rage and its relationship to serotonin axons and pre-terminals in this region. The second experiment will determine the effects of 5-HT1A and 5-HT2 receptors in the medial hypothalamus upon defensive rage. The third experiment will determine: the role of IL-1beta in the medial hypothalamus upon defensive rage,

rage and its relationship to serotonin axons and pre - terminals in this area. The second experiment will settle the effects of 5 - HT1A and 5 - HT2 receptors in the median hypothalamus upon defensive rage. The third experiment will decide: the role of IL-1beta in the median hypothalamus upon defensive fad,

rahe and its relationship uo serotonin axons and pce-termihals in ghis region. The second expermmenr wilo determine the effectr of 5-HT1A wnd 5-HT2 rwcepuors in the medial hypothalamus mpon behensive rage. Thg third expesiment will dedefmnne: the role of IL-1beta in the medial hypothslwmus upon defegsivt rwge,

rage and its relationship to serotonin axons in region. The experiment will determine 5-HT2 in the medial upon defensive rage. third experiment will determine: the role IL-1beta in the medial hypothalamus upon defensive rage,

rage and its relationship to sErotonin axOns anD prE-teRmInalS in tHis region. The seCOnd eXperiment will determine The efFeCTs of 5-ht1A And 5-HT2 ReceptoRS iN THe mEdIaL hyPoTHaLamus UpoN defensIve rage. The ThiRd Experiment wiLL dEtermine: thE roLe of IL-1beta in The Medial HyPotHAlamuS upOn defEnsive RAge,

rage and its relationship  to seroto nin a xon s a nd  pre -ter minals in this regi on. The second experim ent w il l  det e rm ine t he effe c ts o f 5 -H T1 A a nd 5- HT2 r ece ptors i n the medi alhy pothalamus u p on  defensive  ra ge. The thir d e xperim en t w i ll de ter mine:  the r o le ofIL-1betain the me d ial hyp o t ha lamu s upon defensiver ag e ,

rage_and its_relationship to serotonin axons_and pre-terminals_in_this region._The_second experiment will_determine the effects_of 5-HT1A and 5-HT2_receptors in the_medial_hypothalamus upon defensive rage. The third experiment will determine: the role of IL-1beta in_the_medial hypothalamus_upon_defensive_rage,


the link between fat intake and obesity, relatively little is known about the chemosensory mechanisms that underlie the taste of fat and how these mechanisms might contribute to dietary fat intake. Our previous research has identified differences in how the taste systems in obesity-prone and -resistant rodents respond to fatty acids, a cue for

the link between fat intake and obesity, relatively little is know about the chemosensory mechanism that underlie the taste of fat and how these mechanisms might put up to dietary fat intake. Our former research has identified differences in how the preference system in obesity - prone and -resistant rodents respond to fatty acids, a cue for

thf link between fat intakt and obesity, relcrively littls is knodn about the chemosensory merhanusms ukat underlie the tasge of fat and how theww mechanisms might contrjnute co dietary fat iktake. Our psevious researwh hcs identified differences in how the taste xydtems in obesijy-promq ans -resistant rodents respond to fatfy acidv, a cue for

the link between fat intake and obesity, is about the mechanisms that underlie how mechanisms might contribute dietary fat intake. previous research has identified differences in the taste systems in obesity-prone and -resistant rodents respond to fatty acids, a for

the link between fat intake anD obesity, reLativEly LitTlE is kNown About the chemosENsorY mechanisms that underliE the tAsTE of fAT aNd how These meCHaNISms MiGhT coNtRIbUte to DieTary fat Intake. Our pRevIoUs research haS IdEntified diFfeRences in how tHe tAste syStEms IN obesIty-Prone And -resIStant rOdents resPoND to fatTY acids, a CUE fOr

the link between fat inta ke and obe sity,  re lat iv elylitt le is known ab o ut t he chemosensory mechan ismsth a t un d er lie t he tast e  o f fat  a nd  ho wt he se me cha nisms m ight contr ibu te  to dietaryf at  intake. O urprevious res ear ch has  i den t ified  di ffere nces i n  how t he tastesy s tems i n  obesit y - pr oneand -resistant ro d en t s respond to f atty a ci d s, a  cu e f or

the_link between_fat intake and obesity,_relatively little_is_known about_the_chemosensory mechanisms that_underlie the taste_of fat and how_these mechanisms might_contribute_to dietary fat intake. Our previous research has identified differences in how the taste_systems_in obesity-prone_and_-resistant_rodents respond to fatty acids,_a cue for


the objective because they keep the sample volume minimal and remove unwanted materials that could degrade detection, while quickly isolating and concentrating target species. Physically, this is made possible by exploit a unique combination of dielectrophoretic, flow and electrophoretic forces combined into the two techniques (gradient dielectrophoresis and electrophoretic

the objective because they keep the sample volume minimal and absent undesirable materials that could degrade signal detection, while quickly isolate and concentrating target coinage. Physically, this is form possible by overwork a alone combination of dielectrophoretic, flow and electrophoretic force combined into the two techniques (gradient dielectrophoresis and electrophoretic

thf objective because they keep the samplg colume minimzl and rdmove unwanted materials thav coyld dtyrade detection, whild quickly isolatibg aid concentrating target speciea. Phyvmcally, this is kade possitle by exploit a uuique combination of dielectrophoretyc, flow ajd electrophorgtic gjrcea combined into the two techniques (gradieit dielectrophotesis and electrophoretic

the objective because they keep the sample and unwanted materials could degrade detection, target Physically, this is possible by exploit unique combination of dielectrophoretic, flow and forces combined into the two techniques (gradient dielectrophoresis and electrophoretic

the objective because they keEp the samplE voluMe mIniMaL and RemoVe unwanted mateRIals That could degrade detectIon, whIlE QuicKLy IsolaTing and COnCENtrAtInG taRgET sPecieS. PhYsicallY, this is madE poSsIble by exploiT A uNique combiNatIon of dielectRopHoretiC, fLow ANd eleCtrOphorEtic foRCes comBined into ThE Two tecHNiques (gRADiEnt dIelectrophoresis aND eLEctrophoretic

the objective because the y keep the  samp levol um e mi nima l and remove u n want ed materials that coul d deg ra d e de t ec tion,  whileq ui c k lyis ol ati ng an d con cen trating  target sp eci es . Physically ,  t his is mad e p ossible by e xpl oit aun iqu e  comb ina tionof die l ectrop horetic,fl o w ande lectrop h o re ticforces combined i n to the two techni ques ( gr a di e n t d iel ectrophore si s and electro p ho r e t ic

the_objective because_they keep the sample_volume minimal_and_remove unwanted_materials_that could degrade_detection, while quickly_isolating and concentrating target_species. Physically, this_is_made possible by exploit a unique combination of dielectrophoretic, flow and electrophoretic forces combined_into_the two_techniques_(gradient_dielectrophoresis and electrophoretic


t-tubules decreases in CHF. This will be tested by (1) determining if calcium influx via reverse mode NCX modulates calcium-induced calcium release (CICR), (2) determining if calcium influx via reverse mode NCX replaces calcium entry via L-type calcium channels as the primary source of trigger calcium

t - tubules decreases in CHF. This will be tested by (1) determining if calcium inflow via rearward mode NCX modulates calcium - induced calcium dismissal (CICR), (2) determine if calcium influx via reverse manner NCX replaces calcium entry via liter - type calcium channels as the basal source of trigger calcium

t-tkbules decreases in CHF. Uhis will be testgd by (1) dxterminjng if cxlcium influx via reverse move NXX moeulates calcium-induced calcium gelease (CUCR), (2) eetermininj if calgnum ihnlux rie reverse mode KCX replacev calcium entrf xic L-type calcium channels as the primwry soutcf of trigger cwlcilm

t-tubules decreases in CHF. This will be (1) if calcium via reverse mode (CICR), determining if calcium via reverse mode replaces calcium entry via L-type calcium as the primary source of trigger calcium

t-tubules decreases in CHF. ThiS will be tesTed by (1) DetErmInIng iF calCium influx via rEVersE mode NCX modulates calciUm-indUcED calCIuM releAse (CICR), (2) DEtERMinInG iF caLcIUm InfluX viA reversE mode NCX rePlaCeS calcium entrY ViA L-type calcIum Channels as thE prImary sOuRce OF trigGer CalciUm

t-tubules decreases in CH F. This wi ll be  te ste dby ( 1) d etermining ifc alci um influx via reversemodeNC X  mod u la tes c alcium- i nd u c edca lc ium  r e le ase ( CIC R), (2)  determini ngif  calcium inf l ux  via rever semode NCX rep lac es cal ci ume ntryvia  L-ty pe cal c ium ch annels as  t h e prim a ry sour c e  o f tr igger calcium

t-tubules_decreases in_CHF. This will be_tested by_(1)_determining if_calcium_influx via reverse_mode NCX modulates_calcium-induced calcium release (CICR),_(2) determining if_calcium_influx via reverse mode NCX replaces calcium entry via L-type calcium channels as the_primary_source of_trigger_calcium


congenic for the H-2b genotype derived from strain C57L/J. These mice have been shown in our laboratory to have delayed and reduced leukemia incidence with respect to AKR/J and preliminary evidence incicates that they also have an altered immune responsiveness. This study is designed to confirm and expand upon these

congenic for the H-2b genotype derived from strain C57L / J. These mice have been shown in our laboratory to have stay and reduce leukemia incidence with respect to AKR / J and preliminary evidence incicates that they also have an adapted immune responsiveness. This study is designed to confirm and expand upon these

cojgenic for the H-2b genotyke derived from sjrqin C57L/O. These mice haxe been shown in our laboratlrt to yave delayed and reducdd leukempa incidebce xith respect to EIR/J and prelijlnary xvidence incicajes that thef also have an autzred immune responsiveness. This studr is dexihned to confiri anc expznd upon these

congenic for the H-2b genotype derived from These have been in our laboratory leukemia with respect to and preliminary evidence that they also have an altered responsiveness. This study is designed to confirm and expand upon these

congenic for the H-2b genotype dErived from StraiN C57L/j. ThEsE micE havE been shown in ouR LaboRatory to have delayed and ReducEd LEukeMIa IncidEnce witH ReSPEct To aKr/J aNd PReLiminAry EvidencE incicates ThaT tHey also have aN AlTered immunE reSponsiveness. thiS study Is DesIGned tO coNfirm And expANd upon These

congenic for the H-2b gen otype deri ved f rom  st ra in C 57L/ J. These miceh avebeen shown in our labo rator yt o ha v edelay ed andr ed u c edle uk emi ai nc idenc e w ith res pect to AK R/J  a nd prelimina r yevidence i nci cates that t hey  alsoha vea n alt ere d imm une re s ponsiv eness. Th is studyi s desig n e dto c onfirm and expand up o n these

congenic_for the_H-2b genotype derived from_strain C57L/J._These_mice have_been_shown in our_laboratory to have_delayed and reduced leukemia_incidence with respect_to_AKR/J and preliminary evidence incicates that they also have an altered immune responsiveness. This_study_is designed_to_confirm_and expand upon these


HEX also binds with high affinity to free ASARM- peptide and also inactivates the peptide by hydrolysis. In HYP, as well as a loss of PHEX function, there is a marked up regulation of MEPE and osteoblastic protease activity. This results in degradation of MEPE and DMP1

HEX also binds with high affinity to free ASARM- peptide and besides demobilize the peptide by hydrolysis. In HYP, as well as a loss of PHEX affair, there be a marked up regulation of MEPE and osteoblastic protease activeness. This resultant role in degradation of MEPE and DMP1

HEX also binds with high afninity to free ASARM- pe'tide ahd also knactivates the peptide by hbdrooysis. In HYP, as well as a luss of PHVX functiin, tiere is a marked up regulation lf MZPX and osteoblasjic protease activity. This rdsblts in degradation of MEPE and DMP1

HEX also binds with high affinity to peptide also inactivates peptide by hydrolysis. a of PHEX function, is a marked regulation of MEPE and osteoblastic protease This results in degradation of MEPE and DMP1

HEX also binds with high affinIty to free AsARM- pEptIde AnD alsO inaCtivates the pepTIde bY hydrolysis. In HYP, as well As a loSs OF PHEx FuNctioN, there iS A mARKed Up ReGulAtIOn Of MEPe anD osteobLastic protEasE aCtivity. This rESuLts in degraDatIon of MEPE and dMP1

HEX also binds with high a ffinity to  free  AS ARM -pept ideand also inact i vate s the peptide by hydro lysis .I n HY P ,as we ll as a lo s s  of  P HE X f un c ti on, t her e is amarked upreg ul ation of MEP E  a nd osteobl ast ic proteaseact ivity.  T his resul tsin de gradat i on ofMEPE andDM P 1

HEX also_binds with_high affinity to free_ASARM- peptide_and_also inactivates_the_peptide by hydrolysis._In HYP, as_well as a loss_of PHEX function,_there_is a marked up regulation of MEPE and osteoblastic protease activity. This results in_degradation_of MEPE_and_DMP1


modulated by dietary experience. There is new and emerging data that argues to the plasticity of the peripheral taste system, yet our understanding of how the system changes in relation to experience is poor at best. Specifically, we will use an approach including a multidisciplinary approach to answer the following question: 1. Is the fatty acid transduction pathway

modulated by dietary experience. There is new and emerging datum that argue to the plasticity of the peripheral taste arrangement, yet our sympathy of how the system changes in sexual intercourse to experience is poor at best. Specifically, we will practice an overture including a multidisciplinary overture to answer the following question: 1. Is the fatty acid transduction nerve pathway

mofulated by dietary experlence. There is ngw and ekerginf data tfat argues to the plasticity od the peripheral taste systdm, yet oug understqndiig of how the system chakyes ih relctmon to experienge is poor dt best. Specifhcxlpy, we will use an approach includind a mulyifisciplinary akproabh to znswer the following question: 1. Is fhe fatuy acid transductipn pathway

modulated by dietary experience. There is new data argues to plasticity of the understanding how the system in relation to is poor at best. Specifically, we use an approach including a multidisciplinary approach to answer the following question: 1. the fatty acid transduction pathway

modulated by dietary experieNce. There is New anD emErgInG datA thaT argues to the plASticIty of the peripheral tastE systEm, YEt ouR UnDerstAnding oF HoW THe sYsTeM chAnGEs In relAtiOn to expErience is pOor At Best. SpecificALlY, we will use An aPproach incluDinG a multIdIscIPlinaRy aPproaCh to anSWer the Following QuEStion: 1. IS The fattY ACiD traNsduction pathway

modulated by dietary expe rience. Th ere i s n ewan d em ergi ng data that a r gues  to the plasticity ofthe p er i pher a ltaste  system ,  y e t  ou run der st a nd ing o f h ow thesystem cha nge sin relationt oexperience  is  poor at bes t.Specif ic all y , wewil l use  an ap p roachincluding  a multid i sciplin a r yappr oach to answer th e  f o llowing questi on: 1.  I s  t h e  fa tty  acid tran sd uctio n  pathwa y

modulated_by dietary_experience. There is new_and emerging_data_that argues_to_the plasticity of_the peripheral taste_system, yet our understanding_of how the_system_changes in relation to experience is poor at best. Specifically, we will use an_approach_including a_multidisciplinary_approach_to answer the following question:_1. Is the fatty acid_transduction pathway


-C virus expression in the mouse. We feel there is considerable complementarity and synergy between the human and mouse programs. ViraCore is a biotechnology company that is creating a drug discovery tool that is capable of presenting complex receptors in a nanometer-sized particle format. Specific ally, ViraCore is using

-C virus expression in the mouse. We feel there is considerable complementarity and synergy between the human and shiner broadcast. ViraCore is a biotechnology company that is creating a drug discovery cock that is able of presenting complex receptors in a nanometer - sized atom format. Specific ally, ViraCore is using

-C vlrus expression in the muuse. We feel thgrw is cmnsidedable cooplementarity and synergy bevweeb the human and mouse progrxms. ViraClre is a biouechnology companb that is creaflng a vrug discovery jool that is capable of prasdncing complex receptors in a nanometew-sized lagticle format. Fpecpfyc amly, ViraCore is using

-C virus expression in the mouse. We is complementarity and between the human a company that is a drug discovery that is capable of presenting complex in a nanometer-sized particle format. Specific ally, ViraCore is using

-C virus expression in the mousE. We feel theRe is cOnsIdeRaBle cOmplEmentarity and sYNergY between the human and mouSe proGrAMs. ViRACOre is A biotecHNoLOGy cOmPaNy tHaT Is CreatIng A drug diScovery tooL thAt Is capable of pREsEnting compLex Receptors in a NanOmeter-SiZed PArticLe fOrmat. specifIC ally, VIraCore is UsINg

-C virus expression in the  mouse. We  feel  th ere  i s co nsid erable complem e ntar ity and synergy betwee n the  h u mana nd  mous e progr a ms . Vir aC or e i sa  b iotec hno logy co mpany that  is  c reating a dr u gdiscoverytoo l that is ca pab le ofpr ese n tingcom plexrecept o rs ina nanomet er - sizedp article f or mat.  Specific ally, V i ra C ore is using

-C virus_expression in_the mouse. We feel_there is_considerable_complementarity and_synergy_between the human_and mouse programs._ViraCore is a biotechnology_company that is_creating_a drug discovery tool that is capable of presenting complex receptors in a nanometer-sized_particle_format. Specific_ally,_ViraCore_is using


its, A., and G. Scheele. Proc. Nat. Acad. Sci. USA 73, 156-160 1976. Secretory Proteins of the Exocrine Pancreas. Scheele, G.A., in Cell Biology (P.L. Altman and D.D. Katz, eds.), Federation of

its, A., and G. Scheele. Proc. Nat. Acad. Sci. USA 73, 156 - 160 1976. Secretory Proteins of the Exocrine Pancreas. Scheele, G.A., in Cell Biology (P.L. Altman and D.D. Katz, eds .), Federation of

its, A., and G. Scheele. Proc. Nau. Acad. Sci. USA 73, 156-160 1976. Secretmry Prkteins ow the Exocrine Pancreas. Schexle, T.A., in Cell Biology (P.L. Altmav and D.D. Natz, eds.), Fedtration of

its, A., and G. Scheele. Proc. Nat. USA 156-160 1976. Proteins of the Cell (P.L. Altman and Katz, eds.), Federation

its, A., and G. Scheele. Proc. Nat. AcaD. Sci. USA 73, 156-160 1976. SecRetorY PrOteInS of tHe ExOcrine Pancreas. sCheeLe, G.A., in Cell Biology (P.L. AltMan anD D.d. katz, EDs.), federAtion of

its, A., and G. Scheele. P roc. Nat.Acad.  Sc i.US A 73 , 15 6-160 1976. Se c reto ry Proteins of the Exo crine  P a ncre a s.  Sche ele, G. A ., i n C el lBio lo g y(P.L.  Al tman an d D.D. Kat z,ed s.), Federat i on  of

its, A.,_and G._Scheele. Proc. Nat. Acad._Sci. USA_73,_156-160 1976._Secretory_Proteins of the_Exocrine Pancreas. Scheele,_G.A., in Cell Biology_(P.L. Altman and_D.D._Katz, eds.), Federation of


hepatic effects of alcohol, we have expanded the dual brain and behavior focus present in the parent grant to incorporate research on the effects of alcohol and THC on the liver. In the proposed project, we will investigate sex differences in the acute in vivo pharmacological effects of alcoho and THC co-administration, as well as

hepatic effects of alcohol, we have expanded the dual brain and demeanor concentrate present in the parent grant to incorporate inquiry on the effects of alcohol and THC on the liver. In the nominate project, we will investigate sexual activity differences in the acute in vivo pharmacological effects of alcoho and THC carbon monoxide - administration, as well as

heoatic effects of alcohol, we have expandgd the dnal brajn and bdhavior focus present in the pqrent grant to incorporate fesearch ln the edfecus of alcohol and THC on bke libcr. In vhe proposed prpject, we whll investigata rer differences in the acute in vivo prarmacokohical effects jf aksoho and THC co-administration, as well zs

hepatic effects of alcohol, we have expanded brain behavior focus in the parent the of alcohol and on the liver. the proposed project, we will investigate differences in the acute in vivo pharmacological effects of alcoho and THC co-administration, well as

hepatic effects of alcohol, we Have expandEd the DuaL brAiN and BehaVior focus preseNT in tHe parent grant to incorpoRate rEsEArch ON tHe effEcts of aLCoHOL anD ThC On tHe LIvEr. In tHe pRoposed Project, we wIll InVestigate sex DIfFerences in The Acute in vivo pHarMacoloGiCal EFfectS of AlcohO and THc Co-admiNistratioN, aS Well as

hepatic effects of alcoho l, we have  expa nde d t he  dua l br ain and behavi o r fo cus present in the par ent g ra n t to in corpo rate re s ea r c h o nth e e ff e ct s ofalc ohol an d THC on t heli ver. In thep ro posed proj ect , we will in ves tigate  s exd iffer enc es in  the a c ute in  vivo pha rm a cologi c al effe c t sof a lcoho and THC co- a dm i nistration, as  wellas

hepatic_effects of_alcohol, we have expanded_the dual_brain_and behavior_focus_present in the_parent grant to_incorporate research on the_effects of alcohol_and_THC on the liver. In the proposed project, we will investigate sex differences in_the_acute in_vivo_pharmacological_effects of alcoho and THC_co-administration, as well as


mostly with a mixture of aminoglycoside and Beta-lactam antibiotics, is used to combat the infection, treatment often fails, owing to the emergence of alginate-producing P. aeruginosa isolates. The genetic and molecular mechanism of alginate overproduction has been elucidated in great detail. Yet, a possible therapeutic intervention

mostly with a mixture of aminoglycoside and Beta - lactam antibiotics, is used to battle the contagion, discussion often fails, owing to the egress of alginate - producing P. aeruginosa isolates. The genetic and molecular mechanism of alginate overproduction has been elucidated in bang-up detail. Yet, a potential curative intervention

modtly with a mixture of aoinoglycoside aue Beta-nactam antibiogics, is used to combat the iifecrion, ugeatment often fails, uwing to nhe emergwnce if alginatx-lroduciky P. asvuginmwa isolates. Thg genetic ang molecular mewhxnnsm of alginate overproduction has bqen eluvifated in great detsyl. Ysn, c possible therapeutic intervenfion

mostly with a mixture of aminoglycoside and is to combat infection, treatment often of P. aeruginosa isolates. genetic and molecular of alginate overproduction has been elucidated great detail. Yet, a possible therapeutic intervention

mostly with a mixture of aminoGlycoside aNd BetA-laCtaM aNtibIotiCs, is used to combAT the Infection, treatment ofteN failS, oWIng tO ThE emerGence of ALgINAte-PrOdUciNg p. AeRuginOsa IsolateS. The genetiC anD mOlecular mechANiSm of alginaTe oVerproductioN haS been eLuCidATed in GreAt detAil. Yet, A PossibLe therapeUtIC interVEntion

mostly with a mixture ofaminoglyco sideand  Be ta -lac tamantibiotics, i s  use d to combat the infect ion,tr e atme n toften  fails, ow i n g t oth e e me r ge nce o f a lginate -producing  P.  a eruginosa is o la tes. The g ene tic and mole cul ar mec ha nis m  of a lgi nateoverpr o ductio n has bee ne lucida t ed in g r e at  det ail. Yet, a possi b le therapeutic in terven ti o n

mostly_with a_mixture of aminoglycoside and_Beta-lactam antibiotics,_is_used to_combat_the infection, treatment_often fails, owing_to the emergence of_alginate-producing P. aeruginosa_isolates._The genetic and molecular mechanism of alginate overproduction has been elucidated in great detail._Yet,_a possible_therapeutic_intervention


community discoveries in clinical and translational research. RELEVANCE (See instructions): The University of Massachusetts Center for Clinical and Translational Science (UMCCTS) will transform the conduct of clinical and translational research by providing an "academic home" for all university clinical investigators. The UMCCTS will provide robust pilot grant

community discoveries in clinical and translational research. RELEVANCE (See education ): The University of Massachusetts Center for Clinical and Translational Science (UMCCTS) will translate the conduct of clinical and translational research by provide an " academic home plate " for all university clinical investigators. The UMCCTS will provide full-bodied pilot grant

colmunity discoveries in cuinical and trauwlatioial ressarch. REUEVANCE (See instructions): The Ubiverwity of Massachusetts Zenter fog Clinicao anv Translational Science (MICCTA) wiln transform the conduct ox clinical and tfauslational research by providing an "wcademiv jome" for all ugivegsyty dlinical investigators. The UMCCTS sill prmvide robust lilot grant

community discoveries in clinical and translational research. instructions): University of Center for Clinical transform conduct of clinical translational research by an "academic home" for all university investigators. The UMCCTS will provide robust pilot grant

community discoveries in cliNical and trAnslaTioNal ReSearCh. RElEVANCE (See instRUctiOns): The University of MassAchusEtTS CenTEr For ClInical aND TRANslAtIoNal scIEnCe (UMCcTS) Will traNsform the cOndUcT of clinical aND tRanslationAl rEsearch by proVidIng an "aCaDemIC home" For All unIversiTY cliniCal investIgATors. ThE uMCCTS wILL pRoviDe robust pilot granT

community discoveries inclinical a nd tr ans lat io nalrese arch. RELEVANC E  (Se e instructions): The U niver si t y of Ma ssach usettsC en t e r f or  C lin ic a land T ran slation al Science  (U MC CTS) will tr a ns form the c ond uct of clini cal  and t ra nsl a tiona l r esear ch byp rovidi ng an "ac ad e mic ho m e" fora l luniv ersity clinical i n ve s tigators. TheUMCCTS  w i ll p rov ide  robust pi lo t gra n t

community_discoveries in_clinical and translational research._RELEVANCE (See_instructions):_The University_of_Massachusetts Center for_Clinical and Translational_Science (UMCCTS) will transform_the conduct of_clinical_and translational research by providing an "academic home" for all university clinical investigators. The_UMCCTS_will provide_robust_pilot_grant


to undetectable levels when germ cells reach stage X. This cycle of gene expression is a response to germ cells which causes sequential repression, stimulation and re-repression of transcription of the cathepsin L gene. We have identified 2 domains in the cathepsin L gene that potentially respond to these signals: [1] An

to undetectable levels when germ cells strive stagecoach X. This cycle of gene expression is a response to microbe cells which causes consecutive repression, stimulation and re - repression of transcription of the cathepsin L gene. We have identify 2 domains in the cathepsin L gene that potentially respond to these signal: [ 1 ] An

to undetectable levels whek germ cells reaey stagx X. Thia cycle uf gene expression is a resplnwe to germ cells which causds sequennial reprwssiib, stimulatmkn and vz-reprsdsiou if transcriptipn of the wathepsin L gete. Wz have identified 2 domains in the caehepsin L gene that potgntiakjy rsspond to these signals: [1] An

to undetectable levels when germ cells reach This of gene is a response sequential stimulation and re-repression transcription of the L gene. We have identified 2 in the cathepsin L gene that potentially respond to these signals: [1] An

to undetectable levels when gErm cells reAch stAge x. ThIs CyclE of gEne expression iS A resPonse to germ cells which cAuses SeQUentIAl RepreSsion, stIMuLATioN aNd Re-rEpREsSion oF trAnscripTion of the cAthEpSin L gene. We haVE iDentified 2 dOmaIns in the cathEpsIn L genE tHat POtentIalLy resPond to THese siGnals: [1] An

to undetectable levels wh en germ ce lls r eac h s ta ge X . Th is cycle of ge n e ex pression is a response  to g er m  cel l swhich  causes se q u ent ia lrep re s si on, s tim ulation  and re-re pre ss ion of trans c ri ption of t hecathepsin Lgen e. Weha vei denti fie d 2 d omains in the  cathepsi nL  genet hat pot e n ti ally  respond to these si g nals: [1] An

to_undetectable levels_when germ cells reach_stage X._This_cycle of_gene_expression is a_response to germ_cells which causes sequential_repression, stimulation and_re-repression_of transcription of the cathepsin L gene. We have identified 2 domains in the_cathepsin_L gene_that_potentially_respond to these signals: [1]_An


Oragene saliva kits. However, the parent study included no specific aims or funding to examine DNA for genetic risk factors. This application aims to study genetic variation in candidate genes, which were previously shown to be associated with clubfoot in family studies. The candidate genes will be identified in a separate study of clubfoot which

Oragene saliva kits. However, the parent study included no specific aims or support to test DNA for genetic risk factors. This lotion aims to study genetic version in candidate genes, which were previously read to be associated with clubfoot in family report. The candidate genes will be identified in a separate study of clubfoot which

Orwgene saliva kits. Howevev, the parent stubt inclnded no specifiz aims or funding to examine DBA foe genetic risk factors. This apppication aimw to study jsnetic ycriatjln iu randidate genes, which wera previously svodn to be associated with clubfoot in samily xtkdies. The candydatt gqnes will be identified in a separate atudy oh clubfoot whicn

Oragene saliva kits. However, the parent study specific or funding examine DNA for aims study genetic variation candidate genes, which previously shown to be associated with in family studies. The candidate genes will be identified in a separate study clubfoot which

Oragene saliva kits. However, tHe parent stUdy inCluDed No SpecIfic Aims or funding tO ExamIne DNA for genetic risk faCtors. thIS appLIcAtion Aims to sTUdY GEneTiC vAriAtIOn In canDidAte geneS, which were PreViOusly shown to BE aSsociated wIth Clubfoot in faMilY studiEs. the CAndidAte Genes Will be IDentifIed in a sepArATe studY Of clubfOOT wHich

Oragene saliva kits. Howe ver, the p arent  st udy  i nclu dedno specific ai m s or  funding to examine DN A for  g e neti c  r isk f actors. Th i s  ap pl ic ati on ai ms to  st udy gen etic varia tio nin candidate ge nes, which  we re previousl y s hown t obea ssoci ate d wit h club f oot in  family s tu d ies. T h e candi d a te  gen es will be identi f ie d  in a separate  study  o f  c l u bfo otwhich

Oragene_saliva kits._However, the parent study_included no_specific_aims or_funding_to examine DNA_for genetic risk_factors. This application aims_to study genetic_variation_in candidate genes, which were previously shown to be associated with clubfoot in family_studies._The candidate_genes_will_be identified in a separate_study of clubfoot which


genetic strategies and genetic mosaic analysis to test the function of neurotrophin receptors p75, TrkB, and TrkC in development and refinement of central somatosensory circuitry. The somatosensory system relies on activity for proper structural maturation of both axons and dendrites, and thus represents an excellent opportunity to test

genetic strategies and genetic mosaic analysis to screen the affair of neurotrophin receptors p75, TrkB, and TrkC in development and refinement of cardinal somatosensory circuitry. The somatosensory system relies on activity for proper geomorphologic maturation of both axons and dendrite, and therefore represents an excellent opportunity to test

gejetic strategies and genttic mosaic analysis to vest ths functiun of neurotrophin receptors p75, TrkB, and TrkC in developmevt and revinement of rentral somatoseiaory civeuitrg. The womatosensory xystem relhes on activitf wox proper structural maturation of boeh axonx wnd dendrites, wnd uhuf relgewents an excellent opportunitg to tevt

genetic strategies and genetic mosaic analysis to function neurotrophin receptors TrkB, and TrkC central circuitry. The somatosensory relies on activity proper structural maturation of both axons dendrites, and thus represents an excellent opportunity to test

genetic strategies and genetIc mosaic anAlysiS to TesT tHe fuNctiOn of neurotrophIN recEptors p75, TrkB, and TrkC in deVelopMeNT and REfInemeNt of cenTRaL SOmaToSeNsoRy CIrCuitrY. ThE somatoSensory sysTem ReLies on activiTY fOr proper stRucTural maturatIon Of both AxOns ANd denDriTes, anD thus rEPresenTs an excelLeNT opporTUnity to TESt

genetic strategies and ge netic mosa ic an aly sis  t o te st t he function of neur otrophin receptors p75 , Trk B, andT rk C indevelop m en t and  r ef ine me n tof ce ntr al soma tosensorycir cu itry. The so m at osensory s yst em relies on  ac tivity  f orp roper  st ructu ral ma t uratio n of both  a x ons an d  dendri t e s,  and  thus representsa ne xcellent oppor tunity  t o  t e s t

genetic_strategies and_genetic mosaic analysis to_test the_function_of neurotrophin_receptors_p75, TrkB, and_TrkC in development_and refinement of central_somatosensory circuitry. The_somatosensory_system relies on activity for proper structural maturation of both axons and dendrites, and_thus_represents an_excellent_opportunity_to test


omodulatory effect that patent Schistosoma haematobium has upon the humoral and cellular response elicited to acute Plasmodium falciparum infection and how this immune response affects the incidence and severity of clinical malarial disease. We expect these studies to 1) demonstrate the importance of co-parasitic infections in the developing

omodulatory effect that patent Schistosoma haematobium has upon the humoral and cellular response elicited to acute Plasmodium falciparum infection and how this immune reception involve the incidence and severity of clinical malarial disease. We expect these studies to 1) prove the importance of co - parasitic infections in the develop

omofulatory effect that pattnt Schistosoma hcwmatobmum has upon thd humoral and cellular respoise wliciuvd to acute Plasmodiuo falcipagum infecrion qnd how thma immunc resllnse effects the incldence and veverity of clhnkccl malarial disease. We expect these ftudies tl 1) demonstrate the ympodnakce of co-parasitic infections in the deneloping

omodulatory effect that patent Schistosoma haematobium has humoral cellular response to acute Plasmodium immune affects the incidence severity of clinical disease. We expect these studies to demonstrate the importance of co-parasitic infections in the developing

omodulatory effect that pateNt SchistosOma haEmaTobIuM has Upon The humoral and cELlulAr response elicited to acUte PlAsMOdiuM FaLcipaRum infeCTiON And HoW tHis ImMUnE respOnsE affectS the incideNce AnD severity of cLInIcal malariAl dIsease. We expeCt tHese stUdIes TO 1) demoNstRate tHe impoRTance oF co-parasiTiC InfectIOns in thE DEvElopIng

omodulatory effect that pa tent Schis tosom a h aem at obiu m ha s upon the hum o raland cellular responseelici te d  toa cu te Pl asmodiu m  f a l cip ar um  in fe c ti on an d h ow this  immune re spo ns e affects th e  i ncidence a ndseverity ofcli nicalma lar i al di sea se. W e expe c t thes e studies  t o  1) de m onstrat e th e im portance of co-pa r as i tic infections  in th ed ev e l opi ng

omodulatory effect_that patent_Schistosoma haematobium has upon_the humoral_and_cellular response_elicited_to acute Plasmodium_falciparum infection and_how this immune response_affects the incidence_and_severity of clinical malarial disease. We expect these studies to 1) demonstrate the importance_of_co-parasitic infections_in_the_developing


. subject didn't wear the footwear), the sensor unit will notify an alarm (via sound or vibration) and will mark the time of the alarm in the on-board memory system. In the clinical part of the study, two different tests are designed to address its validity as well as its application in (a)

. subject didn't wear the footwear), the sensor unit will advise an alarm clock (via audio or vibration) and will mark the fourth dimension of the alarm in the on - board memory organization. In the clinical share of the study, two unlike examination are designed to cover its validity as well as its application in (a )

. suhject didn't wear the foouwear), the sensor onut wiln notiry an alxrm (via sound or vibration) aid wull mqrk the time of the alxrm in thv on-board memiey system. Mh the clinicam parc if the study, teo differett tests are daskgued to address its validity as well ws its spolication in (a)

. subject didn't wear the footwear), the will an alarm sound or vibration) of alarm in the memory system. In clinical part of the study, two tests are designed to address its validity as well as its application in

. subject didn't wear the footweAr), the sensoR unit WilL noTiFy an AlarM (via sound or vibRAtioN) and will mark the time of tHe alaRm IN the ON-bOard mEmory sySTeM. iN thE cLiNicAl PArT of thE stUdy, two dIfferent teSts ArE designed to aDDrEss its valiDitY as well as its AppLicatiOn In (a)

. subject didn't wear thefootwear),  thesen sor  u nitwill  notify an ala r m (v ia sound or vibration)  andwi l l ma r kthe t ime oft he a lar min  th eo n- board  me mory sy stem. In t hecl inical parto fthe study,  tw o differenttes ts are  d esi g ned t o a ddres s itsv alidit y as well  a s  its a p plicati o n  i n (a )

. subject_didn't wear_the footwear), the sensor_unit will_notify_an alarm_(via_sound or vibration)_and will mark_the time of the_alarm in the_on-board_memory system. In the clinical part of the study, two different tests are designed_to_address its_validity_as_well as its application in_(a)


dermoscopic features of individual nevi. Mouthwash derived DNA collected at the baseline examination will be used for MC1R genotyping. The insights into nevus risk factors and evolution gleaned from this study will have significant implications for reduction of melanoma mortality through improved risk stratification and more informed prevention. The current work is

dermoscopic features of individual nevi. Mouthwash derived DNA gather at the baseline interrogation will be used for MC1R genotyping. The insights into nevus hazard factors and evolution gleaned from this cogitation will have significant deduction for reduction of melanoma mortality through better risk stratification and more informed prevention. The current work is

degmoscopic features of inaividual nevi. Mouthwasi derivsd DNA cullected at the baseline exalibatiob will be used for MC1R genotypijg. The ibsigits into nevus rmak factors ans evonntion gleaned ftom this stugy will have shgviyicant implications for reduction of melanoka mortality thrjugh ymprkneb risk stratification and more jnformev prevention. Thr current work is

dermoscopic features of individual nevi. Mouthwash derived at baseline examination be used for nevus factors and evolution from this study have significant implications for reduction of mortality through improved risk stratification and more informed prevention. The current work is

dermoscopic features of indiVidual nevi. mouthWasH deRiVed DnA coLlected at the baSElinE examination will be used For MC1r gENotyPInG. The iNsights INtO NEvuS rIsK faCtORs And evOluTion gleAned from thIs sTuDy will have siGNiFicant implIcaTions for reduCtiOn of meLaNomA MortaLitY throUgh impROved riSk stratifIcATion anD More infORMeD preVention. The current WOrK Is

dermoscopic features of i ndividualnevi.  Mo uth wa sh d eriv ed DNA collect e d at  the baseline examinat ion w il l  beu se d for  MC1R g e no t y pin g.  T hein s ig hts i nto  nevusrisk facto rsan d evolutiong le aned fromthi s study will  ha ve sig ni fic a nt im pli catio ns for reduct ion of me la n oma mo r talityt h ro ughimproved risk str a ti f ication and mo re inf or m ed p rev ent ion. The c ur rentw ork is

dermoscopic_features of_individual nevi. Mouthwash derived_DNA collected_at_the baseline_examination_will be used_for MC1R genotyping._The insights into nevus_risk factors and_evolution_gleaned from this study will have significant implications for reduction of melanoma mortality through_improved_risk stratification_and_more_informed prevention. The current work_is


Earlier findings in monkeys suggested that systemic injection of haloperidol, but not of scopolamine, retards the learning of a set of concurrent visual discriminations in which the stimulus pairs within the set are each presented just once every 24 hours. In a new study, using a version of this task in which the

Earlier findings in monkeys suggested that systemic injection of haloperidol, but not of scopolamine, idiot the eruditeness of a stage set of concurrent visual discrimination in which the stimulus pairs within the stage set are each presented just once every 24 hour. In a new study, use a version of this task in which the

Eaglier findings in monkeyr suggested thaj wystemmc injedtion of haloperidol, but not of scopllqmine, retards the learning uf a set lf concuerenu visual discrimiiztions lu whidm the wtimulus pairs within tha set are each pfedented just once every 24 hours. In a gew stucy, using a versijn og thia task in which the

Earlier findings in monkeys suggested that systemic haloperidol, not of retards the learning visual in which the pairs within the are each presented just once every hours. In a new study, using a version of this task in which

Earlier findings in monkeys sUggested thAt sysTemIc iNjEctiOn of Haloperidol, but NOt of Scopolamine, retards the lEarniNg OF a seT Of ConcuRrent viSUaL DIscRiMiNatIoNS iN whicH thE stimulUs pairs witHin ThE set are each pREsEnted just oNce Every 24 hours. In A neW study, UsIng A VersiOn oF this Task in WHich thE

Earlier findings in monke ys suggest ed th atsys te micinje ction of halop e rido l, but not of scopolam ine,re t ards th e lea rning o f  a s etof  c onc ur r en t vis ual  discri minationsinwh ich the stim u lu s pairs wi thi n the set ar e e ach pr es ent e d jus t o nce e very 2 4  hours . In a ne ws tudy,u sing av e rs ionof this task in w h ic h  the

Earlier_findings in_monkeys suggested that systemic_injection of_haloperidol,_but not_of_scopolamine, retards the_learning of a_set of concurrent visual_discriminations in which_the_stimulus pairs within the set are each presented just once every 24 hours. In_a_new study,_using_a_version of this task in_which the


measuring vessel permeability. We have conducted ultrastructure studies in conjunction with Donald McDonalds lab in UCSF(4). We conducted an murine study in which radiolabeled (14C) permeability agent was compared (using Quantitative AutoRadiography (QAR) with DCE-MRI in a brain tumor

measuring vessel permeability. We have conducted ultrastructure studies in conjunction with Donald McDonalds lab in UCSF(4). We behave an murine discipline in which radiolabeled (14C) permeability agent was compared (using Quantitative AutoRadiography (QAR) with DCE - MRI in a genius tumor

mewsuring vessel permeabillty. We have condocred ulvrastrudture stjdies in conjunction with Doiald McDobalds lab in UCSF(4). We cunducted wn murinw stndy in which radmklabeled (14C) pedleabnlmty agent was cpmpared (ushng Quantitatiee AbtoRadiography (QAR) with DCE-MRI in a frain timlr

measuring vessel permeability. We have conducted ultrastructure conjunction Donald McDonalds in UCSF(4). We which (14C) permeability agent compared (using Quantitative (QAR) with DCE-MRI in a brain

measuring vessel permeabiliTy. We have coNductEd uLtrAsTrucTure Studies in conjuNCtioN with Donald McDonalds laB in UCsF(4). wE conDUcTed an Murine sTUdY IN whIcH rAdiOlABeLed (14C) pErmEabilitY agent was cOmpArEd (using QuantITaTive AutoRaDioGraphy (QAR) witH DCe-MRI in A bRaiN Tumor

measuring vessel permeabi lity. We h ave c ond uct ed  ult rast ructure studie s  inconjunction with Donal d McD on a ldsl ab  in U CSF(4). We c ond uc te d a nm ur ine s tud y in wh ich radiol abe le d (14C) perm e ab ility agen t w as compared(us ing Qu an tit a tiveAut oRadi ograph y  (QAR)  with DCE -M R I in a brain t u m or

measuring_vessel permeability._We have conducted ultrastructure_studies in_conjunction_with Donald_McDonalds_lab in UCSF(4)._We conducted an_murine study in which_radiolabeled (14C) permeability_agent_was compared (using Quantitative AutoRadiography (QAR) with DCE-MRI in a brain tumor


Systems. (2) Standardize the methodology for identifying farmers'markets, which will allow others to accurately quantify and disseminate information about markets to consumers and public health practitioners. (3) Provide greater clarity regarding disparities in access to farmers'markets and regarding potential associations between access to farmers'markets and

Systems. (2) Standardize the methodology for identifying farmers'markets, which will allow others to accurately quantify and disseminate information about grocery store to consumer and public health practitioners. (3) Provide great clearness regarding disparities in access to farmers'markets and see potential associations between entree to farmers'markets and

Sydtems. (2) Standardize the mtthodology for idgnrifyinj farmeds'marketr, which will allow others to axcurauvly quantify and dissdminate ijformatiin auout markets to rknsumers and lmblic iealth practitipners. (3) Proeide greater cnaficy regarding disparities in access tj farmets'larkets and redardpnd pofvnuial associations between access fo farmtrs'markets and

Systems. (2) Standardize the methodology for identifying will others to quantify and disseminate and health practitioners. (3) greater clarity regarding in access to farmers'markets and regarding associations between access to farmers'markets and

Systems. (2) Standardize the methOdology for IdentIfyIng FaRmerS'marKets, which will aLLow oThers to accurately quantIfy anD dISsemINaTe infOrmatioN AbOUT maRkEtS to CoNSuMers aNd pUblic heAlth practiTioNeRs. (3) Provide greATeR clarity reGarDing disparitIes In acceSs To fARmers'MarKets aNd regaRDing poTential asSoCIationS Between ACCeSs to Farmers'markets and

Systems. (2) Standardizethe method ology  fo r i de ntif ying  farmers'marke t s, w hich will allow others  to a cc u rate l yquant ify and di s s emi na te  in fo r ma tionabo ut mark ets to con sum er s and public he alth pract iti oners. (3) P rov ide gr ea ter clari tyregar ding d i sparit ies in ac ce s s to f a rmers'm a r ke ts a nd regarding pote n ti a l associations  betwe en ac c e sstofarmers'ma rk ets a n d

Systems._(2) Standardize_the methodology for identifying_farmers'markets, which_will_allow others_to_accurately quantify and_disseminate information about_markets to consumers and_public health practitioners._(3)_Provide greater clarity regarding disparities in access to farmers'markets and regarding potential associations between_access_to farmers'markets_and


methodological rigor for standardized data collection, processing, and analytics. The Administrative Core will oversee the operations of the Sites, the Data Coordinating Core (DCC), and the DAAC and coordinate with federal and private partners to achieve the aims of this cooperative agreement. The will utilize informatics and technology to develop, maintain

methodological rigor for standardized data collection, processing, and analytics. The Administrative Core will oversee the operation of the Sites, the Data Coordinating Core (DCC), and the DAAC and organize with federal and private partners to achieve the aim of this cooperative agreement. The will utilize information science and technology to develop, maintain

mehhodological rigor for suandardized data eillectmon, prodessing, xnd analytics. The Administravive Core will oversee the operxtions of the Sitws, tie Data Coordinavjng Corc (DCC), wnd chx DAAC and coorcinate witv federal and [rkvcte partners to achieve the aims of ehis coppfrative agreemgnt. Tnq wiml utilize informatics and technolkgy to vevelop, maintaim

methodological rigor for standardized data collection, processing, The Core will the operations of Core and the DAAC coordinate with federal private partners to achieve the aims this cooperative agreement. The will utilize informatics and technology to develop, maintain

methodological rigor for staNdardized dAta coLleCtiOn, ProcEssiNg, and analytics. tHe AdMinistrative Core will ovErsee ThE OperATiOns of The SiteS, ThE dAta coOrDinAtINg core (DcC), aNd the DAaC and coordInaTe With federal aND pRivate partNerS to achieve thE aiMs of thIs CooPEratiVe aGreemEnt. The WIll utiLize inforMaTIcs and TEchnoloGY To DeveLop, maintain

methodological rigor forstandardiz ed da tacol le ctio n, p rocessing, and anal ytics. The Administrat ive C or e  wil l  o verse e the o p er a t ion sof  th eS it es, t heData Co ordinating  Co re  (DCC), andt he  DAAC andcoo rdinate with  fe deralan d p r ivate  pa rtner s to a c hievethe aimsof this c o operati v e  a gree ment. The will ut i li z e informaticsand te ch n ol o g y t o d evelop, ma in tain

methodological_rigor for_standardized data collection, processing,_and analytics._The_Administrative Core_will_oversee the operations_of the Sites,_the Data Coordinating Core_(DCC), and the_DAAC_and coordinate with federal and private partners to achieve the aims of this cooperative_agreement._The will_utilize_informatics_and technology to develop, maintain


AM for IL-12 production. Studies during the first three years of this program will test these hypotheses by evaluating cytokine expression patterns of AM collected in a temporal fashion following in vivo FIV infection. The last year of this research will correlate the results of the in vitro studies with in vivo challenge of FIV-infected cats

AM for IL-12 production. Studies during the first three years of this platform will screen these hypotheses by evaluating cytokine expression practice of AM collected in a temporal manner following in vivo FIV infection. The last class of this inquiry will correlate the results of the in vitro studies with in vivo challenge of FIV - infect cats

AM for IL-12 production. Studits during the first threx years of this program will test these hypltyeses by evaluating cytokind expresspon patteens id AM collerfed in a tempkval fcsiion following ln vivo FIV infection. The lxsc year of this research will correlaee the tedults of the ig viuro stuspew with in vivo challenge of FJV-infecued cats

AM for IL-12 production. Studies during the years this program test these hypotheses of collected in a fashion following in FIV infection. The last year of research will correlate the results of the in vitro studies with in vivo of FIV-infected cats

AM for IL-12 production. Studies dUring the fiRst thRee YeaRs Of thIs prOgram will test tHEse hYpotheses by evaluating cYtokiNe EXpreSSiOn patTerns of am cOLLecTeD iN a tEmPOrAl fasHioN followIng in vivo FiV iNfEction. The lasT YeAr of this reSeaRch will correLatE the reSuLts OF the iN viTro stUdies wITh in viVo challenGe OF FIV-inFEcted caTS

AM for IL-12 production.Studies du ringthe  fi rs t th reeyears of thisp rogr am will test these hyp othes es by e v al uatin g cytok i ne e xpr es si onpa t te rns o f A M colle cted in atem po ral fashionf ol lowing inviv o FIV infect ion . Thela sty ear o f t his r esearc h  willcorrelate  t h e resu l ts of t h e  i n vi tro studies withi nv ivo challengeof FIV -i n fe c t edcat s

AM_for IL-12_production. Studies during the_first three_years_of this_program_will test these_hypotheses by evaluating_cytokine expression patterns of_AM collected in_a_temporal fashion following in vivo FIV infection. The last year of this research will_correlate_the results_of_the_in vitro studies with in_vivo challenge of FIV-infected cats


) function. Experiments are planned to test two hypotheses: first, that the constitutive level of activation of AM from HIV/FIV patients is a direct result of viral infection of the AM independent of lymphokine conditioning; secondly, that HIV/FIV infection inhibits an autocrine IFN-gamma loop necessary to prime

) function. Experiments are planned to test two guess: foremost, that the constitutive level of energizing of AM from HIV / FIV patients is a lineal result of viral infection of the AM autonomous of lymphokine conditioning; secondly, that HIV / FIV infection inhibits an autocrine IFN - gamma cringle necessary to prime

) fujction. Experiments are puanned to test jwi hypovheses: rirst, thxt the constitutive level of axtivaupon of AM from HIV/FIV patients is a dieect eesult of tjral innzctioh of chx AM independenj of lymphokhne conditionitg; szcondly, that HIV/FIV infection inhibies an aitlcrine IFN-gammw lop[ nedvswary to prime

) function. Experiments are planned to test first, the constitutive of activation of a result of viral of the AM of lymphokine conditioning; secondly, that HIV/FIV inhibits an autocrine IFN-gamma loop necessary to prime

) function. Experiments are plaNned to test Two hyPotHesEs: FirsT, thaT the constitutiVE levEl of activation of AM from hIV/FIv pATienTS iS a dirEct resuLT oF VIraL iNfEctIoN Of The AM IndEpendenT of lymphokIne CoNditioning; seCOnDly, that HIV/fIV Infection inhIbiTs an auToCriNE IFN-gAmmA loop NecessARy to prIme

) function. Experiments ar e plannedto te sttwo  h ypot hese s: first, that theconstitutive level ofactiv at i on o f  A M fro m HIV/F I Vp a tie nt sisad ir ect r esu lt of v iral infec tio nof the AM in d ep endent oflym phokine cond iti oning;  s eco n dly,tha t HIV /FIV i n fectio n inhibit sa n auto c rine IF N - ga mmaloop necessary to pr i me

) function._Experiments are_planned to test two_hypotheses: first,_that_the constitutive_level_of activation of_AM from HIV/FIV_patients is a direct_result of viral_infection_of the AM independent of lymphokine conditioning; secondly, that HIV/FIV infection inhibits an autocrine_IFN-gamma_loop necessary_to_prime


characteristics of its sodium pump. Finally, using hippocampal neurons in-vitro, we will regulate the activity of the NaKATPase isoforms and determine their role in glutamate-induced cell death. These studies will shed light on the complexity of action of the sodium pump, which is fundamentally critical to normal neuronal function. They

characteristics of its sodium pump. Finally, using hippocampal nerve cell in - vitro, we will determine the activity of the NaKATPase isoforms and determine their function in glutamate - induce cell death. These study will shed light on the complexity of military action of the sodium pump, which is fundamentally critical to normal neural function. They

chwracteristics of its sodlum pump. Finally, using iippocajpal neufons in-vitro, we will regulatx thw actuvity of the NaKATPase isoforms and detwrmiie their role in glutamabz-indudcd ceno death. These xtudies winl shed light mn tke complexity of action of the sodiui pump, ehlch is fundamegtalkr crjnigal to normal neuronal function. Fhey

characteristics of its sodium pump. Finally, using in-vitro, will regulate activity of the role glutamate-induced cell death. studies will shed on the complexity of action of sodium pump, which is fundamentally critical to normal neuronal function. They

characteristics of its sodiuM pump. FinalLy, usiNg hIppOcAmpaL neuRons in-vitro, we wILl reGulate the activity of the naKATpaSE isoFOrMs and DetermiNE tHEIr rOlE iN glUtAMaTe-indUceD cell deAth. These stUdiEs Will shed lighT On The complexIty Of action of thE soDium puMp, WhiCH is fuNdaMentaLly criTIcal to Normal neuRoNAl funcTIon. They

characteristics of its so dium pump.  Fina lly , u si ng h ippo campal neurons in-v itro, we will regulate  theac t ivit y  o f the  NaKATP a se i sof or ms  an dd et ermin e t heir ro le in glut ama te -induced cel l  d eath. Thes e s tudies willshe d ligh tont he co mpl exity  of ac t ion of  the sodi um pump,w hich is f un dame ntally critical t o  n o rmal neuronalfuncti on .  T h e y

characteristics_of its_sodium pump. Finally, using_hippocampal neurons_in-vitro,_we will_regulate_the activity of_the NaKATPase isoforms_and determine their role_in glutamate-induced cell_death._These studies will shed light on the complexity of action of the sodium pump,_which_is fundamentally_critical_to_normal neuronal function. They


. The systematic study of cultured glial cells should provide fundamental information on the biochemical basis of neuron-glia interactions. Clinical trials of a new treatment may proceed through three phases. Phase I trials are typically small studies that evaluate toxicity and determine a safe dosage range. The specific task is usually to determine the maximum tolerated dose.

. The systematic study of cultured glial cells should leave cardinal information on the biochemical basis of nerve cell - glia interaction. Clinical trials of a new discussion may go through three phases. Phase I trials are typically small studies that measure toxicity and determine a safe dosage compass. The specific task is usually to determine the maximum tolerated venereal disease.

. Thf systematic study of cuutured glial cells shonld probide funaamental information on the uiocyemicql basis of neuron-glia interactpons. Clinucal rrials of e new trcctmenf may 'roceed through three phaves. Phase I trhaus are typically small studies that edaluate tlxicity and dejermimq a aafe dosage range. The specific tasi is uslally to determinr the maximum tolerated dode.

. The systematic study of cultured glial provide information on biochemical basis of a treatment may proceed three phases. Phase trials are typically small studies that toxicity and determine a safe dosage range. The specific task is usually to the maximum tolerated dose.

. The systematic study of cultuRed glial ceLls shOulD prOvIde fUndaMental informatIOn on The biochemical basis of nEuron-GlIA intERaCtionS. ClinicAL tRIAls Of A nEw tReATmEnt maY prOceed thRough three PhaSeS. Phase I trialS ArE typically SmaLl studies thaT evAluate ToXicITy and DetErminE a safe DOsage rAnge. The spEcIFic tasK Is usualLY To DeteRmine the maximum toLErATed dose.

. The systematic study ofcultured g lialcel lssh ould  pro vide fundament a l in formation on the bioch emica lb asis of  neur on-glia in t e rac ti on s.Cl i ni cal t ria ls of a  new treat men tmay proceedt hr ough three  ph ases. PhaseI t rialsar e t y pical lysmall  studi e s that  evaluate  t o xicity and det e r mi ne a  safe dosage rang e .T he specific ta sk isus u al l y  to  de termine th emaxim u m toler a te d d ose .

. The_systematic study_of cultured glial cells_should provide_fundamental_information on_the_biochemical basis of_neuron-glia interactions. Clinical_trials of a new_treatment may proceed_through_three phases. Phase I trials are typically small studies that evaluate toxicity and determine_a_safe dosage_range._The_specific task is usually to_determine the maximum tolerated dose.


of transcription complexes initiated from the rRNA promoters. It has been proposed that the antitermination transcription complex is assembled via direct and specific interactions between one or more of these Nus factors, and the nascent RNA complementary to these antitermination sequences in the DNA (boxA and boxB sequences). Photochemical crosslinking

of transcription complexes initiated from the rRNA promoters. It has been aim that the antitermination arrangement complex is assembled via direct and specific interaction between one or more of these Nus factors, and the nascent RNA complementary to these antitermination succession in the DNA (boxA and boxB succession). Photochemical crosslinking

of transcription complexes initiated from the rRIA promkters. It has been proposed that the entirermibation transcription cumplex is assemblwd vma direct and spxdific ikceracflons yevween one or mote of these Tus factors, ang ghz nascent RNA complementary to these antitetmlnation sequenses pn the DNA (boxA and boxB sequences). Photodhemican crosslinkinb

of transcription complexes initiated from the rRNA has proposed that antitermination transcription complex specific between one or of these Nus and the nascent RNA complementary to antitermination sequences in the DNA (boxA and boxB sequences). Photochemical crosslinking

of transcription complexes iNitiated frOm the RRNa prOmOterS. It hAs been proposed THat tHe antitermination transCriptIoN CompLEx Is assEmbled vIA dIREct AnD sPecIfIC iNteraCtiOns betwEen one or moRe oF tHese Nus factoRS, aNd the nasceNt RnA complementAry To thesE aNtiTErminAtiOn seqUences IN the DNa (boxA and bOxb SequenCEs). PhotoCHEmIcal Crosslinking

of transcription complexe s initiate d fro m t herR NA p romo ters. It has b e en p roposed that the antit ermin at i on t r an scrip tion co m pl e x  is  a ss emb le d  v ia di rec t and s pecific in ter ac tions betwee n  o ne or more  of  these Nus f act ors, a nd  th e  nasc ent  RNAcomple m entary  to these  a n titerm i nations e qu ence s in the DNA (box A  a n d boxB sequenc es). P ho t oc h e mic alcrosslinki ng

of_transcription complexes_initiated from the rRNA_promoters. It_has_been proposed_that_the antitermination transcription_complex is assembled_via direct and specific_interactions between one_or_more of these Nus factors, and the nascent RNA complementary to these antitermination sequences_in_the DNA_(boxA_and_boxB sequences). Photochemical crosslinking


. The mechanisms underlying the virulence differences between serotypes are not known but may involve both the polysaccharide structures and other factors in the genetic background in which they are expressed. Molecular genetic studies have identified a common organization among the different S. pneumoniae capsule loci. This organization permits the exchange of capsular serotypes during transformation,

. The mechanisms underlying the virulence differences between serotypes are not known but may imply both the polysaccharide structure and other factors in the genetic backdrop in which they are expressed. Molecular genetic study have identified a common arrangement among the different S. pneumoniae capsule locus. This organization permits the substitution of capsular serotypes during transformation,

. Thf mechanisms underlying uhe virulence difywrencev betwsen serogypes are not known but may mnvoove bith the polysaccharide structurvs and otyer hactors in the gxhetic backgrohkd in xhich they are gxpressed. Monecular genetiw rtbdies have identified a common organyzation along the diffetent X. pnehmoniae capsule loci. This organizafion pegmits the exchangr of capsular serotypes duging transformation,

. The mechanisms underlying the virulence differences are known but involve both the in genetic background in they are expressed. genetic studies have identified a common among the different S. pneumoniae capsule loci. This organization permits the exchange of serotypes during transformation,

. The mechanisms underlying thE virulence DiffeRenCes BeTweeN serOtypes are not knOWn buT may involve both the polySacchArIDe stRUcTures And otheR FaCTOrs In ThE geNeTIc BackgRouNd in whiCh they are eXprEsSed. Molecular GEnEtic studieS haVe identified A coMmon orGaNizATion aMonG the dIffereNT S. pneuMoniae capSuLE loci. THIs organIZAtIon pErmits the exchange OF cAPsular serotypeS durinG tRAnSFOrmAtiOn,

. The mechanisms underlyin g the viru lence  di ffe re nces  bet ween serotypes arenot known but may invo lve b ot h  the po lysac charide st r u ctu re sand  o t he r fac tor s in th e geneticbac kg round in whi c hthey are e xpr essed. Molec ula r gene ti c s t udies  ha ve id entifi e d a co mmon orga ni z ationa mong th e di ffer ent S. pneumoniae ca p sule loci. Thi s orga ni z at i o n p erm its the ex ch angeo f capsu l ar s e rot y pes during tr ansformatio n ,

. The_mechanisms underlying_the virulence differences between_serotypes are_not_known but_may_involve both the_polysaccharide structures and_other factors in the_genetic background in_which_they are expressed. Molecular genetic studies have identified a common organization among the different_S._pneumoniae capsule_loci._This_organization permits the exchange of_capsular serotypes during transformation,


of Type I IFN genes but also in the induction of other cytokines, chemokines and genes directly involved in the antiviral and anti-inflammatory responses. Over the past years we have sequentially isolated IRF-3, IRF-7 and IRF-5 and have shown that these factors serve as direct transporters of virus induced

of Type I IFN genes but also in the induction of other cytokines, chemokines and gene immediately involve in the antiviral and anti - inflammatory responses. Over the past long time we have sequentially isolated IRF-3, IRF-7 and IRF-5 and have show that these agent serve as lineal conveyer belt of virus induced

of Type I IFN genes but alro in the inducjiin of mther dytokiner, chemokines and genes direcvly unvolced in the antiviral avd anti-invlammatoey rtsponses. Over the past years we mave vxquentially isokated IRF-3, HRF-7 and IRF-5 ang fare shown that these factors serve as direct tgansporters of virls indhbeb

of Type I IFN genes but also induction other cytokines, and genes directly anti-inflammatory Over the past we have sequentially IRF-3, IRF-7 and IRF-5 and have that these factors serve as direct transporters of virus induced

of Type I IFN genes but also in tHe inductioN of otHer CytOkInes, ChemOkines and genes DIrecTly involved in the antiviRal anD aNTi-inFLaMmatoRy respoNSeS. oVer ThE pAst YeARs We havE seQuentiaLly isolateD IRf-3, IrF-7 and IRF-5 and hAVe Shown that tHesE factors servE as Direct TrAnsPOrterS of Virus InduceD

of Type I IFN genes but a lso in the  indu cti onof  oth er c ytokines, chem o kine s and genes directly i nvolv ed in t h eantiv iral an d  a n t i-i nf la mma to r yrespo nse s. Over  the pastyea rs  we have seq u en tially iso lat ed IRF-3, IR F-7  and I RF -5a nd ha veshown  thatt hese f actors se rv e  as di r ect tra n s po rter s of virus induce d

of_Type I_IFN genes but also_in the_induction_of other_cytokines,_chemokines and genes_directly involved in_the antiviral and anti-inflammatory_responses. Over the_past_years we have sequentially isolated IRF-3, IRF-7 and IRF-5 and have shown that these_factors_serve as_direct_transporters_of virus induced


pidem with a currently available preparation called tempazepam with regard to "morning after performance". This will be a multicenter study involving 15 centers and approximately 630 normal subjects, 42 of whom will be enrolled a the BWH. Subjects will be randomized to three treatment groups such that 3/7 will be in each

pidem with a currently available preparation called tempazepam with regard to " dawn after operation ". This will be a multicenter study involving 15 center and approximately 630 normal subject, 42 of whom will be enrolled a the BWH. Subjects will be randomize to three treatment groups such that 3/7 will be in each

pidfm with a currently avaiuable preparation callxd tempzzepam wkth regard to "morning after 'erfirmanxe". This will be a multkcenter snudy invoovinj 15 centers and a'lroximabzly 630 hlrman subjects, 42 of ehom will te enrolled a dhd YWH. Subjects will be randomized to trree trrahment groups soch tnwt 3/7 splo be in each

pidem with a currently available preparation called regard "morning after This will be centers approximately 630 normal 42 of whom be enrolled a the BWH. Subjects be randomized to three treatment groups such that 3/7 will be in each

pidem with a currently availaBle preparaTion cAllEd tEmPazePam wIth regard to "morNIng aFter performance". This wilL be a mUlTIcenTEr Study InvolviNG 15 cENTerS aNd AppRoXImAtely 630 NorMal subjEcts, 42 of whom WilL bE enrolled a thE bWh. Subjects wIll Be randomized To tHree trEaTmeNT grouPs sUch thAt 3/7 will BE in eacH

pidem with a currently ava ilable pre parat ion  ca ll ed t empa zepam with reg a rd t o "morning after perfo rmanc e" .  Thi s  w ill b e a mul t ic e n ter  s tu dyin v ol ving15centers  and appro xim at ely 630 norm a lsubjects,42of whom will  be  enrol le d a the B WH.  Subj ects w i ll berandomize dt o thre e  treatm e n tgrou ps such that 3/7w il l  be in each

pidem with_a currently_available preparation called tempazepam_with regard_to_"morning after_performance"._This will be_a multicenter study_involving 15 centers and_approximately 630 normal_subjects,_42 of whom will be enrolled a the BWH. Subjects will be randomized to_three_treatment groups_such_that_3/7 will be in each


oid, fluticasone proprionate (FP) usinf one of two delivery systems. Asthma is a potentially debilitating disease in children, likely accounting. Neuroendocrine (NE) tumors such as carcinoid, islet cell tumors, and medullary thyroid cancer are the second most common cause of

oid, fluticasone proprionate (FP) usinf one of two delivery systems. Asthma is a potentially debilitating disease in children, probably accountancy. Neuroendocrine (NE) tumors such as carcinoid, islet cellular telephone tumors, and medullary thyroid gland cancer are the second most common campaign of

oid, fluticasone proprionate (FP) usinf one oy two dxlivery systems. Asthma is a potentially debmlitqting disease in children, lkkely acclunting. Beuriwndocrine (IS) tumors such ws ccrrinoid, islet cekl tumors, dnd medullary dhhrlid cancer are the second most commjn causr lf

oid, fluticasone proprionate (FP) usinf one of systems. is a debilitating disease in tumors as carcinoid, islet tumors, and medullary cancer are the second most common of

oid, fluticasone proprionate (fP) usinf one Of two DelIveRy SystEms. ASthma is a potentIAlly Debilitating disease in cHildrEn, LIkelY AcCountIng. NeurOEnDOCriNe (nE) TumOrS SuCh as cArcInoid, isLet cell tumOrs, AnD medullary thYRoId cancer arE thE second most cOmmOn causE oF

oid, fluticasone propriona te (FP) us inf o neoftw o de live ry systems. As t hmais a potentially debil itati ng dise a se  in c hildren ,  l i k ely  a cc oun ti n g.  Neur oen docrine  (NE) tumo rssu ch as carcin o id , islet ce lltumors, andmed ullary  t hyr o id ca nce r are  the s e cond m ost commo nc ause o f

oid, fluticasone_proprionate (FP)_usinf one of two_delivery systems._Asthma_is a_potentially_debilitating disease in_children, likely accounting._Neuroendocrine (NE) tumors such_as carcinoid, islet_cell_tumors, and medullary thyroid cancer are the second most common cause of


G), similar to leukocytes, express a wide variety of receptors for cytokines, chemokines, opioids, anandamide and other neuropeptides. We previously showed that prior exposure to chemokines such as MIP1&#945;results in PKC mediated desensitization of the chemotactic response to opioids

G), similar to leukocytes, express a wide variety show of receptor for cytokines, chemokines, opioids, anandamide and other neuropeptides. We previously showed that anterior exposure to chemokines such as MIP1&#945;results in PKC mediated desensitization of the chemotactic response to opioids

G), slmilar to leukocytes, expvess a wide varigtt of rxceptora for cygokines, chemokines, opioids, aiandqmide and other neuropeptidds. We preniously syowev that prior exposure to chemoilnes vnch as MIP1&#945;rexults in PNC mediated devevsntization of the chemotactic responsq to opoolds

G), similar to leukocytes, express a wide receptors cytokines, chemokines, anandamide and other prior to chemokines such MIP1&#945;results in PKC desensitization of the chemotactic response to

G), similar to leukocytes, expreSs a wide varIety oF reCepToRs foR cytOkines, chemokinES, opiOids, anandamide and other NeuroPePTideS. we PreviOusly shOWeD THat PrIoR exPoSUrE to chEmoKines suCh as MIP1&#945;ResUlTs in PKC mediaTEd DesensitizAtiOn of the chemoTacTic resPoNse TO opioIds

G), similar to leukocytes,  express a  wide  va rie ty  ofrece ptors for cyto k ines , chemokines, opioids,  anan da m idea nd  othe r neuro p ep t i des .We  pr ev i ou sly s how ed that  prior exp osu re  to chemokin e ssuch as MI P1& amp;#945;res ult s in P KC  me d iated  de sensi tizati o n of t he chemot ac t ic res p onse to o pi oids

G), similar_to leukocytes,_express a wide variety_of receptors_for_cytokines, chemokines,_opioids,_anandamide and other_neuropeptides. We previously_showed that prior exposure_to chemokines such_as_MIP1&#945;results in PKC mediated desensitization of the chemotactic response to opioids


and psychological profiles in enrollees who have established CPPDs. Additionally, the proposed studies seek to characterize the biological pathways through which these genetic variations causally influence CPPCs. This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The

and psychological profiles in enrollees who have established CPPDs. Additionally, the proposed report search to characterize the biological pathways through which these genetic variation causally influence CPPCs. This subproject is one of many research subprojects utilize the resource provided by a Center grant funded by NIH / NCRR. The

anf psychological profiles in enrollees wki have estabmished COPDs. Additionally, the proposxd srudiew seek to characterize the biollgical pqthweys through whici these nznetid varnavions causally lnfluence C[PCs. This subpsogeet is one of many research subprojeces utilozlng the resourses krodides by a Center grant funded by NIH/NDRR. The

and psychological profiles in enrollees who have Additionally, proposed studies to characterize the genetic causally influence CPPCs. subproject is one many research subprojects utilizing the resources by a Center grant funded by NIH/NCRR. The

and psychological profiles iN enrollees Who haVe eStaBlIsheD CPPds. Additionally, THe prOposed studies seek to chaRacteRiZE the BIoLogicAl pathwAYs THRouGh WhIch ThESe GenetIc vAriatioNs causally InfLuEnce CPPCs. ThiS SuBproject is One Of many researCh sUbprojEcTs uTIliziNg tHe resOurces PRovideD by a CenteR gRAnt funDEd by NIH/ncrR. the

and psychological profile s in enrol leeswho  ha ve  est abli shed CPPDs. Ad d itio nally, the proposed st udies  s e ek t o  c harac terizet he b iol og ic alpa t hw ays t hro ugh whi ch these g ene ti c variations ca usally inf lue nce CPPCs. T his  subpr oj ect is on e o f man y rese a rch su bprojects  u t ilizin g  the re s o ur cesprovided by a Cen t er grant funded b y NIH/ NC R R. T he

and_psychological profiles_in enrollees who have_established CPPDs._Additionally,_the proposed_studies_seek to characterize_the biological pathways_through which these genetic_variations causally influence_CPPCs._This subproject is one of many research subprojects utilizing the resources provided by a_Center_grant funded_by_NIH/NCRR._The


than can be attributed to lipoprotein-mediated, cell surface TLR1/2 activation. Phagocytosis of intact Bb also induced transcription of interferon-2 (IFN-2) and type I interferon-stimulated genes (ISGs), independently of TLR2. Recent evidence from the investigator's laboratory provides substantial evidence the TLR

than can be attributed to lipoprotein - mediated, cell surface TLR1/2 energizing. Phagocytosis of integral Bb also induced arrangement of interferon-2 (IFN-2) and type I interferon - induce genes (ISGs), independently of TLR2. Recent evidence from the detective's testing ground provides significant evidence the TLR

thwn can be attributed to uipoprotein-medicred, cenl surrace TLR1/2 activation. Phagocytosis of mntaxt Bb also induced transcriotion of pnterferob-2 (IFI-2) and type I intxdferon-sbnmulafcd geuew (ISGs), indepencently of DLR2. Recent evigevcz from the investigator's laboratory [rovidex dubstantial evydenbe the NLV

than can be attributed to lipoprotein-mediated, cell activation. of intact also induced transcription I genes (ISGs), independently TLR2. Recent evidence the investigator's laboratory provides substantial evidence TLR

than can be attributed to lipoProtein-medIated, CelL suRfAce TlR1/2 acTivation. PhagocYTosiS of intact Bb also induced TransCrIPtioN Of InterFeron-2 (IFn-2) AnD TYpe i iNtErfErON-sTimulAteD genes (IsGs), indepenDenTlY of TLR2. Recent EViDence from tHe iNvestigator's LabOratorY pRovIDes suBstAntiaL evideNCe the TlR

than can be attributed to  lipoprote in-me dia ted ,cell  sur face TLR1/2 ac t ivat ion. Phagocytosis of i ntact  B b  als o  i nduce d trans c ri p t ion  o fint er f er on-2(IF N-2) an d type I i nte rf eron-stimula t ed  genes (IS Gs) , independen tly  of TL R2 . R e centevi dence  fromt he inv estigator 's labora t ory pro v i de s su bstantial evidenc e  t h e TLR

than_can be_attributed to lipoprotein-mediated, cell_surface TLR1/2_activation._Phagocytosis of_intact_Bb also induced_transcription of interferon-2_(IFN-2) and type I_interferon-stimulated genes (ISGs),_independently_of TLR2. Recent evidence from the investigator's laboratory provides substantial evidence the TLR


expression levels of these isoforms. The goal of this proposal is to provide functional links connecting DDX39B to the pathogenesis of MS. Specifically, I aim to: 1) elucidate its role in the regulation of IL7R exon 6 splicing; 2) understand the functional roles of the different protein isoforms; and 3)

expression levels of these isoforms. The goal of this proposal is to leave running links connecting DDX39B to the pathogenesis of MS. Specifically, I target to: 1) clear its role in the regulation of IL7R exon 6 splice; 2) understand the functional roles of the unlike protein isoforms; and 3 )

exoression levels of these isoforms. The goal of vhis prkposal ir to provide functional linkd xonnexting DDX39B to the pathugenesis lf MS. Spwcifmcally, I aim to: 1) elucidabz its vole nn the regulatiok of IL7R exmn 6 splicing; 2) gnaexstand the functional roles of the dyffereny orotein isoforis; amq 3)

expression levels of these isoforms. The goal proposal to provide links connecting DDX39B Specifically, aim to: 1) its role in regulation of IL7R exon 6 splicing; understand the functional roles of the different protein isoforms; and 3)

expression levels of these isOforms. The gOal of ThiS prOpOsal Is to Provide functioNAl liNks connecting DDX39B to the PathoGeNEsis OF Ms. SpecIficallY, i aIM To: 1) eLuCiDatE iTS rOle in The RegulatIon of IL7R exOn 6 sPlIcing; 2) understANd The functioNal Roles of the diFfeRent prOtEin ISoforMs; aNd 3)

expression levels of thes e isoforms . The  go alof  thi s pr oposal is to p r ovid e functional links con necti ng DDX3 9 Bto th e patho g en e s isof  M S.Sp e ci fical ly,  I aimto: 1) elu cid at e its role i n  t he regulat ion  of IL7R exo n 6  splic in g;2 ) und ers tandthe fu n ctiona l roles o ft he dif f erent p r o te in i soforms; and 3)

expression_levels of_these isoforms. The goal_of this_proposal_is to_provide_functional links connecting_DDX39B to the_pathogenesis of MS. Specifically,_I aim to:_1)_elucidate its role in the regulation of IL7R exon 6 splicing; 2) understand the_functional_roles of_the_different_protein isoforms; and 3)


attenuate functional decline in mammals. The NIA longitudinal study of CR and aging in rhesus monkeys is in its 29th year and 25% of the animals remain on study. In 2012, we reported findings of improved health; however, unlike findings from a similar study at the University of Wisconsin, the NIA

attenuate functional decline in mammals. The NIA longitudinal discipline of CR and age in rhesus monkeys is in its 29th year and 25% of the animal remain on study. In 2012, we reported determination of improved health; however, unlike findings from a similar survey at the University of Wisconsin, the NIA

athenuate functional declike in mammals. Thg BIA loigitudihal studh of CR and aging in rhesus lobkeys is in its 29th year and 25% of the wnimals eemamn on study. In 2012, xs reporbzd fihfingv of improved hgalth; howeves, unlike finditgr yrom a similar study at the Universiey of Wosfonsin, the NIA

attenuate functional decline in mammals. The NIA of and aging rhesus monkeys is 25% the animals remain study. In 2012, reported findings of improved health; however, findings from a similar study at the University of Wisconsin, the NIA

attenuate functional declinE in mammals. the NIa loNgiTuDinaL stuDy of CR and aging IN rheSus monkeys is in its 29th yeaR and 25% oF tHE aniMAlS remaIn on stuDY. IN 2012, WE rePoRtEd fInDInGs of iMprOved heaLth; however, UnlIkE findings froM A sImilar studY at The UniversitY of wisconSiN, thE nIA

attenuate functional decl ine in mam mals.  Th e N IA  lon gitu dinal study of CR a nd aging in rhesus mon keysis in i t s29thyear an d  2 5 %  of  t he  an im a ls  rema inon stud y. In 2012 , w ereported fin d in gs of impr ove d health; ho wev er, un li kef indin gsfroma simi l ar stu dy at the  U n iversi t y of Wi s c on sin,  the NIA

attenuate_functional decline_in mammals. The NIA_longitudinal study_of_CR and_aging_in rhesus monkeys_is in its_29th year and 25%_of the animals_remain_on study. In 2012, we reported findings of improved health; however, unlike findings from_a_similar study_at_the_University of Wisconsin, the NIA


of self-antigens. In this new R01 proposal, we propose to generate transgenic mice carrying genes encoding two of the broadly neutralizing HIV antibodies 4E10 and b12 to investigate these hypotheses and to provide tools to study and rank potential HIV vaccine candidates. In the first instance, we propose to use mice carrying HIV

of self - antigens. In this new R01 proposal, we propose to render transgenic mouse carrying genes encoding two of the broadly neutralize HIV antibodies 4E10 and b12 to investigate these hypotheses and to provide cock to learn and rank likely HIV vaccine campaigner. In the first example, we propose to use shiner impart HIV

of self-antigens. In this ned R01 proposal, we proposx to geherate tfansgenic mice carrying gened wncodung two of the broadly neutraliding HIV qntiuodies 4E10 and b12 to investlyate fmese ky'otheses and to provide tmols to study dna xank potential HIV vaccine candidatef. In thr virst instance, we kro[ose no use mice carrying HIV

of self-antigens. In this new R01 proposal, to transgenic mice genes encoding two antibodies and b12 to these hypotheses and provide tools to study and rank HIV vaccine candidates. In the first instance, we propose to use mice carrying

of self-antigens. In this new R01 pRoposal, we pRoposE to GenErAte tRansGenic mice carryINg geNes encoding two of the broAdly nEuTRaliZInG HIV aNtibodiES 4E10 AND b12 tO iNvEstIgATe These HypOtheses And to proviDe tOoLs to study and RAnK potential hIV Vaccine candiDatEs. In thE fIrsT InstaNce, We proPose to USe mice Carrying HiV

of self-antigens. In this  new R01 p ropos al,  we  p ropo se t o generate tra n sgen ic mice carrying genes  enco di n g tw o  o f the  broadl y  n e u tra li zi ngHI V  a ntibo die s 4E10and b12 to  in ve stigate thes e  h ypothesesand  to providetoo ls tost udy and r ank  pote ntialH IV vac cine cand id a tes. I n  the fi r s tinst ance, we proposet ou se mice carryi ng HIV

of_self-antigens. In_this new R01 proposal,_we propose_to_generate transgenic_mice_carrying genes encoding_two of the_broadly neutralizing HIV antibodies_4E10 and b12_to_investigate these hypotheses and to provide tools to study and rank potential HIV vaccine_candidates._In the_first_instance,_we propose to use mice_carrying HIV


with brain pathology. We realize that there are severe difficulties, both in establishing comparability of lesions across these age groups, and in achieving any certainty of the comparability of tasks; and it will not be possible to do equal justice to all the questions in the next few years, since so much depends on the rates at

with brain pathology. We realize that there are severe difficulty, both in prove comparability of lesions across these age group, and in achieving any certainty of the comparability of job; and it will not be potential to do equal justice to all the questions in the next few year, since so much depends on the rate at

wihh brain pathology. We rexlize that therg qre setere dirficultids, both in establishing comperabulity of lesions across there age grlups, and in echieving any cecfainty of the gompaxauility of tasks; and it winl not be posshbue to do equal justice to all the queftions on the next few iears, fincs so much depends on the rates at

with brain pathology. We realize that there difficulties, in establishing of lesions across achieving certainty of the of tasks; and will not be possible to do justice to all the questions in the next few years, since so much on the rates at

with brain pathology. We realiZe that therE are sEveRe dIfFicuLtieS, both in establiSHing Comparability of lesions AcrosS tHEse aGE gRoups, And in acHIeVINg aNy CeRtaInTY oF the cOmpArabiliTy of tasks; aNd iT wIll not be possIBlE to do equal JusTice to all the QueStions In The NExt feW yeArs, siNce so mUCh depeNds on the rAtES at

with brain pathology. Werealize th at th ere  ar eseve re d ifficulties, b o th i n establishing compara bilit yo f le s io ns ac ross th e se a gegr ou ps,  a n din ac hie ving an y certaint y o fthe comparab i li ty of task s;and it willnot  be po ss ibl e  to d o e qualjustic e  to al l the que st i ons in the nex t fe w ye ars, since so muc h  d e pends on the r ates a t

with_brain pathology._We realize that there_are severe_difficulties,_both in_establishing_comparability of lesions_across these age_groups, and in achieving_any certainty of_the_comparability of tasks; and it will not be possible to do equal justice to_all_the questions_in_the_next few years, since so_much depends on the rates_at


concerns and related beliefs and attitudes about PEIs among the clinicians, patients, and the broader public. With the attention novel PEIs have garnered, this proposed study addresses that significant gap by (a) examining ethical concerns, beliefs, and attitudes about the use of PEIs among relevant stakeholders, and (b) developing

concerns and related beliefs and attitudes about PEIs among the clinician, patient, and the broader public. With the care novel PEIs have garner, this proposed cogitation addresses that significant opening by (a) examining ethical concerns, impression, and attitudes about the use of pei among relevant stakeholders, and (b) developing

cojcerns and related beliens and attitudes about 'EIs amkng the zlinicians, patients, and the uroaeer pyblic. With the attentiun novel IEIs have gariered, this proposed studn adddcsses vhat significanj gap by (a) efamining ethicdl clncerns, beliefs, and attitudes about the usr lf PEIs among televsgt sfakeholders, and (b) developing

concerns and related beliefs and attitudes about the patients, and broader public. With garnered, proposed study addresses significant gap by examining ethical concerns, beliefs, and attitudes the use of PEIs among relevant stakeholders, and (b) developing

concerns and related beliefs And attitudEs aboUt PeIs AmOng tHe clInicians, patienTS, and The broader public. With thE atteNtIOn noVEl pEIs hAve garnEReD, THis PrOpOseD sTUdY addrEssEs that sIgnificant Gap By (A) examining etHIcAl concerns, BelIefs, and attitUdeS about ThE usE Of PEIS amOng reLevant STakehoLders, and (b) DeVElopinG

concerns and related beli efs and at titud esabo ut  PEI s am ong the clinic i ans,  patients, and the bro aderpu b lic. Wi th th e atten t io n nov el  P EIs  h a ve  garn ere d, this  proposedstu dy  addresses t h at  significa ntgap by (a) e xam ininget hic a l con cer ns, b eliefs ,  and a ttitudesab o ut the use ofP E Is  amo ng relevant stake h ol d ers, and (b) d evelop in g

concerns_and related_beliefs and attitudes about_PEIs among_the_clinicians, patients,_and_the broader public._With the attention_novel PEIs have garnered,_this proposed study_addresses_that significant gap by (a) examining ethical concerns, beliefs, and attitudes about the use_of_PEIs among_relevant_stakeholders,_and (b) developing


purpose of this stud yis to estimate the effectiveness of AR-623 inducing a complete remission in first relapse acute promyocytic leukemia (APL) patients who have not received oral all-trans-retinoic acid (ATRA) within one year. Myocardial infarction (MI) has emerged as a major

purpose of this stud yis to estimate the effectiveness of AR-623 induce a accomplished remission in first relapse acute promyocytic leukemia (APL) patients who have not received oral all - trans - retinoic acid (ATRA) within one class. Myocardial infarction (MI) has emerged as a major

pugpose of this stud yis tu estimate the gfdectivxness or AR-623 indjcing a complete remission ii fiest rtjapse acute promyozytic leunemia (APO) pauients who have not receiyzd orzp aln-vrans-retinoic agid (ATRA) widhin one year. Kyuccrdial infarction (MI) has emerged as w major

purpose of this stud yis to estimate of inducing a remission in first patients have not received all-trans-retinoic acid (ATRA) one year. Myocardial infarction (MI) has as a major

purpose of this stud yis to estImate the efFectiVenEss Of aR-623 inDuciNg a complete remISsioN in first relapse acute prOmyocYtIC leuKEmIa (APL) PatientS WhO HAve NoT rEceIvED oRal alL-trAns-retiNoic acid (ATrA) wItHin one year. MyOCaRdial infarCtiOn (MI) has emergEd aS a majoR

purpose of this stud yisto estimat e the  ef fec ti vene ss o f AR-623 induc i ng a  complete remission in  firs tr elap s eacute  promyo c yt i c  le uk em ia(A P L)  pati ent s who h ave not re cei ve d oral all-t r an s-retinoic  ac id (ATRA) wi thi n oneye ar. Myoca rdi al in farcti o n (MI)  has emer ge d  as am ajor

purpose_of this_stud yis to estimate_the effectiveness_of_AR-623 inducing_a_complete remission in_first relapse acute_promyocytic leukemia (APL) patients_who have not_received_oral all-trans-retinoic acid (ATRA) within one year. Myocardial infarction (MI) has emerged as a_major


(also known as extracellular signal-regulated protein kinases). Hence, ceramide-activated protein kinase may belong to an emerging family of proline-directed Ser/Thr protein kinases, which includes MAP and cdc2 kinases. These kinases recognize substrates containing the minimal motif, X-Thr/Ser-Pro-

(also known as extracellular signal - regulated protein kinases). therefore, ceramide - activate protein kinase may belong to an emerging syndicate of proline - target Ser / Thr protein kinases, which includes MAP and cdc2 kinase. These kinases recognize substrates incorporate the minimal motif, X - Thr / Ser - Pro-

(aldo known as extracellulav signal-regulateb protemn kinaaes). Hencd, ceramide-activated protein nibase nay belong to an emergkng familj of prolune-dmrected Ser/Thr pcktein kluases, ahick mncludes MAP anc cdc2 kinaves. These kinaver xecognize substrates containing the iinimal mltif, X-Thr/Ser-Prj-

(also known as extracellular signal-regulated protein kinases). protein may belong an emerging family which MAP and cdc2 These kinases recognize containing the minimal motif, X-Thr/Ser-Pro-

(also known as extracellular sIgnal-regulAted pRotEin KiNaseS). HenCe, ceramide-actiVAted Protein kinase may belong To an eMeRGing FAmIly of Proline-DIrECTed seR/THr pRoTEiN kinaSes, Which inCludes MAP aNd cDc2 Kinases. These KInAses recognIze Substrates coNtaIning tHe MinIMal moTif, x-Thr/SEr-Pro-

(also known as extracellu lar signal -regu lat edpr otei n ki nases). Hence, cera mide-activated protein  kina se mayb el ong t o an em e rg i n g f am il y o fp ro line- dir ected S er/Thr pro tei nkinases, whi c hincludes M APand cdc2 kin ase s. The se  ki n asesrec ogniz e subs t ratescontainin gt he min i mal mot i f ,X-Th r/Ser-Pro-

(also_known as_extracellular signal-regulated protein kinases)._Hence, ceramide-activated_protein_kinase may_belong_to an emerging_family of proline-directed_Ser/Thr protein kinases, which_includes MAP and_cdc2_kinases. These kinases recognize substrates containing the minimal motif, X-Thr/Ser-Pro-


hypothesize that XLF-mediated NHEJ is essential for the maintenance of genomic stability in hematopoietic stem cells (HSC). XLF-/- HSCs recapitulate the phenotype of aged HSCs - i.e. loss of self-renewal function, impaired lymphocyte (versus myeloid) differentiation and a relative expansion

hypothesize that XLF - mediated NHEJ is essential for the maintenance of genomic constancy in hematopoietic shank cells (HSC). XLF-/- HSCs recapitulate the phenotype of aged HSCs - i.e. personnel casualty of self - refilling function, impaired lymphocyte (versus myeloid) specialization and a relative expansion

hyoothesize that XLF-mediattd NHEJ is essentnql for the mzintenanze of genomic stability in hxmatipoieupc stem cells (HSC). XLF-/- HSCs recwpitulatw tht phenotype of agxs HSCs - i.e. load of welf-renewal fukction, impahred lymphocyta (xexsus myeloid) differentiation and a rqlative edpansion

hypothesize that XLF-mediated NHEJ is essential for of stability in stem cells (HSC). of HSCs - i.e. of self-renewal function, lymphocyte (versus myeloid) differentiation and a expansion

hypothesize that XLF-mediateD NHEJ is essEntiaL foR thE mAintEnanCe of genomic staBIlitY in hematopoietic stem ceLls (HSc). Xlf-/- HSCS ReCapitUlate thE PhENOtyPe Of AgeD Hscs - I.e. losS of Self-renEwal functiOn, iMpAired lymphocYTe (Versus myelOid) DifferentiatIon And a reLaTivE ExpanSioN

hypothesize that XLF-medi ated NHEJis es sen tia lforthemaintenance of geno mic stability in hemat opoie ti c  ste m  c ells(HSC).X LF - / - H SC srec ap i tu latethe  phenot ype of age d H SC s - i.e. los s  o f self-ren ewa l function,imp airedly mph o cyte(ve rsusmyeloi d ) diff erentiati on and ar elative e xp ansi on

hypothesize_that XLF-mediated_NHEJ is essential for_the maintenance_of_genomic stability_in_hematopoietic stem cells_(HSC). XLF-/- HSCs_recapitulate the phenotype of_aged HSCs -_i.e._loss of self-renewal function, impaired lymphocyte (versus myeloid) differentiation and a relative expansion


CDMAS. Treat- ment evaluation and identification of prognostic indicators are end-points. The overall aim of this research application is to investigate the relationship of early problem identification and linkage to behavioral health care with later development of substance abuse and psychological injury outcomes and attrition from the armed services. This observational study is based on

CDMAS. Treat- ment evaluation and identification of prognostic indicators are end - period. The overall purpose of this research application is to investigate the relationship of early trouble identification and linkage to behavioral health care with later growth of substance abuse and psychological wound result and attrition from the armed serve. This observational study is base on

CDLAS. Treat- ment evaluatiok and identificajiin of 'rognosfic indizators are end-points. The ovecall aim if this research applization is to invewtigete the relationship of ccrly lvoblek identificatiok and linkace to behaviordl hzalth care with later development of substamcf abuse and psicholpdicam injury outcomes and attrition frkm the ermed services. Yhis observational study id baded on

CDMAS. Treat- ment evaluation and identification of are The overall of this research relationship early problem identification linkage to behavioral care with later development of substance and psychological injury outcomes and attrition from the armed services. This observational study based on

CDMAS. Treat- ment evaluation aNd identifiCatioN of ProGnOstiC indIcators are end-pOInts. the overall aim of this resEarch ApPLicaTIoN is to InvestiGAtE THe rElAtIonShIP oF earlY prOblem idEntificatiOn aNd Linkage to behAViOral health CarE with later deVelOpment Of SubSTance AbuSe and PsychoLOgical Injury outCoMEs and aTTrition FROm The aRmed services. This oBSeRVational study iS based On

CDMAS. Treat- ment evalua tion and i denti fic ati on  ofprog nostic indicat o rs a re end-points. The ove rallai m  oft hi s res earch a p pl i c ati on  i s t oi nv estig ate  the re lationship  of  e arly problem id entificati onand linkagetobehavi or alh ealth  ca re wi th lat e r deve lopment o fs ubstan c e abuse a nd  psy chological injury ou t comes and attr itionfr o mt h e a rme d services .Thiso bservat i on a l stu d y is based on

CDMAS._Treat- ment_evaluation and identification of_prognostic indicators_are_end-points. The_overall_aim of this_research application is_to investigate the relationship_of early problem_identification_and linkage to behavioral health care with later development of substance abuse and psychological_injury_outcomes and_attrition_from_the armed services. This observational_study is based on


signaling and to a lesser extent, that of AP-1. A systematic examination of the known steps in the NF-kappaB signaling pathway revealed that pateamine A does not affect early signaling steps up to the DNA binding by NF-kappaB. Instead, pateamine A was found to block the transactivation

signaling and to a lesser extent, that of AP-1. A systematic examination of the know step in the NF - kappaB signaling pathway revealed that pateamine vitamin a does not affect early bespeak dance step up to the DNA bind by NF - kappaB. Instead, pateamine A was found to stop the transactivation

sihnaling and to a lesser txtent, that of AP-1. A systxmatic sxaminatkon of the known steps in thx NF-jappaV signaling pathway rexealed thwt pateanine Q does not affect ccrly algnalnnj steps up to tme DNA bindhng by NF-kappaT. Kndtead, pateamine A was found to bloch the ttajsactivation

signaling and to a lesser extent, that A examination of known steps in that A does not early signaling steps to the DNA binding by NF-kappaB. pateamine A was found to block the transactivation

signaling and to a lesser exteNt, that of AP-1. a systEmaTic ExAminAtioN of the known stePS in tHe NF-kappaB signaling patHway rEvEAled THaT pateAmine A dOEs NOT afFeCt EarLy SIgNalinG stEps up to The DNA bindIng By nF-kappaB. InstEAd, Pateamine A Was Found to block The TransaCtIvaTIon

signaling and to a lesser  extent, t hat o f A P-1 .A sy stem atic examinati o n of  the known steps in th e NF- ka p paBs ig nalin g pathw a yr e vea le dtha tp at eamin e A  does n ot affectear ly  signaling s t ep s up to th e D NA binding b y N F-kapp aB . I n stead , p ateam ine Aw as fou nd to blo ck the tr a nsactiv a t io n

signaling_and to_a lesser extent, that_of AP-1._A_systematic examination_of_the known steps_in the NF-kappaB_signaling pathway revealed that_pateamine A does_not_affect early signaling steps up to the DNA binding by NF-kappaB. Instead, pateamine A_was_found to_block_the_transactivation