surveillance procedures between 35 and 45 days of age. Lead exposure at the levels employed had no statistically significant effect on growth and did not result in overt signs of toxicity. Thymic weights were significantly decreased in both males and females of the two lead dosage groups. Furthermore, lead exposure resulted in suppression of responsiveness of lymphocytes to

surveillance procedures between 35 and 45 days of age. Lead vulnerability at the degree employed had no statistically significant impression on growth and did not result in overt sign of the zodiac of toxicity. Thymic weights were importantly decrease in both males and female of the two lead dosage group. Furthermore, lead vulnerability resulted in suppression of responsiveness of lymphocytes to

sugveillance procedures beuween 35 and 45 days of age. Nead esposure xt the levels employed had nl wtatiwtically significant ewfect on hrowth abd dmd not result in overt slyns or toxncmty. Thymic weigmts were sicnificantly dewrdaded in both males and females of thq two lraf dosage groupf. Fugtrermkge, lead exposure resulted in sulpressimn of responsoveness of lymphocytes to

surveillance procedures between 35 and 45 days Lead at the employed had no and not result in signs of toxicity. weights were significantly decreased in both and females of the two lead dosage groups. Furthermore, lead exposure resulted in of responsiveness of lymphocytes to

surveillance procedures betWeen 35 and 45 dayS of agE. LeAd eXpOsurE at tHe levels employED had No statistically signifiCant eFfECt on GRoWth anD did not REsULT in OvErT siGnS Of ToxicIty. thymic wEights were SigNiFicantly decrEAsEd in both maLes And females of The Two leaD dOsaGE grouPs. FUrtheRmore, lEAd expoSure resulTeD In suppREssion oF REsPonsIveness of lymphocyTEs TO

surveillance procedures b etween 35and 4 5 d ays  o f ag e. L ead exposure a t  the  levels employed had n o sta ti s tica l ly  sign ificant ef f e cton  g row th an d did  no t resul t in overt  si gn s of toxicit y .Thymic wei ght s were signi fic antlyde cre a sed i n b oth m ales a n d fema les of th et wo lea d  dosage g ro ups.  Furthermore, lea d  e x posure resulte d in s up p re s s ion  of  responsiv en ess o f  lympho c yt e s to

surveillance_procedures between_35 and 45 days_of age._Lead_exposure at_the_levels employed had_no statistically significant_effect on growth and_did not result_in_overt signs of toxicity. Thymic weights were significantly decreased in both males and females_of_the two_lead_dosage_groups. Furthermore, lead exposure resulted_in suppression of responsiveness of_lymphocytes to


split between genetic, molecular biology, whole animal studies and small molecule screening, with training and instruction in each, and in the particular areas that this project involves: murine biology, cancer biology, cell culture technique and high-throughput drug screening. Dr. Kasinski's goal is to become a faculty member in an interdisciplinary

split between genetic, molecular biology, whole animal report and humble molecule screening, with training and education in each, and in the particular areas that this undertaking involves: murine biology, cancer biology, cellular telephone acculturation technique and gamey - throughput drug screening. Dr. Kasinski's goal is to become a staff member in an interdisciplinary

sppit between genetic, molegular biology, whole anikal sthdies ana small molecule screening, wmth rrainung and instruction in each, and in the partmcular areas thav this pvjjecf invmoves: murine biplogy, cancar biology, celn zupture technique and high-throughput qrug sctefning. Dr. Kasinfki's doal ps to become a faculty member ih an inuerdisciplinary

split between genetic, molecular biology, whole animal small screening, with and instruction in areas this project involves: biology, cancer biology, culture technique and high-throughput drug screening. Kasinski's goal is to become a faculty member in an interdisciplinary

split between genetic, molecuLar biology, Whole AniMal StUdieS and Small molecule sCReenIng, with training and instRuctiOn IN eacH, AnD in thE particULaR AReaS tHaT thIs PRoJect iNvoLves: murIne biology, CanCeR biology, cell CUlTure techniQue And high-throuGhpUt drug ScReeNIng. Dr. kasInski'S goal iS To becoMe a facultY mEMber in AN interdISCiPlinAry

split between genetic, mo lecular bi ology , w hol eanim al s tudies and sma l l mo lecule screening, with  trai ni n g an d  i nstru ction i n  e a c h,an dinth e  p artic ula r areas  that this  pr oj ect involves :  m urine biol ogy , cancer bio log y, cel lcul t ure t ech nique  and h i gh-thr oughput d ru g  scree n ing. Dr . Ka sins ki's goal is to b e co m e a faculty me mber i na ni n ter dis ciplinary

split_between genetic,_molecular biology, whole animal_studies and_small_molecule screening,_with_training and instruction_in each, and_in the particular areas_that this project_involves:_murine biology, cancer biology, cell culture technique and high-throughput drug screening. Dr. Kasinski's goal_is_to become_a_faculty_member in an interdisciplinary


to make substitutions at residues thought to play a role as a covalent catalyst, a metal ligand, or Bronsted base/acid. Second, fluorinated substrate(s) will be used that cannot undergo turnover. Third, rapid quench approaches will be tried. The second aim is to determine the manner by which PB

to make substitutions at residues thought to toy a function as a covalent catalyst, a metal ligand, or Bronsted base / acid. Second, fluorinated substrate(s) will be used that cannot undergo dollar volume. Third, rapid quench approaches will be tried. The second bearing is to decide the manner by which PB

to make substitutions at rtsidues thought to play e role zs a covxlent catalyst, a metal liganv, or Bronwted base/acid. Second, fuuorinatef substrqte(s) qill be usxs that gcnnot mnderyo turnover. Thirc, rapid quanch approachev dipl be tried. The second aim is to deeermine tje manner by wrich [B

to make substitutions at residues thought to role a covalent a metal ligand, substrate(s) be used that undergo turnover. Third, quench approaches will be tried. The aim is to determine the manner by which PB

to make substitutions at resiDues thoughT to plAy a RolE aS a coValeNt catalyst, a metAL ligAnd, or Bronsted base/acid. SEcond, FlUOrinATeD subsTrate(s) wILl BE UseD tHaT caNnOT uNdergO tuRnover. THird, rapid qUenCh Approaches wiLL bE tried. The sEcoNd aim is to detErmIne the MaNneR By whiCh Pb

to make substitutions atresidues t hough t t o p la y arole  as a covalent cata lyst, a metal ligand,or Br on s tedb as e/aci d. Seco n d, f luo ri na ted  s u bs trate (s)  will b e used tha t c an not undergot ur nover. Thi rd,  rapid quenc h a pproac he s w i ll be  tr ied.The se c ond ai m is to d et e rminet he mann e r  b y wh ich PB

to_make substitutions_at residues thought to_play a_role_as a_covalent_catalyst, a metal_ligand, or Bronsted_base/acid. Second, fluorinated substrate(s)_will be used_that_cannot undergo turnover. Third, rapid quench approaches will be tried. The second aim is_to_determine the_manner_by_which PB


PD is not only limited to tooth loss and associated loss of self-esteem but also impacts general health. Our recent findings indicate that resolution of inflammation is an active process and reveal an urgent need to clinically navigate this essentially uncharted terrain of infammation-resolution. To address this scientific opportunity and important mission in oral health

PD is not only limited to tooth loss and associated loss of self - admiration but besides impacts general health. Our late findings argue that resolution of inflammation is an active procedure and reveal an urgent motivation to clinically navigate this essentially chartless terrain of infammation - resolution. To address this scientific opportunity and important mission in oral health

PD is not only limited to uooth loss and associatev loss kf self-erteem but also impacts generel hwalth. Our recent findings ivdicate tjat resooutiib of inflammation lf an wctire process and rgveal an urgant need to clhnkcclly navigate this essentially unchawted tetrwin of infammajion-rtsojutikn. To address this scientific oppodtunity and importany mission in oral health

PD is not only limited to tooth associated of self-esteem also impacts general that of inflammation is active process and an urgent need to clinically navigate essentially uncharted terrain of infammation-resolution. To address this scientific opportunity and important mission oral health

PD is not only limited to tooth Loss and assOciatEd lOss Of Self-EsteEm but also impacTS genEral health. Our recent finDings InDIcatE ThAt resOlution OF iNFLamMaTiOn iS aN AcTive pRocEss and rEveal an urgEnt NeEd to clinicalLY nAvigate thiS esSentially uncHarTed terRaIn oF InfamMatIon-reSolutiON. To addRess this sCiENtific OPportunITY aNd imPortant mission in oRAl HEalth

PD is not only limited to  tooth los s and  as soc ia tedloss  of self-estee m  but  also impacts generalhealt h. Ourr ec ent f indings in d i cat eth atre s ol ution  of  inflam mation isanac tive process an d reveal a n u rgent need t o c linica ll y n a vigat e t his e ssenti a lly un charted t er r ain of infamma t i on -res olution. To addre s st his scientific  oppor tu n it y and  im portant mi ss ion i n  oral h e al t h

PD_is not_only limited to tooth_loss and_associated_loss of_self-esteem_but also impacts_general health. Our_recent findings indicate that_resolution of inflammation_is_an active process and reveal an urgent need to clinically navigate this essentially uncharted_terrain_of infammation-resolution._To_address_this scientific opportunity and important_mission in oral health


Newborns and Children (ACHDNC) (authorized by the Children's Health Act of 2000), and by the Secretary of HHS. Most states now use this or very similar panels for newborn screening. Currently, there are thousands of rare disorders that have been identified and hundreds that could potentially benefit from newborn screening.

Newborns and Children (ACHDNC) (authorized by the Children's Health Act of 2000), and by the Secretary of HHS. Most states now use this or very exchangeable panel for newborn screening. Currently, there are thousand of rare disorders that have been identified and hundreds that could potentially profit from newborn cover.

Neaborns and Children (ACHDKC) (authorized by the Chmldren's Health Xct of 2000), and by the Secretary od HHS. Most states now use tfis or vegy similae paiels for newborn screeniky. Curdcntly, vhere are thoussnds of rase disorders tvag kave been identified and hundreds thwt coulc ootentially begefiu fwom hvwnorn screening.

Newborns and Children (ACHDNC) (authorized by the Act 2000), and the Secretary of this very similar panels newborn screening. Currently, are thousands of rare disorders that been identified and hundreds that could potentially benefit from newborn screening.

Newborns and Children (ACHDNC) (Authorized By the chiLdrEn'S HeaLth ACt of 2000), and by the SeCRetaRy of HHS. Most states now usE this Or VEry sIMiLar paNels for NEwBORn sCrEeNinG. CURrEntly, TheRe are thOusands of rAre DiSorders that hAVe Been identiFieD and hundreds ThaT could PoTenTIally BenEfit fRom newBOrn scrEening.

Newborns and Children (AC HDNC) (aut horiz edbyth e Ch ildr en's Health Ac t  of2000), and by the Secr etary  o f  HHS .  M ost s tates n o wu s e t hi sorve r ysimil arpanelsfor newbor n s cr eening. Curr e nt ly, thereare  thousands o f r are di so rde r s tha t h ave b een id e ntifie d and hun dr e ds tha t  couldp o te ntia lly benefit fromn ew b orn screening.

Newborns_and Children_(ACHDNC) (authorized by the_Children's Health_Act_of 2000),_and_by the Secretary_of HHS. Most_states now use this_or very similar_panels_for newborn screening. Currently, there are thousands of rare disorders that have been identified_and_hundreds that_could_potentially_benefit from newborn screening.


aims, we plan to test the overall hypothesis that the HCN1 channel that contributes to the Ih current in PFC PNs is important for the regulation of alcohol drinking, and specifically that (a) binge drinking of alcohol during adolescence inhibits persistent firing and excitability in the PFC via reduction of Ih

aims, we plan to test the overall hypothesis that the HCN1 distribution channel that contribute to the Ih current in PFC PNs is important for the regulation of alcohol drink, and specifically that (a) binge drinking of alcohol during adolescence inhibits persistent fire and excitability in the PFC via reduction of Ih

ails, we plan to test the oyerall hypothesis that vhe HCN1 channel that contributes to the Ih rurrwnt ib PFC PNs is important for the gegulatiob of qlcohol drmhking, akb spedlficanoy that (a) bingg drinking ox alcohol duritg abolescence inhibits persistent firind and eccltability in tre PGS viz reduction of Ih

aims, we plan to test the overall the channel that to the Ih important the regulation of drinking, and specifically (a) binge drinking of alcohol during inhibits persistent firing and excitability in the PFC via reduction of Ih

aims, we plan to test the overalL hypothesiS that The hCN1 ChAnneL thaT contributes to THe Ih Current in PFC PNs is imporTant fOr THe reGUlAtion Of alcohOL dRINkiNg, AnD spEcIFiCally ThaT (a) binge Drinking of AlcOhOl during adolEScEnce inhibiTs pErsistent firIng And excItAbiLIty in The pFC viA reducTIon of IH

aims, we plan to test the  overall h ypoth esi s t ha t th e HC N1 channel tha t  con tributes to the Ih cur rentin PFCP Ns  is i mportan t  f o r  th ere gul at i on  of a lco hol dri nking, and  sp ec ifically tha t  ( a) binge d rin king of alco hol  durin gado l escen ceinhib its pe r sisten t firingan d  excit a bilityi n  t he P FC via reductiono fI h

aims,_we plan_to test the overall_hypothesis that_the_HCN1 channel_that_contributes to the_Ih current in_PFC PNs is important_for the regulation_of_alcohol drinking, and specifically that (a) binge drinking of alcohol during adolescence inhibits persistent_firing_and excitability_in_the_PFC via reduction of Ih


growth as a result of disruption of the genes for the only annotated M. pneumoniae protein phosphatase and cognate ser/thr protein kinase. We will confirm cause and effect for these mutants and explore the impact of loss of protine kinase or phosphatase function on the phosphorylation of terminal organelle proteins HMW1 and HMW

growth as a result of disruption of the genes for the lone annotate M. pneumoniae protein phosphatase and cognate ser / thr protein kinase. We will confirm cause and effect for these mutant and explore the impact of passing of protine kinase or phosphatase routine on the phosphorylation of terminal organelle protein HMW1 and HMW

grlwth as a result of disrmption of the geuws for the ohly annogated M. pneumoniae protein piospyatast and cognate ser/thf protein kinase. Qe wmll confirm causx and efnzct fkv thevx mutants and ewplore the hmpact of loss ow 'rotine kinase or phosphatase functijn on tne phosphorylatijn og terjpncl organelle proteins HMW1 and HJW

growth as a result of disruption of for only annotated pneumoniae protein phosphatase We confirm cause and for these mutants explore the impact of loss of kinase or phosphatase function on the phosphorylation of terminal organelle proteins HMW1 and

growth as a result of disruptiOn of the genEs for The OnlY aNnotAted m. pneumoniae proTEin pHosphatase and cognate seR/thr pRoTEin kINaSe. We wIll confIRm CAUse AnD eFfeCt FOr These MutAnts and Explore the ImpAcT of loss of proTInE kinase or pHosPhatase functIon On the pHoSphORylatIon Of terMinal oRGanellE proteins hMw1 And HMW

growth as a result of dis ruption of  thegen esfo r th e on ly annotated M .  pne umoniae protein phosph atase  a n d co g na te se r/thr p r ot e i n k in as e.We wi ll co nfi rm caus e and effe ctfo r these muta n ts  and explo rethe impact o f l oss of  p rot i ne ki nas e orphosph a tase f unction o nt he pho s phoryla t i on  ofterminal organell e  p r oteins HMW1 an d HMW

growth_as a_result of disruption of_the genes_for_the only_annotated_M. pneumoniae protein_phosphatase and cognate_ser/thr protein kinase. We_will confirm cause_and_effect for these mutants and explore the impact of loss of protine kinase or_phosphatase_function on_the_phosphorylation_of terminal organelle proteins HMW1_and HMW


inhibited by acute increases in arterial blood pressure. Further it is proposed that caudal VLM neurons influence the activity of rostral VLM neurons either through monosynaptic connections or through indirect pathways. Thus, interactions between caudal and rostral VLM neurons constitute neuronal mechanisms in the VLM of the cat that

inhibited by acute increases in arterial blood atmospheric pressure. far it is proposed that caudal VLM neurons influence the bodily process of rostral VLM neurons either through monosynaptic connections or through collateral pathways. Thus, interactions between caudal and rostral VLM nerve cell establish neuronal mechanism in the VLM of the cat that

injibited by acute increasts in arterial blood prevsure. Rurther kt is proposed that caudal VPM neurins influence the actixity of rlstral VOM nturons either through monosynapflc counxctions or throogh indirect pathways. Thus, ivtzractions between caudal and rostral VLM neirlns constitute neugogal jvcmanisms in the VLM of the cat thzt

inhibited by acute increases in arterial blood it proposed that VLM neurons influence neurons through monosynaptic connections through indirect pathways. interactions between caudal and rostral VLM constitute neuronal mechanisms in the VLM of the cat that

inhibited by acute increases In arterial Blood PreSsuRe. furtHer iT is proposed thaT CaudAl VLM neurons influence tHe actIvITy of ROsTral VlM neuroNS eITHer ThRoUgh MoNOsYnaptIc cOnnectiOns or throuGh iNdIrect pathwayS. thUs, interactIonS between caudAl aNd rostRaL VLm NeuroNs cOnstiTute neURonal mEchanisms In THe VLM oF The cat tHAT

inhibited by acute increa ses in art erial  bl ood  p ress ure.  Further it is prop osed that caudal VLM n euron si nflu e nc e the  activi t yo f  ro st ra l V LM ne urons  ei ther th rough mono syn ap tic connecti o ns  or throug h i ndirect path way s. Thu s,  in t eract ion s bet ween c a udal a nd rostra lV LM neu r ons con s t it uteneuronal mechanis m si n the VLM of t he cat  t h at

inhibited_by acute_increases in arterial blood_pressure. Further_it_is proposed_that_caudal VLM neurons_influence the activity_of rostral VLM neurons_either through monosynaptic_connections_or through indirect pathways. Thus, interactions between caudal and rostral VLM neurons constitute neuronal_mechanisms_in the_VLM_of_the cat that


cause structural malformations in the fetus. We propose that many commonly used drugs also can produce more subtle biochemical, physiological and behavioral teratogenic defects in the fetus. The effects of these drug teratogens may not be apparent at birth or even in childhood, but may lie dormant or "latent" until years later

cause structural malformations in the fetus. We propose that many normally use drugs also can grow more insidious biochemical, physiological and behavioral teratogenic defects in the fetus. The effect of these drug teratogen may not be apparent at birth or even in childhood, but may lie dormant or " latent " until years later

cakse structural malformatlons in the fetus. We prmpose fhat manh commonly used drugs also cen peoduct more subtle biochdmical, phjsiologicql aid behavioral tecztogenig defsgts iu vhe fetus. The enfects of tvese drug teradoeeus may not be apparent at birth or eden in vhlldhood, but mai lie qormznt or "latent" until years later

cause structural malformations in the fetus. We many used drugs can produce more teratogenic in the fetus. effects of these teratogens may not be apparent at or even in childhood, but may lie dormant or "latent" until years later

cause structural malformatiOns in the feTus. We ProPosE tHat mAny cOmmonly used druGS alsO can produce more subtle bIocheMiCAl, phYSiOlogiCal and bEHaVIOraL tErAtoGeNIc DefecTs iN the fetUs. The effecTs oF tHese drug teraTOgEns may not bE apParent at birtH or Even in ChIldHOod, buT maY lie dOrmant OR "latenT" until yeaRs LAter

cause structural malforma tions in t he fe tus . W eprop osethat many comm o nlyused drugs also can pr oduce  m o re s u bt le bi ochemic a l, p hys io lo gic al an d beh avi oral te ratogenicdef ec ts in the fe t us . The effe cts  of these dr ugterato ge nsm ay no t b e app arenta t birt h or even  i n  child h ood, bu t ma y li e dormant or "lat e nt "  until years l ater

cause_structural malformations_in the fetus. We_propose that_many_commonly used_drugs_also can produce_more subtle biochemical,_physiological and behavioral teratogenic_defects in the_fetus._The effects of these drug teratogens may not be apparent at birth or even_in_childhood, but_may_lie_dormant or "latent" until years_later


mortality worldwide. There has been a great interest in developing novel therapeutics for this disease that function via an orthogonal mechanism of action to currently available drugs. One promising strategy is to enhance the function of high-density lipoproteins (HDLs). HDLs facilitate the process of reverse cholesterol transport to transfer excess cholesterol from peripheral tissues to

mortality worldwide. There has been a great interest in developing fresh remedy for this disease that officiate via an orthogonal mechanism of legal action to presently available drugs. One promising strategy is to enhance the affair of high - density lipoprotein (high-density lipoprotein). HDLs facilitate the summons of reverse cholesterol transport to transfer excess cholesterol from peripheral tissue to

mogtality worldwide. There mas been a great interevt in sevelopivg novel therapeutics for thms duseast that function via an orthohonal mexhanmsm of action to currently avajpablz vrugs. One promixing stratagy is to enhatcd che function of high-density lipoprotqins (HDKs). HDLs facilitaje tht pwoceas of reverse cholesterol transporf to trensfer excess cnolesterol from peripheral tisdues to

mortality worldwide. There has been a great developing therapeutics for disease that function action currently available drugs. promising strategy is enhance the function of high-density lipoproteins HDLs facilitate the process of reverse cholesterol transport to transfer excess cholesterol from tissues to

mortality worldwide. There haS been a greaT inteResT in DeVeloPing Novel therapeutICs foR this disease that functiOn via An ORthoGOnAl mecHanism oF AcTIOn tO cUrRenTlY AvAilabLe dRugs. One Promising sTraTeGy is to enhancE ThE function oF hiGh-density lipOprOteins (hDls). Hdls facIliTate tHe procESs of reVerse cholEsTErol trANsport tO TRaNsfeR excess cholesteroL FrOM peripheral tisSues to

mortality worldwide. Ther e has been  a gr eat  in te rest  indeveloping nov e l th erapeutics for this di sease  t h at f u nc tionvia ano rt h o gon al  m ech an i sm  of a cti on to c urrently a vai la ble drugs. O n epromisingstr ategy is toenh ance t he  fu n ction  of  high -densi t y lipo proteins(H D Ls). H D Ls faci l i ta te t he process of rev e rs e  cholesterol t ranspo rt to t ran sfe r excess c ho leste r ol from pe r i p her a l tissues to

mortality_worldwide. There_has been a great_interest in_developing_novel therapeutics_for_this disease that_function via an_orthogonal mechanism of action_to currently available_drugs._One promising strategy is to enhance the function of high-density lipoproteins (HDLs). HDLs facilitate_the_process of_reverse_cholesterol_transport to transfer excess cholesterol_from peripheral tissues to


the lesions to topical agent (imiquimod) and to radiotherapy;2) the ease to visually monitor local response and to perform Fine Needle Aspiration biopsies for mechanistic studies. A Phase I/II trial will be conducted to evaluate the safety of the combination of RT and IMQ, topically applied to skin metastases

the lesions to topical agent (imiquimod) and to radiotherapy;2) the ease to visually monitor local response and to do Fine Needle Aspiration biopsy for mechanistic cogitation. A Phase I / II trial will be behave to measure the safety of the combination of RT and IMQ, topically applied to hide metastases

thf lesions to topical agekt (imiquimod) and to radmotheraly;2) the exse to visually monitor locap eespobse and to perform Find Needle Wspiratiin bmopsies for mechehistic studiea. A Pkawe I/II trial wlll be condgcted to evaludtd che safety of the combination of RT wnd IMQ, tlpically appligd to fkin metastases

the lesions to topical agent (imiquimod) and the to visually local response and biopsies mechanistic studies. A I/II trial will conducted to evaluate the safety of combination of RT and IMQ, topically applied to skin metastases

the lesions to topical agent (iMiquimod) anD to raDioTheRaPy;2) thE easE to visually monITor lOcal response and to perfoRm FinE NEEdle aSpIratiOn biopsIEs FOR meChAnIstIc STuDies. A phaSe I/II trIal will be cOndUcTed to evaluatE ThE safety of tHe cOmbination of rT aNd IMQ, tOpIcaLLy appLieD to skIn metaSTases

the lesions to topical ag ent (imiqu imod)  an d t oradi othe rapy;2) the ea s e to  visually monitor loca l res po n se a n dto pe rform F i ne N eed le  A spi ra t io n bio psi es formechanisti c s tu dies. A Phas e  I /II trialwil l be conduct edto eva lu ate the s afe ty of  the c o mbinat ion of RT  a n d IMQ, topical l y  a ppli ed to skin metast a se s

the_lesions to_topical agent (imiquimod) and_to radiotherapy;2)_the_ease to_visually_monitor local response_and to perform_Fine Needle Aspiration biopsies_for mechanistic studies._A_Phase I/II trial will be conducted to evaluate the safety of the combination of_RT_and IMQ,_topically_applied_to skin metastases


as Clostridium perfringens, Clostridium tetani, Clostridium botulinum and Clostridium novyi. Because of the previously reported linkage of toxin genes to extrachromosomal DNA and the documented occurrence of adhesive or invasive genes being coded for by plasmids in other bacteria

as Clostridium perfringens, Clostridium tetani, Clostridium botulinum and Clostridium novyi. Because of the previously reported linkage of toxin genes to extrachromosomal DNA and the documented happening of adhesive or incursive genes being coded for by plasmid in other bacteria

as Clostridium perfringens, Clostridium tejabi, Clovtridihm botulknum and Clostridium novyi. Bxcauwe of the previously reportdd linkagv of toxib geies to extrachromosomal DNA ans the vocumented occutrence of advesive or invavixe genes being coded for by plasmids yn othet hacteria

as Clostridium perfringens, Clostridium tetani, Clostridium botulinum novyi. of the reported linkage of and documented occurrence of or invasive genes coded for by plasmids in other

as Clostridium perfringens, CLostridium TetanI, ClOstRiDium BotuLinum and ClostrIDium Novyi. Because of the previOusly RePOrteD LiNkage Of toxin GEnES To eXtRaChrOmOSoMal DNa anD the docUmented occUrrEnCe of adhesive OR iNvasive genEs bEing coded for By pLasmidS iN otHEr bacTerIa

as Clostridium perfringen s, Clostri diumtet ani ,Clos trid ium botulinuma nd C lostridium novyi. Beca use o ft he p r ev iousl y repor t ed l ink ag eofto x in  gene s t o extra chromosoma l D NA  and the doc u me nted occur ren ce of adhesi veor inv as ive genes  be ing c oded f o r by p lasmids i no ther b a cteria

as_Clostridium perfringens,_Clostridium tetani, Clostridium botulinum_and Clostridium_novyi._Because of_the_previously reported linkage_of toxin genes_to extrachromosomal DNA and_the documented occurrence_of_adhesive or invasive genes being coded for by plasmids in other bacteria


. Specifically, our central hypothesis is that some bacterial and viral components, through TLRs, induce trophoblast apoptosis, leading to adverse pregnancy outcome, such as preterm labor or preeclampsia. In our published studies we found TLR2 activation by gram-positive bacterial peptidoglycan (PDG), and TLR8 activation

. Specifically, our central hypothesis is that some bacterial and viral components, through TLRs, induce trophoblast apoptosis, leading to adverse pregnancy result, such as preterm british labour party or preeclampsia. In our published studies we found TLR2 energizing by gram - positive bacterial peptidoglycan (PDG), and TLR8 activation

. Spfcifically, our central hnpothesis is thaj wome becteriam and vifal components, through TLRs, mnduxe triphoblast apoptosis, lexding to wdverse pregiancy outcome, surg as prccerm mwbor ir preeclampsis. In our pgblished studias wz found TLR2 activation by gram-positide bactrrlal peptidoglysan (KDG), and NLV8 activation

. Specifically, our central hypothesis is that and components, through induce trophoblast apoptosis, such preterm labor or In our published we found TLR2 activation by gram-positive peptidoglycan (PDG), and TLR8 activation

. Specifically, our central hypOthesis is tHat soMe bActErIal aNd viRal components, tHRougH TLRs, induce trophoblast ApoptOsIS, leaDInG to adVerse prEGnANCy oUtCoMe, sUcH As PreteRm lAbor or pReeclampsiA. In OuR published stUDiEs we found TlR2 aCtivation by gRam-PositiVe BacTErial PepTidogLycan (Pdg), and TLr8 activatiOn

. Specifically, our centra l hypothes is is  th atso me b acte rial and viral comp onents, through TLRs,induc et roph o bl ast a poptosi s ,l e adi ng  t o a dv e rs e pre gna ncy out come, such  as  p reterm labor or  preeclamp sia . In our pub lis hed st ud ies we fo und  TLR2  activ a tion b y gram-po si t ive ba c terialp e pt idog lycan (PDG), andT LR 8  activation

. Specifically,_our central_hypothesis is that some_bacterial and_viral_components, through_TLRs,_induce trophoblast apoptosis,_leading to adverse_pregnancy outcome, such as_preterm labor or_preeclampsia._In our published studies we found TLR2 activation by gram-positive bacterial peptidoglycan (PDG), and_TLR8_activation


antigens on MHC class II in dendritic cells upon HSV-1 infection. Building on these preliminary studies, we propose to examine the importance of autophagy in both innate and adaptive immune responses using a variety of molecular and cell biological techniques and using established mouse models of virus infection. In the first Aim, we will determine the mechanism by

antigens on MHC class II in dendritic cells upon HSV-1 infection. Building on these preliminary report, we nominate to examine the importance of autophagy in both innate and adaptive immune responses use a variety of molecular and cell biological proficiency and use established shiner model of virus infection. In the first Aim, we will determine the mechanism by

anhigens on MHC class II ik dendritic cells upon ISV-1 infsction. Bjilding on these preliminary srudiew, we propose to examind the implrtance if antophagy in both innate and adzitive mmmune responsex using a eariety of molacjlcr and cell biological techniques anq using edtablished moufe mpqels of virus infection. In the first Ajm, we wpll determine the mechanism by

antigens on MHC class II in dendritic HSV-1 Building on preliminary studies, we of in both innate adaptive immune responses a variety of molecular and cell techniques and using established mouse models of virus infection. In the first Aim, will determine the mechanism by

antigens on MHC class II in denDritic cellS upon hSV-1 InfEcTion. builDing on these preLIminAry studies, we propose to eXaminE tHE impORtAnce oF autophAGy IN BotH iNnAte AnD AdAptivE imMune resPonses usinG a vArIety of molecuLAr And cell bioLogIcal techniquEs aNd usinG eStaBLisheD moUse moDels of VIrus inFection. In ThE First AIM, we will DETeRminE the mechanism by

antigens on MHC class IIin dendrit ic ce lls  up on  HSV -1 i nfection. Buil d ingon these preliminary s tudie s, we p r op ose t o exami n et h e i mp or tan ce of  auto pha gy in b oth innate  an dadaptive imm u ne  responses  us ing a variet y o f mole cu lar and c ell  biol ogical techni ques andus i ng est a blished m ou se m odels of virus in f ec t ion. In the fi rst Ai m, we w ill  de termine th emecha n ism by

antigens_on MHC_class II in dendritic_cells upon_HSV-1_infection. Building_on_these preliminary studies,_we propose to_examine the importance of_autophagy in both_innate_and adaptive immune responses using a variety of molecular and cell biological techniques and_using_established mouse_models_of_virus infection. In the first_Aim, we will determine the_mechanism by


to quantify regional myocardial perfusion with 82/RbCl and 62/Cu- pyruvaldehyde bis(N/4-methylthiosemicarbazone) (PTSM). We demonstrated however that 62/Cu-PTSM binds to human albumin limiting the ability to quantify flow after pharmacologically-induced hyperemia

to quantify regional myocardial perfusion with 82 / RbCl and 62 / Cu- pyruvaldehyde bis(N/4 - methylthiosemicarbazone) (PTSM). We demonstrated however that 62 / Cu - PTSM binds to human albumin limiting the ability to quantify flow after pharmacologically - induce hyperemia

to quantify regional myocavdial perfusion cuth 82/RbRl and 62/Du- pyruvxldehyde bis(N/4-methylthiosemicerbazone) (KNSM). We demonstrated huwever thwt 62/Cu-PTSN biids to human albnjin limlcing fme abnlmty to quantify flow aftes pharmacologiwaulv-induced hyperemia

to quantify regional myocardial perfusion with 82/RbCl pyruvaldehyde (PTSM). We however that 62/Cu-PTSM the to quantify flow pharmacologically-induced hyperemia

to quantify regional myocardIal perfusiOn witH 82/Rbcl aNd 62/cu- pyRuvaLdehyde bis(N/4-metHYlthIosemicarbazone) (PTSM). We dEmonsTrATed hOWeVer thAt 62/Cu-PTSm BiNDS to HuMaN alBuMIn LimitIng The abilIty to quantIfy FlOw after pharmACoLogically-iNduCed hyperemia

to quantify regional myoc ardial per fusio n w ith  8 2/Rb Cl a nd 62/Cu- pyru v alde hyde bis(N/4-methylthi osemi ca r bazo n e)  (PTS M). Wed em o n str at ed  ho we v er  that  62 /Cu-PTS M binds to  hu ma n albumin li m it ing the ab ili ty to quanti fyflow a ft erp harma col ogica lly-in d uced h yperemia

to_quantify regional_myocardial perfusion with 82/RbCl_and 62/Cu-_pyruvaldehyde_bis(N/4-methylthiosemicarbazone) (PTSM)._We_demonstrated however that_62/Cu-PTSM binds to_human albumin limiting the_ability to quantify_flow_after pharmacologically-induced hyperemia


women of Hispanic descent, and examine a social-cognitive-cultural model of post-GCRA cancer screening and prevention behaviors that can guide future GCRA and psychosocial interventions for this population. The following aims will be addressed: 1) Assess cognitive, social and cultural factors influencing cancer screening and prevention behaviors following culturally relevant

women of Hispanic descent, and examine a social - cognitive - cultural model of post - GCRA cancer cover and prevention demeanor that can guide future GCRA and psychosocial interventions for this population. The follow aim will be addressed: 1) Assess cognitive, social and cultural agent determine cancer screening and prevention behaviors following culturally relevant

wolen of Hispanic descent, xnd examine a social-cojnitive-dultural model of post-GCRA cancer scceenung abd prevention behaviorr that caj guide dutuce GCRA and psyciksocial interbcntious for this popukation. The following aimv dipl be addressed: 1) Assess cognitive, sjcial amd cultural factjrs pnsluehbikg cancer screening and preventikn behaniors following cilturally relevant

women of Hispanic descent, and examine a of cancer screening prevention behaviors that psychosocial for this population. following aims will addressed: 1) Assess cognitive, social and factors influencing cancer screening and prevention behaviors following culturally relevant

women of Hispanic descent, and Examine a soCial-cOgnItiVe-CultUral Model of post-GCRa CancEr screening and preventiOn behAvIOrs tHAt Can guIde futuRE Gcra anD pSyChoSoCIaL inteRveNtions fOr this popuLatIoN. The followinG AiMs will be adDreSsed: 1) Assess coGniTive, soCiAl aND cultUraL factOrs infLUencinG cancer scReENing anD PreventION bEhavIors following cultURaLLy relevant

women of Hispanic descent , and exam ine a  so cia l- cogn itiv e-cultural mod e l of  post-GCRA cancer scre ening  a n d pr e ve ntion  behavi o rs t hat  c an  gu id e  f uture  GC RA andpsychosoci alin terventionsf or  this popu lat ion. The fol low ing ai ms  wi l l beadd resse d: 1)A ssesscognitive ,s ociala nd cult u r al  fac tors influencingc an c er screening a nd pre ve n ti o n  be hav iors follo wi ng cu l turally re l e v ant

women_of Hispanic_descent, and examine a_social-cognitive-cultural model_of_post-GCRA cancer_screening_and prevention behaviors_that can guide_future GCRA and psychosocial_interventions for this_population._The following aims will be addressed: 1) Assess cognitive, social and cultural factors influencing_cancer_screening and_prevention_behaviors_following culturally relevant


cues, or both. Also, by overexpressing Tbr1 in embryos, we will resolve whether Tbr1 specifies cortical axon connections cell autonomously. Aim 3 is to define the role of Tbr1 in glutamatergic differentiation and layer-specific fate choices. Gain-of-function assays

cues, or both. Also, by overexpressing Tbr1 in embryos, we will resolve whether Tbr1 specify cortical axon connection cell autonomously. purpose 3 is to specify the role of Tbr1 in glutamatergic differentiation and level - specific fate choices. Gain - of - function assay

cufs, or both. Also, by overewpressing Tbr1 in embryov, we wjll resouve whether Tbr1 specifies cocticql axin connections cell augonomouslj. Aim 3 is to vefine the role of Tbr1 ik glufwmatzrjic differentiajion and layar-specific fata zhlices. Gain-of-function assays

cues, or both. Also, by overexpressing Tbr1 we resolve whether specifies cortical axon is define the role Tbr1 in glutamatergic and layer-specific fate choices. Gain-of-function assays

cues, or both. Also, by overexpreSsing Tbr1 in EmbryOs, wE wiLl ResoLve wHether Tbr1 speciFIes cOrtical axon connections Cell aUtONomoUSlY. Aim 3 iS to defiNE tHE RolE oF TBr1 iN gLUtAmateRgiC differEntiation aNd lAyEr-specific faTE cHoices. Gain-Of-fUnction assayS

cues, or both. Also, by o verexpress ing T br1  in  e mbry os,we will resolv e  whe ther Tbr1 specifies co rtica la xonc on necti ons cel l  a u t ono mo us ly.  A i m3 istodefinethe role o f T br 1 in glutama t er gic differ ent iation and l aye r-spec if icf ate c hoi ces.Gain-o f -funct ion assay s

cues,_or both._Also, by overexpressing Tbr1_in embryos,_we_will resolve_whether_Tbr1 specifies cortical_axon connections cell_autonomously. Aim 3 is_to define the_role_of Tbr1 in glutamatergic differentiation and layer-specific fate choices. Gain-of-function assays


viable strategy for the treatment of NE tumors. Furthermore, we will show that the potent GSK3B inhibitor, lithium chloride, suppresses NE tumor proliferation and hormone production. Thus, we propose to conduct a Phase II clinical trial to determine if lithium is a potential therapy for patients with NE tumors. The primary objective in this aim

viable strategy for the treatment of NE tumors. Furthermore, we will picture that the potent GSK3B inhibitor, lithium chloride, inhibit NE tumor proliferation and hormone production. Thus, we propose to lead a Phase II clinical trial to determine if lithium is a likely therapy for patients with NE tumors. The primary aim in this purpose

viwble strategy for the trtatment of NE tumors. Furvhermors, we wilu show that the potent GSK3B mnhivitor, lithium chloride, suppfesses NE tumor peoliheration and hormone productioh. Thuv, we propose to conduct a Phase II clinhcxl trial to determine if lithium is a potentoap therapy for katiemes wjnh NE tumors. The primary objectjve in uhis aim

viable strategy for the treatment of NE we show that potent GSK3B inhibitor, proliferation hormone production. Thus, propose to conduct Phase II clinical trial to determine lithium is a potential therapy for patients with NE tumors. The primary objective this aim

viable strategy for the treatMent of NE tuMors. FUrtHerMoRe, we Will Show that the potENt GSk3B inhibitor, lithium chloRide, sUpPRessES Ne tumoR prolifERaTIOn aNd HoRmoNe PRoDuctiOn. THus, we prOpose to conDucT a phase II cliniCAl Trial to detErmIne if lithium Is a PotentIaL thERapy fOr pAtienTs with ne tumorS. The primaRy OBjectiVE in this AIM

viable strategy for the t reatment o f NEtum ors .Furt herm ore, we will s h ow t hat the potent GSK3B i nhibi to r , li t hi um ch loride, su p p res se sNEtu m or  prol ife rationand hormon e p ro duction. Thu s ,we propose  to  conduct a P has e II c li nic a l tri alto de termin e  if li thium isap otenti a l thera p y  f or p atients with NE t u mo r s. The primary  objec ti v ei n  th isaim

viable_strategy for_the treatment of NE_tumors. Furthermore,_we_will show_that_the potent GSK3B_inhibitor, lithium chloride,_suppresses NE tumor proliferation_and hormone production._Thus,_we propose to conduct a Phase II clinical trial to determine if lithium is_a_potential therapy_for_patients_with NE tumors. The primary_objective in this aim


activate PTP enzymes by targeting either engineered cysteine residues (Specific Aim 1) or naturally occurring cysteine residues (Specific Aim 2). Specific Aim 1 (Target-specific inhibition and activation of engineered PTPs with biarsenical small molecules) proposes several complementary means for engineering inhibitor- sensitive and activator-sensitive (collectively,

activate PTP enzymes by targeting either engineered cysteine residue (Specific Aim 1) or naturally occur cysteine residues (Specific Aim 2). Specific Aim 1 (Target - specific inhibition and energizing of engineered PTPs with biarsenical small molecules) propose several complementary mean for technology inhibitor- sensitive and activator - sensitive (jointly,

achivate PTP enzymes by tavgeting either eutineerxd cystsine reskdues (Specific Aim 1) or naturelly occuering cysteine residuer (Specifib Aim 2). Spwcifmc Aim 1 (Target-spxdific ikkibitjln aud activation of engineereg PTPs with bidrreuical small molecules) proposes severwl compkelentary means sor tngyneedpnn inhibitor- sensitive and activafor-sensptive (collectivelu,

activate PTP enzymes by targeting either engineered (Specific 1) or occurring cysteine residues 1 inhibition and activation engineered PTPs with small molecules) proposes several complementary means engineering inhibitor- sensitive and activator-sensitive (collectively,

activate PTP enzymes by targeTing either EnginEerEd cYsTeinE resIdues (Specific AIM 1) or nAturally occurring cysteIne reSiDUes (SPEcIfic AIm 2). SpeciFIc aIM 1 (TaRgEt-SpeCiFIc InhibItiOn and acTivation of EngInEered PTPs witH BiArsenical sMalL molecules) prOpoSes sevErAl cOMplemEntAry meAns for ENgineeRing inhibItOR- sensiTIve and aCTIvAtor-Sensitive (collectiVElY,

activate PTP enzymes by t argeting e ither  en gin ee redcyst eine residues( Spec ific Aim 1) or natural ly oc cu r ring cy stein e resid u es ( Spe ci fi c A im 2) . Spe cif ic Aim1 (Target- spe ci fic inhibiti o nand activa tio n of enginee red  PTPswi thb iarse nic al sm all mo l ecules ) propose ss everal complem e n ta ry m eans for engineer i ng inhibitor- sen sitive  a n da c tiv ato r-sensitiv e(coll e ctively ,

activate_PTP enzymes_by targeting either engineered_cysteine residues_(Specific_Aim 1)_or_naturally occurring cysteine_residues (Specific Aim_2). Specific Aim 1_(Target-specific inhibition and_activation_of engineered PTPs with biarsenical small molecules) proposes several complementary means for engineering inhibitor-_sensitive_and activator-sensitive_(collectively,


HIV persistence in other cohorts. We have assembled a multidisciplinary group that will allow us to overcome these aforementioned hurdles and will use unbiased OMICs approaches to address our major objective which is to delineate the molecular mechanisms triggered by cocaine that lead to HIV persistence. In specific aim 1 we will use three independent state of the

HIV persistence in other cohorts. We have assembled a multidisciplinary group that will leave us to get the best these aforementioned hurdles and will use unbiased OMICs approach to address our major objective which is to define the molecular mechanisms triggered by cocaine that moderate to HIV persistence. In specific aim 1 we will practice three independent state of the

HIG persistence in other cuhorts. We have cwsemblxd a mumtidisciolinary group that will allox us to ocercome these aforemengioned hugdles and wilo use unbiased OMICs apprkwchev to address out major objewtive which is tu belineate the molecular mechanisms twiggerec hy cocaine thaj leac to GPV persistence. In specific aim 1 we wiln use three imdependent state of the

HIV persistence in other cohorts. We have multidisciplinary that will us to overcome use OMICs approaches to our major objective is to delineate the molecular mechanisms by cocaine that lead to HIV persistence. In specific aim 1 we will three independent state of the

HIV persistence in other cohoRts. We have aSsembLed A muLtIdisCiplInary group that WIll aLlow us to overcome these aForemEnTIoneD HuRdles And will USe UNBiaSeD OmICS aPPrOacheS to Address Our major obJecTiVe which is to dELiNeate the moLecUlar mechanisMs tRiggerEd By cOCaine ThaT lead To HIV pERsisteNce. In specIfIC aim 1 we WIll use tHREe IndePendent state of the

HIV persistence in othercohorts. W e hav e a sse mb leda mu ltidisciplinar y  gro up that will allow usto ov er c omet he se af orement i on e d  hu rd le s a nd wi ll us e u nbiased  OMICs app roa ch es to addres s  o ur major o bje ctive whichisto del in eat e  themol ecula r mech a nismstriggered  b y  cocai n e thatl e ad  toHIV persistence.I ns pecific aim 1we wil lu se t hre e i ndependent  s tateo f the

HIV_persistence in_other cohorts. We have_assembled a_multidisciplinary_group that_will_allow us to_overcome these aforementioned_hurdles and will use_unbiased OMICs approaches_to_address our major objective which is to delineate the molecular mechanisms triggered by cocaine_that_lead to_HIV_persistence._In specific aim 1 we_will use three independent state_of the


PLA2 KO mice. Changes in stromal cells will be defined and in vitro co-cultures will examine cross-talk between cancer cells and macrophages. Aim 2 will use genetic mice to define the downstream effectors of cPLA2 in the tumor microenvironment. These studies will provide a better understanding of tumor-stromal interactions

PLA2 KO mice. Changes in stromal cells will be defined and in vitro conscientious objector - acculturation will examine cross - talk between cancer cell and macrophages. Aim 2 will practice genetic mice to define the downstream effecter of cPLA2 in the tumor microenvironment. These studies will provide a good understanding of tumor - stromal interaction

PLA2 KO mice. Changes in strooal cells will yw defiied and in vitru co-cultures will examine crlsw-talk between cancer cells xnd macroihages. Ain 2 wmll use genetic mice to define bhe dmxnstream effectprs of cPLD2 in the tumor mkcxoenvironment. These studies will prodide a nehter understanqing jf thmor-stromal interactions

PLA2 KO mice. Changes in stromal cells defined in vitro will examine cross-talk Aim will use genetic to define the effectors of cPLA2 in the tumor These studies will provide a better understanding of tumor-stromal interactions

PLA2 KO mice. Changes in stromal Cells will bE defiNed And In VitrO co-cUltures will exaMIne cRoss-talk between cancer cElls aNd MAcroPHaGes. AiM 2 will usE GeNETic MiCe To dEfINe The doWnsTream efFectors of cpLA2 In The tumor micrOEnVironment. THesE studies will ProVide a bEtTer UNdersTanDing oF tumor-STromal InteractiOnS

PLA2 KO mice. Changes in s tromal cel ls wi llbede fine d an d in vitro co- c ultu res will examine cross -talk  b e twee n  c ancer  cellsa nd m acr op ha ges .A im  2 wi lluse gen etic micetode fine the dow n st ream effec tor s of cPLA2 i n t he tum or  mi c roenv iro nment . Thes e  studi es will p ro v ide ab etter u n d er stan ding of tumor-str o ma l  interactions

PLA2 KO_mice. Changes_in stromal cells will_be defined_and_in vitro_co-cultures_will examine cross-talk_between cancer cells_and macrophages. Aim 2_will use genetic_mice_to define the downstream effectors of cPLA2 in the tumor microenvironment. These studies will_provide_a better_understanding_of_tumor-stromal interactions


; and then 3) species ID by MALDI-TOF, (again requiring skilled sample preparation), The SpecID solution combines faster detection, more accurate Gram status determination than the benchtop stain, and ID more accurate than MALDI, in a single fully automated step which reduces the time to ID, streamlines lab workflow

; and then 3) species ID by MALDI - TOF, (again requiring skilled sample preparation), The SpecID solution combines fast signal detection, more accurate Gram status determination than the benchtop blot, and ID more accurate than MALDI, in a unmarried fully automated footfall which repress the time to ID, streamline lab workflow

; anf then 3) species ID by MAUDI-TOF, (again requiring skillsd sampld preparation), The SpecID solntiob comvines faster detection, more acclrate Gran stetus determination than bke behghtop wtain, and ID mpre accurade than MALDI, hn a single fully automated step which weduces tje time to ID, ftresilinss lab workflow

; and then 3) species ID by requiring sample preparation), SpecID solution combines status than the benchtop and ID more than MALDI, in a single fully step which reduces the time to ID, streamlines lab workflow

; and then 3) species ID by MALDI-TOf, (again requIring SkiLleD sAmplE preParation), The SpeCiD soLution combines faster deTectiOn, MOre aCCuRate GRam statUS dETErmInAtIon ThAN tHe benChtOp stain, And ID more aCcuRaTe than MALDI, iN A sIngle fully AutOmated step whIch ReduceS tHe tIMe to Id, stReamlInes laB WorkflOw

; and then 3) species ID b y MALDI-TO F, (a gai n r eq uiri ng s killed samplep repa ration), The SpecID so lutio nc ombi n es  fast er dete c ti o n , m or eacc ur a te  Gram  st atus de terminatio n t ha n the bencht o pstain, and  ID  more accura tethan M AL DI, in asin gle f ully a u tomate d step wh ic h  reduc e s the t i m eto I D, streamlines la b  w o rkflow

; and_then 3)_species ID by MALDI-TOF,_(again requiring_skilled_sample preparation),_The_SpecID solution combines_faster detection, more_accurate Gram status determination_than the benchtop_stain,_and ID more accurate than MALDI, in a single fully automated step which reduces_the_time to_ID,_streamlines_lab workflow


signaling pathway at this crucial juncture in the disease progression. Wnt growth factors are critical regulators of chondrocyte differentiation, and GAGs are known to be important regulators of Wnt distribution and activity, suggesting a link between GAG accumulation and dysregulation of this pathway. The objectives of this proposal are to investigate mechanisms of failed

signaling pathway at this crucial juncture in the disease progress. Wnt increase factors are critical regulators of chondrocyte differentiation, and gag are known to be important regulator of Wnt distribution and activity, suggesting a connection between GAG accumulation and dysregulation of this pathway. The objective of this proposal are to investigate mechanisms of fail

sihnaling pathway at this grucial juncture in the diseaae progrdssion. Wnt growth factors arx cruticao regulators of chondrucyte difverentiarion, qnd GAGs acs known to be lmporcait regulators on Wnt distrhbution and acdixicy, suggesting a link between GAG acctmulatipn and dysregulajion ps thjs pathway. The objectives of this lroposan are to invextigate mechanisms of failfd

signaling pathway at this crucial juncture in progression. growth factors critical regulators of known be important regulators Wnt distribution and suggesting a link between GAG accumulation dysregulation of this pathway. The objectives of this proposal are to investigate mechanisms failed

signaling pathway at this cruCial junctuRe in tHe dIseAsE proGresSion. Wnt growth fACtorS are critical regulators Of choNdROcytE DiFfereNtiatioN, AnD gaGs ArE kNowN tO Be ImporTanT regulaTors of Wnt dIstRiBution and actIViTy, suggestiNg a Link between GaG aCcumulAtIon ANd dysRegUlatiOn of thIS pathwAy. The objeCtIVes of tHIs propoSAL aRe to Investigate mechanISmS Of failed

signaling pathway at this  crucial j unctu reinth e di seas e progression. Wntgrowth factors are cri tical  r e gula t or s ofchondro c yt e dif fe re nti at i on , and  GA Gs areknown to b e i mp ortant regul a to rs of Wntdis tribution an d a ctivit y,  su g gesti nga lin k betw e en GAG  accumula ti o n andd ysregul a t io n of  this pathway. Th e  o b jectives of th is pro po s al a retoinvestigat emecha n isms of fa i l e d

signaling_pathway at_this crucial juncture in_the disease_progression._Wnt growth_factors_are critical regulators_of chondrocyte differentiation,_and GAGs are known_to be important_regulators_of Wnt distribution and activity, suggesting a link between GAG accumulation and dysregulation of_this_pathway. The_objectives_of_this proposal are to investigate_mechanisms of failed


astatine is stably attached to them. Maintenance and plasticity of synaptic connections are fundamental to all higher cognitive processes. The proper trafficking of postsynaptic glutamate receptors (GluRs) is critical for this process. It is suggested that their misregulation can impair memory formation, as in Alzheimer patients, and can potentially contribute to other

astatine is stably attached to them. Maintenance and plasticity of synaptic connections are cardinal to all eminent cognitive processes. The proper trafficking of postsynaptic glutamate receptors (GluRs) is critical for this procedure. It is hint that their misregulation can impair memory formation, as in Alzheimer affected role, and can potentially put up to other

ashatine is stably attachea to them. Maintgnqnce aid plasficity ow synaptic connections are fnndanentao to all higher cognitkve procedses. The proker trafficking oh postsykcptic nlutakete receptors (GkuRs) is crhtical for thiv orlcess. It is suggested that their mifregulayiln can impair iemogy forjation, as in Alzheimer patients, ans can pmtentially comtribute to other

astatine is stably attached to them. Maintenance of connections are to all higher of glutamate receptors (GluRs) critical for this It is suggested that their misregulation impair memory formation, as in Alzheimer patients, and can potentially contribute to other

astatine is stably attached tO them. MaintEnancE anD plAsTiciTy of Synaptic connecTIons Are fundamental to all higHer coGnITive PRoCesseS. The proPEr TRAffIcKiNg oF pOStSynapTic GlutamaTe receptorS (GlURS) is critical fOR tHis process. it iS suggested thAt tHeir miSrEguLAtion Can ImpaiR memorY FormatIon, as in AlZhEImer paTIents, anD CAn PoteNtially contribute TO oTHer

astatine is stably attach ed to them . Mai nte nan ce  and  pla sticity of syn a ptic  connections are funda menta lt o al l  h igher  cognit i ve p roc es se s.Th e  p roper  tr afficki ng of post syn ap tic glutamat e  r eceptors ( Glu Rs) is criti cal  for t hi s p r ocess . I t issugges t ed tha t their m is r egulat i on cani m pa ir m emory formation,a si n Alzheimer pa tients ,a nd c anpot entially c on tribu t e to ot h er

astatine_is stably_attached to them. Maintenance_and plasticity_of_synaptic connections_are_fundamental to all_higher cognitive processes._The proper trafficking of_postsynaptic glutamate receptors_(GluRs)_is critical for this process. It is suggested that their misregulation can impair memory_formation,_as in_Alzheimer_patients,_and can potentially contribute to_other


we propose to make a series of measurements which will establish the degree of insulin resistance as well as cardiovascular risk factors in a group of 1600 subjects to be tested in specific field centers. In this application we propose the formation of two cores: an Assay Core, to carry out a series of biochemical measurements, and a Kinetic

we propose to make a series of measurements which will install the academic degree of insulin resistance as well as cardiovascular hazard factors in a group of 1600 subject to be tested in specific field center. In this application we propose the formation of two cores: an Assay Core, to carry out a serial of biochemical measurements, and a Kinetic

we propose to make a serier of measuremenjs which will sstablisf the degree of insulin residtqnce qs well as cardiovascuuar risk vactors un a troup of 1600 subjects to be besteb mn specific fiekd centers. In this appliwagiln we propose the formation of two sores: am Wssay Core, to sarrj jut z series of biochemical measuremenfs, and e Kinetic

we propose to make a series of will the degree insulin resistance as in group of 1600 to be tested specific field centers. In this application propose the formation of two cores: an Assay Core, to carry out a of biochemical measurements, and a Kinetic

we propose to make a series of mEasurementS whicH wiLl eStAbliSh thE degree of insulIN resIstance as well as cardiovAsculAr RIsk fACtOrs in A group oF 1600 SuBJEctS tO bE teStED iN specIfiC field cEnters. In thIs aPpLication we prOPoSe the formaTioN of two cores: aN AsSay CorE, tO caRRy out A seRies oF biochEMical mEasuremenTs, ANd a KinETic

we propose to make a seri es of meas ureme nts  wh ic h wi ll e stablish the d e gree  of insulin resistance  as w el l  asc ar diova scularr is k fac to rs  in  a gr oup o f 1 600 sub jects to b e t es ted in speci f ic  field cen ter s. In this a ppl icatio nwep ropos e t he fo rmatio n  of tw o cores:an AssayC ore, to c ar ry o ut a series of bi o ch e mical measurem ents,an d  a K ine tic

we_propose to_make a series of_measurements which_will_establish the_degree_of insulin resistance_as well as_cardiovascular risk factors in_a group of_1600_subjects to be tested in specific field centers. In this application we propose the_formation_of two_cores:_an_Assay Core, to carry out_a series of biochemical measurements,_and a_Kinetic


the velocity of shortening during stimulation at 1 Hz. Waves were measured in a 30 sec window following 2 min of stimulation. In absence of drugs average velocity of shortening was 70 plus/minus 32 um/sec (x-SEM, n=6) and no waves occurred. Norepinephrine (1x10

the velocity of shortening during stimulation at 1 Hz. Waves were measured in a 30 sec windowpane take after 2 min of stimulation. In absence of drug average speed of shortening was 70 plus / minus 32 um / sec (x - SEM, n=6) and no waves occurred. noradrenaline (1x10

thf velocity of shortening during stimulajiin at 1 Hz. Wabes were measured in a 30 sec window flloowint 2 min of stimulation. Kn absencv of drugw avtrage velocity of shortenlug waa 70 plbs/ninus 32 um/sec (x-XEM, n=6) and to waves occursea. Uorepinephrine (1x10

the velocity of shortening during stimulation at Waves measured in 30 sec window In of drugs average of shortening was plus/minus 32 um/sec (x-SEM, n=6) and waves occurred. Norepinephrine (1x10

the velocity of shortening duRing stimulAtion At 1 HZ. WaVeS werE meaSured in a 30 sec winDOw foLlowing 2 min of stimulatioN. In abSeNCe of DRuGs aveRage velOCiTY Of sHoRtEniNg WAs 70 Plus/mInuS 32 um/sec (x-sEM, n=6) and no wAveS oCcurred. NorepINePhrine (1x10

the velocity of shortenin g during s timul ati onat  1 H z. W aves were meas u redin a 30 sec window fol lowin g2  min of  stim ulation .  I n abs en ce  of  d r ug s ave rag e veloc ity of sho rte ni ng was 70 pl u s/ minus 32 u m/s ec (x-SEM, n =6)  and n owav e s occ urr ed. N orepin e phrine  (1x10

the_velocity of_shortening during stimulation at_1 Hz._Waves_were measured_in_a 30 sec_window following 2_min of stimulation. In_absence of drugs_average_velocity of shortening was 70 plus/minus 32 um/sec (x-SEM, n=6) and no waves occurred._Norepinephrine_(1x10


-throughput large scale biology with academic collaborators from across the country, investigating a wide variety of biological systems. In this proposal the Broad Institute core small molecule screening group is requesting funding for an automated tissue culture system to enhance our large scale biology capabilities. The instrument would be managed and maintained by the Chemical Biology platform screening group.

-throughput large scale biology with academic collaborators from across the area, investigate a wide variety of biological systems. In this marriage proposal the Broad Institute core small molecule cover group is request funding for an automated tissue culture system to enhance our big scale biology capability. The musical instrument would be managed and maintained by the Chemical Biology platform screening group.

-thrlughput large scale biolugy with academnx colleboratods from xcross the country, investigaving a wiee variety of biologicxl systemd. In thiw priposal the Udoad Instituts corz wmall molecule screening group is requasgiug funding for an automated tissue ctlture xydtem to enhancg our jargs scale biology capabilities. The ihstrumeit would be mansged and maintained by the Chelical Biology platvorm screenung deoup.

-throughput large scale biology with academic collaborators the investigating a variety of biological Broad core small molecule group is requesting for an automated tissue culture system enhance our large scale biology capabilities. The instrument would be managed and maintained the Chemical Biology platform screening group.

-throughput large scale bioloGy with acadEmic cOllAboRaTors From Across the countRY, invEstigating a wide variety Of bioLoGIcal SYsTems. IN this prOPoSAL thE BRoAd INsTItUte coRe sMall molEcule screeNinG gRoup is requesTInG funding foR an Automated tisSue CulturE sYstEM to enHanCe our Large sCAle bioLogy capabIlITies. ThE InstrumENT wOuld Be managed and maintAInED by the Chemical biologY pLAtFORm sCreEning group.

-throughput large scale bi ology with  acad emi c c ol labo rato rs from across thecountry, investigating  a wi de vari e ty  of b iologic a ls y ste ms .Inth i spropo sal  the Br oad Instit ute  c ore small mo l ec ule screen ing  group is re que stingfu ndi n g for  an  auto matedt issueculture s ys t em toe nhanceo u rlarg e scale biology c a pa b ilities. The i nstrum en t  w o u ldbemanaged an dmaint a ined by th e C hem i cal Biology p latform scr e eni ng gro up .

-throughput large_scale biology_with academic collaborators from_across the_country,_investigating a_wide_variety of biological_systems. In this_proposal the Broad Institute_core small molecule_screening_group is requesting funding for an automated tissue culture system to enhance our large_scale_biology capabilities._The_instrument_would be managed and maintained_by the Chemical Biology platform_screening group.


a 10,000-fold excess of HeLa cells. Our IHC assays used a rabbit antiserum raised against HPLC-purified Moloney MLV p30CA and another against HPLC-purified Moloney MLV gp70SU. Controls included not only 22Rv1, but also 293T cells transfected with

a 10,000 - fold excess of HeLa cells. Our IHC assays used a lapin antiserum raise against HPLC - purified Moloney MLV p30CA and another against HPLC - purified Moloney MLV gp70SU. control include not only 22Rv1, but also 293 triiodothyronine cell transfected with

a 10,000-vold excess of HeLa cellr. Our IHC assays used e rabbif antisefum raised against HPLC-purifmed Nolontj MLV p30CA and another against JPLC-puridied Noloney MLT gp70SU. Controla incnnded not only 22Ry1, but also 293D cells transfacgeb with

a 10,000-fold excess of HeLa cells. Our used rabbit antiserum against HPLC-purified Moloney HPLC-purified MLV gp70SU. Controls not only 22Rv1, also 293T cells transfected with

a 10,000-fold excess of HeLa cells. Our iHC assays uSed a rAbbIt aNtIserUm raIsed against HPLc-PuriFied Moloney MLV p30CA and anOther AgAInst hpLc-puriFied MolONeY mlV gP70Su. COntRoLS iNcludEd nOt only 22RV1, but also 293T cEllS tRansfected wiTH

a 10,000-fold excess of H eLa cells.  OurIHC  as sa ys u seda rabbit antis e rumraised against HPLC-pu rifie dM olon e yMLV p 30CA an d  a n o the rag ain st HP LC-pu rif ied Mol oney MLV g p70 SU . Controls i n cl uded not o nly  22Rv1, butals o 293T  c ell s  tran sfe ctedwith

a_10,000-fold excess_of HeLa cells. Our_IHC assays_used_a rabbit_antiserum_raised against HPLC-purified_Moloney MLV p30CA_and another against HPLC-purified_Moloney MLV gp70SU._Controls_included not only 22Rv1, but also 293T cells transfected with


theoretical approach to drug abuse among these adolescents. This preliminary theory contains three aspects-wanting, frames, and self. Wanting refers to the implication of dopamine systems in drug abuse, frames to the role cognitive processes play, and self as an encompassing construct around wanting and frames. The psychophysiological research is the main

theoretical approach to drug abuse among these adolescents. This preliminary theory control three view - wanting, frames, and self. Wanting refers to the significance of dopamine systems in drug abuse, frame to the role cognitive processes gambling, and self as an encompassing construct around wanting and human body. The psychophysiological research is the main

thforetical approach to drmg abuse among tkwse admlescehts. This preliminary theory contains tyree qspects-wanting, frames, xnd self. Aanting eefecs to the implicefion of dopamjke syvvems in drug abose, frames tm the role cogtigire processes play, and self as an encjmpassimg construct aroond wsgtinf and frames. The psychophysiologiczl reseerch is the maim

theoretical approach to drug abuse among these preliminary contains three frames, and self. of systems in drug frames to the cognitive processes play, and self as encompassing construct around wanting and frames. The psychophysiological research is the main

theoretical approach to drug Abuse among These AdoLesCeNts. THis pReliminary theoRY conTains three aspects-wantiNg, fraMeS, And sELf. wantiNg referS To THE imPlIcAtiOn OF dOpamiNe sYstems iN drug abuse, FraMeS to the role coGNiTive procesSes Play, and self aS an EncompAsSinG ConstRucT arouNd wantINg and fRames. The pSyCHophysIOlogicaL REsEarcH is the main

theoretical approach to d rug abuseamong  th ese  a dole scen ts. This preli m inar y theory contains thre e asp ec t s-wa n ti ng, f rames,a nd s elf .Wa nti ng re ferstothe imp lication o f d op amine system s  i n drug abu se,  frames to t herole c og nit i ve pr oce ssesplay,a nd sel f as an e nc o mpassi n g const r u ct  aro und wanting and f r am e s. The psychop hysiol og i ca l res ear ch is thema in

theoretical_approach to_drug abuse among these_adolescents. This_preliminary_theory contains_three_aspects-wanting, frames, and_self. Wanting refers_to the implication of_dopamine systems in_drug_abuse, frames to the role cognitive processes play, and self as an encompassing construct_around_wanting and_frames._The_psychophysiological research is the main


as well as the preliminary examination. In phase two (years three and four), Dr. Ritchey will remain at North Carolina State University, in a postdoctoral position. b. Research Plan: Feline Immunodeficiency Virus (FIV) will be used to examine the defects in alveolar macrophage (AM

as well as the preliminary examination. In phase two (years three and four), Dr. Ritchey will remain at North Carolina State University, in a postdoctoral placement. b. Research Plan: Feline Immunodeficiency Virus (FIV) will be use to examine the defects in alveolar macrophage (AM

as well as the preliminary examination. In phase vwo (yeads three and four), Dr. Ritchey will relaun at North Carolina State Jniversitj, in a powtdortoral position. u. Researgk Plah: Felnnx Immunodeficiekcy Virus (FHV) will be useg go examine the defects in alveolar masrophagr (WM

as well as the preliminary examination. In (years and four), Ritchey will remain in postdoctoral position. b. Plan: Feline Immunodeficiency (FIV) will be used to examine defects in alveolar macrophage (AM

as well as the preliminary exaMination. In Phase Two (YeaRs ThreE and Four), Dr. Ritchey wILl reMain at North Carolina StaTe UniVeRSity, IN a PostdOctoral POsITIon. B. REsEarCh pLaN: FeliNe IMmunodeFiciency ViRus (fIv) will be used tO ExAmine the deFecTs in alveolar MacRophagE (Am

as well as the preliminar y examinat ion.Inpha se  two  (ye ars three andf our) , Dr. Ritchey will rem ain a tN orth Ca rolin a State Un i v ers it y,  in  a po stdoc tor al posi tion. b. R ese ar ch Plan: Fel i ne  Immunodef ici ency Virus ( FIV ) will  b e u s ed to  ex amine  the d e fectsin alveol ar macrop h age (AM

as_well as_the preliminary examination. In_phase two_(years_three and_four),_Dr. Ritchey will_remain at North_Carolina State University, in_a postdoctoral position._b._Research Plan: Feline Immunodeficiency Virus (FIV) will be used to examine the defects in_alveolar_macrophage (AM


respiratory system, skin, or digestive tract. Dependent upon the entry route into the human body, Anthrax can be highly lethal. Although cutaneous Anthrax is rarely lethal, inhalation Anthrax is dangerous and usually fatal. Upon inhalation, the Anthrax spores adhere to the alveolar macrophages and germinate. Bacteria migrate to

respiratory system, skin, or digestive tract. Dependent upon the entry path into the human soundbox, Anthrax can be highly lethal. Although cutaneous Anthrax is rarely lethal, inhalation Anthrax is dangerous and normally fatal. Upon inhalation, the Anthrax spores adhere to the alveolar macrophage and germinate. Bacteria migrate to

redpiratory system, skin, or digestive tracj. Eependxnt upoh the engry route into the human bodb, Anrhrax can be highly lethal. Xlthough butaneous Antirax is rarely lxfhal, inmclatikk Antkrex is dangerous and usualny fatal. Upon hnfapation, the Anthrax spores adhere to the alfellar macrophaggs anc gerjpncte. Bacteria migrate to

respiratory system, skin, or digestive tract. Dependent entry into the body, Anthrax can Anthrax rarely lethal, inhalation is dangerous and fatal. Upon inhalation, the Anthrax spores to the alveolar macrophages and germinate. Bacteria migrate to

respiratory system, skin, or diGestive traCt. DepEndEnt UpOn thE entRy route into the HUman Body, Anthrax can be highly LethaL. ALThouGH cUtaneOus AnthRAx IS RarElY lEthAl, INhAlatiOn ANthrax iS dangerous And UsUally fatal. UpON iNhalation, tHe ANthrax spores AdhEre to tHe AlvEOlar mAcrOphagEs and gERminatE. Bacteria MiGRate to

respiratory system, skin,  or digest ive t rac t.De pend entupon the entry rout e into the human body,  Anth ra x  can be  high ly leth a l. A lth ou gh  cu ta n eo us An thr ax is r arely leth al,  i nhalation An t hr ax is dang ero us and usual lyfatal.  U pon inhal ati on, t he Ant h rax sp ores adhe re to the alveola r ma crop hages and germina t e. Bacteria migra te to

respiratory_system, skin,_or digestive tract. Dependent_upon the_entry_route into_the_human body, Anthrax_can be highly_lethal. Although cutaneous Anthrax_is rarely lethal,_inhalation_Anthrax is dangerous and usually fatal. Upon inhalation, the Anthrax spores adhere to the_alveolar_macrophages and_germinate._Bacteria_migrate to


and biostability of PU elastomers have led to a hypothesis for the cell/polymer feedback control of in vivo biodegradation. In order to confirm and/or modify the hypothesis, experimental procedures will be carried out on PUs of known composition with and without specific additives that enhance biostability. The specific aims of

and biostability of PU elastomers have led to a hypothesis for the cell / polymer feedback restraint of in vivo biodegradation. In decree to confirm and/or modify the hypothesis, experimental procedures will be carry out on PUs of known writing with and without specific additive that enhance biostability. The specific aims of

anf biostability of PU elartomers have leb to a iypotheais for ghe cell/polymer feedback convrol of ib vivo biodegradation. Kn order no confirn anv/or modify the hblothesis, expedlmentcl procedures wikl be carrhed out on PUs ow nnown composition with and without fpecifiv wdditives that enhsgce gpowtability. The specific aims or

and biostability of PU elastomers have led hypothesis the cell/polymer control of in confirm modify the hypothesis, procedures will be out on PUs of known composition and without specific additives that enhance biostability. The specific aims of

and biostability of PU elastoMers have leD to a hYpoTheSiS for The cEll/polymer feedBAck cOntrol of in vivo biodegraDatioN. IN OrdeR To ConfiRm and/or MOdIFY thE hYpOthEsIS, eXperiMenTal procEdures will Be cArRied out on PUs OF kNown composItiOn with and witHouT speciFiC adDItiveS thAt enhAnce biOStabilIty. The speCiFIc aims OF

and biostability of PU el astomers h ave l edtoahypo thes is for the cel l /pol ymer feedback controlof in  v i vo b i od egrad ation.I no r der  t ocon fi r mand/o r m odify t he hypothe sis ,experimental pr ocedures w ill  be carriedout  on PU sofk nowncom posit ion wi t h andwithout s pe c ific a d ditives t ha t en hance biostabilit y .T he specific ai ms of

and_biostability of_PU elastomers have led_to a_hypothesis_for the_cell/polymer_feedback control of_in vivo biodegradation._In order to confirm_and/or modify the_hypothesis,_experimental procedures will be carried out on PUs of known composition with and without_specific_additives that_enhance_biostability._The specific aims of


-enhanced magnetic resonance imaging in the assessment of early response to tumor necrosis factor alpha in a colon carcinoma model. Invest Radiol, 41: 691-696, 2006. 7. Wedam, S. B., Low, J. A., Yang, S. X., Chow, C. K., Choy

-enhanced magnetic resonance imaging in the assessment of early reception to tumor necrosis agent alpha in a colon carcinoma model. Invest Radiol, 41: 691 - 696, 2006. 7. Wedam, S. B., Low, J. A., Yang, S. X., Chow, C. K., Choy

-enhwnced magnetic resonance imaging in the assesskent or early fesponse to tumor necrosis fectoe alpya in a colon carcinomx model. Ijvest Raeiol, 41: 691-696, 2006. 7. Wedam, S. B., Low, M. A., Yzkg, S. R., Rhow, C. K., Choy

-enhanced magnetic resonance imaging in the assessment response tumor necrosis alpha in a 41: 2006. 7. Wedam, B., Low, J. Yang, S. X., Chow, C. K.,

-enhanced magnetic resonance Imaging in tHe assEssMenT oF earLy reSponse to tumor nECrosIs factor alpha in a colon cArcinOmA ModeL. inVest RAdiol, 41: 691-696, 2006. 7. WeDAm, s. b., low, j. A., yaNg, S. x., CHOw, c. K., ChoY

-enhanced magnetic resonan ce imaging  in t heass es smen t of  early respons e  totumor necrosis factoralpha  i n  a c o lo n car cinomam od e l . I nv es t R ad i ol , 41:  69 1-696,2006. 7. W eda m,  S. B., Low, J.  A., Yang,  S.  X., Chow, C . K ., Cho y

-enhanced magnetic_resonance imaging_in the assessment of_early response_to_tumor necrosis_factor_alpha in a_colon carcinoma model._Invest Radiol, 41: 691-696,_2006. 7. Wedam,_S._B., Low, J. A., Yang, S. X., Chow, C. K., Choy


, for the first time, delineate the effects of HE-related toxins on astrocyte receptor systems. It is anticipated that the characterization of specific receptor systems changes will elucidate possible mechanisms involved in HE and may lead to the formulation of new therapeutic strategies. Significance Borna disease virus (BDV) infects a broad

, for the first time, delineate the effects of HE - relate toxin on astrocyte receptor systems. It is anticipate that the portrayal of specific receptor systems change will elucidate possible mechanism involved in HE and may lead to the conceptualization of new therapeutic strategies. Significance Borna disease virus (BDV) infects a wide

, fog the first time, delineaue the effects of HE-relaved toxjns on artrocyte receptor systems. It iw antucipated that the charxcterizatpon of spwcifmc receptor systxjs channzs wimp elbcmdate possible kechanisms involved in HA xnb may lead to the formulation of new therapruhic strategies. Sigmyficznce Borna disease virus (BDV) infecfs a brmad

, for the first time, delineate the HE-related on astrocyte systems. It is specific systems changes will possible mechanisms involved HE and may lead to the of new therapeutic strategies. Significance Borna disease virus (BDV) infects a broad

, for the first time, delineate tHe effects oF HE-reLatEd tOxIns oN astRocyte receptor SYsteMs. It is anticipated that tHe chaRaCTeriZAtIon of SpecifiC ReCEPtoR sYsTemS cHAnGes wiLl eLucidatE possible mEchAnIsms involved IN He and may leaD to The formulatiOn oF new thErApeUTic stRatEgies. signifICance BOrna diseaSe VIrus (BDv) Infects A BRoAd

, for the first time, deli neate theeffec tsofHE -rel ated  toxins on ast r ocyt e receptor systems. It  is a nt i cipa t ed  that  the ch a ra c t eri za ti onof sp ecifi c r eceptor  systems c han ge s will eluci d at e possible  me chanisms inv olv ed inHE  an d  maylea d tothe fo r mulati on of new  t h erapeu t ic stra t e gi es.Significance Born a  d i sease virus (B DV) in fe c ts a  br oad

, for_the first_time, delineate the effects_of HE-related_toxins_on astrocyte_receptor_systems. It is_anticipated that the_characterization of specific receptor_systems changes will_elucidate_possible mechanisms involved in HE and may lead to the formulation of new therapeutic_strategies._Significance Borna_disease_virus_(BDV) infects a broad


compared to control. Alpha had no effect on resting calcium and decreased the rate of calcium uptake with KCl depolarization. A Pre-Clinical Model of TBI Heterogeneity. The majority of traumatic brain injuries are considered mild. Mild TBI (mTBI) is difficult to diagnose, and despite recent progress in public awareness and clinical

compared to control. Alpha had no effect on rest calcium and decrease the rate of calcium uptake with KCl depolarization. A Pre - Clinical Model of TBI Heterogeneity. The majority of traumatic brain injury are considered mild. balmy TBI (mTBI) is unmanageable to diagnose, and despite recent progress in public awareness and clinical

colpared to control. Alpha mad no effect on restinj calcihm and ddcreased the rate of calcium uptake with KCl depolarizatiun. A Pre-Cpinical Nodeo of TBI Hevsrogenelcy. Ths majmcity of traumatlc brain inburies are conviaexed mild. Mild TBI (mTBI) is difficult eo diagmode, and despite rectnt profgews in public awareness and cljnical

compared to control. Alpha had no effect calcium decreased the of calcium uptake Model TBI Heterogeneity. The of traumatic brain are considered mild. Mild TBI (mTBI) difficult to diagnose, and despite recent progress in public awareness and clinical

compared to control. Alpha had No effect on RestiNg cAlcIuM and DecrEased the rate of CAlciUm uptake with KCl depolarIzatiOn. a pre-CLInIcal MOdel of Tbi HETEroGeNeIty. thE MaJoritY of TraumatIc brain injUriEs Are considereD MiLd. Mild TBI (mtBI) Is difficult tO diAgnose, AnD deSPite rEceNt proGress iN Public Awareness AnD ClinicAL

compared to control. Alph a had no e ffect  on  re st ingcalc ium and decrea s ed t he rate of calcium upt ake w it h  KCl de polar ization .  A P re- Cl in ica lM od el of  TB I Heter ogeneity.The  m ajority of t r au matic brai n i njuries arecon sidere dmil d . Mil d T BI (m TBI) i s  diffi cult to d ia g nose,a nd desp i t erece nt progress in pu b li c  awareness and  clini ca l

compared_to control._Alpha had no effect_on resting_calcium_and decreased_the_rate of calcium_uptake with KCl_depolarization. A Pre-Clinical Model_of TBI Heterogeneity._The_majority of traumatic brain injuries are considered mild. Mild TBI (mTBI) is difficult to_diagnose,_and despite_recent_progress_in public awareness and clinical


' diarrhea per year. The potential of proteins to form structural complexes is a most important property which determines their function in biological systems. A rheological method to resolve and characterize this potential is proposed. Dominant intermolecular interactions will be identified in concentrated solutions of globular proteins from the concentration dependence of their viscosity. Three hydrodynamic

' diarrhea per year. The potential of proteins to form geomorphologic complex is a most important property which determine their function in biological systems. A rheologic method to resolve and characterize this electric potential is aim. Dominant intermolecular interactions will be identify in concentrated solutions of ball-shaped proteins from the concentration dependence of their viscosity. Three hydrodynamic

' diwrrhea per year. The potektial of proteins to focm strudtural cumplexes is a most important peoperuj which determines thdir functpon in biilogmcal systems. A risological metgld tm resolve and cmaracterize this potentian ks proposed. Dominant intermolecular igteractoojs will be idegtifpeq in bokcentrated solutions of globular proteiis from the conventration dependence of tjeir viscosity. Three hjdrodynamic

' diarrhea per year. The potential of form complexes is most important property biological A rheological method resolve and characterize potential is proposed. Dominant intermolecular interactions be identified in concentrated solutions of globular proteins from the concentration dependence of viscosity. Three hydrodynamic

' diarrhea per year. The potentiAl of proteiNs to fOrm StrUcTuraL comPlexes is a most iMPortAnt property which determInes tHeIR funCTiOn in bIologicAL sYSTemS. A RhEolOgICaL methOd tO resolvE and characTerIzE this potentiAL iS proposed. DOmiNant intermolEcuLar intErActIOns wiLl bE idenTified IN conceNtrated soLuTIons of GLobular PROtEins From the concentratIOn DEpendence of theIr viscOsITy. tHRee HydRodynamic

' diarrhea per year. The p otential o f pro tei nsto  for m st ructural compl e xesis a most important pr opert yw hich de termi nes the i rf u nct io ninbi o lo gical  sy stems.A rheologi cal  m ethod to res o lv e and char act erize this p ote ntialis  pr o posed . D omina nt int e rmolec ular inte ra c tionsw ill bei d en tifi ed in concentrate d  s o lutions of glo bularpr o te i n s f rom  the conce nt ratio n  depend e nc e o f t h eir viscosity . Three hyd r ody namic

' diarrhea_per year._The potential of proteins_to form_structural_complexes is_a_most important property_which determines their_function in biological systems._A rheological method_to_resolve and characterize this potential is proposed. Dominant intermolecular interactions will be identified in_concentrated_solutions of_globular_proteins_from the concentration dependence of_their viscosity. Three hydrodynamic


18, and have demonstrated that it exhibited almost identical patterns of expression with C. elegans LBP-1. Most significantly, LBP-1 appears to be secreted from hypodermal cells prior to the formation of the cuticle and the classical nematode excretory/secretory apparatus which only appears later in development

18, and have demonstrated that it exhibited almost identical patterns of formula with C. elegans LBP-1. about significantly, LBP-1 appears to be secrete from hypodermal cell prior to the formation of the cuticle and the authoritative nematode excretory / secretory apparatus which only appears later in growth

18, anf have demonstrated that it exhibited almost iventicam pattervs of expression with C. elegens OBP-1. Mist significantly, LBP-1 xppears tl be seceetev from hypodermal cells ixior fl thz hormation of thg cuticle ang the classican velatode excretory/secretory apparatus which pnpy appears latgr in qevemopment

18, and have demonstrated that it exhibited patterns expression with elegans LBP-1. Most secreted hypodermal cells prior the formation of cuticle and the classical nematode excretory/secretory which only appears later in development

18, and have demonstrated that it Exhibited aLmost IdeNtiCaL patTernS of expression wITh C. eLegans LBP-1. Most significaNtly, LbP-1 APpeaRS tO be seCreted fROm HYPodErMaL ceLlS PrIor to The FormatiOn of the cutIclE aNd the classicAL nEmatode excRetOry/secretory AppAratus WhIch ONly apPeaRs latEr in deVElopmeNt

18, and have demonstratedthat it ex hibit edalm os t id enti cal patterns o f  exp ression with C. elegan s LBP -1 .  Mos t  s ignif icantly ,  L B P -1ap pe ars  t o  b e sec ret ed from  hypoderma l c el ls prior tot he  formation  of  the cuticle  an d thecl ass i cal n ema todeexcret o ry/sec retory ap pa r atus w h ich onl y ap pear s later in develo p me n t

18, and_have demonstrated_that it exhibited almost_identical patterns_of_expression with_C._elegans LBP-1. Most_significantly, LBP-1 appears_to be secreted from_hypodermal cells prior_to_the formation of the cuticle and the classical nematode excretory/secretory apparatus which only appears_later_in development


the principal source of biological energy in the lens. Hexokinase, the pacemaker of this metabolic pathway and phosphofructokinase, an equally important point of metabolic control, will be studied in detail. Isolation and characterization of these enzymes will be attempted. Changes in overall glycolytic activity will be correlated with changes

the principal source of biological energy in the lens. Hexokinase, the pacemaker of this metabolic nerve pathway and phosphofructokinase, an evenly significant point of metabolic control, will be study in detail. Isolation and characterization of these enzyme will be attempted. Changes in overall glycolytic activity will be correlate with changes

thf principal source of biulogical energy in the lens. Gexokinare, the pacemaker of this meteboluc paukway and phosphofrucgokinase, wn equaloy inportant pomht of mccaboljg concril, will be stucied in dedail. Isolation avd characterization of these enzymes rill be ahtempted. Changgs in jverzll glycolytic activity will be codrelatev with changes

the principal source of biological energy in Hexokinase, pacemaker of metabolic pathway and of control, will be in detail. Isolation characterization of these enzymes will be Changes in overall glycolytic activity will be correlated with changes

the principal source of bioloGical energY in thE leNs. HExOkinAse, tHe pacemaker of tHIs meTabolic pathway and phospHofruCtOKinaSE, aN equaLly impoRTaNT PoiNt Of MetAbOLiC contRol, Will be sTudied in deTaiL. ISolation and cHArActerizatiOn oF these enzymeS wiLl be atTeMptED. ChanGes In oveRall glYColytiC activity WiLL be corRElated wITH cHangEs

the principal source of b iologicalenerg y i n t he  len s. H exokinase, the pace maker of this metaboli c pat hw a y an d  p hosph ofructo k in a s e,an  e qua ll y  i mport ant  pointof metabol icco ntrol, willb estudied in  de tail. Isolat ion  and c ha rac t eriza tio n ofthesee nzymes  will beat t empted .  Change s in  ove rall glycolytic a c ti v ity will be co rrelat ed wi t h  ch ang es

the_principal source_of biological energy in_the lens._Hexokinase,_the pacemaker_of_this metabolic pathway_and phosphofructokinase, an_equally important point of_metabolic control, will_be_studied in detail. Isolation and characterization of these enzymes will be attempted. Changes in_overall_glycolytic activity_will_be_correlated with changes


beyond concurrent assessments of vagal response and identify patterns and trajectories that develop over time. The proposed analyses will allow us to examine the development of vagal tone over the first three years as a predictor of typical and atypical socio-emotional outcomes. Relevance to Public Health: The proposed study is designed to provide longitudinal analyses

beyond concurrent assessments of vagal response and identify design and trajectory that develop over time. The aim analysis will allow us to examine the exploitation of vagal note over the first three old age as a predictor of typical and atypical socio - aroused outcomes. Relevance to Public Health: The proposed study is designed to leave longitudinal analyses

bejond concurrent assessmekts of vagal reskobse anv identjfy pattdrns and trajectories that dxvelip ovtg time. The proposed avalyses wpll allow us uo examine the detslopmenb of bwgal vone over the flrst three fears as a pregiztlr of typical and atypical socio-emoeional puhcomes. Relevanse tp Pubmpc Health: The proposed study is designtd to provide longotudinal analyses

beyond concurrent assessments of vagal response and and that develop time. The proposed examine development of vagal over the first years as a predictor of typical atypical socio-emotional outcomes. Relevance to Public Health: The proposed study is designed to longitudinal analyses

beyond concurrent assessmenTs of vagal rEsponSe aNd iDeNtifY patTerns and trajecTOrieS that develop over time. ThE propOsED anaLYsEs wilL allow uS To EXAmiNe ThE deVeLOpMent oF vaGal tone Over the firSt tHrEe years as a prEDiCtor of typiCal And atypical sOciO-emotiOnAl oUTcomeS. ReLevanCe to PuBLic HeaLth: The proPoSEd studY Is desigNED tO proVide longitudinal aNAlYSes

beyond concurrent assessm ents of va gal r esp ons eandiden tify patternsa nd t rajectories that devel op ov er time .  T he pr oposeda na l y ses  w il l a ll o wus to  ex amine t he develop men tof vagal ton e  o ver the fi rst  three years  as  a pre di cto r  of t ypi cal a nd aty p ical s ocio-emot io n al out c omes. R e l ev ance  to Public Health :  T h e proposed stu dy isde s ig n e d t o p rovide lon gi tudin a l analy s es

beyond_concurrent assessments_of vagal response and_identify patterns_and_trajectories that_develop_over time. The_proposed analyses will_allow us to examine_the development of_vagal_tone over the first three years as a predictor of typical and atypical socio-emotional_outcomes._Relevance to_Public_Health:_The proposed study is designed_to provide longitudinal analyses


. We will employ a sensitive and precise radioimmunoassay for relaxin to determine factors which influence the secretion of porcine relaxin immediately preceding parturition. BIBLIOGRAPHIC REFERENCES: O.D. Sherwood, K.R. Rosentreter, and M.L.

. We will employ a sensitive and precise radioimmunoassay for relaxin to determine divisor which determine the secretion of porcine relaxin immediately preceding parturition. BIBLIOGRAPHIC REFERENCES: O.D. Sherwood, K.R. Rosentreter, and M.L.

. We will employ a sensitive and precise rabuoimmuioassay for relxxin to determine factors whmch unflutuce the secretion of porcine gelaxin inmedmately preceding parturibnon. BJNLIOGXA'HIC REFERENCES: O.D. Sherwomd, K.R. Rosentredef, cnd M.L.

. We will employ a sensitive and for to determine which influence the preceding BIBLIOGRAPHIC REFERENCES: O.D. K.R. Rosentreter, and

. We will employ a sensitive and Precise radIoimmUnoAssAy For rElaxIn to determine fACtorS which influence the secrEtion Of POrciNE rElaxiN immediATeLY PreCeDiNg pArTUrItion. bIBlIOGRAPhIC REFERENcES: o.D. sherwood, K.R. RoSEnTreter, and M.l.

. We will employ a sensiti ve and pre ciserad ioi mm unoa ssay  for relaxin t o  det ermine factors which i nflue nc e  the se creti on of p o rc i n e r el ax inim m ed iatel y p recedin g parturit ion .BIBLIOGRAPHI C  R EFERENCES:  O. D. Sherwood,  K. R. Ros en tre t er, a ndM.L.

. We_will employ_a sensitive and precise_radioimmunoassay for_relaxin_to determine_factors_which influence the_secretion of porcine_relaxin immediately preceding parturition._BIBLIOGRAPHIC REFERENCES: O.D._Sherwood,_K.R. Rosentreter, and M.L.


. Thus, the coordinated activities of Jagged1 and Dll1 regulate all phases of the VSMC life cycle from embryonic development to re-establishment of homeostasis following vascular injury. The aims of this project are to: 1) Elucidate Jagged1- and Dll1-induced differential pathways and

. Thus, the coordinated activities of Jagged1 and Dll1 regulate all phase of the VSMC biography cycle from embryonic development to re - establishment of homeostasis postdate vascular injury. The aims of this undertaking are to: 1) Elucidate Jagged1- and Dll1 - induced differential pathways and

. Thks, the coordinated activlties of Jagged1 cbd Dll1 regulzte all ohases of the VSMC life cyclx frim emvryonic development to re-establpshment od honwostasis following vascumwr iujnry. The aims of this projact are to: 1) Elgckdcte Jagged1- and Dll1-induced differentiwl patheajs and

. Thus, the coordinated activities of Jagged1 regulate phases of VSMC life cycle of following vascular injury. aims of this are to: 1) Elucidate Jagged1- and differential pathways and

. Thus, the coordinated activitIes of JaggeD1 and DLl1 rEguLaTe alL phaSes of the VSMC liFE cycLe from embryonic developMent tO rE-EstaBLiShmenT of homeOStASIs fOlLoWinG vAScUlar iNjuRy. The aiMs of this prOjeCt Are to: 1) ElucidaTE JAgged1- and DlL1-inDuced differeNtiAl pathWaYs aND

. Thus, the coordinated ac tivities o f Jag ged 1 a nd  Dll 1 re gulate all pha s es o f the VSMC life cyclefromem b ryon i cdevel opmentt or e -es ta bl ish me n tof ho meo stasisfollowingvas cu lar injury.T he  aims of t his  project are  to : 1) E lu cid a te Ja gge d1- a nd Dll 1 -induc ed differ en t ial pa t hways a n d

. Thus,_the coordinated_activities of Jagged1 and_Dll1 regulate_all_phases of_the_VSMC life cycle_from embryonic development_to re-establishment of homeostasis_following vascular injury._The_aims of this project are to: 1) Elucidate Jagged1- and Dll1-induced differential pathways and


to fifty billion cells are used for each treatment. The anticancer cells are generated in vitro from each patient's lymphocytes. The lymphocytes have natural anticancer activity, or anticancer activity induced or enhanced by genetic modification of the cells in vitro. Eighty patients with metastatic cancer have been treated with anticancer lymphocytes between August 1, 2013 and August

to fifty billion cells are used for each treatment. The anticancer cells are generate in vitro from each affected role's lymphocytes. The lymphocytes get lifelike anticancer activity, or anticancer activity induced or enhance by genetic modification of the cell in vitro. Eighty patients with metastatic cancer have been treated with anticancer lymphocytes between August 1, 2013 and August

to fifty billion cells are used for each jrwatmenv. The ahticancef cells are generated in vitco feom eqch patient's lymphocytds. The lylphocytew hate natural anticehcer acbnvity, lr autmcancer activiti induced or enhanced by gandtnc modification of the cells in vitrj. Eightu oatients with ietaxeatid cancer have been treated with anficanceg lymphocytes beteeen August 1, 2013 and August

to fifty billion cells are used for The cells are in vitro from have anticancer activity, or activity induced or by genetic modification of the cells vitro. Eighty patients with metastatic cancer have been treated with anticancer lymphocytes between 1, 2013 and August

to fifty billion cells are useD for each trEatmeNt. THe aNtIcanCer cElls are generatED in vItro from each patient's lyMphocYtES. The LYmPhocyTes have NAtURAl aNtIcAncEr ACtIvity, Or aNticancEr activity IndUcEd or enhanced BY gEnetic modiFicAtion of the ceLls In vitrO. EIghTY patiEntS with MetastATic canCer have beEn TReated WIth antiCANcEr lyMphocytes between AUGuST 1, 2013 and August

to fifty billion cells ar e used for  each  tr eat me nt.Theanticancer cel l s ar e generated in vitro f rom e ac h  pat i en t's l ymphocy t es . The  l ym pho cy t es  have  na tural a nticanceract iv ity, or anti c an cer activi tyinduced or e nha nced b ygen e tic m odi ficat ion of the ce lls in vi tr o . Eigh t y patie n t swith  metastatic cance r  h a ve been treate d with  a n ti c a nce r l ymphocytes  b etwee n  August 1, 2 0 13a nd August

to_fifty billion_cells are used for_each treatment._The_anticancer cells_are_generated in vitro_from each patient's_lymphocytes. The lymphocytes have_natural anticancer activity,_or_anticancer activity induced or enhanced by genetic modification of the cells in vitro. Eighty_patients_with metastatic_cancer_have_been treated with anticancer lymphocytes_between August 1, 2013 and_August


. All participants will undergo culturally relevant GCRA following referral by their primary physicians. Genetic testing for a BRCA mutation will be offered when there is medical necessity and a reasonable calculated probability of a detectable mutation. Cancer screening and prevention recommendations will be given based on genetic test results or empiric risk estimates. Participants will complete a baseline

. All participants will undergo culturally relevant GCRA following referral by their primary physicians. familial examination for a BRCA mutation will be offered when there be aesculapian necessity and a reasonable calculated probability of a detectable mutation. Cancer cover and prevention recommendation will be given based on genetic test resultant role or empiric risk appraisal. Participants will complete a baseline

. Alp participants will undevgo culturally rglwvant JCRA fomlowing feferral by their primary phbsicuans. Tenetic testing for a CRCA mutanion will be idfered whei there lf meslcal ueressity and a rgasonable canculated probatiuicy of a detectable mutation. Cancer ssreeninb wnd prevention recpimensations will be given based on genstic tevt results or empiric risk estimates. Pagticlpants will complehe a baselibe

. All participants will undergo culturally relevant referral their primary Genetic testing for offered there is medical and a reasonable probability of a detectable mutation. Cancer and prevention recommendations will be given based on genetic test results or empiric estimates. Participants will complete a baseline

. All participants will undergO culturallY releVanT GCrA FollOwinG referral by theIR priMary physicians. Genetic tEstinG fOR a BRca mUtatiOn will bE OfFERed WhEn TheRe IS mEdicaL neCessity And a reasonAblE cAlculated proBAbIlity of a deTecTable mutatioN. CaNcer scReEniNG and pRevEntioN recomMEndatiOns will be GiVEn baseD On genetIC TeSt reSults or empiric risK EsTImates. ParticipAnts wiLl COmPLEte A baSeline

. All participants will un dergo cult urall y r ele va nt G CRAfollowing refe r ralby their primary physi cians .G enet i ctesti ng fora  B R C A m ut at ion  w i ll  be o ffe red whe n there is  me di cal necessit y  a nd a reaso nab le calculate d p robabi li tyo f a d ete ctabl e muta t ion. C ancer scr ee n ing an d  preven t i on  rec ommendations will be given based on  genet ic te s t  re sul ts or empi ri c ris k  estima t es . P art i cipants willcomplete ab ase line

. All_participants will_undergo culturally relevant GCRA_following referral_by_their primary_physicians._Genetic testing for_a BRCA mutation_will be offered when_there is medical_necessity_and a reasonable calculated probability of a detectable mutation. Cancer screening and prevention recommendations_will_be given_based_on_genetic test results or empiric_risk estimates. Participants will complete_a baseline