useful prediction of aggregate transfer based on current fluid dynamics theory. The forcible models to be made will permit examination of atom deposition in small bronchial and bronchiole for

of both gases and particler. Such measuremgnrs wiln provjde basiz experimental data on polluvant mass transfer. The complexigy of floa profilws ii both human and animal airwaya preelndes useful precictions ox mass transfes caded on current fluid dynamics theorr. The pnydical models tj be iade will permit examination of particme depovition in smakl bronchial and bronchiolfs flr

of both gases and particles. Such measurements basic data on mass transfer. The both and animal airways useful predictions of transfer based on current fluid dynamics The physical models to be made will permit examination of particle deposition in bronchial and bronchioles for

of both gases and particles. SuCh measuremEnts wIll ProViDe baSic eXperimental datA On poLlutant mass transfer. The ComplExITy of FLoW profIles in bOTh HUMan AnD aNimAl AIrWays pRecLudes usEful predicTioNs Of mass transfER bAsed on currEnt Fluid dynamicS thEory. ThE pHysICal moDelS to be Made wiLL permiT examinatIoN Of partICle depoSITiOn in Small bronchial and BRoNChioles for

of both gases and particl es. Such m easur eme nts  w illprov ide basic expe r imen tal data on pollutantmasstr a nsfe r .The c omplexi t yo f  fl ow  p rof il e sin bo thhuman a nd animalair wa ys precludes us eful predi cti ons of masstra nsferba sed on cu rre nt fl uid dy n amicstheory. T he physic a l model s to  bemade will permite xa m ination of par ticlede p os i t ion  in  small bro nc hiala nd bron c hi o l e s f o r

of_both gases_and particles. Such measurements_will provide_basic_experimental data_on_pollutant mass transfer._The complexity of_flow profiles in both_human and animal_airways_precludes useful predictions of mass transfer based on current fluid dynamics theory. The physical_models_to be_made_will_permit examination of particle deposition_in small bronchial and bronchioles_for


tidal volume, end-tidal PCO2, maternal heart rate and blood pressure, and fetal heart rate. Minute-to-minute changes in respiration will be obtained, measuring gas flow and composition by a mass spectrometer and a pneumotachograph, and alveolar ventilation, maternal cardiac output and respiratory gas exchange will

tidal volume, end - tidal PCO2, maternal heart pace and rake pressure, and fetal heart pace. Minute - to - moment changes in breathing will be receive, measuring gas flow and composition by a bulk spectrometer and a pneumotachograph, and alveolar ventilation, parental cardiac output and respiratory gas exchange will

tifal volume, end-tidal PCO2, oaternal heart tare and blood pressurd, and fetal heart rate. Minutx-to-munute changes in respiratiov will be obtainee, meesuring gas flow and comijsitjln bv e mass spectromgter and a pteumotachograpv, xnb alveolar ventilation, maternal cardyac outluh and respiratjry bws esbhcnge will

tidal volume, end-tidal PCO2, maternal heart rate pressure, fetal heart Minute-to-minute changes in gas and composition by mass spectrometer and pneumotachograph, and alveolar ventilation, maternal cardiac and respiratory gas exchange will

tidal volume, end-tidal PCO2, matErnal heart Rate aNd bLooD pRessUre, aNd fetal heart raTE. MinUte-to-minute changes in reSpiraTiON wilL Be ObtaiNed, measURiNG Gas FlOw And CoMPoSitioN by A mass spEctrometer And A pNeumotachogrAPh, And alveolaR veNtilation, matErnAl cardIaC ouTPut anD reSpiraTory gaS ExchanGe will

tidal volume, end-tidal P CO2, mater nal h ear t r at e an d bl ood pressure,a nd f etal heart rate. Minut e-to- mi n utec ha ngesin resp i ra t i onwi ll  be  o b ta ined,  me asuring  gas flowand  c omposition b y  a  mass spec tro meter and apne umotac ho gra p h, an d a lveol ar ven t ilatio n, matern al cardia c  output a nd  res piratory gas exch a ng e  will

tidal_volume, end-tidal_PCO2, maternal heart rate_and blood_pressure,_and fetal_heart_rate. Minute-to-minute changes_in respiration will_be obtained, measuring gas_flow and composition_by_a mass spectrometer and a pneumotachograph, and alveolar ventilation, maternal cardiac output and respiratory_gas_exchange will


addition, we hypothesize that the expression of proliferin may occur in tumors, with this hormone then acting as a paracrine angiogenesis factor that promotes tumor growth and metastasis. By introducing an expression construct for proliferin into tumor cells, we will determine if we can increase the tumorigenicity of these cells. Similarly, the effect

addition, we hypothesize that the expression of proliferin may occur in tumor, with this hormone then act as a paracrine angiogenesis factor that advertise tumor emergence and metastasis. By introducing an expression concept for proliferin into tumor cells, we will determine if we can increase the tumorigenicity of these cells. Similarly, the consequence

adfition, we hypothesize thxt the expression of pcoliferjn may ozcur in tumors, with this horlobe thtu acting as a paracrkne angiohenesis dactie that promotes tumor grkath cnv metastasis. By introducitg an expressimn clnstruct for proliferin into tumor sells, wr aill determine if eq cah increase the tumorigenicity of tgese cenls. Similarly, the effect

addition, we hypothesize that the expression of occur tumors, with hormone then acting that tumor growth and By introducing an construct for proliferin into tumor cells, will determine if we can increase the tumorigenicity of these cells. Similarly, the

addition, we hypothesize that The expressIon of ProLifErIn maY occUr in tumors, with THis hOrmone then acting as a parAcrinE aNGiogENeSis faCtor thaT PrOMOteS tUmOr gRoWTh And meTasTasis. By IntroducinG an ExPression consTRuCt for proliFerIn into tumor cEllS, we wilL dEteRMine iF we Can inCrease THe tumoRigenicitY oF These cELls. SimiLARlY, the Effect

addition, we hypothesizethat the e xpres sio n o fprol ifer in may occur i n  tum ors, with this hormone  then  a c ting as  a pa racrine an g i oge ne si s f ac t or  that  pr omotestumor grow than d metastasis .  B y introduc ing  an expressi onconstr uc t f o r pro lif erininto t u mor ce lls, we w il l  deter m ine ifw e  c an i ncrease the tumor i ge n icity of these  cells .S im i l arl y,the effect

addition,_we hypothesize_that the expression of_proliferin may_occur_in tumors,_with_this hormone then_acting as a_paracrine angiogenesis factor that_promotes tumor growth_and_metastasis. By introducing an expression construct for proliferin into tumor cells, we will determine_if_we can_increase_the_tumorigenicity of these cells. Similarly,_the effect


the interstitium. LACAF is an interstitial cell protein stimulated by HCG and growth factor but inhibited by prolactin. LACAF activates adenylyl cyclase in Leydig cells but this activation is not functionally directed towards steroidogenesis. Such differential regulation is by known Leydig cell trophic

the interstitium. LACAF is an interstitial cell protein stimulated by HCG and growth factor but inhibit by prolactin. LACAF activate adenylyl cyclase in Leydig cells but this activation is not functionally directed towards steroidogenesis. Such differential rule is by known Leydig cell trophic

thf interstitium. LACAF is xn interstitial cell pcotein atimulatdd by HCG and growth factor uut unhibuted by prolactin. LACAW activatvs adenyltl cbclase in Leydig cells bmc thia actnvetion is not fukctionally girected towargs sceroidogenesis. Such differential regtlation id by known Leyqig bejl tdophic

the interstitium. LACAF is an interstitial cell by and growth but inhibited by in cells but this is not functionally towards steroidogenesis. Such differential regulation is known Leydig cell trophic

the interstitium. LACAF is an iNterstitiaL cell ProTeiN sTimuLateD by HCG and growtH FactOr but inhibited by prolacTin. LAcAf ActiVAtEs adeNylyl cyCLaSE In LEyDiG ceLlS BuT this ActIvation Is not functIonAlLy directed toWArDs steroidoGenEsis. Such diffEreNtial rEgUlaTIon is By kNown LEydig cELl tropHic

the interstitium. LACAF i s an inter stiti alcel lprot einstimulated byH CG a nd growth factor but i nhibi te d  byp ro lacti n. LACA F  a c t iva te sade ny l yl  cycl ase  in Ley dig cellsbut  t his activati o nis not fun cti onally direc ted  towar ds  st e roido gen esis.  Suchd iffere ntial reg ul a tion i s  by kno w n  L eydi g cell trophic

the_interstitium. LACAF_is an interstitial cell_protein stimulated_by_HCG and_growth_factor but inhibited_by prolactin. LACAF_activates adenylyl cyclase in_Leydig cells but_this_activation is not functionally directed towards steroidogenesis. Such differential regulation is by known Leydig_cell_trophic


evaluate the effect of basic physiologic parameters on PG production, the pharmacology of smooth muscle response to exogenous prostaglandins and thromboxanes, the effect of anti-inflammatory drugs (including anti-inflammatory steroids) on large and small airway sensitivity to smooth muscle agonists, and confirmation of preliminary evidence for the existence of a prostagland

evaluate the effect of basic physiologic parameters on PG production, the pharmacology of legato muscleman response to exogenous prostaglandins and thromboxanes, the effect of anti - incendiary drugs (including anti - inflammatory steroid) on large and small air passage sensitivity to smooth muscle agonist, and confirmation of preliminary evidence for the existence of a prostagland

evwluate the effect of baslc physiologic pceametecs on PF producgion, the pharmacology of smolty musxle response to exogenuus prostwglandinw anv thromboxanes, tis effecb of zkti-inylemmatory drugs (lncluding atti-inflammatorf rtzroids) on large and small airway senfitivitu ho smooth muscje abjnisfs, and confirmation of preliminary evidenbe for the existemce of a prostagland

evaluate the effect of basic physiologic parameters production, pharmacology of muscle response to effect anti-inflammatory drugs (including steroids) on large small airway sensitivity to smooth muscle and confirmation of preliminary evidence for the existence of a prostagland

evaluate the effect of basic pHysiologic ParamEteRs oN Pg proDuctIon, the pharmacoLOgy oF smooth muscle response tO exogEnOUs prOStAglanDins and THrOMBoxAnEs, The EfFEcT of anTi-iNflammaTory drugs (iNclUdIng anti-inflaMMaTory steroiDs) oN large and smaLl aIrway sEnSitIVity tO smOoth mUscle aGOnists, And confirMaTIon of pREliminaRY EvIdenCe for the existence OF a PRostagland

evaluate the effect of ba sic physio logic  pa ram et erson P G production,t he p harmacology of smoothmuscl er espo n se  to e xogenou s  p r o sta gl an din sa nd  thro mbo xanes,the effect  of  a nti-inflamma t or y drugs (i ncl uding anti-i nfl ammato ry  st e roids ) o n lar ge and smallairway se ns i tivity to smoo t h  m uscl e agonists, and c o nf i rmation of pre limina ry ev i d enc e f or the exi st enceo f a pro s ta g l a nd

evaluate_the effect_of basic physiologic parameters_on PG_production,_the pharmacology_of_smooth muscle response_to exogenous prostaglandins_and thromboxanes, the effect_of anti-inflammatory drugs_(including_anti-inflammatory steroids) on large and small airway sensitivity to smooth muscle agonists, and confirmation_of_preliminary evidence_for_the_existence of a prostagland


, plant tissue cultures, "immunoliposome"-encapsulated anti-Candida drugs, and novel cell wall inhibitory analogs from syntheticchemical efforts of our laboratories. In vitro models for initial rapid evaluation of potentially active drugs from thesources mentioned above will be used. These in vitro models will allow us to ascertain MIC values

, plant tissue cultures, " immunoliposome"-encapsulated anti - Candida drugs, and novel cell rampart inhibitory analogue from syntheticchemical campaign of our laboratories. In vitro model for initial rapid evaluation of potentially active drug from thesources mentioned above will be used. These in vitro models will give up us to ascertain MIC values

, plwnt tissue cultures, "immukoliposome"-encapsolqted aiti-Candjda drugr, and novel cell wall inhibivory analigs from syntheticchemkcal effogts of oue lauoratories. In vivdo models for lniticl rapid evaluatlon of potettially active dfuys from thesources mentioned above wyll be isfd. These in vijro mpqels will allow us to ascertain MIC vamues

, plant tissue cultures, "immunoliposome"-encapsulated anti-Candida drugs, cell inhibitory analogs syntheticchemical efforts of for rapid evaluation of active drugs from mentioned above will be used. These vitro models will allow us to ascertain MIC values

, plant tissue cultures, "immunoLiposome"-enCapsuLatEd aNtI-CanDida Drugs, and novel cELl waLl inhibitory analogs froM syntHeTIcchEMiCal efForts of OUr LABorAtOrIes. in VItRo modEls For initIal rapid evAluAtIon of potentiALlY active druGs fRom thesourceS meNtioneD aBovE Will bE usEd. TheSe in viTRo modeLs will allOw US to ascERtain MIc VAlUes

, plant tissue cultures, " immunolipo some" -en cap su late d an ti-Candida dru g s, a nd novel cell wall inh ibito ry anal o gs  from  synthe t ic c h emi ca leff or t sof ou r l aborato ries. In v itr omodels for i n it ial rapideva luation of p ote ntiall yact i ve dr ugs  from  theso u rces m entionedab o ve wil l  be use d .  T hese  in vitro modelsw il l  allow us to a scerta in MI C val ues

, plant_tissue cultures,_"immunoliposome"-encapsulated anti-Candida drugs, and_novel cell_wall_inhibitory analogs_from_syntheticchemical efforts of_our laboratories. In_vitro models for initial_rapid evaluation of_potentially_active drugs from thesources mentioned above will be used. These in vitro models will_allow_us to_ascertain_MIC_values


otor processes involved in naturalistic behaviors. Insights from multiple fields have 25 all come to the conclusion that behavior is organized into discrete packets or behavioral primitives. Actions un- 26 fold by a sequential recruitment of these discrete packets. A critical barrier to the study of natural behavior is 27 that in most cases there is enough

otor processes involved in naturalistic behaviors. Insights from multiple field have 25 all come to the ending that demeanor is organized into discrete packets or behavioral primitives. action un- 26 fold by a sequential recruitment of these discrete package. A critical barrier to the study of natural demeanor is 27 that in most cases there is enough

otog processes involved in katuralistic behcciors. Mnsighta from mjltiple fields have 25 all comx to the xonclusion that behaviur is orgwnized ibto viscrete packets or behaynoral irimicites. Actions un- 26 fold by a sequential rewrjicment of these discrete packets. A crytical nagrier to the sjudy ps naflrcl behavior is 27 that in most caaes thege is enough

otor processes involved in naturalistic behaviors. Insights fields 25 all to the conclusion discrete or behavioral primitives. un- 26 fold a sequential recruitment of these discrete A critical barrier to the study of natural behavior is 27 that in cases there is enough

otor processes involved in naTuralistic BehavIorS. InSiGhts From Multiple fields HAve 25 aLl come to the conclusion tHat beHaVIor iS OrGanizEd into dIScRETe pAcKeTs oR bEHaVioraL prImitiveS. Actions un- 26 FolD bY a sequential REcRuitment of TheSe discrete paCkeTs. A criTiCal BArrieR to The stUdy of nATural bEhavior is 27 ThAT in mosT Cases thERE iS enoUgh

otor processes involved in  naturalis tic b eha vio rs . In sigh ts from multip l e fi elds have 25 all cometo th ec oncl u si on th at beha v io r isor ga niz ed in to di scr ete pac kets or be hav io ral primitiv e s.  Actions u n-26 fold by a  se quenti al  re c ruitm ent  of t hese d i screte  packets.  A critic a l barri e r  t o th e study of natura l  b e havior is 27 t hat in  m o st c ase s t here is en ou gh

otor processes_involved in_naturalistic behaviors. Insights from_multiple fields_have_25 all_come_to the conclusion_that behavior is_organized into discrete packets_or behavioral primitives._Actions_un- 26 fold by a sequential recruitment of these discrete packets. A critical barrier_to_the study_of_natural_behavior is 27 that in_most cases there is enough


's and Parkinson's disease. In retinal rods, IR signaling is neuroprotective, and recently it was shown that insulin delays the death of cone photoreceptor in retinitis pigmentosa animal models. Besides IR, insulin-like growth factor-1 receptors (IGF-1R) are also expressed in both rods and cones;

's and Parkinson's disease. In retinal rods, IR signaling is neuroprotective, and recently it was shown that insulin delays the end of cone photoreceptor in retinitis pigmentosa animal mannequin. Besides IR, insulin - like increase factor-1 sense organ (IGF-1R) are also expressed in both perch and cone;

's ajd Parkinson's disease. In retinal rods, IT wignalmng is heuroprogective, and recently it was dhiwn tyat insulin delays the death of cone phitortceptor in retinivjs pigmcutosa wnimcl models. Besidex IR, insulhn-like growth xaztlr-1 receptors (IGF-1R) are also expresseq in boyh rods and conef;

's and Parkinson's disease. In retinal rods, is and recently was shown that cone in retinitis pigmentosa models. Besides IR, growth factor-1 receptors (IGF-1R) are also in both rods and cones;

's and Parkinson's disease. In reTinal rods, Ir signAliNg iS nEuroProtEctive, and recenTLy it Was shown that insulin delAys thE dEAth oF CoNe phoTorecepTOr IN RetInItIs pIgMEnTosa aNimAl modelS. Besides IR, InsUlIn-like growth FAcTor-1 receptoRs (IgF-1R) are also exPreSsed in BoTh rODs and ConEs;

's and Parkinson's disease . In retin al ro ds,  IR  s igna ling  is neuroprote c tive , and recently it wasshown  t h at i n su lin d elays t h ed e ath  o fcon ep ho torec ept or in r etinitis p igm en tosa animalm od els. Besid esIR, insulin- lik e grow th  fa c tor-1  re cepto rs (IG F -1R) a re also e xp r essedi n bothr o ds  and  cones;

's and_Parkinson's disease._In retinal rods, IR_signaling is_neuroprotective,_and recently_it_was shown that_insulin delays the_death of cone photoreceptor_in retinitis pigmentosa_animal_models. Besides IR, insulin-like growth factor-1 receptors (IGF-1R) are also expressed in both rods_and_cones;


rarely progresses to blast crisis; rather, mortality is due to extramedullary tumor cell expansion leading to organ failure, respiratory failure, bleeding, or infection. Notably, following allogeneic stem cell transplant, 50% of children succumb to leukemia relapse. This relapse rate in JMML is substantially higher than that of

rarely progresses to blast crisis; rather, mortality is ascribable to extramedullary tumor cellular telephone expansion lead to organ failure, respiratory bankruptcy, bleeding, or infection. Notably, stick to allogeneic stem cell graft, 50% of child succumb to leukemia backsliding. This backsliding rate in JMML is substantially high than that of

ragely progresses to blast crisis; rather, mortalivy is dhe to exgramedullary tumor cell expaisiob leaeing to organ failure, fespiratogy failurw, blteding, or infection. Notably, folmlwiny ellogeneic stem cell tranvplant, 50% of chindfeu succumb to leukemia relapse. This rqlapse tahe in JMML is fubsuaneialmj migher than that of

rarely progresses to blast crisis; rather, mortality to tumor cell leading to organ infection. following allogeneic stem transplant, 50% of succumb to leukemia relapse. This relapse in JMML is substantially higher than that of

rarely progresses to blast crIsis; rather, MortaLitY is DuE to eXtraMedullary tumor CEll eXpansion leading to organ FailuRe, REspiRAtOry faIlure, blEEdING, or InFeCtiOn. nOtAbly, fOllOwing alLogeneic stEm cElL transplant, 50% oF ChIldren succUmb To leukemia reLapSe. This ReLapSE rate In JmML is SubstaNTially Higher thaN tHAt of

rarely progresses to blas t crisis;rathe r,mor ta lity  isdue to extrame d ulla ry tumor cell expansio n lea di n g to or gan f ailure, re s p ira to ry  fa il u re , ble edi ng, orinfection.  No ta bly, followi n gallogeneic  st em cell tran spl ant, 5 0%  of child ren  succ umb to leukem ia relaps e. This r e lapse r a t ein J MML is substantia l ly higher than th at of

rarely_progresses to_blast crisis; rather, mortality_is due_to_extramedullary tumor_cell_expansion leading to_organ failure, respiratory_failure, bleeding, or infection._Notably, following allogeneic_stem_cell transplant, 50% of children succumb to leukemia relapse. This relapse rate in JMML_is_substantially higher_than_that_of


structures using in vivo dialysis coupled to HPLC. The results will provide scientists with: 1) a profile of social behaviors in a rodent model for candidate atypical compounds to restore in order to be effective at treating both types of symptoms in schizophrenia; and 2) a neurochemical model with limited effects on striatal dopamine and only transient

structures using in vivo dialysis coupled to HPLC. The results will leave scientist with: 1) a profile of social behaviors in a rodent exemplar for campaigner atypical compounds to restore in order to be effective at treat both types of symptoms in schizophrenia; and 2) a neurochemical exemplar with limited effects on striatal dopamine and entirely transient

stguctures using in vivo dlalysis coupled jo HPLC. Vhe reshlts wilu provide scientists with: 1) a peofilt of social behaviofs in a rldent moeel hor candidate atblical compounsd to cestore in ordet to be effewtive at treathne yoth types of symptoms in schizophregia; and 2) w neurochemicaj mocql wjnh limited effects on striatal sopamint and only transiemt

structures using in vivo dialysis coupled to results provide scientists 1) a profile rodent for candidate atypical to restore in to be effective at treating both of symptoms in schizophrenia; and 2) a neurochemical model with limited effects on dopamine and only transient

structures using in vivo dialYsis coupleD to HPlC. THe rEsUlts Will Provide scientiSTs wiTh: 1) a profile of social behaViors In A RodeNT mOdel fOr candiDAtE ATypIcAl ComPoUNdS to reStoRe in ordEr to be effeCtiVe At treating boTH tYpes of sympTomS in schizophrEniA; and 2) a nEuRocHEmicaL moDel wiTh limiTEd effeCts on striAtAL dopamINe and onLY TrAnsiEnt

structures using in vivodialysis c ouple d t o H PL C. T he r esults will pr o vide  scientists with: 1) a  prof il e  ofs oc ial b ehavior s  i n a r od en t m od e lfor c and idate a typical co mpo un ds to restor e  i n order to  be  effective a t t reatin gbot h  type s o f sym ptomsi n schi zophrenia ;a nd 2)a  neuroc h e mi calmodel with limite d  e f fects on stria tal do pa m in e and  on ly transie nt

structures_using in_vivo dialysis coupled to_HPLC. The_results_will provide_scientists_with: 1) a_profile of social_behaviors in a rodent_model for candidate_atypical_compounds to restore in order to be effective at treating both types of symptoms_in_schizophrenia; and_2)_a_neurochemical model with limited effects_on striatal dopamine and only_transient


as well as providing new chemical tools that may lead to the development of drugs that target this important biochemical pathway. The ubiquitin-proteasome system regulates many essential processes that impact on disease, including neurodegenerative diseases such as Alzheimer's and Parkinsons's disease, and also many forms of cancer. Recently, inhibitors of the proteasome

as well as providing new chemical tools that may head to the growth of drugs that target this important biochemical pathway. The ubiquitin - proteasome organization regulates many essential process that shock on disease, including neurodegenerative disease such as Alzheimer's and Parkinsons's disease, and besides many forms of cancer. Recently, inhibitors of the proteasome

as well as providing new cmemical tools thcr may nead tk the dexelopment of drugs that targxt tyis inportant biochemical pxthway. Thv ubiquitun-prireasome system regmjatea manv xssential procexses that hmpact on disedsd, nncluding neurodegenerative diseases such ax Wlzheimer's and Parlynsohs's disease, and also many forms of cancer. Recently, inhobitors of the proteasome

as well as providing new chemical tools lead the development drugs that target ubiquitin-proteasome regulates many essential that impact on including neurodegenerative diseases such as Alzheimer's Parkinsons's disease, and also many forms of cancer. Recently, inhibitors of the proteasome

as well as providing new chemiCal tools thAt may LeaD to ThE devElopMent of drugs thaT TargEt this important biochemIcal pAtHWay. THE uBiquiTin-protEAsOME syStEm RegUlATeS many EssEntial pRocesses thAt iMpAct on disease, INcLuding neurOdeGenerative diSeaSes sucH aS AlZHeimeR's aNd ParKinsonS'S diseaSe, and also MaNY forms OF cancer. rECeNtly, Inhibitors of the prOTeASome

as well as providing newchemical t oolstha t m ay  lea d to  the developme n t of  drugs that target thi s imp or t antb io chemi cal pat h wa y .  Th eub iqu it i n- prote aso me syst em regulat esma ny essential pr ocesses th atimpact on di sea se, in cl udi n g neu rod egene rative diseas es such a sA lzheim e r's and P ar kins ons's disease, an d  a l so many formsof can ce r .R e cen tly , inhibito rs  of t h e prote a so m e

as_well as_providing new chemical tools_that may_lead_to the_development_of drugs that_target this important_biochemical pathway. The ubiquitin-proteasome_system regulates many_essential_processes that impact on disease, including neurodegenerative diseases such as Alzheimer's and Parkinsons's disease,_and_also many_forms_of_cancer. Recently, inhibitors of the_proteasome