dopamine-regulated membrane currents. The suggestion that the striatum behaves as an "action selection" network, raised interest in understanding how dynamic patterns of cortical activity are represented in the striatum and how this representation is modified by changes in dopamine neurotransmission. By simultaneously recording the population activity of cortical neurons and the membrane potential of striatal

dopamine - regulated membrane currents. The suggestion that the striatum behave as an " legal action selection " network, raised pastime in understanding how dynamic convention of cortical activeness are represented in the corpus striatum and how this theatrical performance is modified by changes in dopamine neurotransmission. By simultaneously record the population activity of cortical neurons and the membrane potential of striatal

dooamine-regulated membrane currents. The sogtestioi that fhe strixtum behaves as an "action sepextion" network, raised interert in undvrstandint hox dynamic patteria of covcical wctirivy are represenjed in the sdriatum and hof ghns representation is modified by chagges in dlpamine neurottansmpsfion. By simultaneously recording the pkpulatimn activity og cortical neurons and the memhrane potential of striatal

dopamine-regulated membrane currents. The suggestion that the as "action selection" raised interest in cortical are represented in striatum and how representation is modified by changes in neurotransmission. By simultaneously recording the population activity of cortical neurons and the membrane of striatal

dopamine-regulated membrane Currents. ThE suggEstIon ThAt thE strIatum behaves as AN "actIon selection" network, raiSed inTeREst iN UnDerstAnding hOW dYNAmiC pAtTerNs OF cOrticAl aCtivity Are represeNteD iN the striatum ANd How this repResEntation is moDifIed by cHaNgeS In dopAmiNe neuRotranSMissioN. By simultAnEOusly rECording THE pOpulAtion activity of coRTiCAl neurons and thE membrAnE PoTENtiAl oF striatal

dopamine-regulated membra ne current s. Th e s ugg es tion  tha t the striatum beha ves as an "action sele ction "n etwo r k,  rais ed inte r es t inun de rst an d in g how  dy namic p atterns of  co rt ical activit y  a re represe nte d in the str iat um and  h owt his r epr esent ationi s modi fied by c ha n ges in dopamin e ne urot ransmission. By s i mu l taneously reco rdingth e  p o p ula tio n activity  o f cor t ical ne u ro n s and the membranepotential o f  st riatal

dopamine-regulated_membrane currents._The suggestion that the_striatum behaves_as_an "action_selection"_network, raised interest_in understanding how_dynamic patterns of cortical_activity are represented_in_the striatum and how this representation is modified by changes in dopamine neurotransmission. By_simultaneously_recording the_population_activity_of cortical neurons and the_membrane potential of striatal


binding of these transcriptional factors is in turn highly dependent on the accessibility of the chromatin landscape. To access the underlying genomic information, histone proteins must be repositioned or removed, a function that is performed by ATP-dependent chromatin remodeling complexes. In particular, several components of the mammalian SWI/SNF or BAF

binding of these transcriptional factors is in turn highly dependent on the handiness of the chromatin landscape. To access the underlie genomic information, histone proteins must be repositioned or remove, a function that is performed by ATP - subject chromatin remodeling building complex. In particular, respective component of the mammalian SWI / SNF or BAF

bijding of these transcripuional factors is in turi highlg dependdnt on the accessibility of vhe xhromqtin landscape. To accers the unferlying geninic informefion, histone lvoteius must be reposltioned or semoved, a funcdiun that is performed by ATP-dependent shromaton remodeling coipleqef. In iavticular, several components of tge mammelian SWI/SNF or BAF

binding of these transcriptional factors is in dependent the accessibility the chromatin landscape. information, proteins must be or removed, a that is performed by ATP-dependent chromatin complexes. In particular, several components of the mammalian SWI/SNF or BAF

binding of these transcriptiOnal factorS is in TurN hiGhLy dePendEnt on the accessIBiliTy of the chromatin landscApe. To AcCEss tHE uNderlYing genOMiC INfoRmAtIon, HiSToNe proTeiNs must bE repositioNed Or Removed, a funcTIoN that is perForMed by ATP-depeNdeNt chroMaTin REmodeLinG compLexes. IN ParticUlar, severAl COmponeNTs of the MAMmAliaN SWI/SNF or BAF

binding of these transcri ptional fa ctors  is  in  t urnhigh ly dependent o n  the  accessibility of thechrom at i n la n ds cape.  To acc e ss t heun de rly in g  g enomi c i nformat ion, histo nepr oteins mustb ereposition edor removed,a f unctio ntha t  is p erf ormed  by AT P -depen dent chro ma t in rem o delingc o mp lexe s. In particular, se v eral component s of t he ma m m ali anSWI/SNF or  B AF

binding_of these_transcriptional factors is in_turn highly_dependent_on the_accessibility_of the chromatin_landscape. To access_the underlying genomic information,_histone proteins must_be_repositioned or removed, a function that is performed by ATP-dependent chromatin remodeling complexes. In_particular,_several components_of_the_mammalian SWI/SNF or BAF


versus corticospinal impairments in an animal model of PD. Using intracorticial microstimulation and a comprehensive behavioral testing battery consisting of both cranial motor and limb motor tasks, the proposed studies will (1) determine the differential effects of unilateral versus bilateral striatal dopamine depletion on cranial and limb motor function and corticobul

versus corticospinal impairments in an animal model of PD. Using intracorticial microstimulation and a comprehensive behavioral testing barrage consist of both cranial motor and limb motor tasks, the aim study will (1) determine the differential effects of unilateral versus bilateral striatal dopamine depletion on cranial and arm motor function and corticobul

vegsus corticospinal impaivments in an animal modxl of PS. Using kntracorticial microstimulatmon qnd a comprehensive behaviofal testijg batteey cibsisting oh both cvcnial lotox end limb motor jasks, the prmposed studies wklp (1) determine the differential effeces of umipateral versus bilseeram striatal dopamine depletion on cdanial end limb motor gunction and corticobul

versus corticospinal impairments in an animal model Using microstimulation and comprehensive behavioral testing motor limb motor tasks, proposed studies will determine the differential effects of unilateral bilateral striatal dopamine depletion on cranial and limb motor function and corticobul

versus corticospinal impairMents in an aNimal ModEl oF Pd. UsiNg inTracorticial miCRostImulation and a comprehenSive bEhAViorAL tEstinG batterY CoNSIstInG oF boTh CRaNial mOtoR and limB motor taskS, thE pRoposed studiES wIll (1) determiNe tHe differentiAl eFfects Of UniLAteraL veRsus bIlaterAL striaTal dopamiNe DEpletiON on cranIAL aNd liMb motor function anD CoRTicobul

versus corticospinal impa irments in  an a nim almo delof P D. Using intra c orti cial microstimulationand a  c o mpre h en sivebehavio r al t est in gbat te r yconsi sti ng of b oth crania l m ot or and limbm ot or tasks,the  proposed st udi es wil l(1) deter min e the  diffe r ential  effectsof unilat e ral ver s u sbila teral striatal do p am i ne depletion o n cran ia l  a n d  li mbmotor func ti on an d  cortic o bu l

versus_corticospinal impairments_in an animal model_of PD._Using_intracorticial microstimulation_and_a comprehensive behavioral_testing battery consisting_of both cranial motor_and limb motor_tasks,_the proposed studies will (1) determine the differential effects of unilateral versus bilateral striatal_dopamine_depletion on_cranial_and_limb motor function and corticobul


. Gel electrophoresis, immunoblotting and antibodies that recognize phosphorylated forms of cTnl are used to detect changes in the Tn complex. To test the role of specific PKC sites on cTnI in the evolution of hypertrophy and failure, mice harboring transgenes expressing a mutant form of cTnl (lacking PKC

. Gel electrophoresis, immunoblotting and antibodies that recognize phosphorylated forms of cTnl are used to detect changes in the Tn building complex. To screen the role of specific PKC sites on cTnI in the development of hypertrophy and failure, mouse harboring transgenes express a mutant form of cTnl (lacking PKC

. Gep electrophoresis, immunonlotting and antnvodies that decognizd phosphorylated forms of cTil aee ustb to detect changes kn the Tn complex. To uest the role of specific PKC sjbes ou rTnI in the evokution of vypertrophy ang wanlure, mice harboring transgenes exprqssing s lutant form of cTnk (lacipnn PKC

. Gel electrophoresis, immunoblotting and antibodies that forms cTnl are to detect changes test role of specific sites on cTnI the evolution of hypertrophy and failure, harboring transgenes expressing a mutant form of cTnl (lacking PKC

. Gel electrophoresis, immunobLotting and AntibOdiEs tHaT recOgniZe phosphorylatED forMs of cTnl are used to detecT chanGeS In thE tn ComplEx. To tesT ThE ROle Of SpEciFiC pKc siteS on CTnI in tHe evolutioN of HyPertrophy and FAiLure, mice haRboRing transgenEs eXpressInG a mUTant fOrm Of cTnL (lackiNG PKC

. Gel electrophoresis, imm unoblottin g and  an tib od iesthat  recognize pho s phor ylated forms of cTnl a re us ed to d e te ct ch anges i n  t h e  Tn  c om ple x. To  test  th e roleof specifi c P KC  sites on cT n Iin the evo lut ion of hyper tro phy an dfai l ure,mic e har boring transg enes expr es s ing am utant f o r mof c Tnl (lacking PKC

. Gel_electrophoresis, immunoblotting_and antibodies that recognize_phosphorylated forms_of_cTnl are_used_to detect changes_in the Tn_complex. To test the_role of specific_PKC_sites on cTnI in the evolution of hypertrophy and failure, mice harboring transgenes expressing_a_mutant form_of_cTnl_(lacking PKC


year, the Department of Veterans Affairs introduced a quality measure (the fluoride monitor) that examines, on a quarterly basis, the percent of veterans at high risk for caries who receive fluoride treatments. This project will examine the effectiveness of the introduction of this fluoride monitor in reducing the rate of restorations in medically compromised veterans at

year, the Department of Veterans Affairs introduced a quality measure (the fluoride proctor) that probe, on a quarterly basis, the percent of veterans at gamey risk for caries who meet fluoride discussion. This project will analyze the effectiveness of the introduction of this fluoride admonisher in reducing the rate of restoration in medically compromise veterans at

yewr, the Department of Vettrans Affairs inttoeuced e qualify measufe (the fluoride monitor) that ezamintf, on a quarterly bxsis, the iercent od veuerans at high risk for caries smo reeemve fluoride trgatments. Thiv project will ebaline the effectiveness of the introquction ov this fluoridg monptjr ih reducing the rate of restorationa in mevically compromosed veterans at

year, the Department of Veterans Affairs introduced measure fluoride monitor) examines, on a veterans high risk for who receive fluoride This project will examine the effectiveness the introduction of this fluoride monitor in reducing the rate of restorations in compromised veterans at

year, the Department of VeteraNs Affairs iNtrodUceD a qUaLity MeasUre (the fluoride MOnitOr) that examines, on a quartErly bAsIS, the PErCent oF veteraNS aT HIgh RiSk For CaRIeS who rEceIve fluoRide treatmEntS. THis project wiLL eXamine the eFfeCtiveness of tHe iNtroduCtIon OF this FluOride MonitoR In reduCing the raTe OF restoRAtions iN MEdIcalLy compromised veteRAnS At

year, the Department of V eterans Af fairs  in tro du ceda qu ality measure( thefluoride monitor) that  exam in e s, o n  a  quar terly b a si s ,  th epe rce nt of  vete ran s at hi gh risk fo r c ar ies who rece i ve  fluoridetre atments. Thi s p roject  w ill exami nethe e ffecti v enessof the in tr o ductio n  of thi s fl uori de monitor in red u ci n g the rate ofrestor at i on s inmed ically com pr omise d  vetera n sa t

year,_the Department_of Veterans Affairs introduced_a quality_measure_(the fluoride_monitor)_that examines, on_a quarterly basis,_the percent of veterans_at high risk_for_caries who receive fluoride treatments. This project will examine the effectiveness of the introduction_of_this fluoride_monitor_in_reducing the rate of restorations_in medically compromised veterans at


projects by providing new mechanical, electronic, optic and computer-based design and fabrication services and to develop highly innovative, high-impact research tools, such as the chronically implanted tetrode array recording chambers, the virtual reality visual-vestibular stimulating system, and the forced-choice, Bayesian adaptive protocol-driven opt

projects by providing new mechanical, electronic, optic and calculator - free-base design and fabrication service and to grow highly innovative, high - shock inquiry tools, such as the chronically implanted tetrode array recording chambers, the virtual reality ocular - vestibular stimulating system, and the push - choice, Bayesian adaptive protocol - driven opt

prljects by providing new oechanical, elecjrinic, o'tic ans computdr-based design and fabricatiln servuces and to develop hiehly innonative, hith-imkact research tools, such as the ghronncelly implanted jetrode arraf recording chdmcexs, the virtual reality visual-vestibujar stikupating system, wnd uhe fordvd-ghoice, Bayesian adaptive protocom-driven opt

projects by providing new mechanical, electronic, optic design fabrication services to develop highly as chronically implanted tetrode recording chambers, the reality visual-vestibular stimulating system, and the Bayesian adaptive protocol-driven opt

projects by providing new mecHanical, eleCtronIc, oPtiC aNd coMputEr-based design aND fabRication services and to dEveloP hIGhly INnOvatiVe, high-iMPaCT ResEaRcH toOlS, SuCh as tHe cHronicaLly implantEd tEtRode array recORdIng chamberS, thE virtual realIty Visual-VeStiBUlar sTimUlatiNg systEM, and thE forced-chOiCE, BayesIAn adaptIVE pRotoCol-driven opt

projects by providing new  mechanica l, el ect ron ic , op ticand computer-b a seddesign and fabrication  serv ic e s an d  t o dev elop hi g hl y inn ov at ive ,h ig h-imp act  resear ch tools,suc has the chron i ca lly implan ted  tetrode arr ayrecord in g c h amber s,the v irtual realit y visual- ve s tibula r  stimul a t in g sy stem, and the for c ed - choice, Bayesi an ada pt i ve p rot oco l-driven o pt

projects_by providing_new mechanical, electronic, optic_and computer-based_design_and fabrication_services_and to develop_highly innovative, high-impact_research tools, such as_the chronically implanted_tetrode_array recording chambers, the virtual reality visual-vestibular stimulating system, and the forced-choice, Bayesian adaptive_protocol-driven_opt


the absence of protein synthesis) in cascades of phosphorylation associated with the induction of proliferation and cell division. The HIV nef gene product has also been proposed to act as a regulatory G protein based on reports attributing GTP binding and GTPase activity to these proteins. We expressed different cDNA clones of nef using the same

the absence of protein synthesis) in cascades of phosphorylation associated with the induction of proliferation and cellular telephone part. The HIV nef gene product has also been aim to dissemble as a regulatory G protein establish on reports attributing GTP bind and GTPase activity to these proteins. We express different cDNA clone of nef use the same

thf absence of protein synuhesis) in cascades of phmsphorglation xssociated with the inductioi of proluferation and cell divksion. The HIV nef gent product has also been pvjpossf to ect as a regulajory G protehn based on re[oftd attributing GTP binding and GTPasq activotj to these projeins. Re esirtssed different cDNA clones of ner using the same

the absence of protein synthesis) in cascades associated the induction proliferation and cell product also been proposed act as a G protein based on reports attributing binding and GTPase activity to these proteins. We expressed different cDNA clones of using the same

the absence of protein syntheSis) in cascaDes of PhoSphOrYlatIon aSsociated with tHE indUction of proliferation aNd celL dIVisiON. THe HIV Nef gene PRoDUCt hAs AlSo bEeN PrOposeD to Act as a rEgulatory G ProTeIn based on repORtS attributiNg GtP binding and gTPAse actIvIty TO thesE prOteinS. We expREssed dIfferent cdNa Clones OF nef usiNG ThE samE

the absence of protein sy nthesis) i n cas cad esof  pho spho rylation assoc i ated  with the induction of  prol if e rati o nand c ell div i si o n . T he  H IVne f  g ene p rod uct has  also been  pr op osed to acta sa regulato ryG protein ba sed  on re po rts attri but ing G TP bin d ing an d GTPaseac t ivityt o these p ro tein s. We expressed d i ff e rent cDNA clon es ofne f  u s i ngthe  same

the_absence of_protein synthesis) in cascades_of phosphorylation_associated_with the_induction_of proliferation and_cell division. The_HIV nef gene product_has also been_proposed_to act as a regulatory G protein based on reports attributing GTP binding and_GTPase_activity to_these_proteins._We expressed different cDNA clones_of nef using the same


activity in the human subjects. Dental cementum covering the tooth root is critical for tooth attachment, long-term stability, and function of the dentition, yet regulation of root development and cementum formation remains poorly understood, hampering efforts towards periodontal regeneration. This application is a Pathway to Independence Award proposal that aims to

activity in the human subjects. Dental cementum covering the tooth root is critical for tooth fastening, retentive - term stability, and affair of the teething, yet regulation of root development and cementum constitution remains poorly understand, hampering efforts towards periodontic regeneration. This application is a Pathway to Independence Award proposal that aims to

achivity in the human subjtcts. Dental cemenjun covecing ths tooth foot is critical for tooth avtacyment, long-term stability, ana functioj of the denuition, yet regulavjon of vjot scvelo'mxnt and cementuk formatiot remains poorny uuderstood, hampering efforts towards [eriodomtwl regeneratiog. Thps appmpcction is a Pathway to Independehce Awagd proposal that sims to

activity in the human subjects. Dental cementum tooth is critical tooth attachment, long-term dentition, regulation of root and cementum formation poorly understood, hampering efforts towards periodontal This application is a Pathway to Independence Award proposal that aims to

activity in the human subjectS. Dental cemEntum CovEriNg The tOoth Root is critical FOr toOth attachment, long-term sTabilItY, And fUNcTion oF the denTItION, yeT rEgUlaTiON oF root DevElopmenT and cementUm fOrMation remainS PoOrly undersTooD, hampering efForTs towaRdS peRIodonTal RegenEratioN. this apPlication Is A pathwaY To IndepENDeNce AWard proposal that aIMs TO

activity in the human sub jects. Den tal c eme ntu mcove ring  the tooth roo t  iscritical for tooth att achme nt ,  lon g -t erm s tabilit y ,a n d f un ct ion  o f  t he de nti tion, y et regulat ion  o f root devel o pm ent and ce men tum formatio n r emains  p oor l y und ers tood,  hampe r ing ef forts tow ar d s peri o dontalr e ge nera tion. This applic a ti o n is a Pathway  to In de p en d e nce  Aw ard propos al  that aims to

activity_in the_human subjects. Dental cementum_covering the_tooth_root is_critical_for tooth attachment,_long-term stability, and_function of the dentition,_yet regulation of_root_development and cementum formation remains poorly understood, hampering efforts towards periodontal regeneration. This application_is_a Pathway_to_Independence_Award proposal that aims to


in intracellular Ca2+ level, an immediate peak followed by a sustained Ca2+ release. Additionally, selective inhibition of EGFR by AG1478 or the SK1 inhibitor, (DMS) inhibited the second phase. Also, AngII and EGF increased endogenous SK1 activity and enhanced production of S1P. De

in intracellular Ca2 + level, an immediate peak followed by a free burning Ca2 + dismissal. Additionally, selective inhibition of EGFR by AG1478 or the SK1 inhibitor, (DMS) inhibited the second phase. besides, AngII and EGF increased endogenous SK1 activeness and enhanced production of S1P. De

in intracellular Ca2+ level, xn immediate pecj follmwed bg a sustxined Ca2+ release. Additionallb, seoectice inhibition of EGFR cy AG1478 or nhe SK1 inyibiuor, (DMS) inhibited the second phzde. Anwo, AngII and ENF increaseg endogenous SN1 xccivity and enhanced production of S1P. De

in intracellular Ca2+ level, an immediate peak a Ca2+ release. selective inhibition of SK1 (DMS) inhibited the phase. Also, AngII EGF increased endogenous SK1 activity and production of S1P. De

in intracellular Ca2+ level, an iMmediate peAk folLowEd bY a SustAineD Ca2+ release. AddiTIonaLly, selective inhibition Of EGFr bY aG1478 or THe sK1 inhIbitor, (Dms) iNHIbiTeD tHe sEcONd Phase. alsO, AngII aNd EGF increAseD eNdogenous SK1 aCTiVity and enhAncEd production Of S1p. De

in intracellular Ca2+ lev el, an imm ediat e p eak  f ollo wedby a sustained Ca2+  release. Additionally , sel ec t ivei nh ibiti on of E G FR b y A G1 47 8 o rt he  SK1inh ibitor,  (DMS) inh ibi te d the second ph ase. Also,  An gII and EGFinc reased  e ndo g enous  SK 1 act ivitya nd enh anced pro du c tion o f  S1P. D e

in_intracellular Ca2+_level, an immediate peak_followed by_a_sustained Ca2+_release._Additionally, selective inhibition_of EGFR by_AG1478 or the SK1_inhibitor, (DMS) inhibited_the_second phase. Also, AngII and EGF increased endogenous SK1 activity and enhanced production of_S1P._De


explore a new fundamental strategy for directing the human immune system to kill target cells and to apply that strategy to treating several forms of metastasis-prone cancer beginning with HT-29 human colon cancer cells. The strategy is partially inspired by the concept of prodrugs. A molecule will be made such that when it interacts with u

explore a new fundamental strategy for direct the human immune arrangement to kill target cells and to put on that strategy to treating respective forms of metastasis - prone cancer beginning with HT-29 human colon cancer cells. The scheme is partially prompt by the concept of prodrugs. A molecule will be take such that when it interacts with u

exolore a new fundamental rtrategy for ditexting vhe humzn immund system to kill target celld qnd ti apply that strategy go treatijg severql fiems of meteatasis-pvjne dwncex ueginning with MT-29 human conon cancer celns. Tke strategy is partially inspired by the comcfpt of prodrugf. A kjlechle will be made such that when it interabts with u

explore a new fundamental strategy for directing immune to kill cells and to several of metastasis-prone cancer with HT-29 human cancer cells. The strategy is partially by the concept of prodrugs. A molecule will be made such that when interacts with u

explore a new fundamental strAtegy for diRectiNg tHe hUmAn imMune System to kill taRGet cElls and to apply that straTegy tO tREatiNG sEveraL forms oF MeTAStaSiS-pRonE cANcEr begInnIng with hT-29 human colOn cAnCer cells. The sTRaTegy is partIalLy inspired by The ConcepT oF prODrugs. a moLeculE will bE Made suCh that wheN iT InteraCTs with u

explore a new fundamental  strategyfor d ire cti ng  the  hum an immune syst e m to  kill target cells and  to a pp l y th a tstrat egy tot re a t ing  s ev era lf or ms of  me tastasi s-prone ca nce rbeginning wi t hHT-29 huma n c olon cancercel ls. Th estr a tegyisparti ally i n spired  by the c on c ept of prodrug s .  A  mol ecule will be mad e  s u ch that when i t inte ra c ts w ith  u

explore_a new_fundamental strategy for directing_the human_immune_system to_kill_target cells and_to apply that_strategy to treating several_forms of metastasis-prone_cancer_beginning with HT-29 human colon cancer cells. The strategy is partially inspired by the_concept_of prodrugs._A_molecule_will be made such that_when it interacts with u


approach. Substantial preliminary evidence in his laboratory and others demonstrates the utility of over-expression of therapeutic proteins in hepatic tissues. In principle, this system has the capability to deliver the therapeutic protein to all tissues via secretion from the hepatic platform. Additionally, correction of G6P deficiency examines the important question of direct correction of

approach. Substantial preliminary evidence in his laboratory and others demonstrates the utility program of over - formula of therapeutic proteins in hepatic tissue. In rationale, this system has the capability to deliver the curative protein to all tissue via secretion from the hepatic platform. Additionally, discipline of G6P lack examines the authoritative question of direct discipline of

aporoach. Substantial prelioinary evidence in his laborztory ana others demonstrates the utmlitt of iver-expression of therxpeutic pgoteins ib hekatic tissues. In 'dinciplc, thia syscen has the capanility to daliver the thesaoebtic protein to all tissues via secrqtion ftol the hepatic klatfpwm. Asditionally, correction of G6P deficjency eqamines the imporyant question of direct cogrechion of

approach. Substantial preliminary evidence in his laboratory demonstrates utility of of therapeutic proteins this has the capability deliver the therapeutic to all tissues via secretion from hepatic platform. Additionally, correction of G6P deficiency examines the important question of direct of

approach. Substantial prelimInary evideNce in His LabOrAtorY and Others demonstrATes tHe utility of over-expressIon of ThERapeUTiC protEins in hEPaTIC tiSsUeS. In PrINcIple, tHis System hAs the capabIliTy To deliver the THeRapeutic prOteIn to all tissuEs vIa secrEtIon FRom thE hePatic PlatfoRM. AdditIonally, coRrECtion oF g6P deficIENcY exaMines the important QUeSTion of direct coRrectiOn OF

approach. Substantial pre liminary e viden ceinhi s la bora tory and other s  dem onstrates the utilityof ov er - expr e ss ion o f thera p eu t i c p ro te ins  i n  h epati c t issues.  In princi ple ,this systemh as  the capab ili ty to delive r t he the ra peu t ic pr ote in to  all t i ssuesvia secre ti o n from the hep a t ic  pla tform. Additional l y, correction ofG6P de fi c ie n c y e xam ines the i mp ortan t  questi o no f dir e ct correction  of

approach._Substantial preliminary_evidence in his laboratory_and others_demonstrates_the utility_of_over-expression of therapeutic_proteins in hepatic_tissues. In principle, this_system has the_capability_to deliver the therapeutic protein to all tissues via secretion from the hepatic platform._Additionally,_correction of_G6P_deficiency_examines the important question of_direct correction of


of diseases. To discover what classes of chemical compounds slow aging, we will screen a large and diverse chemical library for extension in the lifespan of the nematode C. elegans. We have developed a number of automated screening methods that exploit C. elegans handling technology. We will also screen a library of compounds generally recognized as safe

of diseases. To discover what classes of chemical compounds decelerate ripening, we will shield a large and divers chemical library for extension in the life of the nematode C. elegans. We have developed a number of automatize screening methods that exploit C. elegans manage technology. We will also shield a library of compounds generally spot as safe

of diseases. To discover whxt classes of ckwmical compohnds slod aging, we will screen a larje abd dicerse chemical library for extejsion in the oifespan oh the nematode G. eleyais. We have devekoped a nukber of automadea dcreening methods that exploit C. elqgans hsnfling technolody. Wt wyll zlso screen a library of compounds generanly recognizec as safe

of diseases. To discover what classes of slow we will a large and in lifespan of the C. elegans. We developed a number of automated screening that exploit C. elegans handling technology. We will also screen a library of generally recognized as safe

of diseases. To discover what cLasses of chEmicaL coMpoUnDs slOw agIng, we will screeN A larGe and diverse chemical liBrary FoR ExteNSiOn in tHe lifesPAn OF The NeMaTodE C. ELeGans. WE haVe develOped a numbeR of AuTomated screeNInG methods thAt eXploit C. elegaNs hAndlinG tEchNOlogy. we wIll alSo screEN a librAry of compOuNDs geneRAlly recOGNiZed aS safe

of diseases. To discoverwhat class es of  ch emi ca l co mpou nds slow aging ,  wewill screen a large an d div er s e ch e mi cal l ibraryf or e xte ns io n i nt he  life spa n of th e nematode  C.  e legans. We h a ve  developed  anumber of au tom ated s cr een i ng me tho ds th at exp l oit C.  elegansha n dlingt echnolo g y .We w ill also screen a li b rary of compou nds ge ne r al l y  re cog nized as s af e

of_diseases. To_discover what classes of_chemical compounds_slow_aging, we_will_screen a large_and diverse chemical_library for extension in_the lifespan of_the_nematode C. elegans. We have developed a number of automated screening methods that exploit_C._elegans handling_technology._We_will also screen a library_of compounds generally recognized as_safe


Acute metabolic acidosis. Rats breathing 21% O2 -0% CO2 (normoxia-normocapnia) had significant decreases in cardiac and skeletal muscle pH. The production of hypoxia-normocapnia (10% O2, 3% CO2) or hypoxic-hypercapnic conditions (

Acute metabolic acidosis. Rats breathing 21% O2 -0% CO2 (normoxia - normocapnia) had significant decrease in cardiac and bony muscle pH. The production of hypoxia - normocapnia (10% O2, 3% CO2) or hypoxic - hypercapnic condition (

Ackte metabolic acidosis. Rxts breathing 21% O2 -0% CO2 (nmrmoxiz-normocaonia) had significant decreasxs ib careiac and skeletal muscue pH. The productuon id hypoxia-normocapnlc (10% O2, 3% GO2) or iypoxic-hypercapkic conditimns (

Acute metabolic acidosis. Rats breathing 21% O2 (normoxia-normocapnia) significant decreases cardiac and skeletal hypoxia-normocapnia O2, 3% CO2) hypoxic-hypercapnic conditions (

Acute metabolic acidosis. RatS breathing 21% o2 -0% CO2 (noRmoXia-NoRmocApniA) had significanT DecrEases in cardiac and skeleTal muScLE pH. THE pRoducTion of hYPoXIA-noRmOcApnIa (10% o2, 3% cO2) Or hypOxiC-hypercApnic condiTioNs (

Acute metabolic acidosis.  Rats brea thing  21 % O 2-0%CO2(normoxia-norm o capn ia) had significant de creas es in c a rd iac a nd skel e ta l mus cl epH.  T h eprodu cti on of h ypoxia-nor moc ap nia (10% O2, 3%  CO2) or h ypo xic-hypercap nic  condi ti ons (

Acute_metabolic acidosis._Rats breathing 21% O2_-0% CO2_(normoxia-normocapnia)_had significant_decreases_in cardiac and_skeletal muscle pH._The production of hypoxia-normocapnia_(10% O2, 3%_CO2)_or hypoxic-hypercapnic conditions (


to infarct, and the more infracted brain there is, the more likely it is to hemorrhage after opening the occluded artery. Advances in neuroimaging are shifting the paradigm from?time is brain? to?physiology is brain?. Perfusion imaging (CT and MRI) and diffusion weighted MR imaging (DW

to infarct, and the more infracted brain there is, the more likely it is to hemorrhage after open the obstruct artery. Advances in neuroimaging are shifting the prototype from?time is genius? to?physiology is brain? . Perfusion imaging (CT and MRI) and dispersion slant MR imaging (DW

to infarct, and the more innracted brain thgrw is, tie more likely kt is to hemorrhage after opxnint the occluded artery. Advanzes in nelroimagint art shifting the paczdigm fvjm?tijc is yrein? to?physiologi is brain?. Parfusion imagitg (CC and MRI) and diffusion weighted MR ymaging (DA

to infarct, and the more infracted brain the likely it to hemorrhage after in are shifting the from?time is brain? is brain?. Perfusion imaging (CT and and diffusion weighted MR imaging (DW

to infarct, and the more infracTed brain thEre is, The MorE lIkelY it iS to hemorrhage aFTer oPening the occluded arterY. AdvaNcES in nEUrOimagIng are sHIfTINg tHe PaRadIgM FrOm?timE is Brain? to?Physiology Is bRaIn?. Perfusion iMAgIng (CT and MRi) anD diffusion weIghTed MR iMaGinG (dW

to infarct, and the moreinfractedbrain  th ere  i s, t he m ore likely iti s to  hemorrhage after open ing t he occl u de d art ery. Ad v an c e s i nne uro im a gi ng ar e s hifting  the parad igm  f rom?time isb ra in? to?phy sio logy is brai n?.  Perfu si oni magin g ( CT an d MRI) and di ffusion w ei g hted M R  imagin g (D W

to_infarct, and_the more infracted brain_there is,_the_more likely_it_is to hemorrhage_after opening the_occluded artery. Advances in_neuroimaging are shifting_the_paradigm from?time is brain? to?physiology is brain?. Perfusion imaging (CT and MRI) and diffusion_weighted_MR imaging_(DW


site of action of these agents. Research Biochemicals proposes a program to prepare novel substances with selective agonist or antagonist action at specific DA receptors for use by researchers in neuropharmacology. The objectives of Phase I research are: 1) the synthesis of novel aporphines and related compounds with irreversible binding activity at DA

site of action of these agents. Research Biochemicals proposes a platform to organize novel substances with selective agonist or adversary action at specific DA receptors for function by researchers in neuropharmacology. The objectives of Phase I inquiry are: 1) the deduction of novel aporphines and related compound with irreversible binding activity at district attorney

sihe of action of these agtnts. Research Bioeyemicans proloses a orogram to prepare novel subdtqnces with selective agonisg or antahonist axtioi at specific DA receptovf fod use uy researchers ln neurophasmacology. The mbgeetives of Phase I research are: 1) the fynthesos of novel aporkhinex and geoated compounds with irreversjble biiding activity st DA

site of action of these agents. Research a to prepare substances with selective specific receptors for use researchers in neuropharmacology. objectives of Phase I research are: the synthesis of novel aporphines and related compounds with irreversible binding activity at

site of action of these agents. research BiOchemIcaLs pRoPoseS a prOgram to prepare NOvel Substances with selectivE agonIsT Or anTAgOnist Action aT SpECIfiC Da rEcePtORs For usE by ResearcHers in neurOphArMacology. The oBJeCtives of PhAse i research are: 1) The SyntheSiS of NOvel aPorPhineS and reLAted coMpounds wiTh IRreverSIble binDINg ActiVity at DA

site of action of these a gents. Res earch  Bi och em ical s pr oposes a progr a m to  prepare novel substan ces w it h  sel e ct ive a gonisto ra n tag on is t a ct i on  at s pec ific DA  receptors  fo ruse by resea r ch ers in neu rop harmacology.  Th e obje ct ive s  of P has e I r esearc h  are:1) the sy nt h esis o f  novela p or phin es and related co m po u nds with irrev ersibl eb in d i ngact ivity at D A

site_of action_of these agents. Research_Biochemicals proposes_a_program to_prepare_novel substances with_selective agonist or_antagonist action at specific_DA receptors for_use_by researchers in neuropharmacology. The objectives of Phase I research are: 1) the synthesis_of_novel aporphines_and_related_compounds with irreversible binding activity_at DA


needs of advancements in scientific animal care to meet the requirements of federal and state agencies were not made in the original construction. In the intervening 25 years the MMRL has met these by numerous modifications, and restrictions in the capacity to house and use animals, often at the expense of the interests of the investigators using the research

needs of advancements in scientific animal care to meet the prerequisite of union and state agencies were not make in the original structure. In the intervening 25 years the MMRL has met these by numerous modifications, and restriction in the capacity to house and use animal, frequently at the expense of the interests of the detective using the research

nefds of advancements in sgientific animal care tm meet the reqjirements of federal and stave atencitf were not made in the origpnal consrrucuion. In the intertsning 25 nzars fme MMXL has met these by numerogs modificatiots, aud restrictions in the capacity to hjuse anc kse animals, ofjen au tre esiekse of the interests of the inveatigatogs using the resesrch

needs of advancements in scientific animal care the of federal state agencies were construction. the intervening 25 the MMRL has these by numerous modifications, and restrictions the capacity to house and use animals, often at the expense of the of the investigators using the research

needs of advancements in scieNtific animAl carE to MeeT tHe reQuirEments of federaL And sTate agencies were not madE in thE oRIginAL cOnstrUction. IN ThE INteRvEnIng 25 YeARs The MMrL hAs met thEse by numerOus MoDifications, aND rEstrictionS in The capacity tO hoUse and UsE anIMals, oFteN at thE expenSE of the Interests Of THe inveSTigatorS USiNg thE research

needs of advancements inscientific  anim alcar eto m eetthe requiremen t s of  federal and state age ncies  w e re n o tmadein theo ri g i nal  c on str uc t io n. In  th e inter vening 25yea rs  the MMRL ha s  m et these b y n umerous modi fic ations ,and restr ict ionsin the capaci ty to hou se and us e  animal s ,  o ften  at the expense o f  t h e interests of  the i nv e st i g ato rsusing there searc h

needs_of advancements_in scientific animal care_to meet_the_requirements of_federal_and state agencies_were not made_in the original construction._In the intervening_25_years the MMRL has met these by numerous modifications, and restrictions in the capacity_to_house and_use_animals,_often at the expense of_the interests of the investigators_using the_research


function will improve the hemodynamic profile in these patients. We are beginning recruitment and screening. The Institute of Medicine and others have strongly encouraged research on structural interventions. Outreach HIV/STD testing programs are an example of a structural intervention that have been studied for their individual level effects but not for structural level effects. Nevertheless, some

function will improve the hemodynamic profile in these patients. We are begin recruitment and cover. The Institute of Medicine and others have strongly encouraged inquiry on structural intervention. Outreach HIV / STD examination programs are an example of a structural interposition that have been studied for their individual level effect but not for structural level effect. however, some

fujction will improve the memodynamic profnoe in vhese pztients. De are beginning recruitment abd sceeening. The Institute uf Medicije and orherw have stroifly encourages reszacch on structursl intervettions. Outreacv FIR/STD testing programs are an example of a syrkctural intervgntiom thaf have been studied for their indibidual nevel effects but not for structural legel fffects. Nevertheleds, some

function will improve the hemodynamic profile in We beginning recruitment screening. The Institute strongly research on structural Outreach HIV/STD testing are an example of a structural that have been studied for their individual level effects but not for structural effects. Nevertheless, some

function will improve the hemOdynamic prOfile In tHesE pAtieNts. WE are beginning rECruiTment and screening. The InStituTe OF MedICiNe and Others hAVe STRonGlY eNcoUrAGeD reseArcH on struCtural inteRveNtIons. Outreach hiV/sTD testing ProGrams are an exAmpLe of a sTrUctURal inTerVentiOn that HAve beeN studied fOr THeir inDIvidual LEVeL effEcts but not for struCTuRAl level effects. nevertHeLEsS, SOme

function will improve the  hemodynam ic pr ofi lein  the se p atients. We ar e  beg inning recruitment and  scre en i ng.T he  Inst itute o f  M e d ici ne  a ndot h er s hav e s trongly  encourage d r es earch on str u ct ural inter ven tions. Outre ach  HIV/S TD  te s tingpro grams  are a n  examp le of a s tr u ctural interve n t io n th at have been stud i ed for their indi vidual  l e ve l eff ect s but notfo r str u cturall ev e l eff e cts. Neverthe less, some

function_will improve_the hemodynamic profile in_these patients._We_are beginning_recruitment_and screening. The_Institute of Medicine_and others have strongly_encouraged research on_structural_interventions. Outreach HIV/STD testing programs are an example of a structural intervention that have_been_studied for_their_individual_level effects but not for_structural level effects. Nevertheless, some


biology has been to isolate and study genes through to make critical decisions of cell fate and patterning in embryogenesis. Genetic studies in Drosophila indicate that genes containing the homeobox DNA-binding motif participate in such decisions.Other genes such as the vertebrate Myo-D gene, also have the compelling properties of developmental regulators.

biology has been to isolate and study genes through to seduce critical decision of cell fate and patterning in embryogenesis. genic studies in Drosophila indicate that gene containing the homeobox DNA - binding motif participate in such decision. Other genes such as the vertebrate Myo - five hundred gene, also have the compelling place of developmental regulators.

billogy has been to isolatt and study genes througi to maie critizal decisions of cell fate aid pqtterbing in embryogenesis. Eenetic snudies in Drowiphila indmdate that gensd couteining the homepbox DNA-bitding motif pastkcnpate in such decisions.Other genes stch as yhf vertebrate Mio-D gtne, alsk have the compelling properties or develmpmental regukators.

biology has been to isolate and study to critical decisions cell fate and in indicate that genes the homeobox DNA-binding participate in such decisions.Other genes such the vertebrate Myo-D gene, also have the compelling properties of developmental regulators.

biology has been to isolate anD study geneS throUgh To mAkE criTicaL decisions of ceLL fatE and patterning in embryoGenesIs. gEnetIC sTudieS in DrosOPhILA inDiCaTe tHaT GeNes coNtaIning thE homeobox DnA-bInDing motif parTIcIpate in sucH deCisions.Other GenEs such As The VErtebRatE Myo-D Gene, alSO have tHe compellInG ProperTIes of deVELoPmenTal regulators.

biology has been to isola te and stu dy ge nes  th ro ughto m ake critical d e cisi ons of cell fate and p atter ni n g in em bryog enesis. Ge n e tic  s tu die si nDroso phi la indi cate thatgen es  containingt he  homeoboxDNA -binding mot ifpartic ip ate in su chdecis ions.O t her ge nes suchas the ve r tebrate M yo -D g ene, also have th e  c o mpelling prope rtiesof de v e lop men tal regula to rs.

biology_has been_to isolate and study_genes through_to_make critical_decisions_of cell fate_and patterning in_embryogenesis. Genetic studies in_Drosophila indicate that_genes_containing the homeobox DNA-binding motif participate in such decisions.Other genes such as the vertebrate_Myo-D_gene, also_have_the_compelling properties of developmental regulators.


. Our recent studies In vitro clearly demonstrate the differenfial expression of the funcfional elements ofthe vitamin D system, including CYP27B1-hydroxylase and the VDR in Type I and II interferon-driven, T-lep and L-lep granulomas, respecfively.

. Our recent studies In vitro clearly demonstrate the differenfial formula of the funcfional chemical element ofthe vitamin D system, including CYP27B1 - hydroxylase and the VDR in Type I and II interferon - drive, T - lep and L - lep granulomas, respecfively.

. Oug recent studies In vitru clearly demonstrate vhe difrerenfiau expression of the funcfionel eoemenuf ofthe vitamin D rystem, inbluding CTP27B1-hbdroxylase and tis VDR ik Typs I aud II interferon-criven, T-le[ and L-lep gratuuolas, respecfively.

. Our recent studies In vitro clearly differenfial of the elements ofthe vitamin the in Type I II interferon-driven, T-lep L-lep granulomas, respecfively.

. Our recent studies In vitro clEarly demonStratE thE diFfErenFial Expression of thE FuncFional elements ofthe vitAmin D SySTem, iNClUding cYP27B1-hydROxYLAse AnD tHe VdR IN TYpe I aNd Ii interfEron-driven, t-leP aNd L-lep granulOMaS, respecfivEly.

. Our recent studies In vi tro clearl y dem ons tra te  the  dif ferenfial expr e ssio n of the funcfional el ement so fthe vi tamin  D syst e m, i ncl ud in g C YP 2 7B 1-hyd rox ylase a nd the VDR  in  T ype I and II in terferon-d riv en, T-lep an d L -lep g ra nul o mas,res pecfi vely.

. Our_recent studies_In vitro clearly demonstrate_the differenfial_expression_of the_funcfional_elements ofthe vitamin_D system, including_CYP27B1-hydroxylase and the VDR_in Type I_and_II interferon-driven, T-lep and L-lep granulomas, respecfively.


find why displacement occurs, the factors that control displacement and whether this displacement weakens the interactions of H2A or H2A.Z dimers with the rest of the histone octamer or otherwise disrupts the nucleosome structure. Based on the proximity of Arp5 to nucleosomal DNA, we will test the

find why displacement occurs, the factors that see translation and whether this displacement weakens the interactions of H2A or H2A.Z dimer with the rest of the histone octamer or otherwise disrupts the nucleosome social organization. base on the proximity of Arp5 to nucleosomal DNA, we will test the

fijd why displacement occuvs, the factors tkqt convrol diaplacemevt and whether this displacelebt weqkens the interactions of H2A or H2A.Z dimwrs xith the rest of the hisbjne kgtamex ir otherwise dlsrupts the nucleosome stsuztbre. Based on the proximity of Arp5 to nucleoxolal DNA, we wilj texe ths

find why displacement occurs, the factors that and this displacement the interactions of the of the histone or otherwise disrupts nucleosome structure. Based on the proximity Arp5 to nucleosomal DNA, we will test the

find why displacement occurs, The factors That cOntRol DiSplaCemeNt and whether thIS disPlacement weakens the intEractIoNS of H2a Or h2A.Z diMers witH ThE REst Of ThE hiStONe OctamEr oR otherwIse disruptS thE nUcleosome strUCtUre. Based on The Proximity of ARp5 tO nucleOsOmaL dNA, we WilL test The

find why displacement occ urs, the f actor s t hat  c ontr ol d isplacement an d  whe ther this displacement  weak en s  the in terac tions o f  H 2 A  or  H 2A .Zdi m er s wit h t he rest  of the hi sto ne  octamer oro th erwise dis rup ts the nucle oso me str uc tur e . Bas edon th e prox i mity o f Arp5 to  n u cleoso m al DNA, w ewill  test the

find_why displacement_occurs, the factors that_control displacement_and_whether this_displacement_weakens the interactions_of H2A or_H2A.Z dimers with the_rest of the_histone_octamer or otherwise disrupts the nucleosome structure. Based on the proximity of Arp5 to_nucleosomal_DNA, we_will_test_the


The second aim will optimize transduction cultures of expanded cells and subsequent clinical studies will incorporate these conditions to use marked expanded cells in patients. This will allow the evaluation of the contribution of expanded cells to long to engraftment. Correlative analysis will be performed comparing the contribution of the marked cells in patients with in vitro assays of

The second aim will optimize transduction cultures of expanded cells and subsequent clinical report will integrate these conditions to use distinguish expand cells in patients. This will admit the evaluation of the contribution of boom cells to retentive to engraftment. Correlative analysis will be performed compare the contribution of the marked cells in affected role with in vitro assay of

Thf second aim will optimiee transduction colrures mf expznded ceuls and subsequent clinical dtydies will incorporate thesd conditilns to uwe merked expanded cxmls in ictienfd. Thns will allow thg evaluation of the contritugiln of expanded cells to long to engwaftmeny. Forrelative anwlysps wilm be performed comparing the contrjbution of the markec cells in patients with ij vihro assays of

The second aim will optimize transduction cultures cells subsequent clinical will incorporate these cells patients. This will the evaluation of contribution of expanded cells to long engraftment. Correlative analysis will be performed comparing the contribution of the marked cells patients with in vitro assays of

The second aim will optimize tRansductioN cultUreS of ExPandEd ceLls and subsequeNT cliNical studies will incorpOrate ThESe coNDiTions To use maRKeD EXpaNdEd CelLs IN pAtienTs. THis will Allow the evAluAtIon of the contRIbUtion of expAndEd cells to lonG to EngrafTmEnt. cOrrelAtiVe anaLysis wILl be peRformed coMpARing thE ContribUTIoN of tHe marked cells in paTIeNTs with in vitro aSsays oF

The second aim will optim ize transd uctio n c ult ur es o f ex panded cells a n d su bsequent clinical stud ies w il l  inc o rp orate  thesec on d i tio ns  t o u se ma rkedexp anded c ells in pa tie nt s. This will al low the ev alu ation of the  co ntribu ti ono f exp and ed ce lls to long t o engraft me n t. Cor r elative a na lysi s will be perform e dc omparing the c ontrib ut i on o f t hemarked cel ls  in p a tientsw it h i n v i tro assays of

The_second aim_will optimize transduction cultures_of expanded_cells_and subsequent_clinical_studies will incorporate_these conditions to_use marked expanded cells_in patients. This_will_allow the evaluation of the contribution of expanded cells to long to engraftment. Correlative_analysis_will be_performed_comparing_the contribution of the marked_cells in patients with in_vitro assays_of


This information is essential for making informed judgments about evaluative measures which are the easiest to implement in large-scale survey research. The final specific aim is to incorporate both ESM and DRM assessments into an on-going, nationally representative panel study. This existing study already includes evaluative measures and has been used to make important

This information is essential for making informed judgments about appraising measuring stick which are the easiest to enforce in big - scale survey inquiry. The final specific aim is to incorporate both ESM and DRM appraisal into an on - going, nationally representative panel sketch. This existing study already include appraising measures and has been used to seduce important

Thls information is essentlal for making iudormed judgmsnts abojt evaluative measures which aee tht easiest to implemdnt in lagge-scale wurvty research. The fmhal spegnfic zlm is vo incorporate noth ESM ang DRM assessmettr nnto an on-going, nationally representwtive psnfl study. This gxistpnd sthdy already includes evaluative mezsures end has been usrd to make important

This information is essential for making informed evaluative which are easiest to implement final aim is to both ESM and assessments into an on-going, nationally representative study. This existing study already includes evaluative measures and has been used to important

This information is essentiaL for making InforMed JudGmEnts AbouT evaluative meaSUres Which are the easiest to imPlemeNt IN larGE-sCale sUrvey reSEaRCH. ThE fInAl sPeCIfIc aim Is tO incorpOrate both EsM aNd dRM assessmenTS iNto an on-goiNg, nAtionally repResEntatiVe PanEL studY. ThIs exiSting sTUdy alrEady incluDeS EvaluaTIve measUREs And hAs been used to make iMPoRTant

This information is essen tial for m aking  in for me d ju dgme nts about eval u ativ e measures which are t he ea si e st t o  i mplem ent inl ar g e -sc al esur ve y  r esear ch.  The fi nal specif icai m is to inco r po rate bothESM  and DRM ass ess mentsin toa n on- goi ng, n ationa l ly rep resentati ve panels tudy. T h i sexis ting study alread y  i n cludes evaluat ive me as u re s and  ha s been use dto ma k e impor t an t

This_information is_essential for making informed_judgments about_evaluative_measures which_are_the easiest to_implement in large-scale_survey research. The final_specific aim is_to_incorporate both ESM and DRM assessments into an on-going, nationally representative panel study. This_existing_study already_includes_evaluative_measures and has been used_to make important


are part of baroreflex control of sympathetic nerve activity. The concept that VLM neurons are part of the baroreflex will be investigated in anesthetized cats prepared with a single innervated isolated carotid sinus (other baroreceptor regions denervated) and prepared for the recording of single unit activity of caudal and

are part of baroreflex control of sympathetic nerve natural process. The concept that VLM nerve cell are part of the baroreflex will be investigated in anesthetized cat cook with a single innervated isolate carotid venous sinus (other baroreceptor region denervated) and prepared for the recording of single whole activity of caudal and

arf part of baroreflex conurol of sympathetnx nervx activjty. The zoncept that VLM neurons are pqrt od the baroreflex will ce investpgated in anewrhetized cefs prepared wjbh a vmngle innervatec isolated carotid sinus (oghzr baroreceptor regions denervated) agd prepsrfd for the recjrdimd of single unit activity of caudal ans

are part of baroreflex control of sympathetic The that VLM are part of in cats prepared with single innervated isolated sinus (other baroreceptor regions denervated) and for the recording of single unit activity of caudal and

are part of baroreflex controL of sympathEtic nErvE acTiVity. the cOncept that VLM nEUronS are part of the barorefleX will Be INvesTIgAted iN anesthETiZED caTs PrEpaReD WiTh a siNglE innervAted isolatEd cArOtid sinus (othER bAroreceptoR reGions denervaTed) And prePaRed FOr the RecOrdinG of sinGLe unit Activity oF cAUdal anD

are part of baroreflex co ntrol of s ympat het icne rveacti vity. The conc e pt t hat VLM neurons are pa rt of  t h e ba r or eflex  will b e  i n v est ig at edin an esthe tiz ed cats  preparedwit ha single inn e rv ated isola ted  carotid sin us(other  b aro r ecept orregio ns den e rvated ) and pre pa r ed for the rec o r di ng o f single unit act i vi t y of caudal an d

are_part of_baroreflex control of sympathetic_nerve activity._The_concept that_VLM_neurons are part_of the baroreflex_will be investigated in_anesthetized cats prepared_with_a single innervated isolated carotid sinus (other baroreceptor regions denervated) and prepared for the_recording_of single_unit_activity_of caudal and


there differences in children's ability to conceive of multiple representations with regard to fictional versus epistemic mental states, and (3) what do children understand about the origin of imagination and other mental states? Answers to these questions will fill a gap in our knowledge of children's understanding of imagination specifically, and will aide in developing

there differences in children's ability to conceive of multiple representations with gaze to fabricated versus epistemic mental states, and (3) what do child sympathize about the origin of imagination and other genial state? Answers to these question will fill a gap in our cognition of children's understanding of imagination specifically, and will aide in developing

thfre differences in childven's ability to einceivx of mumtiple rdpresentations with regard tl dictiinal versus epistemic oental stwtes, and (3) whet do children uiserstand abouf the irigin of imaglnation and other mental vtxtzs? Answers to these questions will fyll a gsp in our knowleqge ps chjldren's understanding of imaginatikn specpfically, and will aide in developing

there differences in children's ability to conceive representations regard to versus epistemic mental children about the origin imagination and other states? Answers to these questions will a gap in our knowledge of children's understanding of imagination specifically, and will in developing

there differences in childreN's ability tO concEivE of MuLtipLe rePresentations wITh reGard to fictional versus ePisteMiC MentAL sTates, And (3) what DO cHILdrEn UnDerStANd About The Origin oF imaginatiOn aNd Other mental sTAtEs? Answers tO thEse questions WilL fill a GaP in OUr knoWleDge of ChildrEN's undeRstanding Of IMaginaTIon specIFIcAlly, And will aide in deveLOpINg

there differences in chil dren's abi litytocon ce iveof m ultiple repres e ntat ions with regard to fi ction al vers u sepist emic me n ta l sta te s,  an d( 3)  what  do  childr en underst and  a bout the ori g in  of imagin ati on and other  me ntal s ta tes ?  Answ ers  to t hese q u estion s will fi ll a gapi n our k n o wl edge  of children's un d er s tanding of ima ginati on sp e c ifi cal ly, and wi ll  aide in deve l op i n g

there_differences in_children's ability to conceive_of multiple_representations_with regard_to_fictional versus epistemic_mental states, and_(3) what do children_understand about the_origin_of imagination and other mental states? Answers to these questions will fill a gap_in_our knowledge_of_children's_understanding of imagination specifically, and_will aide in developing


-cancer therapies. Reactive oxygen species (ROS) have increasingly been implicated as modulators of tumorigenicity and many cancer types exhibit elevated ROS levels. An important regulatory enzyme of Redox balance is the mitochondrially expressed manganese superoxide dismutase (Sod2), which catalyzes the conversion of superoxide anion to

-cancer therapies. Reactive oxygen species (ROS) have increasingly been implicated as modulators of tumorigenicity and many cancer types parade lift ROS levels. An important regulatory enzyme of Redox remainder is the mitochondrially expressed manganese superoxide dismutase (Sod2), which catalyzes the conversion of superoxide anion to

-canfer therapies. Reactive owygen species (ROS) have mncreasjngly bedn implicated as modulators lf tumoeigenicity and many cavcer typed exhibir eltvated ROS levels. An impovcant dcgulacocy enzyme of Recox balanca is the mitocvovdxially expressed manganese superoxidq dismuyade (Sod2), which cwtaljzqs tgv gonversion of superoxide anion tk

-cancer therapies. Reactive oxygen species (ROS) have implicated modulators of and many cancer An regulatory enzyme of balance is the expressed manganese superoxide dismutase (Sod2), which the conversion of superoxide anion to

-cancer therapies. Reactive oxYgen specieS (ROS) hAve IncReAsinGly bEen implicated aS ModuLators of tumorigenicity And maNy CAnceR TyPes exHibit elEVaTED ROs lEvEls. an IMpOrtanT reGulatorY enzyme of REdoX bAlance is the mIToChondriallY exPressed mangaNesE superOxIde DIsmutAse (sod2), whIch catALyzes tHe conversIoN Of supeROxide anION tO

-cancer therapies. Reactiv e oxygen s pecie s ( ROS )have  inc reasingly been impl icated as modulators o f tum or i geni c it y and  many c a nc e r  ty pe sexh ib i televa ted  ROS le vels. An i mpo rt ant regulato r yenzyme ofRed ox balance i s t he mit oc hon d riall y e xpres sed ma n ganese  superoxi de dismut a se (Sod 2 ) ,whic h catalyzes the c o nv e rsion of super oxidean i on t o

-cancer therapies._Reactive oxygen_species (ROS) have increasingly_been implicated_as_modulators of_tumorigenicity_and many cancer_types exhibit elevated_ROS levels. An important_regulatory enzyme of_Redox_balance is the mitochondrially expressed manganese superoxide dismutase (Sod2), which catalyzes the conversion of_superoxide_anion to


the study of chronic effects of antidepressants. We propose to study the effects of long-term administration of MAO inhibitors, tricyclic antidepressants, chlorpromazine, and some antihistamines that have been shown to have antidepressant potential on the basis of preclinical pharmacology. The effects of these drugs on the

the study of chronic effects of antidepressants. We propose to analyze the effect of long - term administration of MAO inhibitor, tricyclic antidepressants, chlorpromazine, and some antihistamines that have been shown to hold antidepressant potential on the basis of preclinical pharmacology. The consequence of these drugs on the

thf study of chronic effecus of antidepresscbts. We propoae to stjdy the effects of long-term edmibistrqtion of MAO inhibitorr, tricyclpc antidepreswqnts, chlor'domazinc, and dome entihistamines jhat have bean shown to haee autidepressant potential on the basis of prevllnical pharmacjlogj. Ehe sffects of these drugs on the

the study of chronic effects of antidepressants. to the effects long-term administration of and antihistamines that have shown to have potential on the basis of preclinical The effects of these drugs on the

the study of chronic effects oF antidepreSsantS. We ProPoSe to StudY the effects of lONg-teRm administration of MAO iNhibiToRS, triCYcLic anTidepreSSaNTS, chLoRpRomAzINe, And soMe aNtihistAmines that HavE bEen shown to haVE aNtidepressAnt Potential on tHe bAsis of PrEclINical PhaRmacoLogy. ThE EffectS of these dRuGS on the

the study of chronic effe cts of ant idepr ess ant s.  Weprop ose to study t h e ef fects of long-term adm inist ra t iono fMAO i nhibito r s, t ric yc li c a nt i de press ant s, chlo rpromazine , a nd  some antihi s ta mines that  ha ve been show n t o have  a nti d epres san t pot ential on the  basis of  p r eclini c al phar m a co logy . The effects oft he s e drugs on the

the_study of_chronic effects of antidepressants._We propose_to_study the_effects_of long-term administration_of MAO inhibitors,_tricyclic antidepressants, chlorpromazine, and_some antihistamines that_have_been shown to have antidepressant potential on the basis of preclinical pharmacology. The effects_of_these drugs_on_the


were recovered from patients who were infected following transfusion. The sequence of the hypervariable region and adjacent portions of envelope proteins 1 and 2 were determined for multiple clones obtained from patients who had fulminant hepatitis, from patients who convalesced following acute hepatitis and from patients who progressed to chronic hepatitis C. Distinctive

were recovered from patients who were infected following transfusion. The succession of the hypervariable area and adjacent fortune of envelope proteins 1 and 2 were determined for multiple clone obtained from patients who have fulminant hepatitis, from patients who convalesced following acute hepatitis and from patients who build up to chronic hepatitis C. Distinctive

wege recovered from patienus who were infecjee follmwing fransfuskon. The sequence of the hypecvaruable region and adjacent purtions ov envelope pcoteins 1 and 2 wecs determined rlr mblviple clones objained from [atients who hdd fblminant hepatitis, from patients who convalrsfed following wcutt hqpatjniw and from patients who progrsssed tm chronic hepstitis C. Distinctive

were recovered from patients who were infected The of the region and adjacent and were determined for clones obtained from who had fulminant hepatitis, from patients convalesced following acute hepatitis and from patients who progressed to chronic hepatitis C.

were recovered from patients Who were infEcted FolLowInG traNsfuSion. The sequencE Of thE hypervariable region anD adjaCeNT porTIoNs of eNvelope PRoTEIns 1 AnD 2 wEre DeTErMined For MultiplE clones obtAinEd From patients WHo Had fulminaNt hEpatitis, from PatIents wHo ConVAlescEd fOllowIng acuTE hepatItis and frOm PAtientS Who progRESsEd to Chronic hepatitis C. dIsTInctive

were recovered from patie nts who we re in fec ted  f ollo wing  transfusion.T he s equence of the hyperva riabl er egio n  a nd ad jacentp or t i ons  o fenv el o pe  prot ein s 1 and  2 were de ter mi ned for mult i pl e clones o bta ined from pa tie nts wh ohad fulmi nan t hep atitis ,  frompatientswh o  conva l esced f o l lo wing  acute hepatitisa nd from patientswho pr og r es s e d t o c hronic hep at itisC . Disti n ct i v e

were_recovered from_patients who were infected_following transfusion._The_sequence of_the_hypervariable region and_adjacent portions of_envelope proteins 1 and_2 were determined_for_multiple clones obtained from patients who had fulminant hepatitis, from patients who convalesced following_acute_hepatitis and_from_patients_who progressed to chronic hepatitis_C. Distinctive


protein kinase to transduce the signal. Three lines of evidence support this notion. Firstly, the sphingomyelin pathway is activated within seconds to minutes by TNF in HL-60 cells and by IL-1 in human dermal fibroblasts and mouse EL4 T helper cells. Secondly, cell- permeable ceramide analogs

protein kinase to transduce the signal. Three lines of evidence support this notion. Firstly, the sphingomyelin nerve pathway is activate within seconds to minutes by TNF in HL-60 cell and by IL-1 in human cutaneous fibroblasts and mouse EL4 T benefactor cell. Secondly, cell- permeable ceramide analogue

prltein kinase to transduct the signal. Threg oines mf evisence suoport this notion. Firstly, thx spyingonyelin pathway is actixated witjin secobds uo minutes by TNF in HL-60 ccjls zkd by ML-1 in human derkal fibrobnasts and mousa DL4 T helper cells. Secondly, cell- permewble cetalide analogs

protein kinase to transduce the signal. Three evidence this notion. the sphingomyelin pathway minutes TNF in HL-60 and by IL-1 human dermal fibroblasts and mouse EL4 helper cells. Secondly, cell- permeable ceramide analogs

protein kinase to transduce tHe signal. ThRee liNes Of eViDencE supPort this notion. fIrstLy, the sphingomyelin pathWay is AcTIvatED wIthin Seconds TO mINUteS bY TnF iN Hl-60 CeLls anD by iL-1 in humAn dermal fiBroBlAsts and mouse el4 T Helper cellS. SeCondly, cell- peRmeAble ceRaMidE AnaloGs

protein kinase to transdu ce the sig nal.Thr eeli nesof e vidence suppor t  thi s notion. Firstly, the  sphi ng o myel i npathw ay is a c ti v a ted  w it hin  s e co nds t o m inutesby TNF inHL- 60  cells and b y  I L-1 in hum andermal fibro bla sts an dmou s e EL4  Thelpe r cell s . Seco ndly, cel l- permea b le cera m i de  ana logs

protein_kinase to_transduce the signal. Three_lines of_evidence_support this_notion._Firstly, the sphingomyelin_pathway is activated_within seconds to minutes_by TNF in_HL-60_cells and by IL-1 in human dermal fibroblasts and mouse EL4 T helper cells._Secondly,_cell- permeable_ceramide_analogs


three-session Story Sharing (StS) intervention will be compared to a Communication Skills (CS) condition. Interventions will be randomly assigned to six nursing homes. A convenience sample of 20 NAs in each of the six homes (N=120 NAs) will participate in the study. Based on the outcomes

three - session Story Sharing (StS) intervention will be compared to a Communication Skills (CS) condition. interposition will be randomly impute to six nursing homes. A convenience sample of 20 sodium in each of the six homes (N=120 NAs) will participate in the study. establish on the outcomes

thgee-session Story Sharing (StS) intervention will be cojpared tu a Communication Skills (CS) rondution. Interventions will be randomly assignee to wix nursinj homes. A convskiencz wample of 20 NAs in each ox the six homev (V=120 UAs) will participate in the study. Bafed on yhf outcomes

three-session Story Sharing (StS) intervention will be a Skills (CS) Interventions will be homes. convenience sample of NAs in each the six homes (N=120 NAs) will in the study. Based on the outcomes

three-session Story Sharing (STS) intervenTion wIll Be cOmPareD to a communication SKIlls (cS) condition. InterventioNs wilL bE RandOMlY assiGned to sIX nURSinG hOmEs. A CoNVeNiencE saMple of 20 Nas in each of The SiX homes (N=120 NAs) wiLL pArticipate In tHe study. Based On tHe outcOmEs

three-session Story Shari ng (StS) i nterv ent ion  w illbe c ompared to a C o mmun ication Skills (CS) co nditi on .  Int e rv entio ns will be r and om ly  as si g ne d tosix  nursin g homes. A  co nv enience samp l eof 20 NAsineach of thesix  homes  ( N=1 2 0 NAs ) w ill p artici p ate in  the stud y. Basedo n the o u t co mes

three-session_Story Sharing_(StS) intervention will be_compared to_a_Communication Skills_(CS)_condition. Interventions will_be randomly assigned_to six nursing homes._A convenience sample_of_20 NAs in each of the six homes (N=120 NAs) will participate in the_study._Based on_the_outcomes


multiple affected members. Once the HSS gene has been mapped, we will search for mutations in candidate genes, as well as identify novel transcribed sequences that may contain the HSS gene. We will then characterize the gene and its protein product through homology studies to known sequences. Knowledge of the molecular basis of this disease will lead

multiple affected members. Once the HSS gene has been mapped, we will search for mutation in campaigner genes, as well as name novel transcribe sequences that may check the HSS gene. We will then qualify the gene and its protein product through homology studies to known sequences. Knowledge of the molecular basis of this disease will head

muptiple affected members. Unce the HSS geuw has ueen malped, we dill search for mutations in cqndidqte genes, as well as iaentify nlvel trabscrmbed sequences tizt may gjntajk the ISS gene. We wilk then chasacterize the ceve and its protein product through hoiology xtkdies to known seqlegces. Knowledge of the molecular basis kf this disease will lead

multiple affected members. Once the HSS gene mapped, will search mutations in candidate novel sequences that may the HSS gene. will then characterize the gene and protein product through homology studies to known sequences. Knowledge of the molecular basis this disease will lead

multiple affected members. OnCe the HSS geNe has BeeN maPpEd, we Will Search for mutatIOns iN candidate genes, as well aS idenTiFY novEL tRanscRibed seQUeNCEs tHaT mAy cOnTAiN the HsS gEne. We wiLl then charActErIze the gene anD ItS protein prOduCt through homOloGy studIeS to KNown sEquEnces. knowleDGe of thE moleculaR bASis of tHIs diseaSE WiLl leAd

multiple affected members . Once the  HSSgen e h as  bee n ma pped, we wills earc h for mutations in can didat eg enes ,  a s wel l as id e nt i f y n ov el  tr an s cr ibedseq uencesthat may c ont ai n the HSS ge n e.  We will t hen  characteriz e t he gen eand its p rot ein p roduct throug h homolog ys tudies to know n se quen ces. Knowledge of th e  molecular bas is ofth i sd i sea sewill lead

multiple_affected members._Once the HSS gene_has been_mapped,_we will_search_for mutations in_candidate genes, as_well as identify novel_transcribed sequences that_may_contain the HSS gene. We will then characterize the gene and its protein product_through_homology studies_to_known_sequences. Knowledge of the molecular_basis of this disease will_lead


black girls vary as a function of age and toy structure (high vs. low). High structure toys are defined as those which have highly specific, readily identifiable, and conventional functions (e.g., tea set). Low structure toys are defined as those which have less specific, relatively ambiguous functions (e.g., piece

black girls vary as a function of old age and toy dog structure (high vs. low). gamey structure toys are define as those which give birth highly specific, readily identifiable, and conventional functions (e.g., tea hardening). Low structure miniature are defined as those which get less specific, relatively ambiguous functions (for example, piece

blwck girls vary as a funcuion of age and toy strurture (hjgh vs. luw). High structure toys are dxfinwd as those which have highuy specifpc, readilt idtntifiable, and coibentional fundbions (x.g., tea set). Low xtructure doys are definad ad those which have less specific, rejativelu wmbiguous funcjions (q.g., pjvct

black girls vary as a function of toy (high vs. High structure toys have specific, readily identifiable, conventional functions (e.g., set). Low structure toys are defined those which have less specific, relatively ambiguous functions (e.g., piece

black girls vary as a function Of age and toY struCtuRe (hIgH vs. lOw). HiGh structure toyS Are dEfined as those which have HighlY sPEcifIC, rEadilY identiFIaBLE, anD cOnVenTiONaL funcTioNs (e.g., tea Set). Low struCtuRe Toys are definED aS those whicH haVe less specifIc, rElativElY amBIguouS fuNctioNs (e.g., piECe

black girls vary as a fun ction of a ge an d t oyst ruct ure(high vs. low) .  Hig h structure toys are d efine da s th o se  whic h haveh ig h l y s pe ci fic ,r ea dilyide ntifiab le, and co nve nt ional functi o ns  (e.g., te a s et). Low str uct ure to ys  ar e  defi ned  as t hose w h ich ha ve less s pe c ific,r elative l y  a mbig uous functions (e . g. ,  piece

black_girls vary_as a function of_age and_toy_structure (high_vs._low). High structure_toys are defined_as those which have_highly specific, readily_identifiable,_and conventional functions (e.g., tea set). Low structure toys are defined as those which_have_less specific,_relatively_ambiguous_functions (e.g., piece


ate in the U.S. has increased from 1.8 million tons in 1970 to 25.5 million in 1995. Thus humans are exposed to preservatives constantly; persons in the U.S. consuming the average amount of soda ingest 800 mg of benzoate daily. Food preservatives are weak acids and

ate in the U.S. has increased from 1.8 million tons in 1970 to 25.5 million in 1995. Thus world are debunk to preservatives constantly; person in the U.S. consume the average amount of pop ingest 800 magnesium of benzoate daily. Food preservative are fallible acids and

ate in the U.S. has increased from 1.8 million jobs in 1970 to 25.5 mjllion iv 1995. Thus humans are exposed tl preseevatives constantly; pefsons in nhe U.S. cobsummng the average ejount on sodz ingzsv 800 mg of benzoaje daily. Foog preservativev xrz weak acids and

ate in the U.S. has increased from tons 1970 to million in 1995. preservatives persons in the consuming the average of soda ingest 800 mg of daily. Food preservatives are weak acids and

ate in the U.S. has increased froM 1.8 million toNs in 1970 tO 25.5 miLliOn In 1995. ThUs huMans are exposed TO preServatives constantly; peRsons In THe U.S. COnSuminG the aveRAgE AMouNt Of SodA iNGeSt 800 mg oF beNzoate dAily. Food prEseRvAtives are weaK AcIds and

ate in the U.S. has increa sed from 1 .8 mi lli onto ns i n 19 70 to 25.5 mil l ionin 1995. Thus humans a re ex po s ed t o  p reser vatives co n s tan tl y;  pe rs o ns  in t heU.S. co nsuming th e a ve rage amounto fsoda inges t 8 00 mg of ben zoa te dai ly . F o od pr ese rvati ves ar e  weakacids and

ate in_the U.S._has increased from 1.8_million tons_in_1970 to_25.5_million in 1995._Thus humans are_exposed to preservatives constantly;_persons in the_U.S._consuming the average amount of soda ingest 800 mg of benzoate daily. Food preservatives_are_weak acids_and


sexes are being followed longitudinally for two years. A census of addicts living in or routinely active on the streets in a given geopraphical area will be completed and basic demographic data on these addicts will be obtained. This application requests support through an NIAAA Mentored Research Scientist Development Award (K

sexes are being followed longitudinally for two years. A census of addict survive in or routinely active on the streets in a given geopraphical area will be complete and basic demographic data on these addicts will be obtain. This application requests back through an NIAAA Mentored Research Scientist Development Award (K

sedes are being followed lungitudinally for two bears. A census uf addicts living in or routmnelt actuve on the streets in x given gvopraphicql acea will be completed and basid demmjraphic data on these addhcts will be ottxiued. This application requests suppore throubh an NIAAA Mentjred Wesezgcm Scientist Development Award (K

sexes are being followed longitudinally for two census addicts living or routinely active given area will be and basic demographic on these addicts will be obtained. application requests support through an NIAAA Mentored Research Scientist Development Award (K

sexes are being followed longItudinally For twO yeArs. a cEnsuS of aDdicts living in OR rouTinely active on the streeTs in a GiVEn geOPrAphicAl area wILl BE ComPlEtEd aNd BAsIc demOgrAphic daTa on these aDdiCtS will be obtaiNEd. this applicAtiOn requests suPpoRt throUgH an niAAA MEntOred REsearcH scientIst DeveloPmENt AwarD (k

sexes are being followedlongitudin allyfor  tw oyear s. A  census of add i ctsliving in or routinely  acti ve on t h estree ts in a gi v e n g eo pr aph ic a lareawil l be co mpleted an d b as ic demograph i cdata on th ese  addicts wil l b e obta in ed. Thisapp licat ion re q uestssupport t hr o ugh an NIAAA M e n to redResearch Scientis t  D e velopment Awar d (K

sexes_are being_followed longitudinally for two_years. A_census_of addicts_living_in or routinely_active on the_streets in a given_geopraphical area will_be_completed and basic demographic data on these addicts will be obtained. This application requests_support_through an_NIAAA_Mentored_Research Scientist Development Award (K


or assembly determine biological outcomes. The staff and scientists of the SIBYLS beamline provide comprehensive expertise in the targeted areas of nucleic acid binding proteins. High Throughput (HT) Small Angle X-ray Scattering (SAXS), Macromolecular Crystallography (MX), and hybrid computational methods. MIN

or assembly determine biological outcomes. The staff and scientists of the SIBYLS beamline leave comprehensive expertness in the targeted areas of nucleic acerb bind proteins. High Throughput (HT) Small Angle X - beam Scattering (SAXS), Macromolecular Crystallography (MX), and hybrid computational methods. MIN

or wssembly determine biolonical outcomes. Tkw stafh and sdientistr of the SIBYLS beamline protide compeehensive expertise in the targvted areaw of bucleic acms bindiky profcins. Kijh Throughput (HJ) Small Angla X-ray Scatterhne (DAXS), Macromolecular Crystallography (MX), and hjbrid computatyonak metgods. MIN

or assembly determine biological outcomes. The staff of SIBYLS beamline comprehensive expertise in acid proteins. High Throughput Small Angle X-ray (SAXS), Macromolecular Crystallography (MX), and hybrid methods. MIN

or assembly determine biologIcal outcomEs. The StaFf aNd ScieNtisTs of the SIBYLS bEAmliNe provide comprehensive ExperTiSE in tHE tArgetEd areas OF nUCLeiC aCiD biNdINg ProteIns. high ThrOughput (HT) SMalL ANgle X-ray ScatTErIng (SAXS), MacRomOlecular CrysTalLograpHy (mX), aND hybrId cOmputAtionaL MethodS. MIN

or assembly determine biol ogical out comes . T hest affandscientists oft he S IBYLS beamline provide  comp re h ensi v eexper tise in th e tar ge te d a re a sof nu cle ic acid  binding p rot ei ns. High Thr o ug hput (HT)Sma ll Angle X-r ayScatte ri ng( SAXS) , M acrom olecul a r Crys tallograp hy (MX),a nd hybr i d  c ompu tational methods. MI N

or assembly_determine biological_outcomes. The staff and_scientists of_the_SIBYLS beamline_provide_comprehensive expertise in_the targeted areas_of nucleic acid binding_proteins. High Throughput_(HT)_Small Angle X-ray Scattering (SAXS), Macromolecular Crystallography (MX), and hybrid computational methods. MIN


site. Structures of mutant forms of UreR will also be generated. This work will elucidate the molecular mechanisms of this important regulator of a urovirulence, as well as extend our knowledge on the AraC-fainily of transcriptional activators. This research project is directed toward establishing experimental systems to enable

site. Structures of mutant forms of UreR will also be generate. This workplace will elucidate the molecular mechanisms of this important governor of a urovirulence, as well as extend our knowledge on the AraC - fainily of transcriptional activator. This inquiry project is directed toward establishing experimental systems to enable

sihe. Structures of mutant norms of UreR will also be geherated. Ghis work will elucidate the milecuoar mechanisms of this importann regulatir oh a urovirulence, as well as exfcnd obr knowledge on jhe AraC-fainhly of transcrhpgilnal activators. This research projest is dorfcted toward eftabkyshihg experimental systems to enable

site. Structures of mutant forms of UreR be This work elucidate the molecular of urovirulence, as well extend our knowledge the AraC-fainily of transcriptional activators. This project is directed toward establishing experimental systems to enable

site. Structures of mutant forMs of UreR wiLl alsO be GenErAted. this Work will elucidATe thE molecular mechanisms of This iMpORtanT ReGulatOr of a urOViRULenCe, As WelL aS ExTend oUr kNowledgE on the AraC-FaiNiLy of transcriPTiOnal activaTorS. This researcH prOject iS dIreCTed toWarD estaBlishiNG experImental syStEMs to enABle

site. Structures of mutan t forms of  UreR  wi llal so b e ge nerated. Thisw orkwill elucidate the mol ecula rm echa n is ms of  this i m po r t ant  r eg ula to r  o f a u rov irulenc e, as well  as  e xtend our kn o wl edge on th e A raC-fainilyoftransc ri pti o nal a cti vator s. Thi s  resea rch proje ct is dir e cted to w a rd  est ablishing experim e nt a l systems to e nable

site._Structures of_mutant forms of UreR_will also_be_generated. This_work_will elucidate the_molecular mechanisms of_this important regulator of_a urovirulence, as_well_as extend our knowledge on the AraC-fainily of transcriptional activators. This research project is_directed_toward establishing_experimental_systems_to enable


how PMNs ingest and kill bacteria, and elucidates post-phagocytosis sequelae such as apoptosis, processes crucial for the resolution phase of inflammation. Thus, one of our research objectives is to elucidate molecular processes in human PMNs that facilitate resolution of infection. To that end, we used genomics methodologies to

how PMNs ingest and kill bacteria, and elucidates post - phagocytosis sequelae such as apoptosis, process all-important for the resolution phase of inflammation. therefore, one of our research objective is to elucidate molecular processes in human PMNs that facilitate resolving power of infection. To that end, we use genomics methodologies to

hoa PMNs ingest and kill bxcteria, and elueudates post-pgagocytoris sequelae such as apoptosms, peoceswes crucial for the rerolution ihase of unflemmation. Thus, onx of our reseadgh oblertives is to elocidate molewular processev kn human PMNs that facilitate resolutyon of onvection. To thaj end, re uavd genomics methodologies to

how PMNs ingest and kill bacteria, and sequelae as apoptosis, crucial for the one our research objectives to elucidate molecular in human PMNs that facilitate resolution infection. To that end, we used genomics methodologies to

how PMNs ingest and kill bacteRia, and elucIdateS poSt-pHaGocyTosiS sequelae such aS ApopTosis, processes crucial fOr the ReSOlutIOn Phase Of inflaMMaTIOn. THuS, oNe oF oUR rEsearCh oBjectivEs is to elucIdaTe Molecular proCEsSes in human pMNS that facilitAte ResoluTiOn oF InfecTioN. To thAt end, wE Used geNomics metHoDOlogieS To

how PMNs ingest and killbacteria,and e luc ida te s po st-p hagocytosis se q uela e such as apoptosis, p roces se s  cru c ia l for  the re s ol u t ion  p ha seof in flamm ati on. Thu s, one ofour  r esearch obje c ti ves is toelu cidate molec ula r proc es ses in hu man  PMNs  thatf acilit ate resol ut i on ofi nfectio n .  T o th at end, we used g e no m ics methodolog ies to

how_PMNs ingest_and kill bacteria, and_elucidates post-phagocytosis_sequelae_such as_apoptosis,_processes crucial for_the resolution phase_of inflammation. Thus, one_of our research_objectives_is to elucidate molecular processes in human PMNs that facilitate resolution of infection. To_that_end, we_used_genomics_methodologies to


. hospitals by a single predominant strain. S. aureus in which oxacillin resistance is reduced in the presence of clavulanic acid, the hyperbetalactamase producers, have another, distinct phage pattern. We also are studying loss rates of oxacillin resistance after the strains are cultured from the treated

. hospitals by a single predominant strain. S. aureus in which oxacillin underground is reduce in the presence of clavulanic acid, the hyperbetalactamase producers, have another, clear-cut phage pattern. We besides are studying loss rates of oxacillin electric resistance after the strains are cultured from the cover

. hodpitals by a single preduminant strain. S. aureuv in wgich oxazillin resistance is reduced ib the presence of clavulaniz acid, thv hyperberalartamase producers, have akjthed, disciict phage pattetn. We also ase studying lovs rctes of oxacillin resistance after tre straond are cultured frok the nrtated

. hospitals by a single predominant strain. in oxacillin resistance reduced in the hyperbetalactamase have another, distinct pattern. We also studying loss rates of oxacillin resistance the strains are cultured from the treated

. hospitals by a single predomiNant strain. s. aureUs iN whIcH oxaCillIn resistance is REducEd in the presence of clavuLanic AcID, the HYpErbetAlactamASe PROduCeRs, HavE aNOtHer, diStiNct phagE pattern. We AlsO aRe studying loSS rAtes of oxacIllIn resistance AftEr the sTrAinS Are cuLtuRed frOm the tREated

. hospitals by a single pr edominantstrai n.S.au reus  inwhich oxacilli n  res istance is reduced inthe p re s ence of  clav ulanica ci d ,  th ehy per be t al actam ase  produc ers, haveano th er, distinct ph age patter n.We also arestu dyinglo ssr atesofoxaci llin r e sistan ce afterth e  strai n s are c u l tu redfrom the treated

. hospitals_by a_single predominant strain. S._aureus in_which_oxacillin resistance_is_reduced in the_presence of clavulanic_acid, the hyperbetalactamase producers,_have another, distinct_phage_pattern. We also are studying loss rates of oxacillin resistance after the strains are_cultured_from the_treated


formed by shotgun recombinant DNA phages for those with inserts complementary to probe sequences. After these clones are amplified those with functional HPRT genes will be identified by transfer of their DNA into HPRT- cells using micro-injection or calcium-phosphate precipitation techniques. If the approach outlined above is successful we will attempt to

formed by shotgun recombinant DNA phages for those with inserts complemental to probe sequence. After these clones are amplified those with running HPRT genes will be identify by transfer of their deoxyribonucleic acid into HPRT- cells using micro - injection or calcium - phosphate precipitation technique. If the approach outlined above is successful we will undertake to

fogmed by shotgun recombinxnt DNA phages yir thove witg insertr complementary to probe seqnencws. Afuvr these clones are aoplified nhose wity fuictional HPRT geiss will be idsktifizd by transfer on their DNA into HPRT- celns uding micro-injection or calcium-phosprate prrclpitation techgiquts. Yf tgv cpproach outlined above is succsssful xe will attempt to

formed by shotgun recombinant DNA phages for inserts to probe After these clones HPRT will be identified transfer of their into HPRT- cells using micro-injection or precipitation techniques. If the approach outlined above is successful we will attempt to

formed by shotgun recombinanT DNA phages For thOse WitH iNserTs coMplementary to pRObe sEquences. After these clonEs are AmPLifiED tHose wIth funcTIoNAL HPrT GeNes WiLL bE idenTifIed by trAnsfer of thEir dNa into HPRT- celLS uSing micro-iNjeCtion or calciUm-pHosphaTe PreCIpitaTioN techNiques. iF the apProach outLiNEd abovE Is succeSSFuL we wIll attempt to

formed by shotgun recombi nant DNA p hages  fo r t ho se w ithinserts comple m enta ry to probe sequences.  Afte rt hese cl onesare amp l if i e d t ho se  wi th fu nctio nal  HPRT g enes willbeid entified byt ra nsfer of t hei r DNA into H PRT - cell susi n g mic ro- injec tion o r  calci um-phosph at e  preci p itation t ec hniq ues. If the appro a ch outlined above  is su cc e ss f u l w e w ill attemp tto

formed_by shotgun_recombinant DNA phages for_those with_inserts_complementary to_probe_sequences. After these_clones are amplified_those with functional HPRT_genes will be_identified_by transfer of their DNA into HPRT- cells using micro-injection or calcium-phosphate precipitation techniques._If_the approach_outlined_above_is successful we will attempt_to


generation, organized by Ted M. Dawson, Virginia M.-Y. Lee and Stephen M. Strittmatter, which will be held in Taos, New Mexico from February 21 - 26, 2011. Neurodegenerative diseases are chronic age-dependent progressive disorders that are substantial and growing health problems, which exert a tremendous

generation, organized by Ted M. Dawson, Virginia M.-Y. Lee and Stephen M. Strittmatter, which will be held in Taos, New Mexico from February 21 - 26, 2011. Neurodegenerative diseases are chronic old age - pendent progressive disorders that are substantial and growing health problem, which exert a tremendous

genfration, organized by Ted M. Dawson, Virgiuua M.-Y. Nee ans Stephev M. Strittmatter, which will ue hwld ib Taos, New Mexico from February 21 - 26, 2011. Neueodejenerative diseases are gkronid age-be'endent progresxive disorgers that are vucscantial and growing health problems, rhich ecegt a tremendouf

generation, organized by Ted M. Dawson, Virginia and M. Strittmatter, will be held February - 26, 2011. diseases are chronic progressive disorders that are substantial and health problems, which exert a tremendous

generation, organized by Ted M. dawson, VirgInia M.-y. LeE anD STephEn M. STrittmatter, whiCH wilL be held in Taos, New Mexico From FEbRUary 21 - 26, 2011. nEuRodegEneratiVE dISEasEs ArE chRoNIc Age-dePenDent proGressive diSorDeRs that are subSTaNtial and grOwiNg health probLemS, which ExErt A TremeNdoUs

generation, organized by T ed M. Daws on, V irg ini aM.-Y . Le e and StephenM . St rittmatter, which will  be h el d  inT ao s, Ne w Mexic o  f r o m F eb ru ary  2 1  -  26,201 1. Neur odegenerat ive  d iseases arec hr onic age-d epe ndent progre ssi ve dis or der s  that  ar e sub stanti a l andgrowing h ea l th pro b lems, w h i ch  exe rt a tremendous

generation, organized_by Ted_M. Dawson, Virginia M.-Y._Lee and_Stephen_M. Strittmatter,_which_will be held_in Taos, New_Mexico from February 21_- 26, 2011._Neurodegenerative_diseases are chronic age-dependent progressive disorders that are substantial and growing health problems, which_exert_a tremendous


WCCC Biometry component to aid in the planning, implementation and evaluation of Wisconsin cancer control programs. 3. Public Information and Eduction. To develop and promote needed programs to inform the public about cancer. 4. Professional Information and Education. To conduct necessary and evaluable programs to inform and educate health professionals about cancer.

WCCC Biometry component to aid in the planning, implementation and evaluation of Wisconsin cancer control broadcast. 3. Public Information and Eduction. To originate and promote needed programs to inform the populace about cancer. 4. Professional Information and Education. To conduct necessary and evaluable programs to inform and educate health professional about cancer.

WCFC Biometry component to aid in the plaubing, ikplemehtation xnd evaluation of Wisconsin rancwr cobtrol programs. 3. Public Informatpon and Eeuctmon. To develop ais promobz neescd prmjrams to inform the publiw about cancer. 4. Orlfessional Information and Educatiog. To comdkct necessary wnd tvajuabmv krograms to inform and educate hezlth prmfessionals anout cancer.

WCCC Biometry component to aid in the and of Wisconsin control programs. 3. develop promote needed programs inform the public cancer. 4. Professional Information and Education. conduct necessary and evaluable programs to inform and educate health professionals about cancer.

WCCC Biometry component to aiD in the planNing, iMplEmeNtAtioN and Evaluation of WiSConsIn cancer control programS. 3. PublIc iNforMAtIon anD EductiON. TO DEveLoP aNd pRoMOtE needEd pRograms To inform thE puBlIc about canceR. 4. prOfessional infOrmation and EDucAtion. TO cOndUCt necEssAry anD evaluABle proGrams to inFoRM and edUCate heaLTH pRofeSsionals about cancER.

WCCC Biometry component t o aid in t he pl ann ing ,impl emen tation and eva l uati on of Wisconsin cancer  cont ro l  pro g ra ms. 3 . Publi c  I n f orm at io n a nd Ed uctio n.To deve lop and pr omo te  needed prog r am s to infor m t he public ab out  cance r.  4. Profe ssi onalInform a tion a nd Educat io n . To c o nduct n e c es sary  and evaluable pr o gr a ms to inform a nd edu ca t eh e alt h p rofessiona ls  abou t  cancer .

WCCC_Biometry component_to aid in the_planning, implementation_and_evaluation of_Wisconsin_cancer control programs._3. Public Information_and Eduction. To develop_and promote needed_programs_to inform the public about cancer. 4. Professional Information and Education. To conduct necessary_and_evaluable programs_to_inform_and educate health professionals about_cancer.


Y evolve in a highly precise manner and accurately reconstruct expected evolutionary relationships. Yet we describe an unusual form of recombination exists between X and Y, represented by one-way exon exchange (ectopic gene conversion) from Zfx to Zfy genes, that may be an adaptive mechanism for maintaining function of Y genes located outside the

Y evolve in a highly precise manner and accurately reconstruct expected evolutionary relationships. so far we identify an unusual form of recombination exists between X and Y, typify by one - way exon exchange (ectopic gene conversion) from Zfx to Zfy genes, that may be an adaptive mechanism for wield function of Y genes locate outside the

Y fvolve in a highly precire manner and aexurateny recknstruct expected evolutionary relatmonsyips. Tet we describe an unurual form of reconbinetion exists betxsen X akb Y, rsireseutxd by one-way expn exchanga (ectopic gene cunrersion) from Zfx to Zfy genes, that mwy be am wdaptive mechagism sor jaintaining function of Y genes lodated oltside the

Y evolve in a highly precise manner reconstruct evolutionary relationships. we describe an between and Y, represented one-way exon exchange gene conversion) from Zfx to Zfy that may be an adaptive mechanism for maintaining function of Y genes located the

Y evolve in a highly precise maNner and accUrateLy rEcoNsTrucT expEcted evolutionARy reLationships. Yet we descriBe an uNuSUal fORm Of recOmbinatIOn EXIstS bEtWeeN X ANd y, reprEseNted by oNe-way exon eXchAnGe (ectopic genE CoNversion) frOm ZFx to Zfy genes, ThaT may be An AdaPTive mEchAnism For maiNTaininG function Of y Genes lOCated ouTSIdE the

Y evolve in a highly prec ise manner  andacc ura te ly r econ struct expecte d  evo lutionary relationship s. Ye tw e de s cr ibe a n unusu a lf o rmof  r eco mb i na tionexi sts bet ween X and  Y,  r epresented b y  o ne-way exo n e xchange (ect opi c gene  c onv e rsion ) f rom Z fx toZ fy gen es, thatma y  be an adaptiv e me chan ism for maintaini n gf unction of Y g enes l oc a te d out sid e the

Y_evolve in_a highly precise manner_and accurately_reconstruct_expected evolutionary_relationships._Yet we describe_an unusual form_of recombination exists between_X and Y,_represented_by one-way exon exchange (ectopic gene conversion) from Zfx to Zfy genes, that may_be_an adaptive_mechanism_for_maintaining function of Y genes_located outside the


of many endogenous and foreign OCs in the body. In contrast to the kidney and liver, little is known about OC elimination mechanisms in the brain. This is rather unfortunate because many CNS active compounds, including monoamine neurotransmitters (e.g. dopamine, serotonin), CNS drugs (e.g. amant

of many endogenous and foreign OCs in the body. In contrast to the kidney and liver, little is know about OC elimination mechanism in the brain. This is rather unfortunate because many CNS active compound, including monoamine neurotransmitters (for example dopamine, serotonin), CNS drugs (e.g. amant

of many endogenous and fortign OCs in the body. In rontrasf to the kidney and liver, little is nniwn avout OC elimination mezhanisms pn the brqin. Uhis is rather unhkrtunatc beczmse mcnb CNS active cokpounds, inwluding monoamhnd ueurotransmitters (e.g. dopamine, serotogin), CNS dgugs (e.g. amant

of many endogenous and foreign OCs in In to the and liver, little mechanisms the brain. This rather unfortunate because CNS active compounds, including monoamine neurotransmitters dopamine, serotonin), CNS drugs (e.g. amant

of many endogenous and foreigN OCs in the bOdy. In ConTraSt To thE kidNey and liver, litTLe is Known about OC eliminatioN mechAnISms iN ThE braiN. This is RAtHER unFoRtUnaTe BEcAuse mAny cNS actiVe compoundS, inClUding monoamiNE nEurotransmIttErs (e.g. dopaminE, seRotoniN), CnS dRUgs (e.g. AmaNt

of many endogenous and fo reign OCsin th e b ody .In c ontr ast to the kid n ey a nd liver, little is kn own a bo u t OC el imina tion me c ha n i sms  i nthe  b r ai n. Th isis rath er unfortu nat ebecause many CN S active c omp ounds, inclu din g mono am ine neuro tra nsmit ters ( e .g. do pamine, s er o tonin) ,  CNS dr u g s(e.g . amant

of_many endogenous_and foreign OCs in_the body._In_contrast to_the_kidney and liver,_little is known_about OC elimination mechanisms_in the brain._This_is rather unfortunate because many CNS active compounds, including monoamine neurotransmitters (e.g. dopamine, serotonin),_CNS_drugs (e.g._amant