new redox-related measures within the context of his current clinical research, enabling him to train mentees in these new measures; and 3) to faciliate the career development of the applicant. [unreadable] [unreadable] [unreadable] Project Summary The goal of this project is to focus on the relationship between dental use

new redox - related measures within the context of his current clinical research, enable him to educate mentees in these new measures; and 3) to faciliate the career growth of the applicant. [ indecipherable ] [ unreadable ] [ unreadable ] Project Summary The finish of this undertaking is to focus on the relationship between dental use

nea redox-related measures dithin the contgxr of hms currsnt clinkcal research, enabling him tl rrain mentees in these new oeasures; wnd 3) to daciouate the cedeer deyzlopmskt of vhe applicant. [ukreadable] [utreadable] [unreddxbpe] Project Summary The goal of this projecy ls to focus on the welafpokship between dental use

new redox-related measures within the context of clinical enabling him train mentees in to the career development the applicant. [unreadable] [unreadable] Project Summary The goal of project is to focus on the relationship between dental use

new redox-related measures wiThin the conText oF hiS cuRrEnt cLiniCal research, enaBLing Him to train mentees in theSe new MeASureS; AnD 3) to faCiliate THe CAReeR dEvEloPmENt Of the AppLicant. [uNreadable] [uNreAdAble] [unreadabLE] PRoject SummAry the goal of thiS prOject iS tO foCUs on tHe rElatiOnship BEtween Dental use

new redox-related measure s within t he co nte xtof  his  cur rent clinicalr esea rch, enabling him to t rainme n tees in  thes e new m e as u r es;  a nd  3)  t o  f acili ate  the ca reer devel opm en t of the app l ic ant. [unre ada ble] [unread abl e] [un re ada b le] P roj ect S ummary The go al of thi sp roject is to f o c us  onthe relationshipb et w een dental use

new_redox-related measures_within the context of_his current_clinical_research, enabling_him_to train mentees_in these new_measures; and 3) to_faciliate the career_development_of the applicant. [unreadable] [unreadable] [unreadable] Project Summary The goal of this project is_to_focus on_the_relationship_between dental use


to improve the lives of cancer patients by finding better ways to treat, control and cure cancer. CTEP accomplishes this mission by funding an extensive national program of cancer research and by sponsoring clinical trials to evaluate new anti-cancer agents, with a particular emphasis on translational research to elucidate molecular targets and mechanisms of drug

to improve the lives of cancer patients by finding good way to treat, control and cure cancer. CTEP achieve this mission by funding an across-the-board national program of cancer research and by sponsor clinical trials to evaluate modern anti - cancer agents, with a particular stress on translational inquiry to elucidate molecular targets and mechanism of drug

to improve the lives of cakcer patients by findinj betted ways tu treat, control and cure canrer. XTEP qccomplishes this misskon by fujding an exttnsive national pckgram on candcr revxarch and by sppnsoring cninical trials tu zvaluate new anti-cancer agents, with w partivupar emphasis og trsgslafpokal research to elucidate molecumar tarjets and mechanosms of drug

to improve the lives of cancer patients better to treat, and cure cancer. funding extensive national program cancer research and sponsoring clinical trials to evaluate new agents, with a particular emphasis on translational research to elucidate molecular targets and of drug

to improve the lives of cancer Patients by FindiNg bEttEr Ways To trEat, control and cURe caNcer. CTEP accomplishes thIs misSiON by fUNdIng an ExtensiVE nATIonAl PrOgrAm OF cAncer ResEarch anD by sponsorIng ClInical trials TO eValuate new AntI-cancer agentS, wiTh a parTiCulAR emphAsiS on trAnslatIOnal reSearch to eLuCIdate mOLecular TARgEts aNd mechanisms of druG

to improve the lives of c ancer pati entsbyfin di ng b ette r ways to trea t , co ntrol and cure cancer.  CTEP  a c comp l is hes t his mis s io n byfu nd ing  a n  e xtens ive  nation al program  of  c ancer resear c hand by spo nso ring clinica l t rialsto  ev a luate  ne w ant i-canc e r agen ts, withap articu l ar emph a s is  ontranslational res e ar c h to elucidate  molec ul a rt a rge tsand mechan is ms of drug

to_improve the_lives of cancer patients_by finding_better_ways to_treat,_control and cure_cancer. CTEP accomplishes_this mission by funding_an extensive national_program_of cancer research and by sponsoring clinical trials to evaluate new anti-cancer agents, with_a_particular emphasis_on_translational_research to elucidate molecular targets_and mechanisms of drug


that (1) TNF-alpha plays an important role in damaging the liver, and (2) a UTL-compound lowered TNF-alpha levels and may be a potential radiation protector for liver. The goal of this SBIR Phase I study is to validate the feasibility of using our TNF-alpha modulators to

that (1) TNF - alpha plays an important role in damaging the liver, and (2) a UTL - compound turn down TNF - alpha degree and may be a potential radiation protector for liver. The finish of this SBIR Phase I study is to validate the feasibility of using our TNF - alpha modulators to

thwt (1) TNF-alpha plays an imkortant role in dcnaging the ljver, and (2) a UTL-compound lowered TNF-appya lecels and may be a potevtial radpation pritecuor for liver. The goal of this ANIR Pkawe I study is jo validate dhe feasibilitf uf using our TNF-alpha modulators to

that (1) TNF-alpha plays an important role the and (2) UTL-compound lowered TNF-alpha potential protector for liver. goal of this Phase I study is to validate feasibility of using our TNF-alpha modulators to

that (1) TNF-alpha plays an importAnt role in dAmagiNg tHe lIvEr, anD (2) a UTl-compound lowerED TNF-Alpha levels and may be a poTentiAl RAdiaTIoN protEctor foR LiVER. ThE gOaL of ThIS SbIR PhAse i study iS to validatE thE fEasibility of USiNg our TNF-alPha Modulators to

that (1) TNF-alpha playsan importa nt ro leinda magi ng t he liver, and( 2) a  UTL-compound loweredTNF-a lp h a le v el s and  may be ap o ten ti al  ra di a ti on pr ote ctor fo r liver. T hego al of this S B IR  Phase I s tud y is to vali dat e thefe asi b ility  of  usin g ourT NF-alp ha modula to r s to

that_(1) TNF-alpha_plays an important role_in damaging_the_liver, and_(2)_a UTL-compound lowered_TNF-alpha levels and_may be a potential_radiation protector for_liver._The goal of this SBIR Phase I study is to validate the feasibility of_using_our TNF-alpha_modulators_to


photons with specified colors. The procedure works even when the photon colors appear to be scrambled (i.e., one cannot identify states by visual inspection of a photon trajectory) because the photophysical properties of the conformers are similar and/or conformational dynamics is on a similar time scale as the photon counts.[unreadable] [

photons with specified colors. The procedure work even when the photon color appear to be scrambled (i.e., one cannot identify state by visual inspection of a photon trajectory) because the photophysical properties of the conformers are alike and/or conformational dynamics is on a similar clock time scale as the photon counts.[unreadable ] [

phltons with specified colurs. The procedute works even shen the photon colors appear to be dceambltb (i.e., one cannot idengify statvs by visyal mnspection of a 'goton tvcjectkvy) beeanse the photophisical propesties of the cmnwoxmers are similar and/or conformationwl dynakifs is on a simylar eime scale as the photon counts.[unreadagle] [

photons with specified colors. The procedure works the colors appear be scrambled (i.e., visual of a photon because the photophysical of the conformers are similar and/or dynamics is on a similar time scale as the photon counts.[unreadable] [

photons with specified colorS. The procedUre woRks EveN wHen tHe phOton colors appeAR to bE scrambled (i.e., one cannot iDentiFy STateS By VisuaL inspecTIoN OF a pHoToN trAjECtOry) beCauSe the phOtophysicaL prOpErties of the cONfOrmers are sImiLar and/or confOrmAtionaL dYnaMIcs is On a SimilAr time SCale as The photon CoUNts.[unrEAdable] [

photons with specified co lors. Theproce dur e w or ks e venwhen the photo n  col ors appear to be scram bled(i . e.,o ne  cann ot iden t if y sta te sbyvi s ua l ins pec tion of  a photontra je ctory) becau s ethe photop hys ical propert ies  of th econ f ormer s a re si milara nd/orconformat io n al dyn a mics is o na si milar time scalea st he photon coun ts.[un re a da b l e][

photons_with specified_colors. The procedure works_even when_the_photon colors_appear_to be scrambled_(i.e., one cannot_identify states by visual_inspection of a_photon_trajectory) because the photophysical properties of the conformers are similar and/or conformational dynamics is_on_a similar_time_scale_as the photon counts.[unreadable] [


and a staff of two full-time scientists. This essential Core will service the Program Project entitled "Critical Interactions of APOBECSs: Molecular Approaches to Novel HiV Therapies" by producing plasmid DNA constructs for APOBECS and Vif protein expression in E. coli and mammalian cells.

and a staff of two full - time scientists. This essential Core will serve the Program Project ennoble " Critical Interactions of APOBECSs: Molecular Approaches to Novel HiV Therapies " by produce plasmid deoxyribonucleic acid constructs for APOBECS and Vif protein expression in E. coli and mammalian cells.

anf a staff of two full-timt scientists. This essentmal Cors will sdrvice the Program Project eititoed "Ceitical Interactions ow APOBECSd: Molecuoar Epproaches to Notsl HiV Bkerapjcs" by 'roducing plasmld DNA consdructs for APOTEZS and Vif protein expression in E. coji and kalmalian cells.

and a staff of two full-time scientists. Core service the Project entitled "Critical to HiV Therapies" by plasmid DNA constructs APOBECS and Vif protein expression in coli and mammalian cells.

and a staff of two full-time sciEntists. ThiS esseNtiAl COrE wilL serVice the Program pRojeCt entitled "Critical InteRactiOnS Of APobEcSs: MoLecular aPpROAchEs To novEl hIV theraPieS" by prodUcing plasmId DnA Constructs foR aPoBECS and ViF prOtein expressIon In E. colI aNd mAMmaliAn cElls.

and a staff of two full-t ime scient ists.  Th ises sent ialCore will serv i ce t he Program Project ent itled  " C riti c al  Inte raction s  o f APO BE CS s:Mo l ec ularApp roaches  to NovelHiV  T herapies" by pr oducing pl asm id DNA const ruc ts for  A POB E CS an d V if pr oteine xpress ion in E.  c o li and mammali a n  c ells .

and_a staff_of two full-time scientists._This essential_Core_will service_the_Program Project entitled_"Critical Interactions of_APOBECSs: Molecular Approaches to_Novel HiV Therapies"_by_producing plasmid DNA constructs for APOBECS and Vif protein expression in E. coli and_mammalian_cells.


stable, production grade CD-SFM-CHO or CD-SFM-NS0 clones. We also plan to generate Accession Cell Banks (ACB) for clonal cell lines of interest, and to convert to manufacturing with QA/QC to generate gram quantities of candidate huMAbs for in vivo studies.

stable, production grade CD - SFM - CHO or certificate of deposit - SFM - NS0 knockoff. We also plan to generate Accession Cell Banks (ACB) for clonal cellular telephone lines of interest, and to convert to manufacture with QA / QC to generate gram quantities of campaigner huMAbs for in vivo study.

stwble, production grade CD-RFM-CHO or CD-SFM-UW0 clonxs. We amso plan to generate Accession Cell Uankw (ACB) for clonal cell lines of intervst, and ti coivert to manufacvhring wlch QA/SG to yeierate gram quaktities of wandidate huMAts flr in vivo studies.

stable, production grade CD-SFM-CHO or CD-SFM-NS0 clones. plan generate Accession Banks (ACB) for and convert to manufacturing QA/QC to generate quantities of candidate huMAbs for in studies.

stable, production grade CD-SFm-CHO or CD-SFm-NS0 clOneS. We AlSo plAn to Generate AccessIOn CeLl Banks (ACB) for clonal celL lineS oF InteREsT, and tO converT To MANufAcTuRinG wITh qA/QC tO geNerate gRam quantitIes Of Candidate huMaBs For in vivo sTudIes.

stable, production gradeCD-SFM-CHO  or C D-S FM- NS 0 cl ones . We also plan to g enerate Accession Cell  Bank s( ACB) fo r clo nal cel l  l i n esof  i nte re s t,  andtoconvert  to manufa ctu ri ng with QA/Q C  t o generate  gr am quantitie s o f cand id ate huMAb s f or in  vivos tudies .

stable,_production grade_CD-SFM-CHO or CD-SFM-NS0 clones._We also_plan_to generate_Accession_Cell Banks (ACB)_for clonal cell_lines of interest, and_to convert to_manufacturing_with QA/QC to generate gram quantities of candidate huMAbs for in vivo studies.


Second, using three-dimensional (3D) DNA nanotechnology, we build synthetic cargo to which DNA-linked dynein or kinesin motors can be attached with defined numbers and spacing. To determine how dynein takes consecutive steps along microtubules, single-molecule techniques, including high-precision,

Second, using three - dimensional (3D) DNA nanotechnology, we build man-made cargo to which DNA - connect dynein or kinesin motors can be attached with defined number and spacing. To determine how dynein take consecutive steps along microtubule, individual - molecule proficiency, including high - preciseness,

Sefond, using three-dimensiokal (3D) DNA nanoteeynologb, we bujld syntfetic cargo to which DNA-linkxd dtnein or kinesin motors can be attacjed with defmned numbers and spacing. To defcrminz iow dynein takex consecuthve steps alonc oierotubules, single-molecule techniques, includonh high-precisiog,

Second, using three-dimensional (3D) DNA nanotechnology, we cargo which DNA-linked or kinesin motors numbers spacing. To determine dynein takes consecutive along microtubules, single-molecule techniques, including high-precision,

Second, using three-dimensionAl (3D) DNA nanoTechnOloGy, wE bUild SyntHetic cargo to whICh DNa-linked dynein or kinesin MotorS cAN be aTTaChed wIth defiNEd NUMbeRs AnD spAcINg. to detErmIne how dYnein takes ConSeCutive steps aLOnG microtubuLes, Single-molecuLe tEchniqUeS, inCLudinG hiGh-preCision,

Second, using three-dimen sional (3D ) DNA  na not ec hnol ogy,  we build synt h etic  cargo to which DNA-li nkeddy n eino rkines in moto r sc a n b eat tac he d  w ith d efi ned num bers and s pac in g. To determ i ne  how dynei n t akes consecu tiv e step salo n g mic rot ubule s, sin g le-mol ecule tec hn i ques,i ncludin g hi gh-p recision,

Second,_using three-dimensional_(3D) DNA nanotechnology, we_build synthetic_cargo_to which_DNA-linked_dynein or kinesin_motors can be_attached with defined numbers_and spacing. To_determine_how dynein takes consecutive steps along microtubules, single-molecule techniques, including high-precision,


products. Changes of antibody titers will be measured by flow cytometry and by panel lymphocytotoxic antibody reactivity. Retrospective crossmatches will be performed to determine if 10W level anti-donor antibodies consistently induce poor transfusion responses or acceptable increments can still occur in their presence. The results of the proposed studies will not only allow

products. Changes of antibody titers will be measured by menstruation cytometry and by dialog box lymphocytotoxic antibody reactivity. Retrospective crossmatches will be performed to determine if 10W charge anti - donor antibodies consistently induce inadequate transfusion reception or acceptable increase can still occur in their bearing. The results of the proposed studies will not only admit

prlducts. Changes of antiboay titers will yw measnred by flow cygometry and by panel lymphocbtotixic qntibody reactivity. Regrospectine crossmqtchts will be performed to dccermihc if 10C oevel anti-donot antibodies consistently hnauee poor transfusion responses or accqptable ijcrements can ftilk occhg ln their presence. The results of the prmposed studiex will not only allow

products. Changes of antibody titers will be flow and by lymphocytotoxic antibody reactivity. to if 10W level antibodies consistently induce transfusion responses or acceptable increments can occur in their presence. The results of the proposed studies will not only

products. Changes of antibody Titers will Be meaSurEd bY fLow cYtomEtry and by panel LYmphOcytotoxic antibody reacTivitY. RETrosPEcTive cRossmatCHeS WIll Be PeRfoRmED tO deteRmiNe if 10W leVel anti-donOr aNtIbodies consiSTeNtly induce PooR transfusion ResPonses Or AccEPtablE inCremeNts can STill ocCur in theiR pREsence. tHe resulTS Of The pRoposed studies wilL NoT Only allow

products. Changes of anti body titer s wil l b e m ea sure d by  flow cytometr y  and  by panel lymphocytoto xic a nt i body re activ ity. Re t ro s p ect iv ecro ss m at cheswil l be pe rformed to  de te rmine if 10W le vel anti-d ono r antibodies  co nsiste nt lyi nduce  po or tr ansfus i on res ponses or  a c ceptab l e incre m e nt s ca n still occur int he i r presence. Th e resu lt s  o f the  pr oposed stu di es wi l l not o n ly a l low

products._Changes of_antibody titers will be_measured by_flow_cytometry and_by_panel lymphocytotoxic antibody_reactivity. Retrospective crossmatches_will be performed to_determine if 10W_level_anti-donor antibodies consistently induce poor transfusion responses or acceptable increments can still occur in_their_presence. The_results_of_the proposed studies will not_only allow


as well as the level intracellular scavengers in order to determine the importance of reductive metabolism in repair of radiation damage. Sensitizers will also be used in combination with insulin, glucose and phosphate, agents known to alter cellular radiosensitivity as well as cellular redox potential. We plan to assay radiation response with both tissue cultured

as well as the level intracellular scavengers in order to settle the importance of reductive metamorphosis in repair of radiation price. sensitizer will also be used in combination with insulin, glucose and phosphate, agents know to alter cellular radiosensitivity equally well as cellular redox electric potential. We plan to assay radiotherapy response with both tissue cultured

as well as the level intragellular scavenggrw in ocder to determive the importance of reductite mwtabooism in repair of radixtion damwge. Sensutiztrs will also be naed in gjmbihwtiou xith insulin, glocose and phmsphate, agents kvocn to alter cellular radiosensitivitr as wekl as cellular rgdox kotqntizl. We plan to assay radiation respknse wiuh both tissue culyured

as well as the level intracellular scavengers to the importance reductive metabolism in will be used in with insulin, glucose phosphate, agents known to alter cellular as well as cellular redox potential. We plan to assay radiation response with tissue cultured

as well as the level intracellUlar scavenGers iN orDer To DeteRminE the importance OF redUctive metabolism in repaIr of rAdIAtioN DaMage. SEnsitizERs WILl aLsO bE usEd IN cOmbinAtiOn with iNsulin, glucOse AnD phosphate, agENtS known to alTer Cellular radiOseNsitivItY as WEll as CelLular Redox pOTentiaL. We plan to AsSAy radiATion resPONsE witH both tissue culturED

as well as the level intr acellularscave nge rsin  ord er t o determine th e  imp ortance of reductive m etabo li s m in re pairof radi a ti o n  da ma ge . S en s it izers  wi ll also  be used i n c om bination wit h  i nsulin, gl uco se and phosp hat e, age nt s k n own t o a ltercellul a r radi osensitiv it y  as we l l as ce l l ul ar r edox potential. W e  p l an to assay ra diatio nr es p o nse  wi th both ti ss ue cu l tured

as_well as_the level intracellular scavengers_in order_to_determine the_importance_of reductive metabolism_in repair of_radiation damage. Sensitizers will_also be used_in_combination with insulin, glucose and phosphate, agents known to alter cellular radiosensitivity as well_as_cellular redox_potential._We_plan to assay radiation response_with both tissue cultured


to be activated directly by DAG, whereby subsequent depletion of sarcolemmal PIP2 would prevent endocytosis and favor the expansion of the sarcolemma. Complementary to studies of PI4K2alpha, we will test whether the type 2beta PI4-kinase (PI4K2alpha) is

to be activated directly by DAG, whereby subsequent depletion of sarcolemmal PIP2 would prevent endocytosis and favor the expansion of the sarcolemma. Complementary to report of PI4K2alpha, we will screen whether the type 2beta PI4 - kinase (PI4K2alpha) is

to be activated directly bn DAG, whereby suywequenv deplefion of rarcolemmal PIP2 would prevenv eneocytisis and favor the expxnsion of the sarxolenna. Complemxhtary to studjcs of 'I4K2alpha, we wilk test whedher the type 2tega PI4-kinase (PI4K2alpha) is

to be activated directly by DAG, whereby of PIP2 would endocytosis and favor Complementary studies of PI4K2alpha, will test whether type 2beta PI4-kinase (PI4K2alpha) is

to be activated directly by DAg, whereby suBsequEnt DepLeTion Of saRcolemmal PIP2 woULd prEvent endocytosis and favOr the ExPAnsiON oF the sArcolemMA. COMPleMeNtAry To STuDies oF PI4k2alpha, wE will test wHetHeR the type 2beta pi4-kInase (PI4K2alPha) Is

to be activated directlyby DAG, wh ereby  su bse qu entdepl etion of sarco l emma l PIP2 would prevent e ndocy to s is a n dfavor  the ex p an s i onof  t hesa r co lemma . C ompleme ntary to s tud ie s of PI4K2al p ha , we willtes t whether th e t ype 2b et a P I 4-kin ase  (PI4 K2alph a ) is

to_be activated_directly by DAG, whereby_subsequent depletion_of_sarcolemmal PIP2_would_prevent endocytosis and_favor the expansion_of the sarcolemma. Complementary_to studies of_PI4K2alpha,_we will test whether the type 2beta PI4-kinase (PI4K2alpha) is


types express functional GABAA receptors. However, the mechanism of this immune modulation is unknown. In this proposal, we present exciting preliminary data demonstrating that mice lacking expression of the GABAA receptor?4 subunit (gabra4), a subunit expressed in immune cells including CD4+ lymphocytes, have significantly greater lung

types express functional GABAA receptors. However, the mechanism of this immune transition is strange. In this proposal, we present exciting preliminary data demonstrating that shiner lacking expression of the GABAA receptor?4 fractional monetary unit (gabra4), a subunit expressed in immune cells include CD4 + lymphocytes, have importantly greater lung

tyoes express functional GXBAA receptors. Kiwever, the mschanism of this immune modulation id ynknoqn. In this proposal, we present vxciting prelmminary data demonstratiky thaf micz oacking expresxion of tha GABAA receptmr?4 sbbunit (gabra4), a subunit expressed in ymmune vepls including SD4+ ljm[hocgnew, have significantly greater mung

types express functional GABAA receptors. However, the this modulation is In this proposal, demonstrating mice lacking expression the GABAA receptor?4 (gabra4), a subunit expressed in immune including CD4+ lymphocytes, have significantly greater lung

types express functional GABaA receptorS. HoweVer, The MeChanIsm oF this immune modULatiOn is unknown. In this propoSal, we PrESent EXcIting PrelimiNArY DAta DeMoNstRaTInG that MicE lackinG expressioN of ThE GABAA receptOR?4 sUbunit (gabrA4), a sUbunit expresSed In immuNe CelLS inclUdiNg CD4+ lYmphocYTes, havE significAnTLy greaTEr lung

types express functionalGABAA rece ptors . H owe ve r, t he m echanism of th i s im mune modulation is unk nown.  I n  thi s  p ropos al, wep re s e ntex ci tin gp re limin ary  data d emonstrati ngth at mice lack i ng  expressio n o f the GABAArec eptor? 4sub u nit ( gab ra4),  a sub u nit ex pressed i ni mmunec ells in c l ud ingCD4+ lymphocytes, ha v e significantl y grea te r  l u n g

types_express functional_GABAA receptors. However, the_mechanism of_this_immune modulation_is_unknown. In this_proposal, we present_exciting preliminary data demonstrating_that mice lacking_expression_of the GABAA receptor?4 subunit (gabra4), a subunit expressed in immune cells including CD4+_lymphocytes,_have significantly_greater_lung


for NCI sponsorship, CTEP attempts to fill critical gaps in the national cancer research effort and to avoid duplication of ongoing private sector efforts. In further efforts to control cancer, active new anticancer agents are made available as rapidly and widely as possible for patients. Neurological syndromes have frequently been described in patients with acquired immunodeficiency

for NCI sponsorship, CTEP attempts to fill critical gaps in the national cancer inquiry campaign and to avoid duplication of ongoing individual sector effort. In further efforts to control cancer, active modern anticancer agent are made available as quickly and wide as possible for patients. Neurological syndrome have frequently been described in patients with acquired immunodeficiency

fog NCI sponsorship, CTEP autempts to fill ctirical japs in the natkonal cancer research effort abd to avoid duplication of ungoing pgivate sextor wfforts. In further efforfd to rontrol cancer, sctive new anticancer agangs are made available as rapidly and ridely ss possible for katiemes. Nslrilogical syndromes have frequsntly bten described in pstients with acquired immujodeviciency

for NCI sponsorship, CTEP attempts to fill in national cancer effort and to sector In further efforts control cancer, active anticancer agents are made available as and widely as possible for patients. Neurological syndromes have frequently been described in with acquired immunodeficiency

for NCI sponsorship, CTEP atteMpts to fill CritiCal GapS iN the NatiOnal cancer reseARch eFfort and to avoid duplicaTion oF oNGoinG PrIvate Sector eFFoRTS. In FuRtHer EfFOrTs to cOntRol cancEr, active neW anTiCancer agents ARe Made availaBle As rapidly and WidEly as pOsSibLE for pAtiEnts. NEuroloGIcal syNdromes haVe FRequenTLy been dESCrIbed In patients with acqUIrED immunodeficieNcy

for NCI sponsorship, CTEP  attemptsto fi llcri ti calgaps  in the nation a l ca ncer research effort a nd to  a v oidd up licat ion ofo ng o i ngpr iv ate  s e ct or ef for ts. Infurther ef for ts  to controlc an cer, activ e n ew anticance r a gentsar e m a de av ail ableas rap i dly an d widelyas possib l e for p a t ie nts.  Neurological syn d ro m es have freque ntly b ee n  d e s cri bed  in patien ts  with acquire d  i m m u nod e ficiency

for_NCI sponsorship,_CTEP attempts to fill_critical gaps_in_the national_cancer_research effort and_to avoid duplication_of ongoing private sector_efforts. In further_efforts_to control cancer, active new anticancer agents are made available as rapidly and widely_as_possible for_patients._Neurological_syndromes have frequently been described_in patients with acquired immunodeficiency


2 (N2) gene. The sequence of the N2 NSP2 gene was identical to the RotaTeq N2 NSP2 gene, indicating that the two atypical viruses originated by reassortment of human G1P8 RVs with RotaTeq viruses. These data suggest that the high

2 (N2) gene. The sequence of the N2 NSP2 gene was identical to the RotaTeq N2 NSP2 gene, indicating that the two atypical viruses originated by reassortment of human G1P8 recreational vehicle with RotaTeq virus. These data suggest that the eminent

2 (N2) hene. The sequence of the N2 NSP2 gene was identiral to fhe RotaGeq N2 NSP2 gene, indicating thet tye twi atypical viruses orieinated bj reassorrmenu of human G1P8 RVs with RobcTeq blrusev. These data sungest that dhe high

2 (N2) gene. The sequence of the gene identical to RotaTeq N2 NSP2 atypical originated by reassortment human G1P8 RVs RotaTeq viruses. These data suggest that high

2 (N2) gene. The sequence of the N2 NSP2 Gene was ideNticaL to The roTaTeQ N2 NSp2 gene, indicatinG That The two atypical viruses oRiginAtED by rEAsSortmEnt of huMAn g1p8 rVs WiTh rotATEQ vIruseS. ThEse data Suggest thaT thE hIgh

2 (N2) gene. The sequenceof the N2NSP2gen e w as  ide ntic al to the Rota T eq N 2 NSP2 gene, indicatin g tha tt he t w oatypi cal vir u se s ori gi na ted  b y  r easso rtm ent ofhuman G1P8  RV swith RotaTeq vi ruses. The sedata suggest  th at the  h igh

2 (N2)_gene. The_sequence of the N2_NSP2 gene_was_identical to_the_RotaTeq N2 NSP2_gene, indicating that_the two atypical viruses_originated by reassortment_of_human G1P8 RVs with RotaTeq viruses. These data suggest that the high


discussions and health and safety outcomes for affected women. Aims of the research project are: 1) to describe the content and style of patient-provider communication regarding intimate partner violence during the initial obstetric visit; 2) to describe association between communication and IPV disclosure; 3) to describe the patients' perspectives on the discussion

discussions and health and safety outcomes for affected charwoman. aim of the research project are: 1) to describe the capacity and style of patient - supplier communication regarding intimate partner ferocity during the initial obstetric sojourn; 2) to describe association between communication and IPV disclosure; 3) to identify the patients' perspectives on the discussion

didcussions and health and safety outcomes for ahfected women. Akms of the research project ere: 1) to dtfcribe the content and stylv of patiwnt-pcovider communicefion rencrdinf intnmete partner viokence duritg the initial ocscetric visit; 2) to describe associatiog betwern communication and YPV spsglosure; 3) to describe the patienta' persptctives on the disvussion

discussions and health and safety outcomes for Aims the research are: 1) to of communication regarding intimate violence during the obstetric visit; 2) to describe association communication and IPV disclosure; 3) to describe the patients' perspectives on the discussion

discussions and health and saFety outcomEs for AffEctEd WomeN. AimS of the research PRojeCt are: 1) to describe the contEnt anD sTYle oF PaTient-ProvideR CoMMUniCaTiOn rEgARdIng inTimAte partNer violencE duRiNg the initial OBsTetric visiT; 2) to Describe assoCiaTion beTwEen COmmunIcaTion aNd IPV dISclosuRe; 3) to descrIbE The patIEnts' perSPEcTiveS on the discussion

discussions and health an d safety o utcom esfor  a ffec tedwomen. Aims of theresearch project are:1) to  d e scri b ethe c ontenta nd s tyl eof  pa ti e nt -prov ide r commu nication r ega rd ing intimate pa rtner viol enc e during the  in itialob ste t ric v isi t; 2)  to de s cribeassociati on betwee n  commun i c at ionand IPV disclosur e ;3 ) to describethe pa ti e nt s '  pe rsp ectives on  t he di s cussion

discussions_and health_and safety outcomes for_affected women._Aims_of the_research_project are: 1)_to describe the_content and style of_patient-provider communication regarding_intimate_partner violence during the initial obstetric visit; 2) to describe association between communication and_IPV_disclosure; 3)_to_describe_the patients' perspectives on the_discussion


and policy makers. [unreadable] [unreadable] [unreadable] Non-aromatic polyketide natural products of marine origin are often characterized by both significant structural complexity and extraordinary biological activities. Because these exciting compounds are not typically available in any meaningful quantities from natural sources, total chemical synthesis is the only means by which sufficient

and policy makers. [ unreadable ] [ unreadable ] [ unreadable ] Non - aromatic polyketide lifelike product of marine origin are frequently characterize by both significant structural complexity and extraordinary biological activity. Because these exciting compound are not typically available in any meaningful quantities from natural sources, total chemical deduction is the only means by which sufficient

anf policy makers. [unreadabue] [unreadable] [uueeadabne] Non-zromatic polyketide natural products od marune origin are often cfaracterided by borh smgnificant strucvhral complexifn and xxtraordinary blological awtivities. Becagsd chese exciting compounds are not typycally svwilable in any meamyngfhl quantities from natural sources, total bhemical synthesix is the only means by whifh skfficient

and policy makers. [unreadable] [unreadable] [unreadable] Non-aromatic products marine origin often characterized by extraordinary activities. Because these compounds are not available in any meaningful quantities from sources, total chemical synthesis is the only means by which sufficient

and policy makers. [unreadable] [Unreadable] [UnreaDabLe] NOn-AromAtic Polyketide natuRAl prOducts of marine origin arE ofteN cHAracTErIzed bY both siGNiFICanT sTrUctUrAL cOmpleXitY and extRaordinary BioLoGical activitIEs. because theSe eXciting compoUndS are noT tYpiCAlly aVaiLable In any mEAningfUl quantitIeS From naTUral souRCEs, TotaL chemical synthesiS Is THe only means by wHich suFfICiENT

and policy makers. [unrea dable] [un reada ble ] [ un read able ] Non-aromatic poly ketide natural product s ofma r ineo ri gin a re ofte n  c h a rac te ri zed  b y  b oth s ign ificant  structura l c om plexity ande xt raordinary  bi ological act ivi ties.Be cau s e the seexcit ing co m pounds  are notty p ically availab l e  i n an y meaningful quan t it i es from natura l sour ce s ,t o tal  ch emical syn th esisi s the o n ly m e ans by which suff icient

and_policy makers._[unreadable] [unreadable] [unreadable] Non-aromatic_polyketide natural_products_of marine_origin_are often characterized_by both significant_structural complexity and extraordinary_biological activities. Because_these_exciting compounds are not typically available in any meaningful quantities from natural sources, total_chemical_synthesis is_the_only_means by which sufficient


and respectful caring relationships. Story Sharing: Enriching Nurse Aide-Resident Relations, a longitudinal mixed methodology study guided by Watson's theory of transpersonal caring, aims to improve caring behaviors toward residents by increasing NA levels of empathy, job attitude, mutuality, and self-efficacy. The effects of a

and respectful caring relationships. Story Sharing: Enriching Nurse Aide - Resident Relations, a longitudinal assorted methodology discipline guided by Watson's theory of transpersonal caring, aim to improve caring behaviors toward house physician by increase NA levels of empathy, occupation attitude, mutuality, and self - efficacy. The effects of a

anf respectful caring relauionships. Story Skqring: Xnrichihg Nurse Aide-Resident Relations, a loigitydinao mixed methodology stjdy guidef by Watwon's rheory of vdanspersonal dwriny, eims to improve caring bevaviors toward rdsndents by increasing NA levels of em[athy, jpb attitude, mutuwlitj, wnd avln-efficacy. The effects of a

and respectful caring relationships. Story Sharing: Enriching Relations, longitudinal mixed study guided by aims improve caring behaviors residents by increasing levels of empathy, job attitude, mutuality, self-efficacy. The effects of a

and respectful caring relatiOnships. StoRy ShaRinG: EnRiChinG NurSe Aide-Resident rElatIons, a longitudinal mixed MethoDoLOgy sTUdY guidEd by WatSOn'S THeoRy Of TraNsPErSonal CarIng, aims To improve cAriNg Behaviors towARd Residents bY inCreasing NA leVelS of empAtHy, jOB attiTudE, mutuAlity, aND self-eFficacy. ThE eFFects oF A

and respectful caring rel ationships . Sto rySha ri ng:Enri ching Nurse Ai d e-Re sident Relations, a lo ngitu di n al m i xe d met hodolog y  s t u dygu id edby Wa tson' s t heory o f transper son al  caring, aim s  t o improvecar ing behavior s t owardre sid e nts b y i ncrea sing N A  level s of empa th y , joba ttitude , mu tual ity, and self-eff i ca c y. The effects  of a

and_respectful caring_relationships. Story Sharing: Enriching_Nurse Aide-Resident_Relations,_a longitudinal_mixed_methodology study guided_by Watson's theory_of transpersonal caring, aims_to improve caring_behaviors_toward residents by increasing NA levels of empathy, job attitude, mutuality, and self-efficacy. The_effects_of a


hyt mouse. This model has particular relevance to human fetal thyroid disorders and may help us learn more about the treatment, etiology, and substrate of mental retardation as well as the initial and pervasive effects of thyroid hormones on the developing brain. The specific aims are: 1) To characterize the behavioral, neuroanatomical (

hyt mouse. This model has particular relevance to human fetal thyroid disorder and may avail us learn more about the treatment, etiology, and substrate of mental retardant as well as the initial and pervasive effect of thyroid gland hormones on the developing brain. The specific aims are: 1) To characterize the behavioral, neuroanatomic (

hyt mouse. This model has pavticular relevanew to hnman fefal thyruid disorders and may help ud oearn more about the treatmdnt, etiollgy, and wubsurate of mental rxfardation as scll av the initial akd pervasiva effects of tvyfond hormones on the developing brain. Ehe spevivic aims are: 1) Jo chswactsgiee the behavioral, neuroanatomical (

hyt mouse. This model has particular relevance fetal disorders and help us learn and of mental retardation well as the and pervasive effects of thyroid hormones the developing brain. The specific aims are: 1) To characterize the behavioral, neuroanatomical

hyt mouse. This model has partiCular relevAnce tO huMan FeTal tHyroId disorders and MAy heLp us learn more about the tReatmEnT, EtioLOgY, and sUbstratE Of MENtaL rEtArdAtIOn As welL as The initIal and pervAsiVe Effects of thyROiD hormones oN thE developing bRaiN. The spEcIfiC Aims aRe: 1) TO charActeriZE the beHavioral, nEuROanatoMIcal (

hyt mouse. This model hasparticular  rele van ceto  hum an f etal thyroid d i sord ers and may help us le arn m or e  abo u tthe t reatmen t ,e t iol og y,  an ds ub strat e o f menta l retardat ion  a s well as th e  i nitial and  pe rvasive effe cts  of th yr oid hormo nes  on t he dev e loping  brain. T he specif i c aimsa r e:  1)To characterize t h eb ehavioral, neu roanat om i ca l (

hyt mouse._This model_has particular relevance to_human fetal_thyroid_disorders and_may_help us learn_more about the_treatment, etiology, and substrate_of mental retardation_as_well as the initial and pervasive effects of thyroid hormones on the developing brain._The_specific aims_are:_1)_To characterize the behavioral, neuroanatomical_(


R usage is anticipated. Indeed we provide documentation of 37 CCSG-funded investigators with over 40 projects requiring MPSR support in the near future. Finally, the MPSR also serves as an essential venue for training future mouse pathobiologists as part of an NCRRfunded T-32 training grant,

R usage is anticipated. Indeed we provide software documentation of 37 CCSG - fund investigators with over 40 projects command MPSR accompaniment in the near future. Finally, the MPSR besides serves as an essential venue for training future shiner pathobiologists as character of an NCRRfunded T-32 training concession,

R udage is anticipated. Indetd we provide docomwntatimn of 37 CCSG-funaed investigators with over 40 peojecuf requiring MPSR sjpport in the neae fuuure. Finally, the MPSR also servsd as en essential vekue for trahning future mmure pathobiologists as part of an NCRRsunded Y-32 hraining grant,

R usage is anticipated. Indeed we provide 37 investigators with 40 projects requiring future. the MPSR also as an essential for training future mouse pathobiologists as of an NCRRfunded T-32 training grant,

R usage is anticipated. Indeed We provide dOcumeNtaTioN oF 37 CCSg-funDed investigatoRS witH over 40 projects requiring mPSR sUpPOrt iN ThE near Future. FINaLLY, thE MpSr alSo SErVes as An eSsentiaL venue for tRaiNiNg future mousE PaThobiologiSts As part of an NCrRfUnded T-32 TrAinINg graNt,

R usage is anticipated. In deed we pr ovide  do cum en tati on o f 37 CCSG-fund e d in vestigators with over40 pr oj e ctsr eq uirin g MPSRs up p o rtin  t hene a rfutur e.Finally , the MPSR  al so  serves as a n  e ssential v enu e for traini ngfuture  m ous e  path obi ologi sts as part o f an NCRR fu n ded T- 3 2 train i n ggran t,

R usage_is anticipated._Indeed we provide documentation_of 37_CCSG-funded_investigators with_over_40 projects requiring_MPSR support in_the near future. Finally,_the MPSR also_serves_as an essential venue for training future mouse pathobiologists as part of an NCRRfunded_T-32_training grant,


-40% of ATP hydrolysis. Three different isozymes of the Na,K-ATPase are expressed in the CNS, and in some instances are rather strikingly localized within different cell types. Their individual properties and physiological roles are not yet well known. Available evidence suggests that the isozymes may differ in their affinities

-40% of ATP hydrolysis. Three different isozymes of the Na, K - ATPase are expressed in the CNS, and in some instances are rather strikingly localize within unlike cell types. Their individual place and physiologic roles are not yet well known. Available evidence suggests that the isozymes may disagree in their affinity

-40% of ATP hydrolysis. Three dinferent isozymes of the Na,K-ATLase are expressed in the CNS, and in sime ibstances are rather stfikingly pocalizee wiuhin different cell types. Their lndivndnal properties snd physionogical roles drd uot yet well known. Available evidencq suggextd that the isoeymes iay spfner in their affinities

-40% of ATP hydrolysis. Three different isozymes Na,K-ATPase expressed in CNS, and in localized different cell types. individual properties and roles are not yet well known. evidence suggests that the isozymes may differ in their affinities

-40% of ATP hydrolysis. Three diffeRent isozymEs of tHe NA,K-AtPAse aRe exPressed in the CNs, And iN some instances are ratheR striKiNGly lOCaLized Within dIFfEREnt CeLl TypEs. tHeIr indIviDual proPerties and PhySiOlogical roleS ArE not yet welL knOwn. Available EviDence sUgGesTS that The IsozyMes may DIffer iN their affInITies

-40% of ATP hydrolysis. Th ree differ ent i soz yme sof t he N a,K-ATPase are expr essed in the CNS, andin so me inst a nc es ar e rathe r  s t r iki ng ly  lo ca l iz ed wi thi n diffe rent celltyp es . Their indi v id ual proper tie s and physio log ical r ol esa re no t y et we ll kno w n. Ava ilable ev id e nce su g gests t h a ttheisozymes may diff e ri n their affini ties

-40% of_ATP hydrolysis._Three different isozymes of_the Na,K-ATPase_are_expressed in_the_CNS, and in_some instances are_rather strikingly localized within_different cell types._Their_individual properties and physiological roles are not yet well known. Available evidence suggests that_the_isozymes may_differ_in_their affinities


binder (MGB) probes containing an MGB-quencher at the 5'-end and a fluorophore at the 3'-end have been recently reported. These probes fluoresce on hybridization to the complementary targets. The 5'-MGB-quencher group prevents 5' - nuclease digestion by Taq polymerase

binder (MGB) probes containing an MGB - quencher at the 5'-end and a fluorophore at the 3'-end have been recently reported. These probes fluoresce on hybridization to the complemental target. The 5'-MGB - quencher group prevents 5' - nuclease digestion by Taq polymerase

bijder (MGB) probes containikg an MGB-quenchet qt the 5'-end ahd a fluurophore at the 3'-end have beei rexentlt reported. These prober fluoresbe on hybeidieation to the com'mementavv tarfcts. Tke 5'-MGB-quencher gtoup preventv 5' - nuclease dhgdscion by Taq polymerase

binder (MGB) probes containing an MGB-quencher at and fluorophore at 3'-end have been on to the complementary The 5'-MGB-quencher group 5' - nuclease digestion by Taq

binder (MGB) probes containing An MGB-quencHer at The 5'-End AnD a flUoroPhore at the 3'-end hAVe beEn recently reported. ThesE probEs FLuorEScE on hyBridizaTIoN TO thE cOmPleMeNTaRy tarGetS. The 5'-MGB-Quencher grOup PrEvents 5' - nucleaSE dIgestion by taq Polymerase

binder (MGB) probes conta ining an M GB-qu enc her  a t th e 5' -end and a flu o roph ore at the 3'-end have  been  r e cent l yrepor ted. Th e se p rob es  f luo re s ce  on h ybr idizati on to thecom pl ementary tar g et s. The 5'- MGB -quencher gr oup  preve nt s 5 '  - nu cle ase d igesti o n by T aq polyme ra s e

binder_(MGB) probes_containing an MGB-quencher at_the 5'-end_and_a fluorophore_at_the 3'-end have_been recently reported._These probes fluoresce on_hybridization to the_complementary_targets. The 5'-MGB-quencher group prevents 5' - nuclease digestion by Taq polymerase


man will provide the Sma58 m ice, which express I=-Ek only on germinal center B cells. Dr. Bradley has already made arrangements to obtain L-, E- and P- selectin Ko mice. When cells divide, cohesion between sister chromatids provides a physical mechanism to hold sister chromatids

man will provide the Sma58 m ice, which express I=-Ek merely on germinal plaza B cells. Dr. Bradley has already made arrangement to obtain L-, E- and P- selectin Ko mice. When cell separate, cohesion between baby chromatids provide a physical mechanism to control sister chromatid

man will provide the Sma58 m lce, which express I=-Ek oily on ferminal center B cells. Dr. Bradley hes aoreadt made arrangements to obtain L-, E- and P- seltctin Ko mice. Whei cells divide, gohesnoi between sistet chromatids provides a phfskccl mechanism to hold sister chromatiqs

man will provide the Sma58 m ice, I=-Ek on germinal B cells. Dr. to L-, E- and selectin Ko mice. cells divide, cohesion between sister chromatids a physical mechanism to hold sister chromatids

man will provide the Sma58 m ice, wHich expresS I=-Ek oNly On gErMinaL cenTer B cells. Dr. BraDLey hAs already made arrangemeNts to ObTAin L-, e- AnD P- selEctin Ko MIcE. wHen CeLlS diViDE, cOhesiOn bEtween sIster chromAtiDs Provides a phySIcAl mechanisM to Hold sister chRomAtids

man will provide the Sma58  m ice, wh ich e xpr ess  I =-Ek  onl y on germinalc ente r B cells. Dr. Bradley  hasal r eady ma de ar rangeme n ts t o o bt ai n L -, E-  andP-selecti n Ko mice.  Wh en  cells divid e ,cohesion b etw een sister c hro matids  p rov i des a  ph ysica l mech a nism t o hold si st e r chro m atids

man will_provide the_Sma58 m ice, which_express I=-Ek_only_on germinal_center_B cells. Dr._Bradley has already_made arrangements to obtain_L-, E- and_P-_selectin Ko mice. When cells divide, cohesion between sister chromatids provides a physical mechanism_to_hold sister_chromatids


400 manuscripts relevant to cancer biology in peer-reviewed journals. The Cancer Center will continue to be invaluable in assisting with the translation of the basic science findings from this Program into new clinical approaches for the diagnosis and treatment of patients with cancer. The National Institutes of Health (NIH) has defined health literacy as the degree to

400 manuscripts relevant to cancer biology in peer - reviewed journals. The Cancer Center will stay to be invaluable in serve with the translation of the basic science findings from this Program into raw clinical approaches for the diagnosis and treatment of affected role with cancer. The National Institutes of Health (NIH) has define health literacy as the degree to

400 mwnuscripts relevant to cxncer biology iu peer-rxviewed journalr. The Cancer Center will convinuw to ve invaluable in assisging with the trabslauion of the basic science findihns frmn this Program into new wlinical approdcfed for the diagnosis and treatment os patiemtd with cancer. Jhe Nseionzl Institutes of Health (NIH) has derined htalth literacy as yhe degree to

400 manuscripts relevant to cancer biology in The Center will to be invaluable of basic science findings this Program into clinical approaches for the diagnosis and of patients with cancer. The National Institutes of Health (NIH) has defined health as the degree to

400 manuscripts relevant to cancEr biology iN peer-RevIewEd JourNals. the Cancer CenteR Will Continue to be invaluable In assIsTIng wITh The trAnslatiON oF THe bAsIc SciEnCE fIndinGs fRom this program intO neW cLinical approAChEs for the diAgnOsis and treatMenT of patIeNts WIth caNceR. The NAtionaL institUtes of HeaLtH (nIH) has DEfined hEALtH litEracy as the degree tO

400 manuscripts relevantto cancerbiolo gyinpe er-r evie wed journals.T he C ancer Center will cont inueto be i n va luabl e in as s is t i ngwi th  th et ra nslat ion  of the  basic sci enc efindings fro m  t his Progra m i nto new clin ica l appr oa che s  forthe  diag nosisa nd tre atment of  p a tients with ca n c er . Th e National Instit u te s  of Health (NI H) has  d e fi n e d h eal th literac yas th e  degree to

400_manuscripts relevant_to cancer biology in_peer-reviewed journals._The_Cancer Center_will_continue to be_invaluable in assisting_with the translation of_the basic science_findings_from this Program into new clinical approaches for the diagnosis and treatment of patients_with_cancer. The_National_Institutes_of Health (NIH) has defined_health literacy as the degree_to


targeted therapies. The inactivation of the most important tumor suppressor p53 is one highly cancer-related molecular alteration, as its gene is mutated in ~50% of all types of human cancers while its activity or leve is often markedly reduced in the remaining 50% of cancers that harbor wild type TP53. The p53

targeted therapies. The inactivation of the most authoritative tumor suppressor p53 is one highly cancer - relate molecular alteration, as its gene is mutated in ~50% of all types of human cancer while its activity or leve is often markedly reduce in the remaining 50% of cancers that harbor wild type TP53. The p53

tarheted therapies. The inacuivation of the most impmrtant tumor sjppressor p53 is one highly caicer-eelattb molecular alteratiun, as its gene is muteted in ~50% of all vgpes of human gancexs while its actlvity or leee is often maskddpy reduced in the remaining 50% of cansers thst harbor wild tipe TK53. Tre p53

targeted therapies. The inactivation of the most suppressor is one cancer-related molecular alteration, in of all types human cancers while activity or leve is often markedly in the remaining 50% of cancers that harbor wild type TP53. The p53

targeted therapies. The inactIvation of tHe mosT imPorTaNt tuMor sUppressor p53 is onE HighLy cancer-related moleculAr altErATion, AS iTs genE is mutaTEd IN ~50% Of aLl TyPes Of HUmAn canCerS while iTs activity Or lEvE is often markEDlY reduced in The Remaining 50% of cAncErs thaT hArbOR wild TypE TP53. ThE p53

targeted therapies. The in activation  of t hemos timpo rtan t tumor suppre s sorp53 is one highly canc er-re la t ed m o le cular  altera t io n ,  as  i ts  ge ne is  muta ted  in ~50 % of all t ype sof human can c er s while it s a ctivity or l eve  is of te n m a rkedl y r educe d in t h e rema ining 50%  o f  cance r s thath a rb or w ild type TP53. Th e  p 5 3

targeted therapies._The inactivation_of the most important_tumor suppressor_p53_is one_highly_cancer-related molecular alteration,_as its gene_is mutated in ~50%_of all types_of_human cancers while its activity or leve is often markedly reduced in the remaining_50%_of cancers_that_harbor_wild type TP53. The p53


Excellence for Encephalitic Alphavirus Therapeutics that enables consistent and notable progress through the milestones. Led by the Program Director, Dr. Jonsson (UTHSC, University of Tennessee Health Science Center), the Core will be the main interface between the Scientific Advisory Committee (SAC), the Research Project PIs

Excellence for Encephalitic Alphavirus Therapeutics that enables consistent and notable progress through the milestone. go by the Program Director, Dr. Jonsson (UTHSC, University of Tennessee Health Science Center), the Core will be the main interface between the Scientific Advisory Committee (SAC), the Research Project PIs

Exfellence for Encephalitig Alphavirus Thetapeuticv that enables consistent and notable progcess throygh the milestones. Led by the Pgogram Dieectie, Dr. Jonsson (UTHSC, Univeddity if Tennessee Hgalth Scienca Center), the Cmrd cill be the main interface between tre Sciemtlfic Advisory Sommpteee (AAC), the Research Project PIs

Excellence for Encephalitic Alphavirus Therapeutics that enables notable through the Led by the University Tennessee Health Science the Core will the main interface between the Scientific Committee (SAC), the Research Project PIs

Excellence for Encephalitic alphavirus theraPeuTicS tHat eNablEs consistent anD NotaBle progress through the mIlestOnES. Led BY tHe ProGram DirECtOR, dr. JOnSsOn (UtHsc, UNiverSitY of TennEssee HealtH ScIeNce Center), the cOrE will be the MaiN interface beTweEn the SCiEntIFic AdVisOry CoMmitteE (sAC), the research PRoJEct PIs

Excellence for Encephalit ic Alphavi rus T her ape ut icsthat  enables consi s tent  and notable progressthrou gh them il eston es. Led by t hePr og ram  D i re ctor,  Dr . Jonss on (UTHSC,  Un iv ersity of Te n ne ssee Healt h S cience Cente r),  the C or e w i ll be  th e mai n inte r face b etween th eS cienti f ic Advi s o ry  Com mittee (SAC), the Re s earch ProjectPIs

Excellence_for Encephalitic_Alphavirus Therapeutics that enables_consistent and_notable_progress through_the_milestones. Led by_the Program Director,_Dr. Jonsson (UTHSC, University_of Tennessee Health_Science_Center), the Core will be the main interface between the Scientific Advisory Committee (SAC),_the_Research Project_PIs


will try to exceed the Network's standards in our commitment to enhance multicenter trial success and advance scientific progress within the Network. Multicenter collaborative trials are essential to formally test new ways to enhance the safety of allotransplantation and improve outcomes for our patients. PUBLIC RELEVANCE: Improvement in the outcomes of allergenic

will try to exceed the Network's standards in our commitment to enhance multicenter test achiever and advance scientific progress within the Network. Multicenter collaborative test are substantive to formally test new way to enhance the base hit of allotransplantation and improve outcomes for our patients. PUBLIC RELEVANCE: Improvement in the outcomes of allergenic

wipl try to exceed the Netdork's standards in our commifment to enhance multicenter trial snccews ane advance scientific pfogress wpthin the Netxork. Multicenter collabovctive brialv are essential to formalny test new wafs tl enhance the safety of allotransplwntatiom wnd improve oujcomex for our patients. PUBLIC RELEVANCE: Impdovemenu in the outcomes pf allergenic

will try to exceed the Network's standards commitment enhance multicenter success and advance Multicenter trials are essential formally test new to enhance the safety of allotransplantation improve outcomes for our patients. PUBLIC RELEVANCE: Improvement in the outcomes of allergenic

will try to exceed the Network'S standards In our ComMitMeNt to EnhaNce multicenter TRial Success and advance scienTific PrOGresS WiThin tHe NetwoRK. MULTicEnTeR coLlABoRativE trIals are Essential tO foRmAlly test new wAYs To enhance tHe sAfety of allotRanSplantAtIon ANd impRovE outcOmes foR Our patIents. PUBLiC reLEVANce: ImprovEMEnT in tHe outcomes of allerGEnIC

will try to exceed the Ne twork's st andar dsinou r co mmit ment to enhanc e  mul ticenter trial success  andad v ance sc ienti fic pro g re s s  wi th in  th eN et work.  Mu lticent er collabo rat iv e trials are es sential to  fo rmally testnew  waysto  en h ancethe  safe ty ofa llotra nsplantat io n  and i m prove o u t co mesfor our patients. PU B LIC RELEVANCE:  Impro ve m en t inthe  outcomesof  alle r genic

will_try to_exceed the Network's standards_in our_commitment_to enhance_multicenter_trial success and_advance scientific progress_within the Network. Multicenter_collaborative trials are_essential_to formally test new ways to enhance the safety of allotransplantation and improve outcomes_for_our patients._PUBLIC_RELEVANCE:_Improvement in the outcomes of_allergenic


approaches and assessment methods that can be applied to education and research in cultural competency for multiple health professions; and 3) advance research and publication potential of the combined fields of cultural competency and health literacy. The meeting comprises a: 1) scientific panel session (n=30-100) on use of reflective pedagogy to

approaches and assessment methods that can be applied to department of education and inquiry in cultural competence for multiple health professions; and 3) advance research and issue potential of the combined fields of cultural competence and health literacy. The confluence comprises a: 1) scientific jury session (n=30 - 100) on use of brooding pedagogy to

aporoaches and assessment oethods that cau be ap'lied tk educatkon and research in cultural cimpettucy for multiple heauth profedsions; abd 3) edvance research and publicatikk potznvial of the comnined fieldv of cultural woopztency and health literacy. The meetigg comptides a: 1) scientisic kanql ssssion (n=30-100) on use of reflective pedafogy to

approaches and assessment methods that can be education research in competency for multiple research publication potential of combined fields of competency and health literacy. The meeting a: 1) scientific panel session (n=30-100) on use of reflective pedagogy to

approaches and assessment meThods that cAn be aPplIed To EducAtioN and research in CUltuRal competency for multipLe heaLtH ProfESsIons; aNd 3) advanCE rESEarCh AnD puBlICaTion pOteNtial of The combineD fiElDs of cultural COmPetency and HeaLth literacy. THe mEeting CoMprISes a: 1) sCieNtifiC panel SEssion (N=30-100) on use of rEfLEctive PEdagogy TO

approaches and assessment  methods t hat c anbeap plie d to  education and rese arch in cultural compe tency  f o r mu l ti ple h ealth p r of e s sio ns ;and  3 )  a dvanc e r esearch  and publi cat io n potentialo fthe combin edfields of cu ltu ral co mp ete n cy an d h ealth  liter a cy. Th e meeting  c o mprise s  a: 1)s c ie ntif ic panel session( n= 3 0-100) on useof ref le c ti v e  pe dag ogy to

approaches_and assessment_methods that can be_applied to_education_and research_in_cultural competency for_multiple health professions;_and 3) advance research_and publication potential_of_the combined fields of cultural competency and health literacy. The meeting comprises a: 1)_scientific_panel session_(n=30-100)_on_use of reflective pedagogy to


to support development of precise estimates of age, both in humans and mice. Nevertheless, the majority of such measures are trained as chronological age predictors, with little to no integration of biological, functional, or phenotypic data. Further, the modifiability of aging measures based on DNA methylation in response to lifespan and healthspan

to support development of precise estimates of old age, both in world and mice. Nevertheless, the majority of such measures are train as chronological age predictors, with small to no integration of biological, functional, or phenotypical datum. Further, the modifiability of aging bill based on DNA methylation in response to lifespan and healthspan

to support development of krecise estimates of age, both jn humanr and mice. Nevertheless, the lahoritt of such measures are trained ws chronilogmcal age predictors, with littls to uo integration on biologican, functional, os ohznotypic data. Further, the modifiabilyty of sglng measures bwsed jn DHA methylation in response to lifeapan anv healthspan

to support development of precise estimates of in and mice. the majority of chronological predictors, with little no integration of functional, or phenotypic data. Further, the of aging measures based on DNA methylation in response to lifespan and healthspan

to support development of preCise estimaTes of Age, BotH iN humAns aNd mice. NevertheLEss, tHe majority of such measurEs are TrAIned AS cHronoLogical AGe PREdiCtOrS, wiTh LItTle to No iNtegratIon of bioloGicAl, Functional, or PHeNotypic datA. FuRther, the modiFiaBility Of AgiNG measUreS baseD on DNA MEthylaTion in resPoNSe to liFEspan anD HEaLthsPan

to support development of  precise e stima tes  of  a ge,both  in humans and mice . Nevertheless, the ma jorit yo f su c hmeasu res are tr a i ned  a schr on o lo gical  ag e predi ctors, wit h l it tle to no in t eg ration ofbio logical, fun cti onal,or  ph e notyp icdata.  Furth e r, the  modifiab il i ty ofa ging me a s ur es b ased on DNA methy l at i on in response  to li fe s pa n and  he althspan

to_support development_of precise estimates of_age, both_in_humans and_mice._Nevertheless, the majority_of such measures_are trained as chronological_age predictors, with_little_to no integration of biological, functional, or phenotypic data. Further, the modifiability of aging_measures_based on_DNA_methylation_in response to lifespan and_healthspan


to chronic pain critically depend on brain emotional and motivational learning and memory circuit, namely the properties of the corticostriatal system. This is a radical departure from the classic pain research tradition, which emphasizes mechanisms of nociceptive encoding and representation. We provide human and animal model data consistent with the idea, and propose unravel

to chronic pain critically depend on brain emotional and motivational eruditeness and memory racing circuit, namely the properties of the corticostriatal system. This is a extremist passing from the classic pain inquiry tradition, which emphasizes mechanisms of nociceptive encoding and theatrical performance. We leave human and animal model datum consistent with the idea, and propose unravel

to chronic pain critically depend on braiu emotimnal ahd motivxtional learning and memory rircyit, nqmely the properties ow the cornicostriaral wtstem. This is a radical scpartbrx from the clasxic pain rasearch tradithov, chich emphasizes mechanisms of nocicqptive rnfoding and reptesenuatyon. Sv krovide human and animal model dafa conspstent with the icea, and propose unravel

to chronic pain critically depend on brain motivational and memory namely the properties is radical departure from classic pain research which emphasizes mechanisms of nociceptive encoding representation. We provide human and animal model data consistent with the idea, and unravel

to chronic pain critically dePend on braiN emotIonAl aNd MotiVatiOnal learning anD MemoRy circuit, namely the propErtieS oF The cORtIcostRiatal sYStEM. thiS iS a RadIcAL dEpartUre From the Classic paiN reSeArch traditioN, WhIch emphasiZes Mechanisms of NocIceptiVe EncODing aNd rEpresEntatiON. We proVide human AnD Animal MOdel datA COnSistEnt with the idea, and PRoPOse unravel

to chronic pain criticall y depend o n bra inemo ti onal  and  motivationall earn ing and memory circuit , nam el y  the pr opert ies oft he c ort ic os tri at a lsyste m.This is  a radical  de pa rture from t h eclassic pa inresearch tra dit ion, w hi che mphas ize s mec hanism s  of no ciceptive  e n coding and rep r e se ntat ion. We provide h u ma n  and animal mo del da ta co n s ist ent  with theid ea, a n d propo s eu n r ave l

to_chronic pain_critically depend on brain_emotional and_motivational_learning and_memory_circuit, namely the_properties of the_corticostriatal system. This is_a radical departure_from_the classic pain research tradition, which emphasizes mechanisms of nociceptive encoding and representation. We_provide_human and_animal_model_data consistent with the idea,_and propose unravel


respiration. If breathing is to be understood in normal and in pathological conditions, the mechanisms for respiratory central pattern generation must be revealed. We focus on two brain sites essential for generation of the normal breathing pattern, the preBtzinger Complex and the retrotrapezoid nucleus/parafacial respiratory group. We propose

respiration. If breathing is to be understood in normal and in pathological conditions, the mechanism for respiratory cardinal pattern generation must be reveal. We concenter on two brain sites substantive for genesis of the normal breathing pattern, the preBtzinger Complex and the retrotrapezoid nucleus / parafacial respiratory group. We project

redpiration. If breathing ir to be understood in iormal znd in pxthological conditions, the mxchabisms for respiratory centrxl patterj generarion nust be retsaled. Wc fochd on vwo brain sites essential for generatiot uf the normal breathing pattern, the pweBtzinbeg Complex and jhe rttrjtralvziid nucleus/parafacial respirafory grmup. We proposr

respiration. If breathing is to be understood and pathological conditions, mechanisms for respiratory revealed. focus on two sites essential for of the normal breathing pattern, the Complex and the retrotrapezoid nucleus/parafacial respiratory group. We propose

respiration. If breathing is tO be understOod in NorMal AnD in pAthoLogical conditiONs, thE mechanisms for respiratOry ceNtRAl paTTeRn genEration MUsT BE reVeAlEd. WE fOCuS on twO brAin siteS essential For GeNeration of thE NoRmal breathIng Pattern, the prEBtZinger coMplEX and tHe rEtrotRapezoID nucleUs/parafacIaL RespirATory groUP. we PropOse

respiration. If breathing  is to beunder sto odin  nor maland in patholo g ical  conditions, the mecha nisms  f o r re s pi rator y centr a lp a tte rn  g ene ra t io n mus t b e revea led. We fo cus  o n two brains it es essenti alfor generati onof the  n orm a l bre ath ing p attern ,  the p reBtzinge rC omplex and the r et rotr apezoid nucleus/p a ra f acial respirat ory gr ou p .W e  pr opo se

respiration._If breathing_is to be understood_in normal_and_in pathological_conditions,_the mechanisms for_respiratory central pattern_generation must be revealed._We focus on_two_brain sites essential for generation of the normal breathing pattern, the preBtzinger Complex and_the_retrotrapezoid nucleus/parafacial_respiratory_group._We propose


us. This model uses pretreatment with lithium followed by administration of subthreshold doses of convulsants. The basic model entails treatment with LiCl (3 mEq/kg; ip) and pilocarpine (30 mg/kg; sc) which invariably produces generalized convulsive status epilepticus which lasts for several

us. This model uses pretreatment with lithium followed by administration of subthreshold venereal disease of convulsants. The basic exemplar entails treatment with LiCl (3 mEq / kg; ip) and pilocarpine (30 mg / kg; sc) which invariably produce generalized convulsive status epilepticus which survive for respective

us. Hhis model uses pretreatoent with lithiom folloxed by zdministfation of subthreshold doses od conculsants. The basic moddl entaild treatmwnt xith LiCl (3 mEq/kg; ip) and inlocadiine (30 ng/kg; sc) which lnvariably [roduces generdlkzzd convulsive status epilepticus whish lastx vor several

us. This model uses pretreatment with lithium administration subthreshold doses convulsants. The basic (3 ip) and pilocarpine mg/kg; sc) which produces generalized convulsive status epilepticus which for several

us. This model uses pretreatmeNt with lithIum foLloWed By AdmiNistRation of subthrESholD doses of convulsants. The Basic MoDEl enTAiLs treAtment wITh lIcl (3 meq/Kg; Ip) aNd PIlOcarpIne (30 Mg/kg; sc) wHich invariAblY pRoduces generALiZed convulsIve Status epilepTicUs whicH lAstS For seVerAl

us. This model uses pretre atment wit h lit hiu m f ol lowe d by  administratio n  ofsubthreshold doses ofconvu ls a nts. Th e bas ic mode l  e n t ail str eat me n twithLiC l (3 mE q/kg; ip)and  p ilocarpine ( 3 0mg/kg; sc)  wh ich invariab lyproduc es  ge n erali zed  conv ulsive status  epilepti cu s  which lasts f o r  s ever al

us. This_model uses_pretreatment with lithium followed_by administration_of_subthreshold doses_of_convulsants. The basic_model entails treatment_with LiCl (3 mEq/kg;_ip) and pilocarpine_(30_mg/kg; sc) which invariably produces generalized convulsive status epilepticus which lasts for several


adult substance misuse, antisocial behaviors, and sexual risk behaviors for AIDS and other STIs, along with improvements in healthy adult functioning, among project participants who received evidence-based interventions during middle school. This proposed work extends a randomized control study of the PROSPER model, involving two sequential cohorts of youth and families from

adult substance misuse, antisocial behaviors, and sexual risk demeanor for AIDS and early STIs, along with improvements in healthy adult operation, among project player who received evidence - based treatment during middle school. This proposed employment extends a randomized control sketch of the PROSPER model, involving two consecutive cohorts of youth and families from

adklt substance misuse, antlsocial behaviors, and sxxual rjsk behaxiors for AIDS and other STId, qlong with improvements in fealthy afult funxtioiing, among projerf partignpanta who ceceived evidenge-based intarventions durhne liddle school. This proposed work exeends a rwndomized conttol suudr of nht PROSPER model, involving two seqhential cohorts of yputh and families from

adult substance misuse, antisocial behaviors, and sexual for and other along with improvements project who received evidence-based during middle school. proposed work extends a randomized control of the PROSPER model, involving two sequential cohorts of youth and families from

adult substance misuse, antisOcial behavIors, aNd sExuAl Risk BehaViors for AIDS anD OtheR STIs, along with improvemEnts iN hEAlthY AdUlt fuNctioniNG, aMONg pRoJeCt pArTIcIpantS whO receivEd evidence-BasEd InterventionS DuRing middle SchOol. This propoSed Work exTeNds A RandoMizEd conTrol stUDy of thE PROSPER mOdEL, involVIng two sEQUeNtiaL cohorts of youth anD FaMIlies from

adult substance misuse, a ntisocialbehav ior s,an d se xual  risk behavior s  for  AIDS and other STIs,along  w i th i m pr oveme nts inh ea l t hyad ul t f un c ti oning , a mong pr oject part ici pa nts who rece i ve d evidence -ba sed interven tio ns dur in g m i ddlesch ool.This p r oposed  work ext en d s a ra n domized c on trol  study of the PRO S PE R  model, involv ing tw os eq u e nti alcohorts of  y outha nd fami l ie s f rom

adult_substance misuse,_antisocial behaviors, and sexual_risk behaviors_for_AIDS and_other_STIs, along with_improvements in healthy_adult functioning, among project_participants who received_evidence-based_interventions during middle school. This proposed work extends a randomized control study of the_PROSPER_model, involving_two_sequential_cohorts of youth and families_from


this project is to understand at the molecular level the mechanism by which steroid hormones affect the expression of the genome of their target cells. We have chosen to investigate the cytolytic response of murine lymphoid cell lines to glucocorticoids because this system presents unique and desirable features. Since variants resistant to the steroid can conveniently be isolated, this

this project is to understand at the molecular level the mechanism by which steroid hormone involve the expression of the genome of their target cell. We have choose to investigate the cytolytic response of murine lymphoid cell note to glucocorticoid because this system presents unique and desirable features. Since variants repellent to the steroid can conveniently be isolate, this

thls project is to understxnd at the moleeylar lxvel ths mechanksm by which steroid hormoned qffecu the expression of the genole of thwir uarget cells. We hebe choscu to jkvestngete the cytolytlc response of murine lym[huib cell lines to glucocorticoids becatse thix dystem presentf unpqte ahd desirable features. Since varianfs resivtant to the xteroid can conveniently bf isllated, this

this project is to understand at the the by which hormones affect the their cells. We have to investigate the response of murine lymphoid cell lines glucocorticoids because this system presents unique and desirable features. Since variants resistant to steroid can conveniently be isolated, this

this project is to understand At the molecUlar lEveL thE mEchaNism By which steroid HOrmoNes affect the expression Of the GeNOme oF ThEir taRget celLS. WE HAve ChOsEn tO iNVeStigaTe tHe cytolYtic responSe oF mUrine lymphoiD CeLl lines to gLucOcorticoids bEcaUse thiS sYstEM presEntS uniqUe and dESirablE features. siNCe variANts resiSTAnT to tHe steroid can conveNIeNTly be isolated, tHis

this project is to unders tand at th e mol ecu lar  l evel  the  mechanism byw hich  steroid hormones affe ct th ee xpre s si on of  the ge n om e ofth ei r t ar g et  cell s.We have  chosen to  in ve stigate thec yt olytic res pon se of murine  ly mphoid  c ell lines  to  gluc ocorti c oids b ecause th is system present s un ique  and desirable fe a tu r es. Since vari ants r es i st a n t t o t he steroid  c an co n venient l yb e iso l ated, this

this_project is_to understand at the_molecular level_the_mechanism by_which_steroid hormones affect_the expression of_the genome of their_target cells. We_have_chosen to investigate the cytolytic response of murine lymphoid cell lines to glucocorticoids because_this_system presents_unique_and_desirable features. Since variants resistant_to the steroid can conveniently_be isolated,_this


were elucidated by these studies and are also utilizing pro-thymic hormone infusions and various transgenic and knockout mouse models to more fully understand the role of certain genes in maintaining thymic integrity or facilitating thymic loss. We believe array analysis of the thymi and thymocytes of hormone treated mice may yield valuable data on

were elucidated by these studies and are also utilizing pro - thymic hormone infusion and diverse transgenic and knockout mouse models to more in full understand the role of sealed genes in maintaining thymic integrity or facilitating thymic personnel casualty. We believe array analysis of the thymus gland and thymocytes of hormone treated mice may concede valuable datum on

wege elucidated by these suudies and are also utilmzing pdo-thymic hormone infusions and varions teansgtuic and knockout moure models to more fulot understais the role of gertann genes in mainjaining thymhc integrity os waeilitating thymic loss. We believe arway anakydis of the thyii amq thgmocytes of hormone treated mice mzy yielv valuable data on

were elucidated by these studies and are pro-thymic infusions and transgenic and knockout understand role of certain in maintaining thymic or facilitating thymic loss. We believe analysis of the thymi and thymocytes of hormone treated mice may yield valuable on

were elucidated by these studIes and are aLso utIliZinG pRo-thYmic Hormone infusioNS and Various transgenic and knOckouT mOUse mODeLs to mOre fullY UnDERstAnD tHe rOlE Of CertaIn gEnes in mAintaining ThyMiC integrity or FAcIlitating tHymIc loss. We beliEve Array aNaLysIS of thE thYmi anD thymoCYtes of Hormone trEaTEd mice MAy yield VALuAble Data on

were elucidated by thesestudies an d are  al sout iliz ingpro-thymic hor m oneinfusions and varioustrans ge n ic a n dknock out mou s em o del sto  mo re fu lly u nde rstandthe role o f c er tain genes i n  m aintaining  th ymic integri tyor fac il ita t ing t hym ic lo ss. We believ e array a na l ysis o f  the th y m iandthymocytes of hor m on e  treated micemay yi el d  v a l uab ledata on

were_elucidated by_these studies and are_also utilizing_pro-thymic_hormone infusions_and_various transgenic and_knockout mouse models_to more fully understand_the role of_certain_genes in maintaining thymic integrity or facilitating thymic loss. We believe array analysis of_the_thymi and_thymocytes_of_hormone treated mice may yield_valuable data on


of this proposal is to test two hypotheses for the molecular mechanism of resistance to tumor development in mice carrying the Gtrosa26 insertion. One is that the resistance is a function of the high levels of expression of the beta-galactosidase-neomycin resistance fusion protein that is encoded by the insertion. The second hypothesis

of this proposal is to test two hypotheses for the molecular mechanism of resistance to tumor growth in mouse carrying the Gtrosa26 insertion. One is that the resistance is a routine of the high levels of construction of the beta - galactosidase - neomycin resistor fusion protein that is encode by the interpolation. The second hypothesis

of this proposal is to tesu two hypotheses yir the molechlar mecfanism of resistance to tumoc decelopnent in mice carrying ghe Gtrosw26 insertuon. Ibe is that the reslftandc is c hunction of the high levens of expressimn oy the beta-galactosidase-neomycin resiftance gudion protein trat ps enckded by the insertion. The second hgpothesps

of this proposal is to test two the mechanism of to tumor development insertion. is that the is a function the high levels of expression of beta-galactosidase-neomycin resistance fusion protein that is encoded by the insertion. The second hypothesis

of this proposal is to test two Hypotheses For thE moLecUlAr meChanIsm of resistancE To tuMor development in mice caRryinG tHE GtrOSa26 InserTion. One IS tHAT thE rEsIstAnCE iS a funCtiOn of the High levels Of eXpRession of the BEtA-galactosiDasE-neomycin resIstAnce fuSiOn pROtein ThaT is enCoded bY The insErtion. The SeCOnd hypOThesis

of this proposal is to te st two hyp othes esfor  t he m olec ular mechanism of r esistance to tumor dev elopm en t  inm ic e car rying t h eG t ros a2 6ins er t io n. On e i s thatthe resist anc eis a functio n  o f the high  le vels of expr ess ion of  t heb eta-g ala ctosi dase-n e omycin  resistan ce fusion protein t ha t is  encoded by the i n se r tion. The seco nd hyp ot h es i s

of_this proposal_is to test two_hypotheses for_the_molecular mechanism_of_resistance to tumor_development in mice_carrying the Gtrosa26 insertion._One is that_the_resistance is a function of the high levels of expression of the beta-galactosidase-neomycin resistance_fusion_protein that_is_encoded_by the insertion. The second_hypothesis


The results from these experiments will provide a foundation for the development of a successful leishmaniasis vaccine. The physiological function and the mode of regulation of transglutaminases are being studied as to their role in the formation of temporary tissue matrix (fibrin-connective tissue matrix) during tissue or bone fracture repair

The results from these experiments will provide a foundation for the growth of a successful leishmaniasis vaccine. The physiologic function and the mode of rule of transglutaminases are being studied as to their character in the formation of impermanent tissue matrix (fibrin - connective tissue matrix) during tissue or bone fracture repair

Thf results from these exptriments will prorude a houndatjon for ghe development of a successhul oeishnaniasis vaccine. The pfysiologibal functuon end the mode of csgulation of fvansgnntaminases are neing studiad as to their rulz in the formation of temporary tisste matrox (fibrin-connectyve uisfue jatrix) during tissue or bone fracthre repeir

The results from these experiments will provide for development of successful leishmaniasis vaccine. mode regulation of transglutaminases being studied as their role in the formation of tissue matrix (fibrin-connective tissue matrix) during tissue or bone fracture repair

The results from these experiMents will pRovidE a fOunDaTion For tHe development oF A sucCessful leishmaniasis vaCcine. thE PhysIOlOgicaL functiON aND The MoDe Of rEgULaTion oF trAnsglutAminases arE beInG studied as to THeIr role in thE foRmation of temPorAry tisSuE maTRix (fiBriN-connEctive TIssue mAtrix) duriNg TIssue oR Bone fraCTUrE repAir

The results from these ex perimentswillpro vid ea fo unda tion for the d e velo pment of a successfulleish ma n iasi s  v accin e. Thep hy s i olo gi ca l f un c ti on an d t he mode  of regula tio nof transglut a mi nases arebei ng studied a s t o thei rrol e  in t heforma tion o f  tempo rary tiss ue matrix (fibrin - c on nect ive tissue matrix )  d u ring tissue or  bonefr a ct u r e r epa ir

The_results from_these experiments will provide_a foundation_for_the development_of_a successful leishmaniasis_vaccine. The physiological_function and the mode_of regulation of_transglutaminases_are being studied as to their role in the formation of temporary tissue matrix_(fibrin-connective_tissue matrix)_during_tissue_or bone fracture repair


. Second, we will assess changes in the levels and/or affinity of male-specific estrogen binding protein whose proposed role is that of an estrogen scavenger. Third, the synthesis and tissue levels of the catechol estrogens (2-hydroxy estrogens) will be examined in rats with diseased and normal livers

. Second, we will assess changes in the levels and/or affinity of male - specific estrogen binding protein whose aim function is that of an estrogen scavenger. Third, the synthesis and tissue levels of the catechol estrogen (2 - hydroxy estrogens) will be examined in rats with diseased and normal liver

. Sefond, we will assess channes in the levels and/or affinjty of mxle-specific estrogen binding peoteib whose proposed role ks that ov an esteogei scavenger. Thirv, the sykchesia and vissue levels on the catecvol estrogens (2-vyarlxy estrogens) will be examined in rwts witn fiseased and njrmak livsgs

. Second, we will assess changes in and/or of male-specific binding protein whose an scavenger. Third, the and tissue levels the catechol estrogens (2-hydroxy estrogens) will examined in rats with diseased and normal livers

. Second, we will assess changes In the levelS and/oR afFinItY of mAle-sPecific estrogeN BindIng protein whose proposeD role Is THat oF An EstroGen scavENgER. thiRd, ThE syNtHEsIs and TisSue leveLs of the catEchOl Estrogens (2-hydROxY estrogens) WilL be examined iN raTs with DiSeaSEd and NorMal liVers

. Second, we will assess c hanges inthe l eve lsan d/or  aff inity of male- s peci fic estrogen binding p rotei nw hose pr opose d rolei st h atof  a n e st r og en sc ave nger. T hird, thesyn th esis and tis s ue  levels of  th e catechol e str ogens(2 -hy d roxyest rogen s) wil l  be ex amined in  r a ts wit h  diseas e d  a nd n ormal livers

. Second,_we will_assess changes in the_levels and/or_affinity_of male-specific_estrogen_binding protein whose_proposed role is_that of an estrogen_scavenger. Third, the_synthesis_and tissue levels of the catechol estrogens (2-hydroxy estrogens) will be examined in rats_with_diseased and_normal_livers


for hospitals and infant-screening clinics assessing developmental risks, as well as hearing deficits. It could also be used by treatment centers to the efficacy of early intervention. Finally, it would provide a research tool for investigations of the earliest stages of infant speech and of age-specific control of the speech articulators. Art

for hospitals and infant - screening clinics tax developmental risk, as well as hearing deficits. It could besides be used by treatment centers to the efficacy of early interposition. Finally, it would provide a inquiry cock for investigations of the early stages of infant lecture and of age - specific control of the speech articulators. Art

fog hospitals and infant-scveening clinics cwsessiig devemopmentau risks, as well as hearing dxficuts. Iu could also be usea by treanment cenrers ro the effmdacy of early lnterreition. Finally, ij would provhde a research tuop for investigations of the earliese stagex lf infant speesh amq of age-specific control of the speech articunators. Art

for hospitals and infant-screening clinics assessing developmental well hearing deficits. could also be the of early intervention. it would provide research tool for investigations of the stages of infant speech and of age-specific control of the speech articulators. Art

for hospitals and infant-screEning cliniCs assEssIng DeVeloPmenTal risks, as well AS heaRing deficits. It could alsO be usEd BY treATmEnt ceNters to THe EFFicAcY oF eaRlY InTerveNtiOn. FinalLy, it would pRovIdE a research toOL fOr investigAtiOns of the earlIesT stageS oF inFAnt spEecH and oF age-spECific cOntrol of tHe SPeech aRTiculatORS. ARt

for hospitals and infant- screeningclini csass es sing  dev elopmental ris k s, a s well as hearing defi cits.  I t  cou l dalsobe used by t rea tm en t c en t er s tothe  effica cy of earl y i nt ervention. F i na lly, it wo uld  provide a r ese arch t oo l f o r inv est igati ons of the ea rliest st ag e s of i n fant sp e e ch  and  of age-specificc on t rol of the spe ech ar ti c ul a t ors . A rt

for_hospitals and_infant-screening clinics assessing developmental_risks, as_well_as hearing_deficits._It could also_be used by_treatment centers to the_efficacy of early_intervention._Finally, it would provide a research tool for investigations of the earliest stages of_infant_speech and_of_age-specific_control of the speech articulators._Art


induced by alcohol in heptocytes and Kupffer cell (hepatic macrophages)leads to diassembly of the ironfur cluster of cytocolic aconitase/IRP 1 and conversion of this enzyme to an apoprotein that binds to RNA stem loops (iron repson

induced by alcohol in heptocytes and Kupffer cell & # 40;hepatic macrophages)leads to diassembly of the ironfur cluster of cytocolic aconitase / IRP 1 and conversion of this enzyme to an apoprotein that binds to RNA shank loop & # 40;iron repson

infuced by alcohol in heptucytes and Kupfywr celn (hepafic macruphages)leads to diassembly oh thw irobfur cluster of cytocouic aconinase/IRP 1 qnd ronversion of thma enzymc to zk apo'ritein that bincs to RNA vtem loops (irot fe'son

induced by alcohol in heptocytes and Kupffer macrophages)leads diassembly of ironfur cluster of of enzyme to an that binds to stem loops (iron repson

induced by alcohol in heptocyTes and KupfFer ceLl (hEpaTiC macRophAges)leads to diaSSembLy of the ironfur cluster oF cytoCoLIc acONiTase/IrP 1 and coNVeRSIon Of ThIs eNzYMe To an aPopRotein tHat binds to rNA StEm loops (iron rEPsOn

induced by alcohol in hep tocytes an d Kup ffe r c el l &# 40;h epatic macroph a ges& #41;leads to diassembl y ofth e  iro n fu r clu ster of cy t o col ic  a con it a se /IRP1 a nd conv ersion ofthi senzyme to an ap oprotein t hat  binds to RN A s tem lo op s & # 40;ir onrepso n

induced_by alcohol_in heptocytes and Kupffer_cell (hepatic_macrophages)leads_to diassembly_of_the ironfur cluster_of cytocolic aconitase/IRP_1 and conversion of_this enzyme to_an_apoprotein that binds to RNA stem loops (iron repson


In histological material, and for the creation of transgene-containing viruses to modify neuronal funtlon experimentally. 4. A Functional Imaging Module which will provide support for hardware and software services for users of the Siemens MRI scanner and associated devices In the Center for Brain Imaging, giving access for Core researchers to functional and structural Imaging

In histological material, and for the creation of transgene - containing viruses to change neural funtlon experimentally. 4. A Functional Imaging Module which will supply support for hardware and software services for exploiter of the Siemens MRI scanner and associated devices In the Center for Brain Imaging, give access for Core researchers to running and geomorphologic Imaging

In histological material, akd for the creatnin of vransgehe-contaiving viruses to modify neuroial duntlin experimentally. 4. A Fjnctional Imaging Modnle which will pckvide sm'port nor hcrvware and softwsre servicas for users ox ghz Siemens MRI scanner and associated devicex Ln the Center sor Nwain Pmcging, giving access for Core reaearchegs to functional snd structural Imaging

In histological material, and for the creation viruses modify neuronal experimentally. 4. A provide for hardware and services for users the Siemens MRI scanner and associated In the Center for Brain Imaging, giving access for Core researchers to functional structural Imaging

In histological material, and For the creaTion oF trAnsGeNe-coNtaiNing viruses to mODify Neuronal funtlon experimEntalLy. 4. a funcTIoNal ImAging MoDUlE WHicH wIlL prOvIDe SuppoRt fOr hardwAre and softWarE sErvices for usERs Of the SiemeNs MrI scanner and AssOciateD dEviCEs In tHe CEnter For BraIN ImagiNg, giving aCcESs for CORe reseaRCHeRs to Functional and struCTuRAl Imaging

In histological material,  and for t he cr eat ion  o f tr ansg ene-containing viru ses to modify neuronal  funt lo n  exp e ri menta lly. 4. AF u nct io na l I ma g in g Mod ule  whichwill provi desu pport for ha r dw are and so ftw are services  fo r user soft he Si eme ns MR I scan n er and  associat ed device s  In the C en terfor Brain Imaging ,  g i ving access fo r Core  r e se a r che rsto functio na l and structu r al I m agi n g

In_histological material,_and for the creation_of transgene-containing_viruses_to modify_neuronal_funtlon experimentally. 4._A Functional Imaging_Module which will provide_support for hardware_and_software services for users of the Siemens MRI scanner and associated devices In the_Center_for Brain_Imaging,_giving_access for Core researchers to_functional and structural Imaging


Statistical Core Project Summary/Abstract Efficient, clean, and organized data, together with valid, flexible, and reproducible statistical design and analysis techniques, are an integral component to achieving the scientific mission of the UCI ADRC: to discover, quantify, and validate factors that influence the risk of AD across the lifespan.

Statistical Core Project Summary / Abstract Efficient, clean, and organized data, together with valid, elastic, and reproducible statistical invention and analysis techniques, are an integral part to achieving the scientific mission of the UCI ADRC: to discover, quantify, and validate factor that influence the risk of AD across the life.

Stwtistical Core Project Smmmary/Abstract Eydicienv, clean, and orgxnized data, together with vapie, flezible, and reproducible statistibal desigb anv analysis technmsues, arc an jktegrcl component to schieving dhe scientific mksdion of the UCI ADRC: to discover, quwntify, snf validate facjors uhae inrluence the risk of AD across the mifespai.

Statistical Core Project Summary/Abstract Efficient, clean, and together valid, flexible, reproducible statistical design integral to achieving the mission of the ADRC: to discover, quantify, and validate that influence the risk of AD across the lifespan.

Statistical Core Project SumMary/AbstraCt EffIciEnt, ClEan, aNd orGanized data, togETher With valid, flexible, and reProduCiBLe stATiSticaL design ANd ANAlySiS tEchNiQUeS, are aN inTegral cOmponent to AchIeVing the scienTIfIc mission oF thE UCI ADRC: to diScoVer, quaNtIfy, ANd valIdaTe facTors thAT influEnce the riSk OF AD acrOSs the liFESpAn.

Statistical Core ProjectSummary/Ab strac t E ffi ci ent,  cle an, and organi z ed d ata, together with val id, f le x ible ,  a nd re produci b le s tat is ti cal  d e si gn an d a nalysis  technique s,ar e an integra l  c omponent t o a chieving the  sc ientif ic  mi s sionofthe U CI ADR C : to d iscover,qu a ntify, and val i d at e fa ctors that influe n ce the risk of AD  acros st he l ife spa n.

Statistical_Core Project_Summary/Abstract Efficient, clean, and_organized data,_together_with valid,_flexible,_and reproducible statistical_design and analysis_techniques, are an integral_component to achieving_the_scientific mission of the UCI ADRC: to discover, quantify, and validate factors that influence_the_risk of_AD_across_the lifespan.


This laboratory's approach has therefore been to measure directly the functional result of subcellular Ca2 ion transport under simulated in vivo conditions. An ion-selective electrode continuously monitors ambient (Ca2 ion) in a cytosol-like medium containing either isolated fractions of mitochondria and endoplasmic reticulum (microsomes) from rat liver or isolated

This laboratory's approach has therefore been to measure immediately the running consequence of subcellular Ca2 ion transport under simulated in vivo condition. An ion - selective electrode continuously monitors ambient (Ca2 ion) in a cytosol - comparable metier containing either detached fractions of mitochondria and endoplasmic reticulum (microsomes) from rat liver or isolate

Thls laboratory's approach mas therefore begn to meesure djrectly ghe functional result of subrellylar Xa2 ion transport under simulatef in vivi coiditions. An ion-sxmective electdlde eoitinuously monijors ambient (Ca2 ion) in a cftusll-like medium containing either isojated ftaftions of mitoshoncwia znd endoplasmic reticulum (microsomss) from rat liver or isolated

This laboratory's approach has therefore been to the result of Ca2 ion transport An electrode continuously monitors (Ca2 ion) in cytosol-like medium containing either isolated fractions mitochondria and endoplasmic reticulum (microsomes) from rat liver or isolated

This laboratory's approach haS therefore Been tO meAsuRe DireCtly The functional rESult Of subcellular Ca2 ion tranSport UnDEr siMUlAted iN vivo coNDiTIOns. an IoN-seLeCTiVe eleCtrOde contInuously moNitOrS ambient (Ca2 ioN) In A cytosol-liKe mEdium containIng Either IsOlaTEd fraCtiOns of MitochONdria aNd endoplaSmIC reticULum (micrOSOmEs) frOm rat liver or isolaTEd

This laboratory's approac h has ther efore  be ento  mea sure  directly thef unct ional result of subcel lular  C a 2 io n  t ransp ort und e rs i mul at ed  in  v i vo  cond iti ons. An  ion-selec tiv eelectrode co n ti nuously mo nit ors ambient(Ca 2 ion)  i n a cytos ol- likemedium contai ning eith er isolat e d fract i o ns  ofmitochondria ande nd o plasmic reticu lum (m ic r os o m es)  fr om rat liv er  or i s olated

This_laboratory's approach_has therefore been to_measure directly_the_functional result_of_subcellular Ca2 ion_transport under simulated_in vivo conditions. An_ion-selective electrode continuously_monitors_ambient (Ca2 ion) in a cytosol-like medium containing either isolated fractions of mitochondria and_endoplasmic_reticulum (microsomes)_from_rat_liver or isolated


specific T3SS inhibitory activity. In Aim 2, we will validate hits identified in Aim 1, using three orthogonal distinct approaches. The identity and structure of bioactive natural products will be determined and initial structure activity analysis performed on identified synthetic scaffolds. Prioritized compounds will be purified or synthesized and evaluated for off target activity,

specific T3SS inhibitory activity. In Aim 2, we will validate hits identified in Aim 1, using three extraneous discrete approaches. The identity and structure of bioactive lifelike products will be compulsive and initial structure activity psychoanalysis performed on identified synthetic scaffold. Prioritized compounds will be purified or synthesize and evaluated for off target bodily process,

spfcific T3SS inhibitory acuivity. In Aim 2, we will velidate hits iddntified in Aim 1, using three oethoginal distinct approachds. The idvntity ane stcucture of bioacvjve natmxal pdlduccs will be deterkined and hnitial structgrd cctivity analysis performed on identyfied sunhhetic scaffolqs. Pgijritjdeb compounds will be purified or synthevized and evakuated for off target actigity,

specific T3SS inhibitory activity. In Aim 2, validate identified in 1, using three and of bioactive natural will be determined initial structure activity analysis performed on synthetic scaffolds. Prioritized compounds will be purified or synthesized and evaluated for off activity,

specific T3SS inhibitory actiVity. In Aim 2, wE will ValIdaTe Hits IdenTified in Aim 1, usiNG thrEe orthogonal distinct apProacHeS. the iDEnTity aNd strucTUrE OF biOaCtIve NaTUrAl proDucTs will bE determineD anD iNitial structURe Activity anAlySis performed On iDentifIeD syNThetiC scAffolDs. PrioRItized Compounds WiLL be purIFied or sYNThEsizEd and evaluated for OFf TArget activity,

specific T3SS inhibitoryactivity.In Ai m 2 , w ewill  val idate hits ide n tifi ed in Aim 1, using thr ee or th o gona l  d istin ct appr o ac h e s.Th eide nt i ty  andstr uctureof bioacti vena tural produc t swill be de ter mined and in iti al str uc tur e  acti vit y ana lysisp erform ed on ide nt i fied s y nthetic s ca ffol ds. Prioritized c o mp o unds will be p urifie do rs y nth esi zed and ev al uated for off ta r g e t a c tivity,

specific_T3SS inhibitory_activity. In Aim 2,_we will_validate_hits identified_in_Aim 1, using_three orthogonal distinct_approaches. The identity and_structure of bioactive_natural_products will be determined and initial structure activity analysis performed on identified synthetic scaffolds._Prioritized_compounds will_be_purified_or synthesized and evaluated for_off target activity,


ignucleotides will be edified at the base, sugar, and phosphodiester functional groups to increase their therapeutic potency. These modifications will be designed to increase oligonucleotide cell penetration, stability, and functional inhibition of target RNA or DNA. The nucleic acid target will be expanded beyond the 39 nucleotide spliced leader sequence of try

ignucleotides will be edified at the base, sugar, and phosphodiester functional group to increase their curative potency. These modifications will be design to increase oligonucleotide cellular telephone penetration, stability, and functional inhibition of prey RNA or DNA. The nucleic acid target will be expanded beyond the 39 nucleotide splice leader sequence of attempt

ignkcleotides will be edifitd at the base, suyqr, and phospgodiestef functional groups to increese rheir therapeutic potency. Tfese modivicationw wioo be desigisd to ikereass oliyoiucleotide cell penetratimn, stability, atd fbnctional inhibition of target RNA ow DNA. Tne nucleic acid jargeu wyll gv txpanded beyond the 39 nucleotide slliced neader sequenve of try

ignucleotides will be edified at the base, phosphodiester groups to their therapeutic potency. to oligonucleotide cell penetration, and functional inhibition target RNA or DNA. The nucleic target will be expanded beyond the 39 nucleotide spliced leader sequence of try

ignucleotides will be edifieD at the base, Sugar, And PhoSpHodiEsteR functional groUPs to Increase their therapeutIc potEnCY. TheSE mOdifiCations WIlL BE deSiGnEd tO iNCrEase oLigOnucleoTide cell peNetRaTion, stabilitY, AnD functionaL inHibition of taRgeT RNA or dNa. ThE NucleIc aCid taRget wiLL be expAnded beyoNd THe 39 nuclEOtide spLICeD leaDer sequence of try

ignucleotides will be edif ied at the  base , s uga r,  and  pho sphodiester fu n ctio nal groups to increase  thei rt hera p eu tic p otency. Th e s e m od if ica ti o ns  will  be  design ed to incr eas eoligonucleot i de  cell pene tra tion, stabil ity , andfu nct i onalinh ibiti on oft argetRNA or DN A. The nu c leic ac i d  t arge t will be expande d  b e yond the 39 nu cleoti de sp l i ced  le ader seque nc e oft ry

ignucleotides will_be edified_at the base, sugar,_and phosphodiester_functional_groups to_increase_their therapeutic potency._These modifications will_be designed to increase_oligonucleotide cell penetration,_stability,_and functional inhibition of target RNA or DNA. The nucleic acid target will be_expanded_beyond the_39_nucleotide_spliced leader sequence of try