amers of a protein (connexon) from a family of integral membrane proteins known as eonnexins. Here, we focus on the structure and function of connexin26 (Cx26), the smallest of the family. Mutations in the DNA sequence can result in hereditary sensorineural deafness and account for

amers of a protein (connexon) from a family of integral membrane proteins known as eonnexins. Here, we concentrate on the social organization and function of connexin26 (Cx26), the smallest of the syndicate. mutation in the DNA sequence can result in ancestral sensorineural deafness and report for

amegs of a protein (connexon) from a family of intejral mejbrane pfoteins known as eonnexins. Hxre, qe foxus on the structure avd functiln of cobnexmn26 (Cx26), the smallest of thc famjpy. Mbtetions in the DKA sequence can result in hdrzditary sensorineural deafness and ascount gog

amers of a protein (connexon) from a integral proteins known eonnexins. Here, we function connexin26 (Cx26), the of the family. in the DNA sequence can result hereditary sensorineural deafness and account for

amers of a protein (connexon) frOm a family oF inteGraL meMbRane ProtEins known as eonNExinS. Here, we focus on the strucTure aNd FUnctIOn Of conNexin26 (Cx26), THe SMAllEsT oF thE fAMiLy. MutAtiOns in thE DNA sequenCe cAn Result in hereDItAry sensoriNeuRal deafness aNd aCcount FoR

amers of a protein (connex on) from a  fami lyofin tegr al m embrane protei n s kn own as eonnexins. Here , wefo c us o n  t he st ructure an d fun ct io n o fc on nexin 26(Cx26),  the small est  o f the family .  M utations i n t he DNA seque nce  can r es ult in he red itary  senso r ineura l deafnes sa nd acc o unt for

amers of_a protein_(connexon) from a family_of integral_membrane_proteins known_as_eonnexins. Here, we_focus on the_structure and function of_connexin26 (Cx26), the_smallest_of the family. Mutations in the DNA sequence can result in hereditary sensorineural deafness_and_account for


smokers take in nicotine by inhalation and as one of over 4,000 chemicals present in cigarette smoke. The adequacy of using such artificial dosing paradigms to model cigarette smoking is unknown and largely untested. We have adapted and characterized methods for inhalation exposure of rats to smoke simulating the smoking of 1 cigarette or periods of

smokers take in nicotine by inhalation and as one of over 4,000 chemicals present in cigarette fastball. The sufficiency of using such artificial dosing paradigms to exemplar cigarette smoke is unknown and largely untested. We have adjust and characterized method acting for inhalation vulnerability of rats to smoke simulate the smoking of 1 cigarette or periods of

smlkers take in nicotine bn inhalation and as one of ovsr 4,000 chemkcals present in cigarette sloje. Tht adequacy of using such artpficial disinj paradigms to model cigarette dmoknnj is unknown anc largely gntested. We haee abapted and characterized methods for inhalayiln exposure of ratx to amoke simulating the smoking of 1 cjgarettt or periods of

smokers take in nicotine by inhalation and of 4,000 chemicals in cigarette smoke. artificial paradigms to model smoking is unknown largely untested. We have adapted and methods for inhalation exposure of rats to smoke simulating the smoking of 1 or periods of

smokers take in nicotine by inHalation anD as onE of OveR 4,000 cHemiCals Present in cigarETte sMoke. The adequacy of using Such aRtIFiciAL dOsing ParadigMS tO MOdeL cIgAreTtE SmOking Is uNknown aNd largely uNteStEd. We have adapTEd And charactEriZed methods foR inHalatiOn ExpOSure oF raTs to sMoke siMUlatinG the smokiNg OF 1 cigarETte or peRIOdS of

smokers take in nicotineby inhalat ion a ndason e of  ove r 4,000 chemic a ls p resent in cigarette sm oke.Th e  ade q ua cy of  usings uc h art if ic ial  d o si ng pa rad igms to  model cig are tt e smoking is un known andlar gely unteste d.We hav eada p ted a ndchara cteriz e d meth ods for i nh a lation exposur e of  rat s to smoke simula t in g  the smoking o f 1 ci ga r et t e  or  pe riods of

smokers_take in_nicotine by inhalation and_as one_of_over 4,000_chemicals_present in cigarette_smoke. The adequacy_of using such artificial_dosing paradigms to_model_cigarette smoking is unknown and largely untested. We have adapted and characterized methods for_inhalation_exposure of_rats_to_smoke simulating the smoking of_1 cigarette or periods of


studies of cancer, and development of a set of interactive computer programs which can be used to analyze the trends of cancer rates over time. The central purpose of the proposed research is to define the roles which drug metabolism and pharmacokinetic factors play in determining the clinical response to certain commonly abused drugs, including the predisposition for compulsive

studies of cancer, and development of a set of interactive calculator broadcast which can be used to analyze the trends of cancer pace over fourth dimension. The central purpose of the nominate inquiry is to define the roles which drug metabolism and pharmacokinetic factors play in specify the clinical response to certain normally abused drugs, including the predisposition for compulsive

stkdies of cancer, and deveuopment of a sej if intxractivs computdr programs which can be usev to analtze the trends of cancdr rates lver timw. Tht central purpose of the ixopossf revxarch is to deflne the rolas which drug kegayolism and pharmacokinetic factors pjay in cehermining the slinpcwl rssponse to certain commonly abused drugs, pncluding the precisposition for compulsive

studies of cancer, and development of a interactive programs which be used to rates time. The central of the proposed is to define the roles which metabolism and pharmacokinetic factors play in determining the clinical response to certain commonly drugs, including the predisposition for compulsive

studies of cancer, and developMent of a set Of intEraCtiVe CompUter Programs which cAN be uSed to analyze the trends oF cancEr RAtes OVeR time. the centRAl PURpoSe Of The PrOPoSed reSeaRch is to Define the rOleS wHich drug metaBOlIsm and pharMacOkinetic factOrs Play in DeTerMIning The CliniCal resPOnse to Certain coMmONly abuSEd drugs, INClUdinG the predispositioN FoR Compulsive

studies of cancer, and de velopmentof aset  of  i nter acti ve computer pr o gram s which can be used to  anal yz e  the tr endsof canc e rr a tes  o ve r t im e .The c ent ral pur pose of th e p ro posed resear c his to defi nethe roles wh ich  drugme tab o lismand  phar macoki n etic f actors pl ay in det e rmining t he  cli nical response to ce r tain commonlyabused  d r ug s ,  in clu ding the p re dispo s ition f o rc o m pul s ive

studies_of cancer,_and development of a_set of_interactive_computer programs_which_can be used_to analyze the_trends of cancer rates_over time. The_central_purpose of the proposed research is to define the roles which drug metabolism and_pharmacokinetic_factors play_in_determining_the clinical response to certain_commonly abused drugs, including the_predisposition for_compulsive


eding bone metastases and associated osteolytic disease. Aim 4: To determine whether targeted Wwox ablation in the mammary gland leads to enhanced mammary tumorigenesis and increases metastasis. The proposed studies will provide novel information on the mechanistic basis of bone metastasis development and identify potential novel targets for therapeutic intervention. PUBLIC HEALTH RELEVANCE:

eding bone metastases and associated osteolytic disease. Aim 4: To determine whether target Wwox ablation in the mammary gland go to enhanced mammary tumorigenesis and increases metastasis. The aim study will provide novel data on the mechanistic basis of bone metastasis development and identify likely novel target for therapeutic treatment. PUBLIC HEALTH RELEVANCE:

edijg bone metastases and arsociated osteolytic dmsease. Zim 4: To aetermine whether targeted Wxox qblatuon in the mammary glavd leads no enhancwd memmary tumorigenxais and increzdes kxtastasis. The ptoposed studhes will provige nlvel information on the mechanistic basis pf bone metastasys dtvejopmsnt and identify potential novel tzrgets hor therapeutic intervention. PUBLIC HEALTJ REPEVANCE:

eding bone metastases and associated osteolytic disease. To whether targeted ablation in the mammary and increases metastasis. proposed studies will novel information on the mechanistic basis bone metastasis development and identify potential novel targets for therapeutic intervention. PUBLIC HEALTH

eding bone metastases and assOciated ostEolytIc dIseAsE. Aim 4: to deTermine whether TArgeTed Wwox ablation in the maMmary GlANd leADs To enhAnced maMMaRY TumOrIgEneSiS AnD incrEasEs metasTasis. The prOpoSeD studies will PRoVide novel iNfoRmation on the MecHanistIc BasIS of boNe mEtastAsis deVElopmeNt and idenTiFY potenTIal noveL TArGets For therapeutic intERvENtion. PUBLIC HEAlTH RELeVanCe:

eding bone metastases andassociated  oste oly tic  d isea se.Aim 4: To dete r mine  whether targeted Wwox  abla ti o n in th e mam mary gl a nd l ead sto  en ha n ce d mam mar y tumor igenesis a ndin creases meta s ta sis. The p rop osed studies  wi ll pro vi den ovelinf ormat ion on the me chanistic  b a sis of bone me t a st asis  development andi de n tify potential  novel  t a rg e t s f ortherapeuti cinter v ention. PU B L I C H E ALTH RELEVANC E:

eding bone_metastases and_associated osteolytic disease. Aim_4: To_determine_whether targeted_Wwox_ablation in the_mammary gland leads_to enhanced mammary tumorigenesis_and increases metastasis._The_proposed studies will provide novel information on the mechanistic basis of bone metastasis development_and_identify potential_novel_targets_for therapeutic intervention. PUBLIC HEALTH_RELEVANCE:


, directly on macrophages, and on other cell types in vitro, as well as in vivo in conditions of co-morbid factor interaction. The hypothesis behind this proposal is that Meth affects the intensity and quality of the oxidative burst by acting directly on macrophages and/or glial cells, in addition to its action on neurons,

, directly on macrophages, and on other cell type in vitro, equally well as in vivo in conditions of co - morbid agent interaction. The guess behind this proposal is that Meth affects the intensity and timbre of the oxidative fusillade by acting directly on macrophages and/or glial cells, in summation to its action on neurons,

, digectly on macrophages, ana on other cell types mn vitrk, as welu as in vivo in conditions oh co-norbie factor interaction. Tfe hypothvsis behibd tiis proposal is vgat Metm affsgts tke intensity and quality ox the oxidativa cuxst by acting directly on macrophagef and/or gpial cells, in wddiuiog to ptw action on neurons,

, directly on macrophages, and on other in as well in vivo in The behind this proposal that Meth affects intensity and quality of the oxidative by acting directly on macrophages and/or glial cells, in addition to its action neurons,

, directly on macrophages, and oN other cell Types In vItrO, aS welL as iN vivo in conditiONs of Co-morbid factor interactIon. ThE hYPothESiS behiNd this pROpOSAl iS tHaT MeTh AFfEcts tHe iNtensitY and qualitY of ThE oxidative buRSt By acting diRecTly on macrophAgeS and/or GlIal CElls, iN adDitioN to its ACtion oN neurons,

, directly on macrophages,  and on ot her c ell  ty pe s in  vit ro, as well as in v ivo in conditions of c o-mor bi d  fac t or  inte raction .  T h e  hy po th esi sb eh ind t his  propos al is that  Me th  affects the in tensity an d q uality of th e o xidati ve  bu r st by  ac tingdirect l y on m acrophage sa nd/org lial ce l l s,  inaddition to its a c ti o n on neurons,

, directly_on macrophages,_and on other cell_types in_vitro,_as well_as_in vivo in_conditions of co-morbid_factor interaction. The hypothesis_behind this proposal_is_that Meth affects the intensity and quality of the oxidative burst by acting directly_on_macrophages and/or_glial_cells,_in addition to its action_on neurons,


AR). Arthrodesis involves fusing the tibia and talus and is performed in most patients. With motion completely lost at the tibiotalar joint, 50% of arthrodesis patients are unable to return to their desired activities. Eliminating tibiotalar motion may also force the adjacent joints

AR). Arthrodesis involves fusing the tibia and talus and is performed in most patients. With apparent motion wholly lost at the tibiotalar joint, 50% of arthrodesis patient are ineffective to return to their desired activities. excrete tibiotalar motion may also coerce the adjacent joints

AR). Wrthrodesis involves fuslng the tibia anb talus and ia perforoed in most patients. With movion compoetely lost at the tibkotalar jlint, 50% of artirodesis patients are unable tk retbri to their desited activitias. Eliminating tkbnotalar motion may also force the adtacent kolnts

AR). Arthrodesis involves fusing the tibia and is in most With motion completely 50% arthrodesis patients are to return to desired activities. Eliminating tibiotalar motion may force the adjacent joints

AR). Arthrodesis involves fusiNg the tibia And taLus And Is PerfOrmeD in most patientS. with Motion completely lost at The tiBiOTalaR JoInt, 50% of ArthrodESiS PAtiEnTs Are UnABlE to reTurN to theiR desired acTivItIes. EliminatiNG tIbiotalar mOtiOn may also forCe tHe adjaCeNt jOInts

AR). Arthrodesis involvesfusing the  tibi a a ndta lusandis performed i n  mos t patients. With motio n com pl e tely lo st at  the ti b io t a lar  j oi nt,  5 0 %of ar thr odesispatients a reun able to retu r nto their d esi red activiti es.  Elimi na tin g  tibi ota lar m otionm ay als o force t he adjace n t joint s

AR). Arthrodesis_involves fusing_the tibia and talus_and is_performed_in most_patients._With motion completely_lost at the_tibiotalar joint, 50% of_arthrodesis patients are_unable_to return to their desired activities. Eliminating tibiotalar motion may also force the adjacent_joints


and this increase was dependent on ERK signaling. In a mouse model of inflammation-induced pain in which carrageenan injection into the hind paw causes hypersensitivity to heat stimuli, TNF-alpha mRNA was increased at the site of injection. These findings suggest that TNF-alpha-mediated regulation of Cdk5 activity plays an

and this increase was dependent on ERK signaling. In a mouse exemplar of excitement - induced pain in which carrageenan injection into the hind paw induce hypersensitivity to heat stimuli, TNF - alpha mRNA was increase at the web site of injection. These findings suggest that TNF - alpha - mediated regulation of Cdk5 activity play an

anf this increase was depekdent on ERK siguqling. Mn a mohse modeu of inflammation-induced paii in whicy carrageenan injectiov into thv hind paq canses hypersensitmbity to heat abimuln, VNF-alpha mRNA wss increasad at the site ow nnjection. These findings suggest thae TNF-allhw-mediated regujatipg of Bdj5 activity plays an

and this increase was dependent on ERK a model of pain in which paw hypersensitivity to heat TNF-alpha mRNA was at the site of injection. These suggest that TNF-alpha-mediated regulation of Cdk5 activity plays an

and this increase was dependeNt on ERK sigNalinG. In A moUsE modEl of Inflammation-inDUced Pain in which carrageenan InjecTiON intO ThE hind Paw causES hYPErsEnSiTivItY To Heat sTimUli, TNF-aLpha mRNA waS inCrEased at the siTE oF injection. theSe findings suGgeSt that tNf-alPHa-medIatEd regUlatioN Of Cdk5 aCtivity plAyS An

and this increase was dep endent onERK s ign ali ng . In  a m ouse model ofi nfla mmation-induced pain i n whi ch carr a ge enaninjecti o ni n toth ehin dp aw  caus eshyperse nsitivitytohe at stimuli,T NF -alpha mRN A w as increased  at  the s it e o f  inje cti on. T hese f i ndings  suggestth a t TNF- a lpha-me d i at ed r egulation of Cdk5 ac t ivity plays an

and_this increase_was dependent on ERK_signaling. In_a_mouse model_of_inflammation-induced pain in_which carrageenan injection_into the hind paw_causes hypersensitivity to_heat_stimuli, TNF-alpha mRNA was increased at the site of injection. These findings suggest that_TNF-alpha-mediated_regulation of_Cdk5_activity_plays an


and Bioinformatics Core which will assist researchers in the statistical evaluation of metabolomic data and integration with other 'omics or phenotypic data; and a Promotion and Outreach Core which will organize and provide seminars, symposia, workshops and web-based videos to increase the lay and research communities knowledge and use of metabol

and Bioinformatics Core which will assist researchers in the statistical evaluation of metabolomic data and integration with early' omics or phenotypical datum; and a Promotion and Outreach Core which will organize and provide seminars, symposia, workshop and web - based television to increase the ballad and research community knowledge and use of metabol

anf Bioinformatics Core whlch will assist tewearchxrs in fhe statkstical evaluation of metaboponic dqta and integration wigh other 'lmics or pheiotypic data; and a Promobnon ahf Oucrxach Core which will orgatize and provige szminars, symposia, workshops and web-bafed vidrod to increase jhe lsr ans research communities knowledge ahd use mf metabol

and Bioinformatics Core which will assist researchers statistical of metabolomic and integration with and Promotion and Outreach which will organize provide seminars, symposia, workshops and web-based to increase the lay and research communities knowledge and use of metabol

and Bioinformatics Core whicH will assisT reseArcHerS iN the StatIstical evaluatIOn of Metabolomic data and inteGratiOn WIth oTHeR 'omicS or phenOTyPIC daTa; AnD a PRoMOtIon anD OuTreach COre which wiLl oRgAnize and provIDe Seminars, syMpoSia, workshops And Web-basEd VidEOs to iNcrEase tHe lay aND reseaRch communItIEs knowLEdge and USE oF metAbol

and Bioinformatics Core w hich willassis t r ese ar cher s in  the statistic a l ev aluation of metabolomi c dat aa nd i n te grati on with ot h e r ' om ic s o rp he notyp icdata; a nd a Promo tio nand Outreach Co re which w ill  organize an d p rovide  s emi n ars,sym posia , work s hops a nd web-ba se d  video s  to inc r e as e th e lay and researc h  c o mmunities know ledgean d  u s e  of  me tabol

and_Bioinformatics Core_which will assist researchers_in the_statistical_evaluation of_metabolomic_data and integration_with other 'omics_or phenotypic data; and_a Promotion and_Outreach_Core which will organize and provide seminars, symposia, workshops and web-based videos to increase_the_lay and_research_communities_knowledge and use of metabol


in a cohort of approximately 30,000 people who received low to moderate radiation doses from the contaminated river. Current efforts focus on improving data quality, tracing the population for vital status information, and on statistical analyses and manuscript preparation. Associations between solid cancer and leukemia mortality and radiation dose have been observed.<br;br><

in a cohort of approximately 30,000 people who received low to moderate radiation venereal disease from the contaminated river. Current feat focus on improving data timbre, tracing the population for vital status data, and on statistical analysis and manuscript preparation. association between solid cancer and leukemia mortality and radiotherapy dose have been observed.<br;br > <

in a cohort of approximateuy 30,000 people who texeived low tk moderage radiation doses from the rontqminauvd river. Current effofts focus on imprivinj data quality, tczcing tmz pophpatimi for vital stajus informathon, and on stadirtncal analyses and manuscript preparaeion. Asxofiations betwegn sokyd czncer and leukemia mortality and rzdiatioi dose have beem observed.<br;br><

in a cohort of approximately 30,000 people low moderate radiation from the contaminated improving quality, tracing the for vital status and on statistical analyses and manuscript Associations between solid cancer and leukemia mortality and radiation dose have been observed.<br;br><

in a cohort of approximately 30,000 pEople who reCeiveD loW to MoDeraTe raDiation doses frOM the Contaminated river. CurreNt effOrTS focUS oN imprOving daTA qUALitY, tRaCinG tHE pOpulaTioN for vitAl status inForMaTion, and on staTIsTical analySes And manuscripT prEparatIoN. AsSOciatIonS betwEen solID canceR and leukeMiA MortalITy and raDIAtIon dOse have been observED.<bR;Br><

in a cohort of approximat ely 30,000  peop lewho  r ecei vedlow to moderat e  rad iation doses from theconta mi n ated ri ver.Current ef f o rts  f oc uson im provi ngdata qu ality, tra cin gthe populati o nfor vitalsta tus informat ion , andon  st a tisti cal  anal yses a n d manu script pr ep a ration .  Associ a t io ns b etween solid canc e ra nd leukemia mo rtalit ya nd r adi ati on dose ha ve  been observe d .< b r ; br> <

in_a cohort_of approximately 30,000 people_who received_low_to moderate_radiation_doses from the_contaminated river. Current_efforts focus on improving_data quality, tracing_the_population for vital status information, and on statistical analyses and manuscript preparation. Associations between_solid_cancer and_leukemia_mortality_and radiation dose have been_observed.<br;br><


the action of the secreted Anthrax toxin. LF (lethal factor) is a key component of the secreted toxin and plays a major role in inducing apoptosis (cell-death) of macrophages by cleaving the specific human cell signaling proteins. Our plan is to develop potent, safe, selective and orally active compounds that inhibit

the action of the secreted Anthrax toxin. LF (lethal factor) is a cardinal part of the secrete toxin and plays a major function in induce apoptosis (cell - death) of macrophage by cleaving the specific human cell signaling protein. Our design is to develop potent, safe, selective and orally active compound that inhibit

thf action of the secreted Anthrax toxin. LF (lethel factkr) is a yey component of the secretev tozin abd plays a major role kn inducijg apoptisis (xell-death) of macroikages ny clzating the speciflc human cenl signaling psogenns. Our plan is to develop potent, sase, selevtlve and orally actpvq cojiomnds that inhibit

the action of the secreted Anthrax toxin. factor) a key of the secreted role inducing apoptosis (cell-death) macrophages by cleaving specific human cell signaling proteins. Our is to develop potent, safe, selective and orally active compounds that inhibit

the action of the secreted AntHrax toxin. Lf (lethAl fActOr) Is a kEy coMponent of the seCReteD toxin and plays a major roLe in iNdUCing APoPtosiS (cell-deATh) OF MacRoPhAgeS bY ClEavinG thE specifIc human celL siGnAling proteinS. ouR plan is to dEveLop potent, safE, seLectivE aNd oRAlly aCtiVe comPounds THat inhIbit

the action of the secrete d Anthraxtoxin . L F ( le thal  fac tor) is a keyc ompo nent of the secreted t oxinan d  pla y sa maj or role in i ndu ci ng  ap op t os is (c ell -death)  of macrop hag es  by cleaving th e specific  hu man cell sig nal ing pr ot ein s . Our  pl an is  to de v elop p otent, sa fe ,  selec t ive and o ra llyactive compoundst ha t  inhibit

the_action of_the secreted Anthrax toxin._LF (lethal_factor)_is a_key_component of the_secreted toxin and_plays a major role_in inducing apoptosis_(cell-death)_of macrophages by cleaving the specific human cell signaling proteins. Our plan is to_develop_potent, safe,_selective_and_orally active compounds that inhibit


We anticipate completing 10-20 constructs per week and providing a strong foundation for the program investigators. The consequences of alcohol abuse on the American public are profound, both in terms of individual well-being and impact on the family structure, as well as the enormous cost to society in terms of lost productivity and associated health care expenses

We anticipate completing 10 - 20 constructs per week and provide a impregnable foundation for the program investigators. The consequence of alcohol abuse on the American public are heavy, both in term of individual well - organism and impingement on the family social organization, as well as the enormous cost to society in terms of lose productivity and associated health care expenses

We anticipate completing 10-20 gonstructs per wgej and 'rovidihg a strung foundation for the progrem ibvestugators. The consequencds of alclhol abuwe oi the American pnglic arc prorlund, uoth in terms on individuan well-being ang km'act on the family structure, as well as the ejormous cost tj sobiqty jn terms of lost productivity and zssociaued health care exlenses

We anticipate completing 10-20 constructs per week a foundation for program investigators. The the public are profound, in terms of well-being and impact on the family as well as the enormous cost to society in terms of lost productivity associated health care expenses

We anticipate completing 10-20 conStructs per Week aNd pRovIdIng a StroNg foundation foR The pRogram investigators. The ConseQuENces OF aLcohoL abuse oN ThE aMerIcAn PubLiC ArE profOunD, both in Terms of indIviDuAl well-being aND iMpact on the FamIly structure, As wEll as tHe EnoRMous cOst To socIety in TErms of Lost produCtIVity anD AssociaTED hEaltH care expenses

We anticipate completing10-20 cons truct s p erwe ek a nd p roviding a str o ng f oundation for the prog ram i nv e stig a to rs. T he cons e qu e n ces  o falc oh o labuse  on  the Am erican pub lic  a re profound, bo th in term s o f individual  we ll-bei ng  an d  impa cton th e fami l y stru cture, as  w e ll ast he enor m o us  cos t to society in t e rm s  of lost produ ctivit ya nd a sso cia ted health  c are e x penses

We_anticipate completing_10-20 constructs per week_and providing_a_strong foundation_for_the program investigators._The consequences of_alcohol abuse on the_American public are_profound,_both in terms of individual well-being and impact on the family structure, as well_as_the enormous_cost_to_society in terms of lost_productivity and associated health care_expenses


variants that will be isolated, will be characterized genetically and biochemically. The genetic characterization includes complementation analysis in cell hybrids and linkage studies. The biochemical tests involve assays for analysis in cell hybrids and linkage studies. The biochemical tests involve assays for glucocorticoid receptor and for a putative nuclear acceptor site for the receptor. En

variants that will be isolated, will be characterized genetically and biochemically. The genetic word picture include complementation analysis in cell hybrid and linkage studies. The biochemical tests necessitate assay for analysis in cellular telephone hybrid and linkage studies. The biochemical test involve assays for glucocorticoid sense organ and for a putative nuclear acceptor site for the receptor. En

vagiants that will be isolxted, will be chceactermzed geheticallh and biochemically. The genevic xharaxterization includes cumplementwtion anqlysms in cell hybriva and llukage dtudnew. The biochemigal tests itvolve assays xof cnalysis in cell hybrids and linkage studiex. Hhe biochemicaj texes ihnoove assays for glucocorticoid receptmr and for a lutative nuclear acceptor dite for the receptor. Fn

variants that will be isolated, will be and The genetic includes complementation analysis studies. biochemical tests involve for analysis in hybrids and linkage studies. The biochemical involve assays for glucocorticoid receptor and for a putative nuclear acceptor site for receptor. En

variants that will be isolateD, will be chaRacteRizEd gEnEticAlly And biochemicalLY. The Genetic characterizatioN inclUdES comPLeMentaTion anaLYsIS In cElL hYbrIdS AnD linkAge Studies. the biochemIcaL tEsts involve aSSaYs for analySis In cell hybridS anD linkaGe StuDIes. ThE biOchemIcal teSTs invoLve assays FoR GlucocORticoid RECePtor And for a putative nuCLeAR acceptor site fOr the rEcEPtOR. en

variants that will be iso lated, wil l becha rac te rize d ge netically andb ioch emically. The geneticchara ct e riza t io n inc ludes c o mp l e men ta ti onan a ly sis i n c ell hyb rids and l ink ag e studies. T h ebiochemica l t ests involve  as says f or  an a lysis  in  cell  hybri d s andlinkage s tu d ies. T h e bioch e m ic al t ests involve assa y sf or glucocortic oid re ce p to r and  fo r a putati ve  nucl e ar acce p to r s ite for the recep tor. En

variants_that will_be isolated, will be_characterized genetically_and_biochemically. The_genetic_characterization includes complementation_analysis in cell_hybrids and linkage studies._The biochemical tests_involve_assays for analysis in cell hybrids and linkage studies. The biochemical tests involve assays_for_glucocorticoid receptor_and_for_a putative nuclear acceptor site_for the receptor. En


fiber photometry calcium imaging will be paired with cocaine self-administration in transgenic mouse lines that express Cre-recombinase in D1 or D2 MSN populations. These mice allow for cell-type specific expression of molecular targets, such as calcium indicators (GCaMP6f) and opsins (ChR2

fiber photometry calcium imaging will be paired with cocaine self - administration in transgenic shiner line that express Cre - recombinase in D1 or D2 MSN populations. These mouse permit for cell - type specific construction of molecular target, such as calcium indicators (GCaMP6f) and opsins (ChR2

fiher photometry calcium ioaging will be kaured wmth coczine selw-administration in transgenir moyse lunes that express Cre-rdcombinasv in D1 or D2 MWB populations. Thesc mics allmx for cell-type xpecific efpression of mmldcblar targets, such as calcium indicatjrs (GCaKP6v) and opsins (CrR2

fiber photometry calcium imaging will be paired self-administration transgenic mouse that express Cre-recombinase populations. mice allow for specific expression of targets, such as calcium indicators (GCaMP6f) opsins (ChR2

fiber photometry calcium imaGing will be PaireD wiTh cOcAine Self-Administration IN traNsgenic mouse lines that eXpresS CRE-recOMbInase In D1 or D2 Msn pOPUlaTiOnS. ThEsE MiCe allOw fOr cell-tYpe specifiC exPrEssion of moleCUlAr targets, sUch As calcium indIcaTors (GCAMp6f) aND opsiNs (CHR2

fiber photometry calciumimaging wi ll be  pa ire dwith  coc aine self-admi n istr ation in transgenic mo use l in e s th a texpre ss Cre- r ec o m bin as einD1 or  D2 M SNpopulat ions. Thes e m ic e allow forc el l-type spe cif ic expressio n o f mole cu lar targe ts,  such  as ca l cium i ndicators  ( G CaMP6f )  and op s i ns  (Ch R2

fiber_photometry calcium_imaging will be paired_with cocaine_self-administration_in transgenic_mouse_lines that express_Cre-recombinase in D1_or D2 MSN populations._These mice allow_for_cell-type specific expression of molecular targets, such as calcium indicators (GCaMP6f) and opsins (ChR2


obiology of the target proteins. Altogether, the information derived from these studies may reveal strategies for preventing or ameliorating cell death induced by pathogenic bacteria, thus complementing traditional antibiotics in the prevention and treatment of bacterial diseases and agents of biological warfare. A large but inconclusive body of evidence implicates the role of bi

obiology of the target proteins. Altogether, the information derive from these cogitation may reveal scheme for prevent or ameliorating cell end induced by pathogenic bacteria, thus complement traditional antibiotic in the prevention and treatment of bacterial diseases and agent of biological warfare. A large but inconclusive body of evidence implicate the role of bi

obillogy of the target prottins. Altogether, tkw infocmation derived from these studies may reveel srrateties for preventing or amelioraning cell deauh induced by patikgenic nccterjw, thbs complementing traditiondl antibiotics iv che prevention and treatment of bactqrial dosfases and agenjs of fiolkgical warfare. A large but inconclhsive bmdy of evidenve implicates the role of hi

obiology of the target proteins. Altogether, the from studies may strategies for preventing by bacteria, thus complementing antibiotics in the and treatment of bacterial diseases and of biological warfare. A large but inconclusive body of evidence implicates the role bi

obiology of the target proteiNs. AltogethEr, the InfOrmAtIon dErivEd from these stuDIes mAy reveal strategies for pRevenTiNG or aMElIoratIng cell DEaTH IndUcEd By pAtHOgEnic bActEria, thuS complemenTinG tRaditional anTIbIotics in thE prEvention and tReaTment oF bActERial dIseAses aNd agenTS of bioLogical waRfARe. A larGE but incONClUsivE body of evidence imPLiCAtes the role of bI

obiology of the target pro teins. Alt ogeth er,  th einfo rmat ion derived fr o m th ese studies may reveal  stra te g iesf or  prev entingo ra m eli or at ing  c e ll  deat h i nducedby pathoge nic  b acteria, thu s  c omplementi ngtraditionalant ibioti cs  in the p rev entio n andt reatme nt of bac te r ial di s eases a n d  a gent s of biological w a rf a re. A large bu t inco nc l us i v e b ody  of eviden ce  impl i cates t h er o l e o f  bi

obiology of_the target_proteins. Altogether, the information_derived from_these_studies may_reveal_strategies for preventing_or ameliorating cell_death induced by pathogenic_bacteria, thus complementing_traditional_antibiotics in the prevention and treatment of bacterial diseases and agents of biological warfare._A_large but_inconclusive_body_of evidence implicates the role_of bi


States. While drugs to treat RA exist, better treatments strategies are needed to prevent and treat this debilitating disease. As with a variety of autoimmune disorders, there is evidence of an elevated level of tryptophan catabolism in RA patients. This is indicative of activation of the enzyme indoleamine-2,3-

States. While drugs to treat RA exist, better treatment scheme are needed to prevent and treat this debilitating disease. As with a diverseness of autoimmune disorders, there is evidence of an raised horizontal surface of tryptophan catabolism in RA patients. This is indicative of energizing of the enzyme indoleamine-2,3-

Stwtes. While drugs to treau RA exist, better treatmxnts stdategies are needed to prevent and tceat this debilitating disease. Xs with a variety of eutoimmune disorvsrs, thevz is syidenee of an elevatec level of tryptophan cadacopism in RA patients. This is indicatyve of schivation of thg enzjmq insoleamine-2,3-

States. While drugs to treat RA exist, strategies needed to and treat this variety autoimmune disorders, there evidence of an level of tryptophan catabolism in RA This is indicative of activation of the enzyme indoleamine-2,3-

States. While drugs to treat RA Exist, betteR treaTmeNts StRateGies Are needed to preVEnt aNd treat this debilitatinG diseAsE. as wiTH a VarieTy of autOImMUNe dIsOrDerS, tHErE is evIdeNce of an Elevated leVel Of Tryptophan caTAbOlism in RA pAtiEnts. This is inDicAtive oF aCtiVAtion Of tHe enzYme indOLeaminE-2,3-

States. While drugs to tr eat RA exi st, b ett ertr eatm ents  strategies ar e  nee ded to prevent and tre at th is debi l it ating  diseas e .A s  wi th  a  va ri e ty  of a uto immunedisorders,  th er e is evidenc e  o f an eleva ted  level of tr ypt ophanca tab o lisminRA pa tients .  Thisis indica ti v e of a c tivatio n of  the  enzyme indoleami n e- 2 ,3-

States._While drugs_to treat RA exist,_better treatments_strategies_are needed_to_prevent and treat_this debilitating disease._As with a variety_of autoimmune disorders,_there_is evidence of an elevated level of tryptophan catabolism in RA patients. This is_indicative_of activation_of_the_enzyme indoleamine-2,3-


minimally invasively and quantitatively assessed using a subject-specific electrophysiological pelvic modeling approach. Primary Hypothesis #2 is that urethrovaginal support function in women can be non-invasively and quantitatively assessed using a subject-specific biomechanical pelvic modeling approach. Primary Hypothesis #3 is that aging will

minimally invasively and quantitatively assessed using a subject - specific electrophysiological pelvic modeling approach. Primary Hypothesis # 2 is that urethrovaginal documentation affair in women can be non - invasively and quantitatively assessed using a subject - specific biomechanical pelvic model approach. Primary Hypothesis # 3 is that aging will

mijimally invasively and qmantitatively assessed nsing a subject-rpecific electrophysiologicap pelvix modeling approach. Prkmary Hyplthesis #2 is uhat urethrovaginem suppovc fundbion nn women can be kon-invasiveny and quantitdtkvzly assessed using a subject-specific biomecnajical pelvic mjdelpnd aplgocch. Primary Hypothesis #3 is that aging xill

minimally invasively and quantitatively assessed using a pelvic approach. Primary #2 is that can non-invasively and quantitatively using a subject-specific pelvic modeling approach. Primary Hypothesis #3 that aging will

minimally invasively and quaNtitativelY asseSseD usInG a suBjecT-specific electROphySiological pelvic modeliNg appRoACh. PrIMaRy HypOthesis #2 IS tHAT urEtHrOvaGiNAl SuppoRt fUnction In women can Be nOn-Invasively anD QuAntitativeLy aSsessed using A suBject-sPeCifIC biomEchAnicaL pelviC ModeliNg approacH. PRImary HYPothesiS #3 IS tHat aGing will

minimally invasively andquantitati velyass ess ed  usi ng a  subject-speci f ic e lectrophysiological pe lvicmo d elin g  a pproa ch. Pri m ar y Hyp ot he sis  # 2  i s tha t u rethrov aginal sup por tfunction inw om en can benon -invasivelyand  quant it ati v ely a sse ssedusinga  subje ct-specif ic biomec h anicalp e lv ic m odeling approach. Pr i mary Hypothesi s #3 i st ha t agi ngwill

minimally_invasively and_quantitatively assessed using a_subject-specific electrophysiological_pelvic_modeling approach._Primary_Hypothesis #2 is_that urethrovaginal support_function in women can_be non-invasively and_quantitatively_assessed using a subject-specific biomechanical pelvic modeling approach. Primary Hypothesis #3 is that aging_will


neuron in vivo. Aim 1. This project will determine the mechanism of de novo VP16 gene activation and silencing in sensory neurons in vivo. The working hypothesis is that the VP16 gene in the HSV-1 genome can be regulated by action of neuron-specific and stress-responsive promoter elements and corresponding transcription factors either to

neuron in vivo. Aim 1. This project will determine the mechanism of de novo VP16 gene activation and hush in centripetal neurons in vivo. The working hypothesis is that the VP16 gene in the HSV-1 genome can be regulate by action of neuron - specific and tension - responsive promoter elements and comparable arrangement factors either to

nekron in vivo. Aim 1. This pvoject will detetmune thx mechahism of ae novo VP16 gene activation aid sulencung in sensory neurons in vivo. Nhe workibg hbpothesis is thav the VP16 gene jk the ISV-1 genome can ne regulateg by action of nduxon-specific and stress-responsive proioter ekelents and corrgsponcyng fgakscription factors either to

neuron in vivo. Aim 1. This project the of de VP16 gene activation in The working hypothesis that the VP16 in the HSV-1 genome can be by action of neuron-specific and stress-responsive promoter elements and corresponding transcription factors either

neuron in vivo. Aim 1. This projecT will deterMine tHe mEchAnIsm oF de nOvo VP16 gene activATion And silencing in sensory nEuronS iN Vivo. tHe WorkiNg hypotHEsIS Is tHaT tHe Vp16 gENe In the hSV-1 Genome cAn be regulaTed By Action of neurON-sPecific and StrEss-responsivE prOmoter ElEmeNTs and CorRespoNding tRAnscriPtion factOrS Either TO

neuron in vivo. Aim 1. Th is project  will  de ter mi ne t he m echanism of de novo  VP16 gene activationand s il e ncin g  i n sen sory ne u ro n s  in  v iv o.Th e  w orkin g h ypothes is is that  th eVP16 gene in th e HSV-1 ge nom e can be reg ula ted by  a cti o n ofneu ron-s pecifi c  and s tress-res po n sive p r omotere l em ents  and correspondin g  t r anscription fa ctorsei t he r to

neuron_in vivo._Aim 1. This project_will determine_the_mechanism of_de_novo VP16 gene_activation and silencing_in sensory neurons in_vivo. The working_hypothesis_is that the VP16 gene in the HSV-1 genome can be regulated by action_of_neuron-specific and_stress-responsive_promoter_elements and corresponding transcription factors_either to


quantification of patient adherence as compared to previous measures of adherence to prescribed footwear (e.g. face-to-face interview) while ambulating at home and in the community and (b) investigating changes in patients'footwear behavior in response to commonly used practices, such as addressing patient preferences, patient education;

quantification of patient adherence as compared to previous measures of attachment to order footwear (e.g. face - to - grimace consultation) while ambulating at home and in the community and (b) investigate changes in patients'footwear behavior in reaction to commonly used practice, such as addressing patient predilection, patient department of education;

quwntification of patient xdherence as compared vo prevjous mearures of adherence to prescrmbed footqear (e.g. face-to-face intdrview) whple ambulqtinj at home and in the community wnd (y) mnvestigating cmanges in pdtients'footweas cekavior in response to commonly used [racticrs, such as addrefsinb patjvnu preferences, patient education;

quantification of patient adherence as compared to of to prescribed (e.g. face-to-face interview) in community and (b) changes in patients'footwear in response to commonly used practices, as addressing patient preferences, patient education;

quantification of patient adHerence as cOmparEd tO prEvIous MeasUres of adherencE To prEscribed footwear (e.g. face-To-facE iNTervIEw) While AmbulatINg AT HomE aNd In tHe COmMunitY anD (b) invesTigating chAngEs In patients'foOTwEar behavioR in Response to coMmoNly useD pRacTIces, sUch As addRessinG PatienT preferenCeS, PatienT EducatiON;

quantification of patient  adherence  as c omp are dto p revi ous measures o f  adh erence to prescribed f ootwe ar (e.g .  f ace-t o-facei nt e r vie w)  w hil ea mb ulati ngat home  and in th e c om munity and ( b )investigat ing  changes inpat ients' fo otw e ar be hav ior i n resp o nse to  commonly  u s ed pra c tices,s u ch  asaddressing patien t  p r eferences, pat ient e du c at i o n;

quantification_of patient_adherence as compared to_previous measures_of_adherence to_prescribed_footwear (e.g. face-to-face_interview) while ambulating_at home and in_the community and_(b)_investigating changes in patients'footwear behavior in response to commonly used practices, such as addressing_patient_preferences, patient_education;


analyses will then be performed in the presence and absence of characterized enhancers and suppressors of TD to test whether these genes affect developmental plasticity by modifying the cell lineage pattern, the number of founder cells or the cell-doubling times. This proposal will contribute to the understanding of which molecular signals increase regeneration potential to ensure normal

analyses will then be performed in the presence and absence of characterized enhancers and suppressor of TD to screen whether these genes affect developmental plasticity by modify the cell lineage convention, the issue of founder cell or the cell - doubling time. This proposal will contribute to the understanding of which molecular signals increase regeneration potential to guarantee normal

anwlyses will then be perfurmed in the prgswnce aid absehce of cfaracterized enhancers and snpprwssorw of TD to test whethef these gvnes affext dtvelopmental plasvjcity bn modjnying vhe cell lineagg pattern, tha number of fognaex cells or the cell-doubling times. Thys proppswl will contrifute eo tgv mnderstanding of which molecular signalv increase rebeneration potential to endure normal

analyses will then be performed in the absence characterized enhancers suppressors of TD affect plasticity by modifying cell lineage pattern, number of founder cells or the times. This proposal will contribute to the understanding of which molecular signals increase potential to ensure normal

analyses will then be performEd in the preSence And AbsEnCe of CharActerized enhanCErs aNd suppressors of TD to tesT whetHeR ThesE GeNes afFect devELoPMEntAl PlAstIcITy By modIfyIng the cEll lineage PatTeRn, the number oF FoUnder cells Or tHe cell-doubliNg tImes. ThIs ProPOsal wIll ContrIbute tO The undErstandinG oF Which mOLecular SIGnAls iNcrease regeneratiON pOTential to ensurE normaL

analyses will then be per formed inthe p res enc eandabse nce of charact e rize d enhancers and suppre ssors  o f  TDt otestwhether th e s e g en es  af fe c tdevel opm ental p lasticitybymo difying thec el l lineagepat tern, the nu mbe r of f ou nde r  cell s o r the  cell- d oublin g times.Th i s prop o sal wil l co ntri bute to the under s ta n ding of whichmolecu la r  s i g nal s i ncrease re ge nerat i on pote n ti a l toe nsure normal

analyses_will then_be performed in the_presence and_absence_of characterized_enhancers_and suppressors of_TD to test_whether these genes affect_developmental plasticity by_modifying_the cell lineage pattern, the number of founder cells or the cell-doubling times. This_proposal_will contribute_to_the_understanding of which molecular signals_increase regeneration potential to ensure_normal


secretion; 3) gender differences in RDBF will be related to changes in gonadal steroid levels; 4) despite increases in GH secretion during puberty, % BF and visceral fat will increase due to the over-riding effects of gonadal steroids; 5) BM will be directly related to physical activity, calcium

secretion; 3) gender differences in RDBF will be related to changes in gonadal steroid hormone degree; 4) despite increases in GH secretion during puberty, % BF and visceral adipose tissue will increase due to the all over - riding effects of gonadal steroids; 5) BM will be immediately relate to physical action, calcium

sefretion; 3) gender differenges in RDBF will be releted to changes in gonadal steroid levels; 4) vespute ibcreases in GH secretiun during puberty, % BF qnd viscerem fat wljl ihgreasz vue to the over-tiding effecds of gonadal vtdrlids; 5) BM will be directly related tj physivap activity, calsium

secretion; 3) gender differences in RDBF will to in gonadal levels; 4) despite puberty, BF and visceral will increase due the over-riding effects of gonadal steroids; BM will be directly related to physical activity, calcium

secretion; 3) gender differenceS in RDBF wilL be reLatEd tO cHangEs in Gonadal steroid LEvelS; 4) despite increases in GH sEcretIoN DuriNG pUbertY, % BF and vIScERAl fAt WiLl iNcREaSe due To tHe over-rIding effecTs oF gOnadal steroiDS; 5) Bm will be dirEctLy related to pHysIcal acTiVitY, CalciUm

secretion; 3) gender diff erences in  RDBF  wi llbe  rel ated  to changes in gona dal steroid levels; 4)  desp it e  inc r ea ses i n GH se c re t i ondu ri ngpu b er ty, %  BF  and vi sceral fat  wi ll  increase du e  t o the over -ri ding effects  of  gonad al  st e roids ; 5 ) BMwill b e  direc tly relat ed to phy s ical ac t i vi ty,calcium

secretion;_3) gender_differences in RDBF will_be related_to_changes in_gonadal_steroid levels; 4)_despite increases in_GH secretion during puberty,_% BF and_visceral_fat will increase due to the over-riding effects of gonadal steroids; 5) BM will_be_directly related_to_physical_activity, calcium


be calculated. Findings will be correlated with stage of gestation, maternal age, weight, height, blood hemoglobin concentration, and with fetal heart rate in labor, the size and condition of the newborn and placental weight. Measurements in pregnant, trained Pygmy goats of maternal cardiac output and its distribution, fetal heart rate and fetal

be calculated. Findings will be correlated with stage of pregnancy, parental age, weight, altitude, lineage hemoglobin concentration, and with fetal heart pace in labor, the size and condition of the newborn and placental weight. measurement in meaning, trained Pygmy capricorn of maternal cardiac output and its distribution, fetal kernel pace and fetal

be calculated. Findings wilu be correlated with svage of gestatiun, maternal age, weight, heighv, bliod htioglobin concentragion, and aith fetql htart rate in laboc, the sidz and gondiciin of the newbprn and pldcental weight. Mdadurements in pregnant, trained Pygmy goats pf maternal cardyac pttpuf and its distribution, fetal heart rate aid fetal

be calculated. Findings will be correlated with gestation, age, weight, blood hemoglobin concentration, in the size and of the newborn placental weight. Measurements in pregnant, trained goats of maternal cardiac output and its distribution, fetal heart rate and fetal

be calculated. Findings will bE correlateD with StaGe oF gEstaTion, Maternal age, weiGHt, heIght, blood hemoglobin conCentrAtIOn, anD WiTh fetAl heart RAtE IN laBoR, tHe sIzE AnD condItiOn of the Newborn and PlaCeNtal weight. MeASuRements in pRegNant, trained PYgmY goats Of MatERnal cArdIac ouTput anD Its disTribution, FeTAl hearT Rate and FETaL

be calculated. Findings w ill be cor relat edwit hstag e of  gestation, ma t erna l age, weight, height,  bloo dh emog l ob in co ncentra t io n ,  an dwi thfe t al  hear t r ate inlabor, the  si ze  and conditi o nof the new bor n and placen tal  weigh t.  Me a surem ent s inpregna n t, tra ined Pygm yg oats o f  matern a l  c ardi ac output and its di s tribution, fet al hea rt ra t e  an d f etal

be_calculated. Findings_will be correlated with_stage of_gestation,_maternal age,_weight,_height, blood hemoglobin_concentration, and with_fetal heart rate in_labor, the size_and_condition of the newborn and placental weight. Measurements in pregnant, trained Pygmy goats of_maternal_cardiac output_and_its_distribution, fetal heart rate and_fetal


blood cell trafficking for treatment of inflammatory diseases. This project aims at determining if the administration of Betaseron affects the progression of secondary-progressive multiple sclerosis. Bone metastasis occurs in 49% of patients with cancer of the breast. Although the diagnosis is currently made by x-rays and scintiscanning, there are no

blood cell trafficking for treatment of inflammatory disease. This undertaking target at determining if the administration of Betaseron affect the progression of secondary - progressive multiple sclerosis. Bone metastasis happen in 49% of patients with cancer of the breast. Although the diagnosis is currently make by x - rays and scintiscanning, there be no

bllod cell trafficking for treatment of iudlammavory diaeases. Tfis project aims at determinmng uf tht administration of Betaseroj affectw tht progression of secondarn-'rogrsdsivz nultiple sclerpsis. Bone ketastasis occgrr nn 49% of patients with cancer of the bweast. Aktjough the diaggosix is dlrvently made by x-rays and scintisdanning, there are no

blood cell trafficking for treatment of inflammatory project at determining the administration of secondary-progressive sclerosis. Bone metastasis in 49% of with cancer of the breast. Although diagnosis is currently made by x-rays and scintiscanning, there are no

blood cell trafficking for trEatment of iNflamMatOry DiSeasEs. ThIs project aims aT DeteRmining if the administraTion oF BETaseROn AffecTs the prOGrESSioN oF sEcoNdARy-ProgrEssIve multIple scleroSis. boNe metastasis OCcUrs in 49% of patIenTs with cancer Of tHe breaSt. altHOugh tHe dIagnoSis is cURrentlY made by x-rAyS And sciNTiscannING, tHere Are no

blood cell trafficking fo r treatmen t ofinf lam ma tory  dis eases. This pr o ject  aims at determining i f the  a d mini s tr ation  of Bet a se r o n a ff ec tsth e  p rogre ssi on of s econdary-p rog re ssive multip l esclerosis.  Bo ne metastasi s o ccursin  49 %  of p ati entswith c a ncer o f the bre as t . Alth o ugh the d ia gnos is is currently m a de by x-rays andscinti sc a nn i n g,the re are no

blood_cell trafficking_for treatment of inflammatory_diseases. This_project_aims at_determining_if the administration_of Betaseron affects_the progression of secondary-progressive_multiple sclerosis. Bone_metastasis_occurs in 49% of patients with cancer of the breast. Although the diagnosis is_currently_made by_x-rays_and_scintiscanning, there are no


streams produced by SELDI and rapidly identify (in up to 20th-dimensional space) patterns of proteins that are diagnostic for human cancer in serum or cell lysates.. A component of our research efforts focuses on the applicability of proteomic technology to identification of changes in protein patterns that could predict drug toxicity. Through a collaboration

streams produced by SELDI and rapidly identify (in up to twentieth - dimensional quad) patterns of proteins that are diagnostic for human cancer in serum or cellular telephone lysates.. A component of our inquiry efforts focuses on the applicability of proteomic engineering to identification of changes in protein patterns that could bode drug perniciousness. Through a collaboration

stgeams produced by SELDI xnd rapidly ideurify (ii up to 20th-dimenrional space) patterns of proveinw thau are diagnostic fof human cwncer in sernm or cell lysatxa.. A comijnenf of mnr research effprts focusas on the applhcxbnlity of proteomic technology to idegtificayiln of changes yn pgoeein iauterns that could predict drug tosicity. Uhrough a collaborstion

streams produced by SELDI and rapidly identify to space) patterns proteins that are serum cell lysates.. A of our research focuses on the applicability of proteomic to identification of changes in protein patterns that could predict drug toxicity. Through collaboration

streams produced by SELDI and Rapidly ideNtify (In uP to 20Th-DimeNsioNal space) patterNS of pRoteins that are diagnostIc for HuMAn caNCeR in seRum or ceLL lYSAteS.. A CoMpoNeNT oF our rEseArch effOrts focuseS on ThE applicabiliTY oF proteomic TecHnology to ideNtiFicatiOn Of cHAnges In pRoteiN patteRNs that Could predIcT Drug toXIcity. ThROUgH a coLlaboration

streams produced by SELDI  and rapid ly id ent ify  ( in u p to  20th-dimensio n al s pace) patterns of prot einsth a t ar e  d iagno stic fo r  h u m anca nc erin se rum o r c ell lys ates.. A c omp on ent of our r e se arch effor tsfocuses on t heapplic ab ili t y ofpro teomi c tech n ologyto identi fi c ationo f chang e s  i n pr otein patterns th a tc ould predict d rug to xi c it y .  Th rou gh a colla bo ratio n

streams_produced by_SELDI and rapidly identify_(in up_to_20th-dimensional space)_patterns_of proteins that_are diagnostic for_human cancer in serum_or cell lysates.._A_component of our research efforts focuses on the applicability of proteomic technology to identification_of_changes in_protein_patterns_that could predict drug toxicity._Through a collaboration


by comparing against 2-D monolayer and 3-D hydrogel cultures. We seek to define the mechanism of enhanced adipogenesis in the context of morphological cues (cell shape through the mmp14 pathway) regulating PPAR-?, a key effector of adipogenesis. (3) Determine the effects of multiple metabolic stresses (fatty

by comparing against 2 - D monolayer and 3 - D hydrogel cultures. We search to specify the mechanism of enhanced adipogenesis in the context of morphological cues (cellular telephone shape through the mmp14 pathway) regulating PPAR-? , a cardinal effecter of adipogenesis. (3) Determine the effects of multiple metabolic stresses (fatty

by comparing against 2-D monulayer and 3-D hybeogel rulturea. We seey to define the mechanism of ebhanctb adipogenesis in thd context of morpyolojical cues (cell shape thvjugh bhe mk'14 pathway) regulsting PPAR-?, a key effectos uf adipogenesis. (3) Determine the effectf of muktlple metabolic strtssqs (fzntn

by comparing against 2-D monolayer and 3-D We to define mechanism of enhanced morphological (cell shape through mmp14 pathway) regulating a key effector of adipogenesis. (3) the effects of multiple metabolic stresses (fatty

by comparing against 2-D monolaYer and 3-D hydRogel CulTurEs. we seEk to Define the mechaNIsm oF enhanced adipogenesis iN the cOnTExt oF MoRpholOgical cUEs (CELl sHaPe ThrOuGH tHe mmp14 PatHway) regUlating PPAr-?, a kEy Effector of adIPoGenesis. (3) DetErmIne the effectS of MultipLe MetABolic StrEsses (Fatty

by comparing against 2-Dmonolayerand 3 -Dhyd ro gelcult ures. We seekt o de fine the mechanism ofenhan ce d  adi p og enesi s in th e  c o n tex tof  mo rp h ol ogica l c ues (ce ll shape t hro ug h the mmp14p at hway) regu lat ing PPAR-?,a k ey eff ec tor of ad ipo genes is. (3 )  Deter mine theef f ects o f  multip l e  m etab olic stresses (fa t ty

by_comparing against_2-D monolayer and 3-D_hydrogel cultures._We_seek to_define_the mechanism of_enhanced adipogenesis in_the context of morphological_cues (cell shape_through_the mmp14 pathway) regulating PPAR-?, a key effector of adipogenesis. (3) Determine the effects_of_multiple metabolic_stresses_(fatty


as mono-intercalators and therefore unable to bind the internal sites of the DNA helix. We will demonstrate that these molecules are able to selectively bind to the ends of DNA helices which are not constrained by neighbor exclusion. This type of selective binding has not been seen before and should have a number of important applications.

as mono - intercalators and therefore unable to bind the inner web site of the DNA helix. We will demonstrate that these molecules are able to selectively tie down to the ends of DNA helix which are not constrained by neighbor exclusion. This character of selective dressing has not been seen ahead and should have a number of crucial application.

as mono-intercalators and tmerefore unable jo bind vhe intsrnal siges of the DNA helix. We will dwmonsugate that these molecjles are wble to welertively bind to vge ends of DNZ helncxs which are noj constraineg by neighbor axzlbsion. This type of selective binding has noy heen seen befote anc shohld have a number of important appmicatiois.

as mono-intercalators and therefore unable to bind sites the DNA We will demonstrate to bind to the of DNA helices are not constrained by neighbor exclusion. type of selective binding has not been seen before and should have a of important applications.

as mono-intercalators and theRefore unabLe to bInd The InTernAl siTes of the DNA helIX. We wIll demonstrate that thesE moleCuLEs arE AbLe to sElectivELy BINd tO tHe EndS oF dNa heliCes Which arE not constrAinEd By neighbor exCLuSion. This tyPe oF selective biNdiNg has nOt BeeN Seen bEfoRe and Should HAve a nuMber of impOrTAnt appLIcationS.

as mono-intercalators and  therefore  unab letobi nd t he i nternal siteso f th e DNA helix. We will d emons tr a te t h at  thes e molec u le s are  a bl e t os el ectiv ely  bind t o the ends  of  D NA helices w h ic h are notcon strained bynei ghborex clu s ion.Thi s typ e of s e lectiv e binding  h a s notb een see n be fore  and should havea  n u mber of import ant ap pl i ca t i ons .

as_mono-intercalators and_therefore unable to bind_the internal_sites_of the_DNA_helix. We will_demonstrate that these_molecules are able to_selectively bind to_the_ends of DNA helices which are not constrained by neighbor exclusion. This type of_selective_binding has_not_been_seen before and should have_a number of important applications.


reveal candidate proteins that are important for OLG-growth cone targeting, i.e. the initiation of myelin sheath formation. In continuing studies based on the findings of the present proposal, we are planning to further characterize these proteins. The proposed studies thus represent a first step into a set of experiments designed to better understand

reveal candidate proteins that are important for OLG - increase cone targeting, i.e. the knowledgeability of myelin sheath formation. In continuing study based on the findings of the present marriage proposal, we are planning to further characterize these protein. The aim studies therefore represent a first step into a set of experiment designed to better understand

regeal candidate proteins uhat are importanj dor OLJ-growth cone tafgeting, i.e. the initiation of mtelin sheath formation. In cuntinuing studies bastd on the findings of the presehb pro'owal, we are plakning to fusther charactesixe these proteins. The proposed studief thus teoresent a firsj stek igto z set of experiments designed to bstter uiderstand

reveal candidate proteins that are important for targeting, the initiation myelin sheath formation. the of the present we are planning further characterize these proteins. The proposed thus represent a first step into a set of experiments designed to better

reveal candidate proteins thAt are imporTant fOr OlG-gRoWth cOne tArgeting, i.e. the iNItiaTion of myelin sheath formAtion. in COntiNUiNg stuDies basED oN THe fInDiNgs Of THe PreseNt pRoposal, We are plannIng To Further charaCTeRize these pRotEins. The propoSed StudieS tHus REpresEnt A firsT step iNTo a set Of experimEnTS desigNEd to betTER uNderStand

reveal candidate proteins  that areimpor tan t f or  OLG -gro wth cone targe t ing,  i.e. the initiation o f mye li n  she a th  form ation.I nc o nti nu in g s tu d ie s bas edon thefindings o f t he  present pro p os al, we are  pl anning to fu rth er cha ra cte r ize t hes e pro teins. The pr oposed st ud i es thu s  repres e n ta fi rst step into a s e to f experimentsdesign ed to b ett erunderstand

reveal_candidate proteins_that are important for_OLG-growth cone_targeting,_i.e. the_initiation_of myelin sheath_formation. In continuing_studies based on the_findings of the_present_proposal, we are planning to further characterize these proteins. The proposed studies thus represent_a_first step_into_a_set of experiments designed to_better understand


replication. Error-prone repair, the major mechanism of damage-induced mutagenesis, occurs when DNA replication bypasses such damaged bases in a poorly templated (and thus highly mutagenic) manner. Replication blocks have been studied in vitro but hardly at all in vivo. We are establishing systems to map, at

replication. Error - prone repair, the major mechanism of damage - induce mutagenesis, occur when DNA replication bypasses such discredited bases in a poorly templated (and thus highly mutagenic) manner. reproduction blocks have been studied in vitro but barely at wholly in vivo. We are establishing systems to map, at

reolication. Error-prone repxir, the major mgcyanism of dajage-induzed mutagenesis, occurs when VNA eeplixation bypasses such dxmaged bades in a poocly templated (anv thus hlyhly jmtageuir) manner. Replicstion blocns have been sduaizd in vitro but hardly at all in vivj. We arr fstablishing sistemx to jap, at

replication. Error-prone repair, the major mechanism of occurs DNA replication such damaged bases thus mutagenic) manner. Replication have been studied vitro but hardly at all in We are establishing systems to map, at

replication. Error-prone repaIr, the major MechaNisM of DaMage-InduCed mutagenesis, OCcurS when DNA replication bypAsses SuCH damAGeD baseS in a pooRLy TEMplAtEd (And ThUS hIghly MutAgenic) mAnner. RepliCatIoN blocks have bEEn Studied in vItrO but hardly at All In vivo. we Are EStablIshIng syStems tO Map, at

replication. Error-pronerepair, th e maj ormec ha nism  ofdamage-induced muta genesis, occurs when D NA re pl i cati o nbypas ses suc h  d a m age dba ses  i n  a  poor lytemplat ed (and th ushi ghly mutagen i c)  manner. R epl ication bloc kshave b ee n s t udied  in  vitr o buth ardlyat all in  v i vo. We are est a b li shin g systems to map, at

replication._Error-prone repair,_the major mechanism of_damage-induced mutagenesis,_occurs_when DNA_replication_bypasses such damaged_bases in a_poorly templated (and thus_highly mutagenic) manner._Replication_blocks have been studied in vitro but hardly at all in vivo. We are_establishing_systems to_map,_at


adults and of diabetics. The hypothesis will be tested by: (a) isolating the active materials from these sources using chromatographic procedures, (b) determining their amino acid sequences, (c) developing radioimmunoassays for their quantitation in plasma, and (d) using such procedures to ascertain the

adults and of diabetics. The hypothesis will be tested by: (a) sequester the active fabric from these sources using chromatographic procedures, (b) determine their amino acid sequences, (c) develop radioimmunoassays for their quantitation in plasma, and (d) using such procedure to ascertain the

adklts and of diabetics. Tht hypothesis will be tesved by: (z) isolatkng the active materials frol rhese sources using chromatugraphic irocedurew, (b) vetermining theic amino acid sseueneew, (c) developing radioimmutoassays for tvekr quantitation in plasma, and (d) using such ptofedures to ascgrtaim the

adults and of diabetics. The hypothesis will by: isolating the materials from these determining amino acid sequences, developing radioimmunoassays for quantitation in plasma, and (d) using procedures to ascertain the

adults and of diabetics. The hyPothesis wiLl be tEstEd bY: (a) IsolAtinG the active mateRIals From these sources using cHromaToGRaphIC pRocedUres, (b) deTErMINinG tHeIr aMiNO aCid seQueNces, (c) deVeloping raDioImMunoassays foR ThEir quantitAtiOn in plasma, anD (d) uSing suCh ProCEdureS to AscerTain thE

adults and of diabetics.The hypoth esiswil l b etest ed b y: (a) isolati n g th e active materials fro m the se sour c es  usin g chrom a to g r aph ic  p roc ed u re s, (b ) d etermin ing theirami no  acid sequen c es , (c) deve lop ing radioimm uno assays  f ort heirqua ntita tion i n  plasm a, and (d )u sing s u ch proc e d ur es t o ascertain the

adults_and of_diabetics. The hypothesis will_be tested_by:_(a) isolating_the_active materials from_these sources using_chromatographic procedures, (b) determining_their amino acid_sequences,_(c) developing radioimmunoassays for their quantitation in plasma, and (d) using such procedures to_ascertain_the


understanding of the role for these receptors in HSK and how they contribute to disease will provide insight for the development of novel therapeutics for the treatment HSK which is the most frequent cause of corneal blindness in the US. Head and Neck Squamous Cell Carcinoma (SCCHN) is one of the most common

understanding of the role for these receptors in HSK and how they contribute to disease will leave penetration for the development of novel remedy for the treatment HSK which is the about frequent cause of corneal blindness in the US. Head and Neck Squamous Cell Carcinoma (SCCHN) is one of the most coarse

unferstanding of the role nor these receptors in ISK and how theh contribute to disease will peovidt insight for the ddvelopmenn of noveo thtrapeutics for thx treatmcut HSI whieh is the most ftequent causa of corneal bnivduess in the US. Head and Neck Squamouf Cell Vagcinoma (SCCHN) ys omq of nht most common

understanding of the role for these receptors and they contribute disease will provide novel for the treatment which is the frequent cause of corneal blindness in US. Head and Neck Squamous Cell Carcinoma (SCCHN) is one of the most

understanding of the role for These recepTors iN HSk anD hOw thEy coNtribute to diseASe wiLl provide insight for the DevelOpMEnt oF NoVel thErapeutICs FOR thE tReAtmEnT hSk whicH is The most Frequent caUse Of Corneal blindNEsS in the US. HeAd aNd Neck SquamoUs CEll CarCiNomA (sCCHN) Is oNe of tHe most COmmon

understanding of the role  for these  rece pto rsin  HSK  and  how they cont r ibut e to disease will prov ide i ns i ghtf or  thedevelop m en t ofno ve l t he r ap eutic s f or thetreatmentHSK  w hich is them os t frequent  ca use of corne alblindn es s i n  theUS.  Head  and N e ck Squ amous Cel lC arcino m a (SCCH N )  i s on e of the most com m on

understanding_of the_role for these receptors_in HSK_and_how they_contribute_to disease will_provide insight for_the development of novel_therapeutics for the_treatment_HSK which is the most frequent cause of corneal blindness in the US. Head_and_Neck Squamous_Cell_Carcinoma_(SCCHN) is one of the_most common


includes the RNA Therapeutics Institute, the Center for Stem Cell Biology and Regenerative Medicine, and the Gene Therapy Center. The UMATC joins the Massachusetts Biologic Laboratories, Meyers Primary Care Institute, and Commonwealth Medicine, four innovative components that are rarely found in academic centers, to speed bench to bedside to

includes the RNA Therapeutics Institute, the Center for Stem Cell Biology and Regenerative Medicine, and the Gene Therapy Center. The UMATC joins the Massachusetts Biologic Laboratories, Meyers Primary Care Institute, and Commonwealth Medicine, four innovative components that are rarely find oneself in academic center, to speed bench to bedside to

infludes the RNA Therapeutlcs Institute, thg Xenter for Sfem Cell Biology and Regenerative Mevicibe, ane the Gene Therapy Cenger. The ULATC joibs tie Massachusetts Biologig Labkvatornew, Meyers Primaty Care Insthtute, and Commmndeclth Medicine, four innovative componqnts thst are rarely foond im acasvmlc centers, to speed bench to bedaide to

includes the RNA Therapeutics Institute, the Center Cell and Regenerative and the Gene the Biologic Laboratories, Meyers Care Institute, and Medicine, four innovative components that are found in academic centers, to speed bench to bedside to

includes the RNA TherapeuticS Institute, The CeNteR foR STem CEll BIology and RegenERatiVe Medicine, and the Gene ThErapy ceNTer. THE UmATC jOins the mAsSAChuSeTtS BiOlOGiC LaboRatOries, MeYers PrimarY CaRe institute, and cOmMonwealth MEdiCine, four innoVatIve comPoNenTS that Are RarelY found IN acadeMic centerS, tO Speed bENch to beDSIdE to

includes the RNA Therapeu tics Insti tute,  th e C en terforStem Cell Biol o gy a nd Regenerative Medici ne, a nd theG en e The rapy Ce n te r .  Th eUM ATC  j o in s the  Ma ssachus etts Biolo gic  L aboratories, Me yers Prima ryCare Institu te,  and C om mon w ealth  Me dicin e, fou r  innov ative com po n ents t h at arer a re ly f ound in academicc en t ers, to speedbenchto be d s ide  to

includes_the RNA_Therapeutics Institute, the Center_for Stem_Cell_Biology and_Regenerative_Medicine, and the_Gene Therapy Center._The UMATC joins the_Massachusetts Biologic Laboratories,_Meyers_Primary Care Institute, and Commonwealth Medicine, four innovative components that are rarely found in_academic_centers, to_speed_bench_to bedside to


) and virus will be administered locally by the IP route. Tumor burden and survival curves will be compared between treatment groups in the presence or absence of gemcitabine and in gemcitabine refractory tumors to determine if MYXV virotherapy under the three regimes mentioned above results in an enhancement of therapeutic benefits as measured by

) and virus will be administered locally by the IP route. Tumor burden and survival curves will be compare between discussion groups in the presence or absence of gemcitabine and in gemcitabine fractious tumors to decide if MYXV virotherapy under the three regimes mention above results in an enhancement of therapeutic benefit as measured by

) anf virus will be administtred locally by tkw IP rmute. Thmor buraen and survival curves will bw comkcred between treatmevt groups in the prestnce or absence oh gemcitabine zkd in jemcitabine reftactory tumoss to determina kf MYXV virotherapy under the three rqgimes kejtioned above tesulus yn ah enhancement of therapeutic benefjts as keasured by

) and virus will be administered locally IP Tumor burden survival curves will in presence or absence gemcitabine and in refractory tumors to determine if MYXV under the three regimes mentioned above results in an enhancement of therapeutic benefits measured by

) and virus will be administereD locally by The IP RouTe. TUmOr buRden And survival curVEs wiLl be compared between treAtmenT gROups IN tHe preSence or ABsENCe oF gEmCitAbINe And in GemCitabinE refractorY tuMoRs to determinE If mYXV virothEraPy under the thRee RegimeS mEntIOned aBovE resuLts in aN EnhancEment of thErAPeutic BEnefits AS MeAsurEd by

) and virus will be admini stered loc allybythe  I P ro ute.  Tumor burdena nd s urvival curves will be  comp ar e d be t we en tr eatment gr o u psin  t hepr e se nce o r a bsenceof gemcita bin eand in gemci t ab ine refrac tor y tumors todet ermine  i f M Y XV vi rot herap y unde r  the t hree regi me s  menti o ned abo v e  r esul ts in an enhancem e nt of therapeutic  benef it s  a s mea sur ed by

) and_virus will_be administered locally by_the IP_route._Tumor burden_and_survival curves will_be compared between_treatment groups in the_presence or absence_of_gemcitabine and in gemcitabine refractory tumors to determine if MYXV virotherapy under the three_regimes_mentioned above_results_in_an enhancement of therapeutic benefits_as measured by


of early stage human cancer cells. The proposed studies are expected to provide insight into regulation of normal axon-glial interactions, and to lead to strategies to understand and ultimately treat human schwannomas. [unreadable] [unreadable] [unreadable] Hermann Lotze was an agent in the development of philosophy and medicine

of early stage human cancer cells. The proposed studies are expect to leave insight into regulation of normal axon - glial interactions, and to run to strategies to understand and ultimately process human schwannomas. [ unreadable ] [ unreadable ] [ indecipherable ] Hermann Lotze was an agentive role in the development of philosophy and music

of early stage human cancev cells. The proposed stndies ade expecged to provide insight into ceguoatiob of normal axon-glial knteractilns, and ro ltad to strategies to undevftans and nltimately treaj human schwdnnomas. [unreaddbue] [unreadable] [unreadable] Hermann Lotzq was am wgent in the dgvelokmegt or philosophy and medicine

of early stage human cancer cells. The are to provide into regulation of lead strategies to understand ultimately treat human [unreadable] [unreadable] [unreadable] Hermann Lotze was agent in the development of philosophy and medicine

of early stage human cancer ceLls. The propOsed sTudIes ArE expEcteD to provide insiGHt inTo regulation of normal axOn-gliAl INterACtIons, aNd to leaD To STRatEgIeS to UnDErStand And UltimatEly treat huMan ScHwannomas. [unrEAdAble] [unreadAblE] [unreadable] HErmAnn LotZe Was AN agenT in The deVelopmENt of phIlosophy aNd MEdicinE

of early stage human canc er cells.The p rop ose dstud iesare expected t o  pro vide insight into regu latio no f no r ma l axo n-glial in t e rac ti on s,an d  t o lea d t o strat egies to u nde rs tand and ult i ma tely treat  hu man schwanno mas . [unr ea dab l e] [u nre adabl e] [un r eadabl e] Herman nL otze w a s an ag e n tin t he development of ph i losophy and me dicine

of_early stage_human cancer cells. The_proposed studies_are_expected to_provide_insight into regulation_of normal axon-glial_interactions, and to lead_to strategies to_understand_and ultimately treat human schwannomas. [unreadable] [unreadable] [unreadable] Hermann Lotze was an agent in_the_development of_philosophy_and_medicine


as ADHD are thought to affect as many as 5% of the children in the United States, and better understanding of the basic neuronal mechanisms related to attention is needed for guiding assessment, diagnosis, and treatment of attentional deficits. This project will investigate basic mechanisms of bioelectric information as produced by the actions of sodium channel proteins

as ADHD are thought to affect as many as 5% of the children in the United States, and good reason of the basic neuronal mechanisms related to care is needed for guiding assessment, diagnosis, and discussion of attentional deficit. This project will investigate basic mechanism of bioelectric information as produced by the military action of sodium channel proteins

as ADHD are thought to afftct as many as 5% oy the ciildren in the Jnited States, and better undxrstqndint of the basic neuronau mechanidms relared uo attention is nxsded fov guislng avwessment, diagnpsis, and tseatment of atdevtnonal deficits. This project will invqstigatr hasic mechanisis og bioslectric information as produced bg the abtions of sodium vhannel proteins

as ADHD are thought to affect as 5% the children the United States, basic mechanisms related to is needed for assessment, diagnosis, and treatment of attentional This project will investigate basic mechanisms of bioelectric information as produced by the of sodium channel proteins

as ADHD are thought to affect aS many as 5% of tHe chiLdrEn iN tHe UnIted states, and betteR UndeRstanding of the basic neuRonal MeCHaniSMs RelatEd to attENtION is NeEdEd fOr GUiDing aSseSsment, dIagnosis, anD trEaTment of attenTIoNal deficitS. ThIs project wilL inVestigAtE baSIc mecHanIsms oF bioelECtric iNformatioN aS ProducED by the aCTIoNs of Sodium channel protEInS

as ADHD are thought to af fect as ma ny as  5%  of  t he c hild ren in the Uni t ed S tates, and better unde rstan di n g of th e bas ic neur o na l mec ha ni sms  r e la ted t o a ttentio n is neede d f or  guiding ass e ss ment, diag nos is, and trea tme nt ofat ten t ional  de ficit s. Thi s  proje ct will i nv e stigat e  basicm e ch anis ms of bioelectric in f ormation as pr oduced  b y  t h e  ac tio ns of sodi um  chan n el prot e in s

as_ADHD are_thought to affect as_many as_5%_of the_children_in the United_States, and better_understanding of the basic_neuronal mechanisms related_to_attention is needed for guiding assessment, diagnosis, and treatment of attentional deficits. This project_will_investigate basic_mechanisms_of_bioelectric information as produced by_the actions of sodium channel_proteins


communication and language abilities by such individuals. The proposed studies will address five specific aims related to these overall objectives that have been identified on the basis of the applicant's current and previous research. All of these aims relate to a proposed model of communication development in this population that identifies a number of critical "cusps" that have

communication and language abilities by such individuals. The proposed report will cover five specific aims related to these overall aim that have been name on the basis of the applicant's current and previous inquiry. All of these aims relate to a proposed model of communication growth in this population that identifies a number of critical " cusp " that have

colmunication and language abilities by socy inditiduals. The prooosed studies will address fmve wpecidic aims related to thdse overapl objecrivew that have been idcutifisf on vhe basis of thg applicant's current and psexilus research. All of these aims relaee to a pgoposed model jf cpimunjbauion development in this populatikn that identifies a number of critical "cusps" hhat have

communication and language abilities by such individuals. studies address five aims related to been on the basis the applicant's current previous research. All of these aims to a proposed model of communication development in this population that identifies a of critical "cusps" that have

communication and language aBilities by Such iNdiVidUaLs. ThE proPosed studies wiLL addRess five specific aims reLated To THese OVeRall oBjectivES tHAT haVe BeEn iDeNTiFied oN thE basis oF the applicAnt'S cUrrent and preVIoUs research. all Of these aims rElaTe to a pRoPosED modeL of CommuNicatiON develOpment in tHiS PopulaTIon that IDEnTifiEs a number of criticAL "cUSps" that have

communication and languag e abilitie s bysuc h i nd ivid uals . The proposed stud ies will address fivespeci fi c  aim s  r elate d to th e se o ver al lobj ec t iv es th athave be en identif ied  o n the basiso fthe applic ant 's current a ndprevio us  re s earch . A ll of  these aims r elate toap ropose d  modelo f  c ommu nication developm e nt in this popula tion t ha t  i d e nti fie s a number  o f cri t ical "c u sp s " tha t  have

communication_and language_abilities by such individuals._The proposed_studies_will address_five_specific aims related_to these overall_objectives that have been_identified on the_basis_of the applicant's current and previous research. All of these aims relate to a_proposed_model of_communication_development_in this population that identifies_a number of critical "cusps"_that have


(CNS)-derived HIV isolates and one corresponding lymphocyte-derived HIV isolate. These HIV can be distinguished by their replicating properties in different cells. We shall clone their proviral forms from genetic libraries of virus-infected cellular DNA. Molecular clones of these viruses will be subjected to restriction endonuclease analysis and the resulting

(CNS)-derived HIV isolates and one corresponding lymphocyte - derived HIV isolate. These HIV can be distinguished by their replicating place in unlike cells. We shall clone their proviral forms from familial library of virus - infected cellular DNA. Molecular clones of these virus will be subjected to restriction endonuclease analysis and the result

(CND)-derived HIV isolates ana one corresponbung lykphocyfe-derivea HIV isolate. These HIV can ue dustintuished by their replizating prlperties in vifferent cells. Xs shall clone bheir 'roviral forms nrom genetiw libraries of vkrbs-infected cellular DNA. Molecular cljnes of tjese viruses wyll nq sugjected to restriction endonucleass analyvis and the rrsulting

(CNS)-derived HIV isolates and one corresponding lymphocyte-derived These can be by their replicating shall their proviral forms genetic libraries of cellular DNA. Molecular clones of these will be subjected to restriction endonuclease analysis and the resulting

(CNS)-derived HIV isolates and oNe correspoNding LymPhoCyTe-deRiveD HIV isolate. TheSE HIV Can be distinguished by thEir rePlICatiNG pRoperTies in dIFfEREnt CeLlS. We ShALl Clone TheIr proviRal forms frOm gEnEtic librarieS Of Virus-infecTed Cellular DNA. MOleCular cLoNes OF thesE viRuses Will be SUbjectEd to restrIcTIon endONucleasE ANaLysiS and the resulting

(CNS)-derived HIV isolate s and onecorre spo ndi ng  lym phoc yte-derived HI V  iso late. These HIV can be  dist in g uish e dby th eir rep l ic a t ing  p ro per ti e sin di ffe rent ce lls. We sh all  c lone their p r ov iral forms  fr om genetic l ibr ariesof  vi r us-in fec ted c ellula r  DNA.Molecular  c l ones o f  thesev i ru seswill be subjected to restriction en donucl ea s ea n aly sis  and the r es ultin g

(CNS)-derived_HIV isolates_and one corresponding lymphocyte-derived_HIV isolate._These_HIV can_be_distinguished by their_replicating properties in_different cells. We shall_clone their proviral_forms_from genetic libraries of virus-infected cellular DNA. Molecular clones of these viruses will be_subjected_to restriction_endonuclease_analysis_and the resulting


syntesized in preparation for mitosis. The basis of this regulation will be investigated. The triggering of tubulin synthesis depends on the completion of prior events in the mitotic cycle. The nature of the committment to tubulin syntesis will be investigated using mitotic cycle mutants, cell fusions, and heat shocks.

syntesized in preparation for mitosis. The basis of this regulation will be investigated. The triggering of tubulin deduction depend on the completion of prior events in the mitotic hertz. The nature of the committment to tubulin syntesis will be investigate using mitotic cycle mutant, cellular telephone fusions, and heat shocks.

syjtesized in preparation nor mitosis. The yqsis oh this degulatiun will be investigated. The vrigterint of tubulin synthesis depends ln the cimplttion of prior evxhts in bke mifltic rycle. The naturg of the comkittment to tutuuiu syntesis will be investigated usind mitotoc cycle mutants, celk fusjons, and heat shocks.

syntesized in preparation for mitosis. The basis regulation be investigated. triggering of tubulin of events in the cycle. The nature the committment to tubulin syntesis will investigated using mitotic cycle mutants, cell fusions, and heat shocks.

syntesized in preparation foR mitosis. ThE basiS of ThiS rEgulAtioN will be investiGAted. the triggering of tubulin SynthEsIS depENdS on thE compleTIoN OF prIoR eVenTs IN tHe mitOtiC cycle. THe nature of The CoMmittment to tUBuLin syntesiS wiLl be investigAteD using MiTotIC cyclE muTants, Cell fuSIons, anD heat shocKs.

syntesized in preparation  for mitos is. T hebas is  ofthis  regulation wi l l be  investigated. The tri ggeri ng of t u bu lin s ynthesi s  d e p end son  th ec om pleti onof prio r events i n t he  mitotic cyc l e.  The natur e o f the commit tme nt totu bul i n syn tes is wi ll bei nvesti gated usi ng mitoti c  cyclem u ta nts,  cell fusions, an d  h e at shocks.

syntesized_in preparation_for mitosis. The basis_of this_regulation_will be_investigated._The triggering of_tubulin synthesis depends_on the completion of_prior events in_the_mitotic cycle. The nature of the committment to tubulin syntesis will be investigated using_mitotic_cycle mutants,_cell_fusions,_and heat shocks.


When synthetic GnRH first became available for clinical study, there was not yet an adequate understanding of the physiology of GnRH secretion in the human to support its potential therapeutic application. As a result, early attempts at ovulation induction were unsuccessful. It was soon appreciated that an episodic mode of delivery was essential for normal pituitary

When synthetic GnRH first became available for clinical study, there be not so far an adequate understanding of the physiology of GnRH secretion in the human to support its likely therapeutic application. As a result, early attempt at ovulation induction were unsuccessful. It was soon appreciate that an episodic mode of delivery was substantive for normal pituitary

Whfn synthetic GnRH first necame available for clmnical atudy, thdre was not yet an adequate nndeestaneing of the physiology of GnRH decretiob in rhe human vk suppovc its iotenciel therapeutic spplicatiot. As a result, aaflv attempts at ovulation induction wewe unsuvcfssful. It was foon wpprsbicted that an episodic mode of dslivery was essentiak for normal pituitary

When synthetic GnRH first became available for there not yet adequate understanding of in human to support potential therapeutic application. a result, early attempts at ovulation were unsuccessful. It was soon appreciated that an episodic mode of delivery was for normal pituitary

When synthetic GnRH first becAme availabLe for CliNicAl StudY, theRe was not yet an aDEquaTe understanding of the phYsiolOgY Of Gnrh sEcretIon in thE HuMAN to SuPpOrt ItS PoTentiAl tHerapeuTic applicaTioN. AS a result, earlY AtTempts at ovUlaTion inductioN weRe unsuCcEssFUl. It wAs sOon apPreciaTEd that An episodiC mODe of deLIvery waS ESsEntiAl for normal pituitARy

When synthetic GnRH first  became av ailab lefor  c lini calstudy, there w a s no t yet an adequate unde rstan di n g of th e phy siology of G nRH  s ec ret io n  i n the  hu man tosupport it s p ot ential thera p eu tic applic ati on. As a res ult , earl yatt e mptsatovula tion i n ductio n were un su c cessfu l . It wa s so on a ppreciated that a n  e p isodic mode of  deliv er y  w a s  es sen tial for n or mal p i tuitary

When_synthetic GnRH_first became available for_clinical study,_there_was not_yet_an adequate understanding_of the physiology_of GnRH secretion in_the human to_support_its potential therapeutic application. As a result, early attempts at ovulation induction were unsuccessful._It_was soon_appreciated_that_an episodic mode of delivery_was essential for normal pituitary


learning and evaluates how the optimal EA dosage could be customized to healthy individuals and to chronic stroke patients. Research indicates that training specificity (i.e., training on the tasks you actually want to improve) is important to recovery of activities of daily living (ADL). Here we also test whether customized visual feedback based on optimal

learning and evaluates how the optimal EA dosage could be custom-make to goodly individuals and to chronic stroke patient. Research indicate that training specificity (i.e., training on the job you actually desire to improve) is important to recovery of activities of daily support (ADL). Here we also test whether custom-make visual feedback based on optimal

lewrning and evaluates how the optimal EA dosage could be custumized to healthy individuald qnd ti chronic stroke patievts. Reseagch indicqtes rhat trainmhg speclyicitg (i.e., creining on the tssks you awtually want tm km'rove) is important to recovery of aceivitiex lf daily livind (ADK). Hers we also test whether customized bisual heedback based pn optimal

learning and evaluates how the optimal EA be to healthy and to chronic training (i.e., training on tasks you actually to improve) is important to recovery activities of daily living (ADL). Here we also test whether customized visual feedback on optimal

learning and evaluates how thE optimal EA DosagE coUld Be CustOmizEd to healthy indIViduAls and to chronic stroke pAtienTs. rEseaRCh IndicAtes thaT TrAINinG sPeCifIcITy (I.e., traIniNg on the Tasks you acTuaLlY want to improVE) iS important To rEcovery of actIviTies of DaIly LIving (aDL). here wE also tESt whetHer customIzED visuaL FeedbacK BAsEd on Optimal

learning and evaluates ho w the opti mal E A d osa ge  cou ld b e customized t o  hea lthy individuals and t o chr on i c st r ok e pat ients.R es e a rch  i nd ica te s  t hat t rai ning sp ecificity(i. e. , training o n  t he tasks y ouactually wan t t o impr ov e)i s imp ort ant t o reco v ery of  activiti es of dai l y livin g (A DL).  Here we also tes t  w h ether customiz ed vis ua l  f e e dba ckbased on o pt imal

learning_and evaluates_how the optimal EA_dosage could_be_customized to_healthy_individuals and to_chronic stroke patients._Research indicates that training_specificity (i.e., training_on_the tasks you actually want to improve) is important to recovery of activities of_daily_living (ADL)._Here_we_also test whether customized visual_feedback based on optimal


the results are as positive as we anticipate, and given the excellent safety profile of MYXV, we will pursue the production of clinical grade stocks of MYXV and the filing for an investigational new drug application (IND) at the completion of the proposed study. Project Summary/Abstract The Department of Occupational and Environmental Health

the results are as positive as we anticipate, and give the excellent condom profile of MYXV, we will pursue the production of clinical grad stocks of MYXV and the filing for an investigational new drug lotion (IND) at the completion of the proposed study. Project Summary / Abstract The Department of Occupational and Environmental Health

thf results are as positivt as we anticipatg, qnd giten the excellevt safety profile of MYXV, we wull pyrsue the production ow clinicap grade wtocjw of MYXV ehd the nnling nor au mnvestigational new drug dpplication (ING) xt the completion of the proposed stuqy. Projrch Summary/Abstrwct Uhe Depzgtnent of Occupational and Envidonmentel Health

the results are as positive as we given excellent safety of MYXV, we clinical stocks of MYXV the filing for investigational new drug application (IND) at completion of the proposed study. Project Summary/Abstract The Department of Occupational and Environmental

the results are as positive as We anticipaTe, and GivEn tHe ExceLlenT safety profile OF MYXv, we will pursue the producTion oF cLInicAL gRade sTocks of myXv ANd tHe FiLinG fOR aN inveStiGationaL new drug apPliCaTion (IND) at the COmPletion of tHe pRoposed study. proJect SuMmAry/aBstraCt THe DepArtmenT Of OccuPational aNd eNvironMEntal HeALTh

the results are as positi ve as we a ntici pat e,an d gi venthe excellents afet y profile of MYXV, wewillpu r suet he  prod uctiono fc l ini ca lgra de st ocksofMYXV an d the fili ngfo r an investi g at ional newdru g applicatio n ( IND) a tthe compl eti on of  the p r oposed  study. P ro j ect Su m mary/Ab s t ra ct T he Department ofO cc u pational and E nviron me n ta l Hea lth

the_results are_as positive as we_anticipate, and_given_the excellent_safety_profile of MYXV,_we will pursue_the production of clinical_grade stocks of_MYXV_and the filing for an investigational new drug application (IND) at the completion of_the_proposed study._Project_Summary/Abstract_The Department of Occupational and_Environmental Health


risk factors for rebleeding and the timing of these disastrous events; determination of the safety and effectiveness of antifibrinolytic agents and development of an administration schedule which optimizes the actions in preventing rebleeding and minimizes ischemic neurological complications; documentation of the diagnostic and prognostic value of CT scanning in subarachnoid

risk factors for rebleeding and the timing of these disastrous events; decision of the condom and effectiveness of antifibrinolytic agents and development of an government schedule which optimizes the action in preventing rebleeding and minimizes ischemic neurological complications; software documentation of the diagnostic and predictive value of CT scanning in subarachnoid

ridk factors for rebleedinn and the timing of theve diszstrous dvents; determination of the dadety qnd effectiveness of avtifibrinllytic atentw and development on an zfminnsvration schedulg which optikizes the actimnr nn preventing rebleeding and minimizqs ischrmlc neurologicaj cok[liczniins; documentation of the diaghostic end prognostic falue of CT scanning in suharafhnoid

risk factors for rebleeding and the timing disastrous determination of safety and effectiveness of administration schedule which the actions in rebleeding and minimizes ischemic neurological complications; of the diagnostic and prognostic value of CT scanning in subarachnoid

risk factors for rebleeding aNd the timinG of thEse DisAsTrouS eveNts; determinatiON of tHe safety and effectiveneSs of aNtIFibrINoLytic Agents aND dEVEloPmEnT of An ADmInistRatIon scheDule which oPtiMiZes the actionS In Preventing RebLeeding and miNimIzes isChEmiC NeuroLogIcal cOmplicATions; dOcumentatIoN Of the dIAgnostiC ANd ProgNostic value of CT scANnINg in subarachnoId

risk factors for rebleedi ng and the  timi ngofth esedisa strous events; dete rmination of the safet y and  e f fect i ve nessof anti f ib r i nol yt ic  ag en t sand d eve lopment  of an adm ini st ration sched u le  which opt imi zes the acti ons  in pr ev ent i ng re ble eding  and m i nimize s ischemi cn eurolo g ical co m p li cati ons; documentatio n  o f  the diagnosti c andpr o gn o s tic  va lue of CTsc annin g  in sub a ra c h n oid

risk_factors for_rebleeding and the timing_of these_disastrous_events; determination_of_the safety and_effectiveness of antifibrinolytic_agents and development of_an administration schedule_which_optimizes the actions in preventing rebleeding and minimizes ischemic neurological complications; documentation of the_diagnostic_and prognostic_value_of_CT scanning in subarachnoid


to have early reperfusion and good clinical outcome than those without any ICH. Using the largest available trials with revascularization status, the PI will pursue the following specific aims: (1) determine the relationship between radiological subtypes of ICH and timing of successful revascularization and (2) determine the relationship of ICH

to have early reperfusion and good clinical outcome than those without any ICH. Using the bombastic available test with revascularization status, the PI will pursue the following specific aim: (1) determine the relationship between radiological subtypes of ICH and timing of successful revascularization and (2) specify the relationship of ICH

to have early reperfusion xnd good clinicco outcmme thzn those without any ICH. Using the lergewt avqilable trials with rexascularidation stqtus, rhe PI will pursue the fkplownnj specific aims: (1) determina the relationvhkp between radiological subtypes of ISH and yiling of succesfful wevaabuoarization and (2) determine the relatimnship of ICH

to have early reperfusion and good clinical those any ICH. the largest available PI pursue the following aims: (1) determine relationship between radiological subtypes of ICH timing of successful revascularization and (2) determine the relationship of ICH

to have early reperfusion and Good clinicAl outComE thAn ThosE witHout any ICH. UsinG The lArgest available trials wIth reVaSCulaRIzAtion Status, tHE Pi WIll PuRsUe tHe FOlLowinG spEcific aIms: (1) determiNe tHe Relationship BEtWeen radiolOgiCal subtypes oF ICh and tiMiNg oF SucceSsfUl revAsculaRIzatioN and (2) deterMiNE the reLAtionshIP Of iCH

to have early reperfusion  and goodclini cal  ou tc omethan  those without anyICH. Using the largest  avai la b le t r ia ls wi th reva s cu l a riz at io n s ta t us , the  PI  will p ursue thefol lo wing specifi c  a ims: (1) d ete rmine the re lat ionshi pbet w een r adi ologi cal su b typesof ICH an dt imingo f succe s s fu l re vascularization a n d( 2) determine t he rel at i on s h ipofICH

to_have early_reperfusion and good clinical_outcome than_those_without any_ICH._Using the largest_available trials with_revascularization status, the PI_will pursue the_following_specific aims: (1) determine the relationship between radiological subtypes of ICH and timing of_successful_revascularization and_(2)_determine_the relationship of ICH