a method that could lead to important new applications for regulating cellular or physiological processes in vivo. This device may also lead to novel methods of drug screening and development as it could provide a rapid, well calibrated, and reproducible method of delivering a thermal pulse to cells or purified ion channel protein in single or multi-well format.

a method that could lead to important new application for determine cellular or physiological processes in vivo. This device may also run to novel methods of drug cover and development as it could provide a rapid, well calibrated, and reproducible method acting of deliver a thermal pulse to cell or purified ion channel protein in unmarried or multi - good format.

a lethod that could lead tu important new applicetions ror reguuating cellular or physiologmcal proctfses in vivo. This aevice maj also leqd ti novel metikds of drug sdveeniug and developmekt as it cogld provide a saoib, well calibrated, and reproducible mqthod og felivering a trermsj pumse to cells or purified ion channsl prottin in single or milti-well format.

a method that could lead to important for cellular or processes in vivo. to methods of drug and development as could provide a rapid, well calibrated, reproducible method of delivering a thermal pulse to cells or purified ion channel in single or multi-well format.

a method that could lead to impOrtant new aPplicAtiOns FoR regUlatIng cellular or pHYsioLogical processes in vivo. this dEvICe maY AlSo leaD to noveL MeTHOds Of DrUg sCrEEnIng anD deVelopmeNt as it coulD prOvIde a rapid, welL CaLibrated, anD reProducible meThoD of delIvEriNG a theRmaL pulsE to celLS or purIfied ion cHaNNel proTEin in siNGLe Or muLti-well format.

a method that could leadto importa nt ne w a ppl ic atio ns f or regulatingc ellu lar or physiological p roces se s  inv iv o. Th is devi c em a y a ls olea dt onovel  me thods o f drug scr een in g and develo p me nt as it c oul d provide arap id, we ll  ca l ibrat ed,  andreprod u ciblemethod of  d e liveri n g a the r m al  pul se to cells or pu r if i ed ion channel  prote in in s ing leor multi-w el l for m at.

a_method that_could lead to important_new applications_for_regulating cellular_or_physiological processes in_vivo. This device_may also lead to_novel methods of_drug_screening and development as it could provide a rapid, well calibrated, and reproducible method_of_delivering a_thermal_pulse_to cells or purified ion_channel protein in single or_multi-well format.


hepatitis- negative populations in Europe and the USA. Saturated free fatty acids, by promoting insulin resistance and mediating the progression from simple steatosis to steatohepatitis, are a causative link between obesity and NAFLD. The proposed study will increase understanding of the molecular mechanisms by which saturated FFA contribute to the development

hepatitis- negative populations in Europe and the USA. Saturated free fatso acid, by promoting insulin resistance and intercede the progress from simple steatosis to steatohepatitis, are a causative link between fleshiness and NAFLD. The proposed study will increase understanding of the molecular mechanism by which saturated FFA contribute to the development

heoatitis- negative populatlons in Europe aue the NSA. Sathrated ffee fatty acids, by promoting ibsulib resistance and mediaging the irogressiin fcom simple steatosis to steatogcpaticiw, are a causatlve link bedween obesity dna UAFLD. The proposed study will increafe undetshanding of the moltcujar jvcmanisms by which saturated FFA ckntribuue to the developmrnt

hepatitis- negative populations in Europe and the free acids, by insulin resistance and steatosis steatohepatitis, are a link between obesity NAFLD. The proposed study will increase of the molecular mechanisms by which saturated FFA contribute to the development

hepatitis- negative populatiOns in EuropE and tHe UsA. SAtUratEd frEe fatty acids, by PRomoTing insulin resistance aNd medIaTIng tHE pRogreSsion frOM sIMPle StEaTosIs TO sTeatoHepAtitis, aRe a causatiVe lInK between obesITy And NAFLD. ThE prOposed study wIll IncreaSe UndERstanDinG of thE molecULar mecHanisms by WhICh satuRAted FFA CONtRibuTe to the developmenT

hepatitis- negative popul ations inEurop e a ndth e US A. S aturated freef atty  acids, by promoting i nsuli nr esis t an ce an d media t in g the  p ro gre ss i on  from  si mple st eatosis to  st ea tohepatitis, ar e a causat ive  link betwee n o besity  a ndN AFLD.  Th e pro poseds tudy w ill incre as e  under s tanding o fthemolecular mechani s ms by which satur ated F FA co n t rib ute  to the de ve lopme n t

hepatitis-_negative populations_in Europe and the_USA. Saturated_free_fatty acids,_by_promoting insulin resistance_and mediating the_progression from simple steatosis_to steatohepatitis, are_a_causative link between obesity and NAFLD. The proposed study will increase understanding of the_molecular_mechanisms by_which_saturated_FFA contribute to the development


potential mechanisms that explain contribution of CD8 T cells to elimination of Plasmodium liver stages in mice. We will provide such insights via three complementary speci?c aims. In speci?c Aim 1, we will discriminate between alternative mechanisms of formation of CD8 T cell clusters around sporozoite-infected hepatocytes

potential mechanisms that explain contribution of CD8 T cells to elimination of Plasmodium liver stage in mouse. We will provide such insights via three complementary speci?c aim. In speci?c Aim 1, we will discriminate between alternative mechanisms of geological formation of CD8 T cellular telephone clusters around sporozoite - infected hepatocytes

pohential mechanisms that txplain contributnin of RD8 T cemls to euimination of Plasmodium livxr srages in mice. We will proviae such ijsights cia uhree complementacg speci?g aima. In v'eci?c Aim 1, we wlll discrimhnate between dlgexnative mechanisms of formation of CQ8 T celk flusters arounq sppwozojne-lnfected hepatocytes

potential mechanisms that explain contribution of CD8 to of Plasmodium stages in mice. via complementary speci?c aims. speci?c Aim 1, will discriminate between alternative mechanisms of of CD8 T cell clusters around sporozoite-infected hepatocytes

potential mechanisms that exPlain contrIbutiOn oF CD8 t cElls To elImination of PlaSModiUm liver stages in mice. We wIll prOvIDe suCH iNsighTs via thREe COMplEmEnTarY sPEcI?c aimS. In Speci?c AIm 1, we will diScrImInate between ALtErnative meChaNisms of formaTioN of CD8 T CeLl cLUsterS arOund sPorozoITe-infeCted hepatOcYTes

potential mechanisms that  explain c ontri but ion  o f CD 8 Tcells to elimi n atio n of Plasmodium liverstage si n mi c e.  We w ill pro v id e suc hin sig ht s  v ia th ree  comple mentary sp eci ?c  aims. In sp e ci ?c Aim 1,wewill discrim ina te bet we ena ltern ati ve me chanis m s of f ormationof CD8 Tc ell clu s t er s ar ound sporozoite-i n fe c ted hepatocyte s

potential_mechanisms that_explain contribution of CD8_T cells_to_elimination of_Plasmodium_liver stages in_mice. We will_provide such insights via_three complementary speci?c_aims._In speci?c Aim 1, we will discriminate between alternative mechanisms of formation of CD8_T_cell clusters_around_sporozoite-infected_hepatocytes


identified using data from the slovenian National Cancer Registry, one of the oldest national registries in Europe. Exposure measurements are available for most exposed jobs begining in 1961. Three different methods of measurement were used: konimeter measuring particles/cm3, a gravimetric method measuring milligrams/m3, and membrane

identified using data from the slovenian National Cancer Registry, one of the oldest home register in Europe. photograph measurements are available for about exposed problem begining in 1961. Three different method of measurement were used: konimeter measuring atom / cm3, a gravimetric method measure milligrams / m3, and membrane

idfntified using data from the slovenian Uqtionan Cancsr Regisgry, one of the oldest nationel rwgisteies in Europe. Exposurd measurelents arw aveilable for most exposed jobs gcginiug in 1961. Three difnerent methmds of measurekevt were used: konimeter measuring partycles/cm3, a gravimetric mgthod ieashgikg milligrams/m3, and membrane

identified using data from the slovenian National one the oldest registries in Europe. most jobs begining in Three different methods measurement were used: konimeter measuring particles/cm3, gravimetric method measuring milligrams/m3, and membrane

identified using data from thE slovenian natioNal canCeR RegIstrY, one of the oldesT NatiOnal registries in Europe. exposUrE MeasUReMents Are avaiLAbLE For MoSt ExpOsED jObs beGinIng in 1961. ThRee differeNt mEtHods of measurEMeNt were used: KonImeter measurIng ParticLeS/cm3, A GraviMetRic meThod meASuring MilligramS/m3, ANd membRAne

identified using data fro m the slov enian  Na tio na l Ca ncer  Registry, one of t he oldest national reg istri es in E u ro pe. E xposure me a s ure me nt s a re av ailab lefor mos t exposedjob sbegining in1 96 1. Three d iff erent method s o f meas ur eme n t wer e u sed:konime t er mea suring pa rt i cles/c m 3, a gr a v im etri c method measurin g  m i lligrams/m3, a nd mem br a ne

identified_using data_from the slovenian National_Cancer Registry,_one_of the_oldest_national registries in_Europe. Exposure measurements_are available for most_exposed jobs begining_in_1961. Three different methods of measurement were used: konimeter measuring particles/cm3, a gravimetric method_measuring_milligrams/m3, and_membrane


8 in resistance to paclitaxel. We ar [summary truncated at 7800 characters] We have also completed the first characterization of the active site of NiSOD from Streptomyces seoulensis. This study reveals that Ni site is bound to thiolate donors, like other Ni redox enzymes but unlike any previously characterized SOD

8 in resistance to paclitaxel. We ar [ summary truncated at 7800 characters ] We have also dispatch the inaugural characterization of the active site of NiSOD from Streptomyces seoulensis. This study unwrap that Ni site is bound to thiolate donor, like early Ni redox enzymes but unlike any previously characterized SOD

8 in resistance to paclitaxeu. We ar [summary truncaved at 7800 charactdrs] We have also completed tie furst xharacterization of thd active dite of BiSOV from Streptomyrss seoulensis. Bhis vvudy reveals thst Ni site is bound to tviulcte donors, like other Ni redox enzymqs but inpike any previjuslj sharzbttrized SOD

8 in resistance to paclitaxel. We ar at characters] We also completed the site NiSOD from Streptomyces This study reveals Ni site is bound to thiolate like other Ni redox enzymes but unlike any previously characterized SOD

8 in resistance to paclitaxel. WE ar [summary TruncAteD at 7800 ChAracTers] we have also compLEted The first characterizatiOn of tHe ACtivE SiTe of NISOD froM stREPtoMyCeS seOuLEnSis. ThIs sTudy revEals that Ni SitE iS bound to thioLAtE donors, likE otHer Ni redox enZymEs but uNlIke ANy preVioUsly cHaractERized SoD

8 in resistance to paclita xel. We ar  [sum mar y t ru ncat ed a t 7800 charact e rs]We have also completed  thefi r st c h ar acter ization of t heac ti vesi t eof Ni SOD  from S treptomyce s s eo ulensis. Thi s  s tudy revea lsthat Ni site  is  bound  t o t h iolat e d onors , like otherNi redoxen z ymes b u t unlik e an y pr eviously characte r iz e d SOD

8 in_resistance to_paclitaxel. We ar [summary_truncated at_7800_characters] We_have_also completed the_first characterization of_the active site of_NiSOD from Streptomyces_seoulensis._This study reveals that Ni site is bound to thiolate donors, like other Ni_redox_enzymes but_unlike_any_previously characterized SOD


-eating syndrome). To date, our studies include identification of genes and proteins used by S. aureus and GAS to evade destruction by human neutrophils, hence contributing to virulence, survival and pathogenesis. Alcohol consumption and HIV infection are frequently co-existent pathologies. Muscle wasting is a common feature of both conditions. The

-eating syndrome). To date, our studies include identification of genes and protein use by S. aureus and GAS to evade destruction by human neutrophil, hence put up to virulence, survival and pathogenesis. Alcohol consumption and HIV infection are frequently co - real pathologies. Muscle wasting is a coarse feature of both conditions. The

-eatlng syndrome). To date, our studies includg udentihicatioh of gends and proteins used by S. auceus and TAS to evade destructiun by humwn neutriphiow, hence coifributiky to blruleucx, survival and kathogenesis. Alcohol consukpgiln and HIV infection are frequently co-exisyejt pathologies. Musblq waanikg is a common feature of both cknditiois. The

-eating syndrome). To date, our studies include genes proteins used S. aureus and human hence contributing to survival and pathogenesis. consumption and HIV infection are frequently pathologies. Muscle wasting is a common feature of both conditions. The

-eating syndrome). To date, our stUdies incluDe ideNtiFicAtIon oF genEs and proteins uSEd by s. aureus and GAS to evade deStrucTiON by hUMaN neutRophils, HEnCE ConTrIbUtiNg TO vIruleNce, SurvivaL and pathogEneSiS. Alcohol consUMpTion and HIV InfEction are freQueNtly co-ExIstENt patHolOgies. muscle WAsting Is a common FeATure of BOth condITIoNs. ThE

-eating syndrome). To date , our stud ies i ncl ude  i dent ific ation of genes andproteins used by S. au reusan d  GAS to  evad e destr u ct i o n b yhu man  n e ut rophi ls,  hencecontributi ngto  virulence,s ur vival andpat hogenesis. A lco hol co ns ump t ion a ndHIV i nfecti o n arefrequentl yc o-exis t ent pat h o lo gies . Muscle wastingi sa  common featur e of b ot h  c o n dit ion s. The

-eating syndrome)._To date,_our studies include identification_of genes_and_proteins used_by_S. aureus and_GAS to evade_destruction by human neutrophils,_hence contributing to_virulence,_survival and pathogenesis. Alcohol consumption and HIV infection are frequently co-existent pathologies. Muscle wasting_is_a common_feature_of_both conditions. The


. Based on experience with other analogs given by injection, depression to essentially castrate levels can be attained. This is a desired end in treatment of symptoms associated with prostate cancer. A subdermal implant would constitute a convenient way of continuously dosing with an LHRH agonist. Such an implant has been developed and shown in

. Based on experience with other analogs given by injection, depressive disorder to basically castrate levels can be fall upon. This is a hope end in treatment of symptom consort with prostate cancer. A subdermal implant would constitute a convenient way of endlessly dosing with an LHRH agonist. Such an implant has been developed and shown in

. Baded on experience with ouher analogs giveu by inoection, depresskon to essentially castrate pecels xan be attained. This ir a desirvd end in treetment of symptoms assoclcted slth pxowtate cancer. A subdermal implant would cundtitute a convenient way of continujusly dpslng with an LHTH agpgist. Such an implant has been developes and siown in

. Based on experience with other analogs injection, to essentially levels can be end treatment of symptoms with prostate cancer. subdermal implant would constitute a convenient of continuously dosing with an LHRH agonist. Such an implant has been developed shown in

. Based on experience with otheR analogs giVen by InjEctIoN, depRessIon to essentialLY casTrate levels can be attainEd. ThiS iS A desIReD end iN treatmENt OF SymPtOmS asSoCIaTed wiTh pRostate Cancer. A subDerMaL implant woulD CoNstitute a cOnvEnient way of cOntInuousLy DosINg witH an lHRH aGonist. sUch an iMplant has BeEN develOPed and sHOWn In

. Based on experience with  other ana logsgiv enby  inj ecti on, depression to e ssentially castrate le velsca n  bea tt ained . Thisi sa des ir ed  en di ntreat men t of sy mptoms ass oci at ed with pros t at e cancer.A s ubdermal imp lan t woul dcon s titut e a  conv enient way of  continuo us l y dosi n g witha n  L HRHagonist. Such ani mp l ant has been d evelop ed an d sho wnin

. Based_on experience_with other analogs given_by injection,_depression_to essentially_castrate_levels can be_attained. This is_a desired end in_treatment of symptoms_associated_with prostate cancer. A subdermal implant would constitute a convenient way of continuously dosing_with_an LHRH_agonist._Such_an implant has been developed_and shown in


with the contribution of Hermann Lotze (1817-1881) to the German movement, a broad reform of German medical science on the foundation of philosophical theory construction. His "mechanical" program for medicine was one of many attempts to break loose from vague speculative medical theories such as contagion, humors,

with the contribution of Hermann Lotze (1817 - 1881) to the German movement, a broad reform of German medical science on the initiation of philosophic theory construction. His " mechanical " platform for music was one of many attempts to break loose from obscure speculative medical theory such as contagion, humors,

wihh the contribution of Htrmann Lotze (1817-1881) to jhw Germen movejent, a bfoad reform of German medicap wcienxe on the foundation ow philosoihical thwory xonstruction. His "mcehanidwl" pxojram for medicike was one mf many attempds tl break loose from vague speculativq medicsl theories such as bogtagjon, humors,

with the contribution of Hermann Lotze (1817-1881) German a broad of German medical philosophical construction. His "mechanical" for medicine was of many attempts to break loose vague speculative medical theories such as contagion, humors,

with the contribution of HermAnn Lotze (1817-1881) to The GeRmaN moVeMent, A broAd reform of GermAN medIcal science on the foundaTion oF pHIlosOPhIcal tHeory coNStRUCtiOn. hiS "meChANiCal" prOgrAm for meDicine was oNe oF mAny attempts tO BrEak loose frOm vAgue speculatIve MedicaL tHeoRIes suCh aS contAgion, hUMors,

with the contribution ofHermann Lo tze ( 181 7-1 88 1) t o th e German movem e nt,a broad reform of Germ an me di c al s c ie nce o n the f o un d a tio nof  ph il o so phica l t heory c onstructio n.Hi s "mechanica l "program fo r m edicine wasone  of ma ny  at t empts  to  brea k loos e  fromvague spe cu l ativem edicalt h eo ries  such as contagio n ,h umors,

with_the contribution_of Hermann Lotze (1817-1881)_to the_German_movement, a_broad_reform of German_medical science on_the foundation of philosophical_theory construction. His_"mechanical"_program for medicine was one of many attempts to break loose from vague speculative_medical_theories such_as_contagion,_humors,


. However, valid and precise data for BC, RDBF, and BM and the factors controlling them are lacking for children and adolescents. Girls with the Turner Syndrome (n=8) receiving GH for at least one year, prior to estrogen replacement, and boys with constitutional delay of growth (n=8) not

. However, valid and precise data for BC, RDBF, and BM and the factors controlling them are miss for child and adolescents. Girls with the Turner Syndrome (n=8) pick up GH for at least one class, prior to estrogen replacement, and boys with constitutional delay of increase (n=8) not

. Hoaever, valid and precise aata for BC, RDBY, and BK and fhe facturs controlling them are lacnibg foe children and adolescdnts. Girld with tye Tnrner Syndrome (n=8) receiviky GH rlr ac oeast one year, prior to astrogen replaweoeut, and boys with constitutional delar of grpwhh (n=8) not

. However, valid and precise data for and and the controlling them are Girls the Turner Syndrome receiving GH for least one year, prior to estrogen and boys with constitutional delay of growth (n=8) not

. However, valid and precise datA for BC, RDBF, And BM And The FaCtorS conTrolling them arE LackIng for children and adoleScentS. GIRls wITh The TuRner SynDRoME (N=8) reCeIvIng gH FOr At leaSt oNe year, pRior to estrOgeN rEplacement, anD BoYs with consTitUtional delay Of gRowth (n=8) NoT

. However, valid and preci se data fo r BC,  RD BF,  a nd B M an d the factorsc ontr olling them are lackin g for  c h ildr e nand a dolesce n ts . Gir ls  w ith  t h eTurne r S yndrome  (n=8) rec eiv in g GH for atl ea st one yea r,prior to est rog en rep la cem e nt, a ndboyswith c o nstitu tional de la y  of gr o wth (n= 8 )  n ot

. However,_valid and_precise data for BC,_RDBF, and_BM_and the_factors_controlling them are_lacking for children_and adolescents. Girls with_the Turner Syndrome_(n=8)_receiving GH for at least one year, prior to estrogen replacement, and boys with_constitutional_delay of_growth_(n=8)_not


of this gene(s) and the transcript(s) made from it is proposed as the initial step in understanding regulation of this gene-enzyme system. Expression libraries of Drosophila cDNA will be screened for sequences specific for IDH. The identity of these cloned sequences will be verified by in situ hybridization to salivary gland poly

of this gene(s) and the transcript(s) made from it is proposed as the initial step in understanding rule of this gene - enzyme arrangement. Expression libraries of Drosophila complementary dna will be screened for succession specific for IDH. The identity of these cloned succession will be affirm by in situ hybridization to salivary gland poly

of this gene(s) and the tranrcript(s) made from it iv propksed as ghe initial step in understaidint regylation of this gene-enxyme systvm. Expreswion oibraries of Drosoikila dFNA ciol be screened for sequetces specific xof NDH. The identity of these cloned seqtences eipl be verified by pn sith hybridization to salivary gland loly

of this gene(s) and the transcript(s) made is as the step in understanding Expression of Drosophila cDNA be screened for specific for IDH. The identity of cloned sequences will be verified by in situ hybridization to salivary gland poly

of this gene(s) and the transcriPt(s) made froM it is ProPosEd As thE iniTial step in undeRStanDing regulation of this geNe-enzYmE SystEM. EXpresSion libRArIES of drOsOphIlA CDnA wilL be ScreeneD for sequenCes SpEcific for IDH. tHe Identity of TheSe cloned sequEncEs will Be VerIFied bY in Situ hYbridiZAtion tO salivary GlANd poly

of this gene(s) and the t ranscript( s) ma defro mit i s pr oposed as thei niti al step in understandi ng re gu l atio n  o f thi s gene- e nz y m e s ys te m.Ex p re ssion  li braries  of Drosop hil acDNA will be sc reened for  se quences spec ifi c forID H.T he id ent ity o f thes e  clone d sequenc es will b e  verifi e d  b y in  situ hybridizati o nt o salivary gla nd pol y

of_this gene(s)_and the transcript(s) made_from it_is_proposed as_the_initial step in_understanding regulation of_this gene-enzyme system. Expression_libraries of Drosophila_cDNA_will be screened for sequences specific for IDH. The identity of these cloned sequences_will_be verified_by_in_situ hybridization to salivary gland_poly


be used to follow the fate of internalized viral filaments and examine whether budding viral filaments can mediate cell-to-cell spread of infection. In specific aim 2, we will focus on the pathogenic potential of filamentous influenza virus. Using primary human nasopharyngeal organ and epithelial cultures we will determine whether infection is restricted to

be used to follow the fate of internalized viral filaments and test whether bud viral filaments can mediate cell - to - cellular telephone spread of infection. In specific aim 2, we will concentrate on the pathogenic potential of filamentous influenza virus. use primary human nasopharyngeal organ and epithelial culture we will determine whether infection is restrict to

be used to follow the fate of internalizeb viral filamsnts and examine whether budding virel fulamebts can mediate cell-to-zell sprewd of indectmon. In specific ejm 2, we will fkgus ou vhe pathogenic kotential of filamentous itfuuznza virus. Using primary human nasopraryngesl organ and epijhelisj cumnuves we will determine whether inrection is restrictec to

be used to follow the fate of filaments examine whether viral filaments can In aim 2, we focus on the potential of filamentous influenza virus. Using human nasopharyngeal organ and epithelial cultures we will determine whether infection is restricted

be used to follow the fate of inTernalized Viral FilAmeNtS and ExamIne whether buddINg viRal filaments can mediate Cell-tO-cELl spREaD of inFection. iN sPECifIc AiM 2, we WiLL fOcus oN thE pathogEnic potentIal Of Filamentous iNFlUenza virus. usiNg primary humAn nAsophaRyNgeAL orgaN anD epitHelial CUltureS we will deTeRMine whETher infECTiOn is Restricted to

be used to follow the fat e of inter naliz edvir al  fil amen ts and examine whet her budding viral fila ments  c a n me d ia te ce ll-to-c e ll s pre ad  o f i nf e ct ion.Inspecifi c aim 2, w e w il l focus on t h epathogenic  po tential of f ila mentou sinf l uenza  vi rus.Usingp rimary  human na so p haryng e al orga n an d ep ithelial cultures we will determine  wheth er in f e cti onis restric te d to

be_used to_follow the fate of_internalized viral_filaments_and examine_whether_budding viral filaments_can mediate cell-to-cell_spread of infection. In_specific aim 2,_we_will focus on the pathogenic potential of filamentous influenza virus. Using primary human nasopharyngeal_organ_and epithelial_cultures_we_will determine whether infection is_restricted to


among adolescents in the foster care system in Los Angeles. Previous research has identified children in foster care with histories of abuse and neglect as a population at high risk for a number of developmental and behavioral problems. Researchers, child welfare advocates and journalists have demonstrated that child welfare programs often fail to address the complex needs of maltreated youth

among adolescents in the foster care system in Los Angeles. Previous inquiry has identify children in foster care with histories of maltreatment and disregard as a population at high risk for a issue of developmental and behavioral problem. Researchers, child welfare advocates and journalists have demonstrate that child welfare programs much fail to cover the complex needs of maltreated young person

amlng adolescents in the fuster care systgm in Lov Angemes. Prevkous research has identified cyildrtu in foster care witf historivs of abuwe aid neglect as a 'kpulation at glgh rnsj for a number of develo[mental and bevaxilral problems. Researchers, child welsare adfofates and jourgalixes hzne demonstrated that child welfzre projrams often faik to address the complex nfeds of maltreated youhh

among adolescents in the foster care system Angeles. research has children in foster and as a population high risk for number of developmental and behavioral problems. child welfare advocates and journalists have demonstrated that child welfare programs often fail address the complex needs of maltreated youth

among adolescents in the fostEr care systEm in LOs ANgeLeS. PreViouS research has idENtifIed children in foster carE with HiSToriES oF abusE and negLEcT AS a pOpUlAtiOn AT hIgh riSk fOr a numbEr of develoPmeNtAl and behavioRAl Problems. ReSeaRchers, child wElfAre advOcAteS And joUrnAlistS have dEMonstrAted that cHiLD welfaRE prograMS OfTen fAil to address the coMPlEX needs of maltreAted yoUtH

among adolescents in thefoster car e sys tem  in  L os A ngel es. Previous r e sear ch has identified chil drenin fost e rcarewith hi s to r i esof  a bus ea nd  negl ect  as a p opulationathi gh risk fora  n umber of d eve lopmental an d b ehavio ra l p r oblem s.Resea rchers ,  child  welfaread v ocates and jou r n al ists  have demonstrate d  t h at child welfa re pro gr a ms o fte n f ail to add re ss th e  comple x  n e e d s o f  maltreated y outh

among_adolescents in_the foster care system_in Los_Angeles._Previous research_has_identified children in_foster care with_histories of abuse and_neglect as a_population_at high risk for a number of developmental and behavioral problems. Researchers, child welfare_advocates_and journalists_have_demonstrated_that child welfare programs often_fail to address the complex_needs of_maltreated youth


historical exposure data are available, distinguishing the two broad classes of asbestos fibers. The small Grant Investigator, an occupatinal physician and epidemiology doctoral student, would conduct a detailed historical exposure reconstruction and case control studies of lung cancer and mesothelimoma. The cohort of workers employed in the cement asbestos manufacturing plant of

historical exposure data are available, distinguishing the two wide class of asbestos fibers. The small Grant Investigator, an occupatinal physician and epidemiology doctoral scholar, would conduct a detailed historical exposure reconstruction and font control studies of lung cancer and mesothelimoma. The age group of worker employed in the cementum asbestos manufacturing plant of

hidtorical exposure data ave available, disjibguishmng the two broxd classes of asbestos fiberd. Rhe snall Grant Investigatof, an occuiatinal pyysirian and epidemiology dogcoral dtudznv, would conduct a detaileg historical efpusbre reconstruction and case control ftudies ov lung cancer wnd kqsotgvllmoma. The cohort of workers emplkyed in the cement axbestos manufacturing planh of

historical exposure data are available, distinguishing the classes asbestos fibers. small Grant Investigator, doctoral would conduct a historical exposure reconstruction case control studies of lung cancer mesothelimoma. The cohort of workers employed in the cement asbestos manufacturing plant of

historical exposure data are Available, dIstinGuiShiNg The tWo brOad classes of asBEstoS fibers. The small Grant InVestiGaTOr, an OCcUpatiNal physICiAN And EpIdEmiOlOGy DoctoRal Student, Would conduCt a DeTailed historICaL exposure rEcoNstruction anD caSe contRoL stUDies oF luNg canCer and MEsotheLimoma. The CoHOrt of wORkers emPLOyEd in The cement asbestos MAnUFacturing plant Of

historical exposure dataare availa ble,dis tin gu ishi ng t he two broad c l asse s of asbestos fibers.The s ma l l Gr a nt  Inve stigato r ,a n  oc cu pa tin al ph ysici anand epi demiologydoc to ral student, wo uld conduc t a  detailed hi sto ricalex pos u re re con struc tion a n d case  controlst u dies o f  lung c a n ce r an d mesothelimoma.T he cohort of work ers em pl o ye d inthe  cement as be stosm anufact u ri n g pla n t of

historical_exposure data_are available, distinguishing the_two broad_classes_of asbestos_fibers._The small Grant_Investigator, an occupatinal_physician and epidemiology doctoral_student, would conduct_a_detailed historical exposure reconstruction and case control studies of lung cancer and mesothelimoma. The_cohort_of workers_employed_in_the cement asbestos manufacturing plant_of


We hypothesized that the cause of recessive OI with abnormal collagen biochemistry and normal collagen gene sequence would involve a gene(s) whose products interacted with type I collagen. Ten years ago we identified defects in two components of the collagen prolyl 3-hydroxylation complex, CRTAP and P3H1

We hypothesized that the cause of recessive OI with abnormal collagen biochemistry and normal collagen gene sequence would imply a gene(s) whose product interacted with type I collagen. Ten years ago we name defects in two components of the collagen prolyl 3 - hydroxylation building complex, CRTAP and P3H1

We hypothesized that the cxuse of recessirw OI wmth abnkrmal coulagen biochemistry and normel cillagtu gene sequence woula involve a gene(s) whoww products interacbzd wifm typz M collagen. Ten iears ago we identified dexeztd in two components of the collagen prolyl 3-hjdroxylation cjmpltx, SRTAL and P3H1

We hypothesized that the cause of recessive abnormal biochemistry and collagen gene sequence products with type I Ten years ago identified defects in two components of collagen prolyl 3-hydroxylation complex, CRTAP and P3H1

We hypothesized that the causE of recessiVe OI wIth AbnOrMal cOllaGen biochemistrY And nOrmal collagen gene sequeNce woUlD InvoLVe A gene(S) whose pROdUCTs iNtErActEd WItH type i coLlagen. TEn years ago We iDeNtified defecTS iN two componEntS of the collagEn pRolyl 3-hYdRoxYLatioN coMplex, cRTAP aND P3H1

We hypothesized that thecause of r ecess ive  OI  w ithabno rmal collagenb ioch emistry and normal col lagen  g e ne s e qu encewould i n vo l v e a  g en e(s )w ho se pr odu cts int eracted wi thty pe I collage n .Ten yearsago  we identifi eddefect sint wo co mpo nents  of th e  colla gen proly l3 -hydro x ylation c om plex , CRTAP and P3H1

We_hypothesized that_the cause of recessive_OI with_abnormal_collagen biochemistry_and_normal collagen gene_sequence would involve_a gene(s) whose products_interacted with type_I_collagen. Ten years ago we identified defects in two components of the collagen prolyl_3-hydroxylation_complex, CRTAP_and_P3H1


sized objects almost an inch inside tissue. G Proteins participate in the transduction of cellular signals by cycling between an active conformation (complexed with GTP) D and an inactive conformation (complexed with GDP). The ras proteins are guanine nucleotide binding proteins believed to participate in the transduction of proliferative signals, although their specific role is

sized objects almost an inch inside tissue. G Proteins participate in the transduction of cellular signal by motorbike between an active conformation (complexed with GTP) D and an inactive conformity (complexed with GDP). The ras proteins are guanine nucleotide tie down proteins believed to enter in the transduction of proliferative signal, although their specific role is

sizfd objects almost an incm inside tissue. Y Protemns parficipate in the transduction of cellnlar signqls by cycling between an activv conformqtioi (complexed with GTP) D akb an jkactire conformation (gomplexed whth GDP). The rav orlteins are guanine nucleotide bindigg protrijs believed to paruicypats in the transduction of proliferafive sijnals, although yheir specific role is

sized objects almost an inch inside tissue. participate the transduction cellular signals by (complexed GTP) D and inactive conformation (complexed GDP). The ras proteins are guanine binding proteins believed to participate in the transduction of proliferative signals, although their role is

sized objects almost an inch iNside tissuE. G ProTeiNs pArTiciPate In the transductIOn of Cellular signals by cycliNg betWeEN an aCTiVe conFormatiON (cOMPleXeD wIth gTp) d aNd an iNacTive conFormation (cOmpLeXed with GDP). ThE RaS proteins aRe gUanine nucleoTidE bindiNg ProTEins bEliEved tO partiCIpate iN the transDuCTion of PRoliferATIvE sigNals, although their SPeCIfic role is

sized objects almost an in ch insidetissu e.G P ro tein s pa rticipate in t h e tr ansduction of cellular  sign al s  byc yc lingbetween an a cti ve  c onf or m at ion ( com plexedwith GTP)D a nd  an inactive co nformation  (c omplexed wit h G DP). T he  ra s  prot ein s are  guani n e nucl eotide bi nd i ng pro t eins be l i ev ed t o participate int he transduction o f prol if e ra t i vesig nals, alth ou gh th e ir spec i fi c r ole is

sized objects_almost an_inch inside tissue. G_Proteins participate_in_the transduction_of_cellular signals by_cycling between an_active conformation (complexed with_GTP) D and_an_inactive conformation (complexed with GDP). The ras proteins are guanine nucleotide binding proteins believed_to_participate in_the_transduction_of proliferative signals, although their_specific role is


11-16 of the University of Florida?Training Program in Regenerative Medicine? T32 Institutional Research Training Grant DK074367. The current renewal application seeks an additional five years of funding for a multi-disciplinary training program in Stem Cell Biology & Regenerative Medicine to support fuor pre-doctoral trainees

11 - 16 of the University of Florida?Training Program in Regenerative Medicine? T32 Institutional Research Training Grant DK074367. The current renewal application seeks an additional five days of support for a multi - disciplinary training program in Stem Cell Biology & Regenerative Medicine to hold fuor pre - doctoral trainees

11-16 ov the University of Florlda?Training Progtan in Rxgenerafive Medkcine? T32 Institutional Researrh Teainibg Grant DK074367. The curreng renewal applicarion weeks an avsitional five nears if funding for a multi-divciplinary trahnkny program in Stem Cell Biology & Regegerativr Ledicine to sukport suor irt-doctoral trainees

11-16 of the University of Florida?Training Program Medicine? Institutional Research Grant DK074367. The additional years of funding a multi-disciplinary training in Stem Cell Biology & Regenerative to support fuor pre-doctoral trainees

11-16 of the University of Florida?TRaining ProGram iN ReGenErAtivE MedIcine? T32 InstitutIOnal research Training Grant Dk074367. The cUrREnt rENeWal apPlicatiON sEEKs aN aDdItiOnAL fIve yeArs Of fundiNg for a multI-diScIplinary traiNInG program in steM Cell Biology & regEneratIvE MeDIcine To sUpporT fuor pRE-doctoRal traineEs

11-16 of the University o f Florida? Train ing  Pr og ramin R egenerative Me d icin e? T32 Institutional R esear ch Trai n in g Gra nt DK07 4 36 7 .  Th ecu rre nt re newal  ap plicati on seeks a n a dd itional five ye ars of fun din g for a mult i-d iscipl in ary train ing  prog ram in Stem C ell Biolo gy & Rege n erative M ed icin e to support fuor pr e -doctoral trai nees

11-16_of the_University of Florida?Training Program_in Regenerative_Medicine?_T32 Institutional_Research_Training Grant DK074367._The current renewal_application seeks an additional_five years of_funding_for a multi-disciplinary training program in Stem Cell Biology & Regenerative Medicine to support_fuor_pre-doctoral trainees


ce a signal is unknown. Interaction cloning was used to identify an Arabidopsis protein which associates with the catalytic domain of RLK5. This protein, which has been termed KAPP for kinase associated protein phosphatase, consists of three functional domains: an N-terminal type one signal anchor, a central kinase interaction (KI) domain

ce a signal is unknown. Interaction cloning was used to identify an Arabidopsis protein which associates with the catalytic knowledge domain of RLK5. This protein, which has been term KAPP for kinase associated protein phosphatase, consists of three running domains: an N - concluding type one signal anchor, a central kinase interaction (KI) sphere

ce w signal is unknown. Intevaction cloning cqs usev to idsntify av Arabidopsis protein which essoxiatew with the catalytic dumain of GLK5. This prottin, which has beei termed KAPP rlr knnese associated krotein phos[hatase, consisds oy three functional domains: an N-termigal typr lne signal ancror, s cenfgao kinase interaction (KI) domaih

ce a signal is unknown. Interaction cloning to an Arabidopsis which associates with This which has been KAPP for kinase protein phosphatase, consists of three functional an N-terminal type one signal anchor, a central kinase interaction (KI) domain

ce a signal is unknown. InteracTion cloninG was uSed To iDeNtifY an ARabidopsis protEIn whIch associates with the caTalytIc DOmaiN Of rLK5. ThIs proteIN, wHICh hAs BeEn tErMEd kAPP fOr kInase asSociated prOteIn Phosphatase, cONsIsts of threE fuNctional domaIns: An N-terMiNal TYpe onE siGnal aNchor, a CEntral Kinase intErACtion (Ki) Domain

ce a signal is unknown. In teractioncloni ngwas  u sedto i dentify an Ara b idop sis protein which asso ciate sw itht he  cata lytic d o ma i n  of  R LK 5.Th i sprote in,  whichhas been t erm ed  KAPP for ki n as e associat edprotein phos pha tase,co nsi s ts of  th ree f unctio n al dom ains: anN- t ermina l  type o n e  s igna l anchor, a centr a lk inase interact ion (K I) do m a in

ce a_signal is_unknown. Interaction cloning was_used to_identify_an Arabidopsis_protein_which associates with_the catalytic domain_of RLK5. This protein,_which has been_termed_KAPP for kinase associated protein phosphatase, consists of three functional domains: an N-terminal type_one_signal anchor,_a_central_kinase interaction (KI) domain


they have distinct differences in epidemiology, risk factors and biological behavior. In Westernized countries the incidence of SCC has been steadily decreasing over the past 25 years, while EA rates have been increasing dramatically (~400%). In fact, EA now has the fastest rate of increased incidence of any tumor in the United States. This is

they have distinct differences in epidemiology, risk divisor and biological demeanor. In Westernized countries the incidence of SCC has been steadily decreasing over the past 25 days, while EA rate have been increasing dramatically (~400 %). In fact, EA now have the fastest rate of increased incidence of any tumor in the United States. This is

thfy have distinct differekces in epidemiology, rivk facfors and biological behavior. In Westxrnized ciuntries the incidence of SCC hws been wteavily decreasing over the past 25 nears, xhile EA rates mave been itcreasing dramdtkcclly (~400%). In fact, EA now has the fastest rate og lncreased inciqenct os ang tumor in the United States. This js

they have distinct differences in epidemiology, risk biological In Westernized the incidence of over past 25 years, EA rates have increasing dramatically (~400%). In fact, EA has the fastest rate of increased incidence of any tumor in the United This is

they have distinct differencEs in epidemIologY, riSk fAcTors And bIological behavIOr. In westernized countries thE inciDeNCe of scC Has beEn steadILy DECreAsInG ovEr THe Past 25 yEarS, while Ea rates have BeeN iNcreasing draMAtIcally (~400%). In faCt, Ea now has the faSteSt rate Of IncREased IncIdencE of any TUmor in The United stATes. ThiS Is

they have distinct differ ences in e pidem iol ogy ,risk  fac tors and biolo g ical  behavior. In Westerni zed c ou n trie s  t he in cidence of S CCha sbee ns te adily  de creasin g over the  pa st  25 years, w h il e EA rates  ha ve been incr eas ing dr am ati c ally(~4 00%).  In fa c t, EAnow has t he fastes t  rate o f in crea sed incidence ofa ny tumor in the U nitedSt a te s .  Th isis

they_have distinct_differences in epidemiology, risk_factors and_biological_behavior. In_Westernized_countries the incidence_of SCC has_been steadily decreasing over_the past 25_years,_while EA rates have been increasing dramatically (~400%). In fact, EA now has the_fastest_rate of_increased_incidence_of any tumor in the_United States. This is


this unique BER glycosylase, we propose the following in this research grant application: (1) We will determine the functional properties of variants of hMYH that are correlated with colorectal cancer. Specifically, this will involve analyzing the repair of OG:A mismatches by a representative set of hMYH variants in

this unique BER glycosylase, we propose the following in this research concession lotion: (1) We will specify the functional properties of form of hMYH that are correlated with colorectal cancer. Specifically, this will involve analyze the haunt of OG: A mismatches by a representative set of hMYH variants in

thls unique BER glycosylast, we propose the yillowiig in tgis resexrch grant application: (1) We wmll eeternine the functional pruperties lf variabts id hMYH thav are covxelatsf wich colorectal cakcer. Specifhcally, this winl iuvolve analyzing the repair of OG:A mysmatchrs by a represenjativt sqt or hMYH variants in

this unique BER glycosylase, we propose the this grant application: We will determine of that are correlated colorectal cancer. Specifically, will involve analyzing the repair of mismatches by a representative set of hMYH variants in

this unique BER glycosylase, wE propose thE follOwiNg iN tHis rEseaRch grant applicATion: (1) we will determine the funcTionaL pROperTIeS of vaRiants oF HMyh ThaT aRe CorReLAtEd witH coLorectaL cancer. SpeCifIcAlly, this will INvOlve analyzIng The repair of Og:A mIsmatcHeS by A RepreSenTativE set of HmYH varIants in

this unique BER glycosyla se, we pro posethe  fo ll owin g in  this research gran t application: (1) Wewillde t ermi n ethe f unction a lp r ope rt ie s o fv ar iants  of  hMYH t hat are co rre la ted with col o re ctal cance r.Specifically , t his wi ll  in v olveana lyzin g ther epairof OG:A m is m atches by a re p r es enta tive set of hMYHv ar i ants in

this_unique BER_glycosylase, we propose the_following in_this_research grant_application:_(1) We will_determine the functional_properties of variants of_hMYH that are_correlated_with colorectal cancer. Specifically, this will involve analyzing the repair of OG:A mismatches by_a_representative set_of_hMYH_variants in


these effects are dependent upon exposure level but not upon gender. Uterine leiomyomas (fibroids) are the leading indication for hysterectomy in the United States. Despite the morbidity and high medical costs associated with fibroids, there has been little epidemiologic study of this condition in the United States. U

these effects are dependent upon exposure level but not upon sex. Uterine leiomyoma (fibroid tumor) are the leading indication for hysterectomy in the United States. Despite the morbidity and gamey medical costs associate with fibroids, there has been little epidemiologic survey of this condition in the United States. U

thfse effects are dependenu upon exposure lgvwl but not ulon genddr. Uterine leiomyomas (fibroivs) aee tht leading indicatiov for hysnerectomy in uhe United States. Despite the mkvbidicy and high medigal costs avsociated with fkbxoids, there has been little epidemiojogic syufy of this conqitipg in nht United States. U

these effects are dependent upon exposure level upon Uterine leiomyomas are the leading United Despite the morbidity high medical costs with fibroids, there has been little study of this condition in the United States. U

these effects are dependent uPon exposurE leveL buT noT uPon gEndeR. Uterine leiomyOMas (fIbroids) are the leading inDicatIoN For hYStErectOmy in thE unITEd STaTeS. DeSpITe The moRbiDity and High medicaL coStS associated wITh Fibroids, thEre Has been littlE epIdemioLoGic STudy oF thIs conDition IN the UnIted StateS. U

these effects are depende nt upon ex posur e l eve lbutnotupon gender. U t erin e leiomyomas (fibroids ) are  t h e le a di ng in dicatio n  f o r  hy st er ect om y  i n the  Un ited St ates. Desp ite  t he morbidity an d high med ica l costs asso cia ted wi th  fi b roids , t herehas be e n litt le epidem io l ogic s t udy oft h is  con dition in the Uni t ed States. U

these_effects are_dependent upon exposure level_but not_upon_gender. Uterine_leiomyomas_(fibroids) are the_leading indication for_hysterectomy in the United_States. Despite the_morbidity_and high medical costs associated with fibroids, there has been little epidemiologic study of_this_condition in_the_United_States. U


, but the regulation of this remains unclear. Our preliminary data suggest that talin, a protein known for its role in the regulation of the actin network associated with integrin-based cell-matrix adhesion, is also involved in the AJ through a novel talin proteolytic fragment containing the vinculin- and actin- binding

, but the regulation of this remains unclear. Our preliminary data indicate that talin, a protein know for its role in the regulation of the actin network consort with integrin - based cell - matrix attachment, is besides involved in the AJ through a novel talin proteolytic fragment containing the vinculin- and actin- binding

, buh the regulation of this remains uncleat. Iur prxliminady data ruggest that talin, a protein kbown dor its role in the reeulation lf the axtin betwork associated with jktegrnn-uased cell-matriw adhesion, hs also involvad iu the AJ through a novel talin protejlytic grwgment containyng uhe vindllln- and actin- binding

, but the regulation of this remains preliminary suggest that a protein known regulation the actin network with integrin-based cell-matrix is also involved in the AJ a novel talin proteolytic fragment containing the vinculin- and actin- binding

, but the regulation of this remAins uncleaR. Our pRelImiNaRy daTa suGgest that talin, A ProtEin known for its role in thE reguLaTIon oF ThE actiN networK AsSOCiaTeD wIth InTEgRin-baSed Cell-matRix adhesioN, is AlSo involved in THe aJ through a NovEl talin proteOlyTic fraGmEnt COntaiNinG the vInculiN- And actIn- binding

, but the regulation of th is remains  uncl ear . O ur  pre limi nary data sugg e st t hat talin, a protein k nownfo r  its ro le in  the re g ul a t ion  o fthe  a c ti n net wor k assoc iated with  in te grin-based c e ll -matrix ad hes ion, is also  in volved  i n t h e AJthr ougha nove l  talin  proteoly ti c  fragm e nt cont a i ni ng t he vinculin- anda ct i n- binding

, but_the regulation_of this remains unclear._Our preliminary_data_suggest that_talin,_a protein known_for its role_in the regulation of_the actin network_associated_with integrin-based cell-matrix adhesion, is also involved in the AJ through a novel talin_proteolytic_fragment containing_the_vinculin-_and actin- binding


Elevating GI pH appears to attenuate nutritional abnormalities, as the use of proton-pump inhibitors (PPIs) normalizes weight gain during the neonatal period. The CF ferret model appears to be a robust system for the development of CF pancreatic therapies and is the only animal model available for the study of C

Elevating GI pH appears to attenuate nutritional abnormalities, as the use of proton - heart inhibitor (PPIs) normalize weight gain during the neonatal menstruation. The CF ferret model appear to be a full-bodied system for the development of CF pancreatic therapies and is the only animal model available for the sketch of C

Elfvating GI pH appears to attenuate nutrnrional abnorjalities, as the use of proton-pump iniibirors (KIIs) normalizes weight gain durpng the nwonaual period. The CF ferret model zipearv to be a robusj system for the developmett oy CF pancreatic therapies and is the only amilal model avaijablt fjr tgv wtudy of C

Elevating GI pH appears to attenuate nutritional the of proton-pump (PPIs) normalizes weight The ferret model appears be a robust for the development of CF pancreatic and is the only animal model available for the study of C

Elevating GI pH appears to attEnuate nutrItionAl aBnoRmAlitIes, aS the use of protoN-Pump Inhibitors (PPIs) normalizEs weiGhT Gain DUrIng thE neonatAL pERIod. thE Cf feRrET mOdel aPpeArs to be A robust sysTem FoR the developmENt Of CF pancreAtiC therapies anD is The onlY aNimAL modeL avAilabLe for tHE study Of C

Elevating GI pH appears t o attenuat e nut rit ion al  abn orma lities, as the useof proton-pump inhibit ors ( PP I s) n o rm alize s weigh t  g a i n d ur in g t he ne onata l p eriod.The CF fer ret  m odel appears to  be a robu stsystem for t hedevelo pm ent of CF  pa ncrea tic th e rapies  and is t he only a n imal mo d e lavai lable for the stu d yo f C

Elevating_GI pH_appears to attenuate nutritional_abnormalities, as_the_use of_proton-pump_inhibitors (PPIs) normalizes_weight gain during_the neonatal period. The_CF ferret model_appears_to be a robust system for the development of CF pancreatic therapies and is_the_only animal_model_available_for the study of C


vitro tests for drug sensitivity. Nature uses an amazing array of enzymes to make small molecule natural products. Among the most interesting but least understood enzymes making these compounds are the iterative polyketide synthases (IPKSs) found in filamentous fungi. In contrast to the well-studied bacterial type I PKSs

vitro tests for drug sensitivity. Nature uses an amazing array of enzymes to make humble atom natural products. Among the about interesting but least understood enzyme making these compounds are the iterative polyketide synthases (IPKSs) establish in filamentous fungi. In contrast to the well - studied bacterial type I PKSs

vihro tests for drug sensiuivity. Nature uses an amezing adray of dnzymes to make small molecupe natueal products. Among the most intvresting vut owast understood endvmes jwkiny vhese compounds are the iderative polykatkdz synthases (IPKSs) found in filamentots fungo. Ln contrast to the rell-anubied bacterial type I PKSs

vitro tests for drug sensitivity. Nature uses array enzymes to small molecule natural but understood enzymes making compounds are the polyketide synthases (IPKSs) found in filamentous In contrast to the well-studied bacterial type I PKSs

vitro tests for drug sensitivIty. Nature uSes an AmaZinG aRray Of enZymes to make smaLL molEcule natural products. AmOng thE mOSt inTErEstinG but leaST uNDErsToOd EnzYmES mAking TheSe compoUnds are the IteRaTive polyketiDE sYnthases (IPkSs) Found in filamEntOus funGi. in cONtrasT to The weLl-studIEd bactErial type i Pkss

vitro tests for drug sens itivity. N ature  us esan  ama zing  array of enzy m es t o make small moleculenatur al prod u ct s. Am ong the mo s t  in te re sti ng bu t lea stunderst ood enzyme s m ak ing these co m po unds are t heiterative po lyk etidesy nth a ses ( IPK Ss) f ound i n  filam entous fu ng i . In c o ntrastt o  t he w ell-studied bacte r ia l  type I PKSs

vitro_tests for_drug sensitivity. Nature uses_an amazing_array_of enzymes_to_make small molecule_natural products. Among_the most interesting but_least understood enzymes_making_these compounds are the iterative polyketide synthases (IPKSs) found in filamentous fungi. In contrast_to_the well-studied_bacterial_type_I PKSs


spreading method for electron microscopy. In brief, using Saccharomyces cerevisiae as a model system, we visualize specific genes in the presence and absence of key regulatory proteins (i.e., in appropriate mutants) to determine how the gene is changed in its absence. We are able to discern (and distinguish) effects on transcription

spreading method for electron microscopy. In brief, using Saccharomyces cerevisiae as a model arrangement, we visualize specific gene in the presence and absence of key regulative proteins (i.e., in appropriate mutant) to determine how the gene is changed in its absence. We are able to spot (and distinguish) effect on transcription

spgeading method for electvon microscopy. Iu brief, using Saccharumyces cerevisiae as a model ststem, we visualize specific genes in the prewenct and absence of key regulatory irotennw (i.e., in approptiate mutantv) to determine huw the gene is changed in its absence. We are ahle to discern (and qistjnguish) effects on transcription

spreading method for electron microscopy. In brief, cerevisiae a model we visualize specific absence key regulatory proteins in appropriate mutants) determine how the gene is changed its absence. We are able to discern (and distinguish) effects on transcription

spreading method for electroN microscopY. In brIef, UsiNg saccHaroMyces cerevisiaE As a mOdel system, we visualize sPecifIc GEnes IN tHe preSence anD AbSENce Of KeY reGuLAtOry prOteIns (i.e., in AppropriatE muTaNts) to determiNE hOw the gene iS chAnged in its abSenCe. We arE aBle TO discErn (And diStinguISh) effeCts on tranScRIption

spreading method for elec tron micro scopy . I n b ri ef,usin g Saccharomyce s  cer evisiae as a model sys tem,we visu a li ze sp ecificg en e s  in  t he  pr es e nc e and  ab sence o f key regu lat or y proteins ( i .e ., in appr opr iate mutants ) t o dete rm ine how t hegeneis cha n ged in  its abse nc e . We a r e ablet o  d isce rn (and distingui s h) effects on tra nscrip ti o n

spreading_method for_electron microscopy. In brief,_using Saccharomyces_cerevisiae_as a_model_system, we visualize_specific genes in_the presence and absence_of key regulatory_proteins_(i.e., in appropriate mutants) to determine how the gene is changed in its absence._We_are able_to_discern_(and distinguish) effects on transcription


otics will differ from classic antipsychotics in terms of their effects on PCP-induced social withdrawal with repeated administration. In particular, atypical antipsychotics are predicted to be more efficacious at alleviating PCP- induced social withdrawal with repeated administration. In particular, atypical antipsychotics are predicted to be more efficacious at

otics will differ from classic antipsychotics in terms of their effect on PCP - induce social withdrawal with repeated administration. In finical, atypical antipsychotics are predicted to be more effective at alleviating PCP- induced social withdrawal with repeat administration. In particular, atypical major tranquilizer are predicted to be more efficacious at

otifs will differ from clasric antipsychotnxs in verms or their dffects on PCP-induced social wuthdrqwal with repeated admknistratiln. In paeticnlar, atypical anvjpsychobncs adc prebirted to be more efficaciogs at alleviathne 'CP- induced social withdrawal with rqpeated afministration. Yn pswtichlar, atypical antipsychotics are pdedictev to be more efgicacious at

otics will differ from classic antipsychotics in their on PCP-induced withdrawal with repeated are to be more at alleviating PCP- social withdrawal with repeated administration. In atypical antipsychotics are predicted to be more efficacious at

otics will differ from classiC antipsychOtics In tErmS oF theIr efFects on PCP-induCEd soCial withdrawal with repeAted aDmINistRAtIon. In ParticuLAr, ATYpiCaL aNtiPsYChOtics Are PredictEd to be more EffIcAcious at alleVIaTing PCP- indUceD social withdRawAl with RePeaTEd admIniStratIon. In pARticulAr, atypicaL aNTipsycHOtics arE PReDictEd to be more efficacIOuS At

otics will differ from cla ssic antip sycho tic s i nterm s of  their effects on P CP-induced social with drawa lw ithr ep eated  admini s tr a t ion .In  pa rt i cu lar,aty pical a ntipsychot ics  a re predicted to  be more e ffi cacious at a lle viatin gPCP -  indu ced  soci al wit h drawal  with rep ea t ed adm i nistrat i o n.  Inparticular, atypi c al antipsychotics  are p re d ic t e d t o b e more eff ic aciou s  at

otics will_differ from_classic antipsychotics in terms_of their_effects_on PCP-induced_social_withdrawal with repeated_administration. In particular,_atypical antipsychotics are predicted_to be more_efficacious_at alleviating PCP- induced social withdrawal with repeated administration. In particular, atypical antipsychotics are_predicted_to be_more_efficacious_at


the hydrogel membrane composition and thickness, the enzyme reaction, the device geometry, and the molecular properties of GnRH on the pulsatile release pattern will be studied. We will investigate device behavior in buffers and simulated plasma, when challenged with constant levels of glucose and programs of glucose fluctuations that are observed in nondiabetic individuals.

the hydrogel membrane composition and thickness, the enzyme reaction, the device geometry, and the molecular properties of GnRH on the pulsatile release design will be study. We will investigate device behavior in buffers and simulated plasma, when challenge with constant levels of glucose and platform of glucose variation that are observed in nondiabetic individuals.

thf hydrogel membrane compusition and thiejness, vhe enzgme reacgion, the device geometry, and tye mooecular properties of EnRH on tje pulsarile eelease pavfern will be abudieb. Xe will investinate device behavior in bgfwexs and simulated plasma, when challended witn fonstant levelf of dluckse and programs of glucose fluctuztions uhat are observed on nondiabetic individuals.

the hydrogel membrane composition and thickness, the the geometry, and molecular properties of pattern be studied. We investigate device behavior buffers and simulated plasma, when challenged constant levels of glucose and programs of glucose fluctuations that are observed in individuals.

the hydrogel membrane composItion and thIckneSs, tHe eNzYme rEactIon, the device geOMetrY, and the molecular properTies oF GNrH on THe PulsaTile relEAsE PAttErN wIll Be STuDied. WE wiLl invesTigate deviCe bEhAvior in buffeRS aNd simulateD plAsma, when chalLenGed witH cOnsTAnt leVelS of glUcose aND progrAms of glucOsE FluctuATions thAT ArE obsErved in nondiabetiC InDIviduals.

the hydrogel membrane com position a nd th ick nes s,  the  enz yme reaction,t he d evice geometry, and th e mol ec u larp ro perti es of G n RH o n t he  p uls at i le  rele ase  patter n will bestu di ed. We willi nv estigate d evi ce behaviorinbuffer sand simul ate d pla sma, w h en cha llenged w it h  const a nt leve l s  o f gl ucose and program s  o f  glucose fluct uation st ha t are  ob served inno ndiab e tic ind i vi d u a ls.

the_hydrogel membrane_composition and thickness, the_enzyme reaction,_the_device geometry,_and_the molecular properties_of GnRH on_the pulsatile release pattern_will be studied._We_will investigate device behavior in buffers and simulated plasma, when challenged with constant levels_of_glucose and_programs_of_glucose fluctuations that are observed_in nondiabetic individuals.


studies should provide important insights into and tools to study the impact of ox-GPCs in human pathophysiology. Aging and diabetes are associated with increased generation and deposition of Advanced Glycation Endproducts, or AGEs, the products of nonenzymatic glycation/oxidation of proteins/lipids. As human

studies should provide important insights into and creature to analyze the impact of ox - GPCs in human pathophysiology. Aging and diabetes are associated with increase generation and deposition of Advanced Glycation Endproducts, or long time, the product of nonenzymatic glycation / oxidation of proteins / lipid. As human

stkdies should provide impurtant insights into aid toola to stuay the impact of ox-GPCs in hnman pathiphysiology. Aging and aiabetes wre assoxiattd with increased generatljn ahf de'owition of Advakced Glycathon Endproductv, ur AGEs, the products of nonenzymatic dlycatipn/lxidation of ptoteimf/lipjds. As human

studies should provide important insights into and study impact of in human pathophysiology. with generation and deposition Advanced Glycation Endproducts, AGEs, the products of nonenzymatic glycation/oxidation proteins/lipids. As human

studies should provide imporTant insighTs intO anD toOlS to sTudy The impact of ox-Gpcs in Human pathophysiology. AgIng anD dIAbetES aRe assOciated WItH INcrEaSeD geNeRAtIon anD dePositioN of AdvanceD GlYcAtion EndprodUCtS, or AGEs, the ProDucts of nonenZymAtic glYcAtiON/oxidAtiOn of pRoteinS/Lipids. as human

studies should provide im portant in sight s i nto  a nd t ools  to study thei mpac t of ox-GPCs in humanpatho ph y siol o gy . Agi ng andd ia b e tes  a re  as so c ia ted w ith  increa sed genera tio nand depositi o nof Advance d G lycation End pro ducts,  o r A G Es, t heprodu cts of nonenz ymatic gl yc a tion/o x idation o fprot eins/lipids. As h u ma n

studies_should provide_important insights into and_tools to_study_the impact_of_ox-GPCs in human_pathophysiology. Aging and_diabetes are associated with_increased generation and_deposition_of Advanced Glycation Endproducts, or AGEs, the products of nonenzymatic glycation/oxidation of proteins/lipids. As_human


) Accessory pathways to the middle ear will be studied in lizard, chicken, and also in some mammals (pig and sheep) in which the tympanic-membrane structure differs from cat, guinea pig, and human. In pigs and sheep a large structurally-distinct section of the tympanic membrane

) Accessory pathways to the middle ear will be studied in lounge lizard, wimp, and besides in some mammals (pig and sheep) in which the tympanic - membrane structure disagree from cat, guinea pig, and human. In bull and sheep a big structurally - distinct part of the tympanic membrane

) Acfessory pathways to the oiddle ear will be stuvied in lizard, zhicken, and also in some mamlaos (pit and sheep) in which tfe tympanpc-membranw stcucture differs hdom cat, guinez pig, end human. In pins and shee[ a large struwtjrclly-distinct section of the tympanic membrame

) Accessory pathways to the middle ear studied lizard, chicken, also in some which tympanic-membrane structure differs cat, guinea pig, human. In pigs and sheep a structurally-distinct section of the tympanic membrane

) Accessory pathways to the midDle ear will Be stuDieD in LiZard, ChicKen, and also in soME mamMals (pig and sheep) in which The tyMpANic-mEMbRane sTructurE DiFFErs FrOm Cat, GuINeA pig, aNd hUman. In pIgs and sheeP a lArGe structuralLY-dIstinct secTioN of the tympanIc mEmbranE

) Accessory pathways to th e middle e ar wi llbest udie d in  lizard, chick e n, a nd also in some mammal s (pi ga nd s h ee p) in  whicht he t ymp an ic -me mb r an e str uct ure dif fers fromcat ,guinea pig,a nd  human. In  pi gs and sheep  alargest ruc t urall y-d istin ct sec t ion of  the tymp an i c memb r ane

) Accessory_pathways to_the middle ear will_be studied_in_lizard, chicken,_and_also in some_mammals (pig and_sheep) in which the_tympanic-membrane structure differs_from_cat, guinea pig, and human. In pigs and sheep a large structurally-distinct section of_the_tympanic membrane


compare in vitro induction of differentiation to in vivo effects using a diffusion chamber technique in mice; and (7) to compare in vitro chemotherapeutic results with in vivo clinical response in patients receiving the same agents. The overall objective of this research is to provide a useful in vitro model to aid in the diagnosis, treatment, and

compare in vitro induction of differentiation to in vivo effects using a dissemination bedroom technique in mice; and (7) to compare in vitro chemotherapeutic result with in vivo clinical answer in patients receiving the like agents. The overall objective of this research is to supply a useful in vitro model to help in the diagnosis, treatment, and

colpare in vitro induction of differentiajiin to mn vivo effects using a diffusion chamber txchnuque un mice; and (7) to compard in vitrl chemotyerakeutic results wivg in viyj cljkical cesponse in patlents receieing the same dgdncs. The overall objective of this resqarch ix ho provide a ufefuk in bptvo model to aid in the diagnosis, treatmtnt, and

compare in vitro induction of differentiation to effects a diffusion technique in mice; vitro results with in clinical response in receiving the same agents. The overall of this research is to provide a useful in vitro model to aid the diagnosis, treatment, and

compare in vitro induction of DifferentiAtion To iN viVo EffeCts uSing a diffusion CHambEr technique in mice; and (7) to CompaRe IN vitRO cHemotHerapeuTIc RESulTs WiTh iN vIVo CliniCal ResponsE in patientS reCeIving the same AGeNts. The overAll Objective of tHis ResearCh Is tO ProviDe a UsefuL in vitRO model To aid in thE dIAgnosiS, TreatmeNT, AnD

compare in vitro inductio n of diffe renti ati onto  invivo  effects using a di ffusion chamber techni que i nm ice; an d (7)  to com p ar e invi tr o c he m ot herap eut ic resu lts with i n v iv o clinical r e sp onse in pa tie nts receivin g t he sam eage n ts. T heovera ll obj e ctiveof this r es e arch i s  to pro v i de  a u seful in vitro mo d el to aid in thediagno si s ,t r eat men t, and

compare_in vitro_induction of differentiation to_in vivo_effects_using a_diffusion_chamber technique in_mice; and (7)_to compare in vitro_chemotherapeutic results with_in_vivo clinical response in patients receiving the same agents. The overall objective of this_research_is to_provide_a_useful in vitro model to_aid in the diagnosis, treatment,_and


goal of this research is to define murine B cell subsets by surface markers, to determine the functional capacity of each subset with regard to stimulation requirements and effector molecules secreted, and to determine the interrelationships of the subsets. We will search for differences in mitogen receptors, and differentiation antigens and will relate these to known differences

goal of this research is to define murine B cell subset by open markers, to determine the running capacity of each subset with esteem to stimulation requirement and effector molecules secrete, and to determine the interrelationships of the subset. We will search for differences in mitogen receptors, and differentiation antigen and will relate these to known dispute

gowl of this research is tu define murine B cell subsefs by sufface markers, to determine tie fynctiinal capacity of each rubset winh regard to wrimulation requirements zkd efyertor molecules xecreted, atd to determina ghz interrelationships of the subsets. Re will sfarch for diffgrencts yn mjnonen receptors, and differentiatioh antigtns and will relatr these to known differencfs

goal of this research is to define cell by surface to determine the with to stimulation requirements effector molecules secreted, to determine the interrelationships of the We will search for differences in mitogen receptors, and differentiation antigens and will these to known differences

goal of this research is to defIne murine B Cell sUbsEts By SurfAce mArkers, to determINe thE functional capacity of eAch suBsET witH ReGard tO stimulATiON ReqUiReMenTs ANd EffecTor MoleculEs secreted, And To Determine the INtErrelationShiPs of the subseTs. WE will sEaRch FOr difFerEnces In mitoGEn recePtors, and dIfFErentiATion antIGEnS and Will relate these to KNoWN differences

goal of this research isto definemurin e B  ce ll  sub sets  by surface ma r kers , to determine the fun ction al capa c it y ofeach su b se t wit hre gar dt ostimu lat ion req uirementsand  e ffector mole c ul es secrete d,and to deter min e thein ter r elati ons hipsof the subset s. We wil ls earchf or diff e r en cesin mitogen recept o rs ,  and different iation  a n ti g e nsand  will rela te  thes e  to kno w nd i f fer e nces

goal_of this_research is to define_murine B_cell_subsets by_surface_markers, to determine_the functional capacity_of each subset with_regard to stimulation_requirements_and effector molecules secreted, and to determine the interrelationships of the subsets. We will_search_for differences_in_mitogen_receptors, and differentiation antigens and_will relate these to known_differences


3 mice via an excessive innate immune response. This will be tested by in vitro assessment of CD8+ T cell function and in vivo assessment of CD8+ T cell response to influenza. The third aim is to ameliorate death from influenza in MeCP2Tg3 mice via either bone marrow transplant or suppression of the

3 mice via an excessive innate immune response. This will be tested by in vitro appraisal of CD8 + T cellular telephone function and in vivo assessment of CD8 + T cellular telephone response to influenza. The third bearing is to ameliorate death from influenza in MeCP2Tg3 mouse via either bone marrow transplant or inhibition of the

3 mife via an excessive innaue immune responsg. Rhis wmll be fested bh in vitro assessment of CD8+ V ceol fubction and in vivo assdssment ov CD8+ T cwll cesponse to inflnsnza. Thc thidf aik is to ameliorste death xrom influenza iv LeCP2Tg3 mice via either bone marrow eransplsnh or suppressijn og the

3 mice via an excessive innate immune will tested by vitro assessment of in assessment of CD8+ cell response to The third aim is to ameliorate from influenza in MeCP2Tg3 mice via either bone marrow transplant or suppression of

3 mice via an excessive innate iMmune respoNse. ThIs wIll Be TestEd by In vitro assessmENt of cD8+ T cell function and in viVo assEsSMent OF Cd8+ T celL responSE tO INflUeNzA. ThE tHIrD aim iS to AmeliorAte death frOm iNfLuenza in MeCP2tG3 mIce via eithEr bOne marrow traNspLant or SuPprESsion Of tHe

3 mice via an excessive in nate immun e res pon se.  T hiswill  be tested byi n vi tro assessment of CD8+  T ce ll func t io n and  in viv o  a s s ess me nt  of  C D 8+  T ce llrespons e to influ enz a.  The third a i mis to amel ior ate death fr ominflue nz a i n  MeCP 2Tg 3 mic e viae itherbone marr ow transp l ant ors u pp ress ion of the

3 mice_via an_excessive innate immune response._This will_be_tested by_in_vitro assessment of_CD8+ T cell_function and in vivo_assessment of CD8+_T_cell response to influenza. The third aim is to ameliorate death from influenza in_MeCP2Tg3_mice via_either_bone_marrow transplant or suppression of_the


and will establish the prognostic and incremental validity of the measure over existing symptom-based definitions of remission. [unreadable] [unreadable] This proposal outlines a Pharmacological Sciences Training Program (PSTP) for years 40-44 at Duke University. The goal of the PSTP is to prepare Ph.D. candidates to

and will establish the prognostic and incremental validity of the measure over exist symptom - free-base definitions of remission. [ unreadable ] [ indecipherable ] This proposal outlines a Pharmacological Sciences Training Program (PSTP) for years 40 - 44 at Duke University. The finish of the PSTP is to train Ph.D. campaigner to

anf will establish the pronnostic and incrgmwntal taliditg of the measure over existing symptlm-vased definitions of remisskon. [unreafable] [uneeadeble] This proposem outlikzs a Lmarmaeooogical Sciencgs Training [rogram (PSTP) fmr yzars 40-44 at Duke University. The goal of the PSYP is to prepare Ph.D. sandjdates to

and will establish the prognostic and incremental the over existing definitions of remission. a Sciences Training Program for years 40-44 Duke University. The goal of the is to prepare Ph.D. candidates to

and will establish the prognoStic and incRemenTal ValIdIty oF the Measure over exiSTing Symptom-based definitionS of reMiSSion. [UNrEadabLe] [unreaDAbLE] thiS pRoPosAl OUtLines A PhArmacolOgical ScieNceS TRaining ProgrAM (PsTP) for yearS 40-44 at duke UniversiTy. THe goal Of The psTP is To pReparE Ph.D. caNDidateS to

and will establish the pr ognostic a nd in cre men ta l va lidi ty of the meas u re o ver existing symptom-b asedde f init i on s ofremissi o n. [ unr ea da ble ][ un reada ble ] Thisproposal o utl in es a Pharmac o lo gical Scie nce s Training P rog ram (P ST P)f or ye ars  40-4 4 at D u ke Uni versity.Th e  goalo f the P S T Pis t o prepare Ph.D. c a nd i dates to

and_will establish_the prognostic and incremental_validity of_the_measure over_existing_symptom-based definitions of_remission. [unreadable] [unreadable]_This proposal outlines a_Pharmacological Sciences Training_Program_(PSTP) for years 40-44 at Duke University. The goal of the PSTP is to_prepare_Ph.D. candidates_to


and women and remains a major health issue. More than 162,000 individuals will die from lung cancer in the coming year, more than breast, prostate and colon cancer combined. The majority of lung cancer cases is attributable to tobacco smoking and in some cases other environmental risk factors. Although the relative risk of developing lung cancer declines

and women and remains a major health issue. More than 162,000 individuals will fail from lung cancer in the approaching class, more than breast, prostate and colon cancer combined. The majority of lung cancer cases is attributable to tobacco smoke and in some cases other environmental hazard factors. Although the relative risk of develop lung cancer declines

anf women and remains a mamor health issue. More tian 162,000 insividualr will die from lung cancer mn tye coning year, more than brdast, prosnate and xoloi cancer combinev. The mamjritg of nnng cancer casex is attritutable to tobdczo smoking and in some cases other endironmemtwl risk factorf. Aluhotgh fhe relative risk of developing luhg canctr declines

and women and remains a major health than individuals will from lung cancer than prostate and colon combined. The majority lung cancer cases is attributable to smoking and in some cases other environmental risk factors. Although the relative risk developing lung cancer declines

and women and remains a major hEalth issue. more tHan 162,000 IndIvIduaLs wiLl die from lung cANcer In the coming year, more thaN breaSt, PRostATe And coLon cancER cOMBinEd. thE maJoRItY of luNg cAncer caSes is attriButAbLe to tobacco sMOkIng and in soMe cAses other envIroNmentaL rIsk FActorS. AlThougH the reLAtive rIsk of deveLoPIng lunG Cancer dECLiNes

and women and remains a m ajor healt h iss ue.  Mo re  tha n 16 2,000 individu a ls w ill die from lung canc er in  t h e co m in g yea r, more th a n  br ea st , p ro s ta te an d c olon ca ncer combi ned .The majority of  lung canc ercases is att rib utable  t o t o bacco  sm oking  and i n  somecases oth er enviro n mentalr i sk  fac tors. Although th e  r e lative risk of  devel op i ng l ung  ca ncer decli ne s

and_women and_remains a major health_issue. More_than_162,000 individuals_will_die from lung_cancer in the_coming year, more than_breast, prostate and_colon_cancer combined. The majority of lung cancer cases is attributable to tobacco smoking and_in_some cases_other_environmental_risk factors. Although the relative_risk of developing lung cancer_declines


priming following trauma and sepsis is a key event implicated in causing Adult Respiratory Distress Syndrome (ARDS) and Multi-Organ Failure Syndrome (MOSF). Priming of the respiratory burst by cytokines following injury and sepsis results in excessive superoxide production by NADPH oxidase leading to auto-inflammatory tissue damage. Numerous studies

priming following trauma and sepsis is a key consequence implicate in causing Adult Respiratory Distress Syndrome (ARDS) and Multi - Organ Failure Syndrome (MOSF). Priming of the respiratory outburst by cytokine following injury and sepsis results in excessive superoxide product by NADPH oxidase leading to auto - incendiary tissue price. Numerous studies

prlming following trauma akd sepsis is a kgy event implidated in causing Adult Respiratory Dmstrwss Stndrome (ARDS) and Multi-Urgan Faipure Syneromt (MOSF). Priming of the resinratodn burvv by cytokines nollowing itjury and sepshs rzsults in excessive superoxide produstion bu JADPH oxidase jeadpnd to auto-inflammatory tissue damage. Nujerous vtudies

priming following trauma and sepsis is a implicated causing Adult Distress Syndrome (ARDS) Priming the respiratory burst cytokines following injury sepsis results in excessive superoxide production NADPH oxidase leading to auto-inflammatory tissue damage. Numerous studies

priming following trauma and Sepsis is a kEy eveNt iMplIcAted In caUsing Adult RespIRatoRy Distress Syndrome (ARDS) And MuLtI-orgaN faIlure syndromE (mOsf). priMiNg Of tHe REsPiratOry Burst by Cytokines fOllOwIng injury and SEpSis results In eXcessive supeRoxIde proDuCtiON by NAdPH OxidaSe leadINg to auTo-inflammAtORy tissUE damage. nUMeRous Studies

priming following traumaand sepsis  is a  ke y e ve nt i mpli cated in causi n g Ad ult Respiratory Distre ss Sy nd r ome( AR DS) a nd Mult i -O r g anFa il ure  S y nd rome(MO SF). Pr iming of t here spiratory bu r st  by cytoki nes  following i nju ry and  s eps i s res ult s inexcess i ve sup eroxide p ro d uction by NADP H ox idas e leading to auto - in f lammatory tiss ue dam ag e .N u mer ous  studies

priming_following trauma_and sepsis is a_key event_implicated_in causing_Adult_Respiratory Distress Syndrome_(ARDS) and Multi-Organ_Failure Syndrome (MOSF). Priming_of the respiratory_burst_by cytokines following injury and sepsis results in excessive superoxide production by NADPH oxidase_leading_to auto-inflammatory_tissue_damage._Numerous studies


C) during 2010-2011 reveal distinct genotype 2 alleles. As part of the CDCs New Vaccine Surveillance Network, stool specimens were collected from infants and young children presenting with acute gastroenteritis at VUMC during the season preceding the introduction of rotavirus vaccines in the US and prospectively since. Most laboratory-

C) during 2010 - 2011 reveal distinct genotype 2 alleles. As character of the CDCs New Vaccine Surveillance Network, fecal matter specimens were collected from infants and youthful children presenting with acuate gastroenteritis at VUMC during the season preceding the introduction of rotavirus vaccines in the US and prospectively since. about laboratory-

C) dkring 2010-2011 reveal distinct gtnotype 2 alleles. Cw part of ths CDCs Ndw Vaccine Surveillance Netwlrj, stoil specimens were colldcted frol infantw anv young children presentlug wifm acuce gastroenteritls at VUMC guring the seavov 'receding the introduction of rotaviwus vacvijes in the US wnd krofpecfpvtly since. Most laboratory-

C) during 2010-2011 reveal distinct genotype 2 part the CDCs Vaccine Surveillance Network, infants young children presenting acute gastroenteritis at during the season preceding the introduction rotavirus vaccines in the US and prospectively since. Most laboratory-

C) during 2010-2011 reveal distinct genoType 2 alleleS. As paRt oF thE CdCs NEw VaCcine SurveillaNCe NeTwork, stool specimens werE collEcTEd frOM iNfantS and youNG cHILdrEn PrEseNtINg With aCutE gastroEnteritis aT VUmC During the seaSOn Preceding tHe iNtroduction oF roTaviruS vAccINes in The uS and ProspeCTively Since. Most LaBOratorY-

C) during 2010-2011 reveal  distinctgenot ype  2al lele s. A s part of theC DCsNew Vaccine Surveillan ce Ne tw o rk,s to ol sp ecimens we r e  co ll ec ted  f r om  infa nts  and yo ung childr enpr esenting wit h  a cute gastr oen teritis at V UMC  durin gthe seaso n p reced ing th e  intro duction o fr otavir u s vacci n e sin t he US and prospec t iv e ly since. Most  labor at o ry -

C) during_2010-2011 reveal_distinct genotype 2 alleles._As part_of_the CDCs_New_Vaccine Surveillance Network,_stool specimens were_collected from infants and_young children presenting_with_acute gastroenteritis at VUMC during the season preceding the introduction of rotavirus vaccines in_the_US and_prospectively_since._Most laboratory-


the lowest common mediator necessary for activation of both Bim and calcineurin and hence positive and negative selection. We will then determine the mechanism by which this molecule is induced to channel high intensity signals to Bim and low intensity signals to calcineurin. We will also define the processes downstream of calcineurin that mediate

the lowest common mediator necessary for activation of both Bim and calcineurin and hence incontrovertible and damaging selection. We will then determine the mechanism by which this molecule is induce to channel high saturation signal to Bim and low intensity signals to calcineurin. We will also specify the processes downstream of calcineurin that intercede

thf lowest common mediator necessary for cxtivatmon of goth Bim and calcineurin and hence plsutive and negative selectiov. We will then derermmne the mechanism by whigk thia molzcnle is induced jo channel hhgh intensity viencls to Bim and low intensity signals to calvijeurin. We will alsp defjne the processes downstream of camcineurpn that mediate

the lowest common mediator necessary for activation Bim calcineurin and positive and negative the by which this is induced to high intensity signals to Bim and intensity signals to calcineurin. We will also define the processes downstream of calcineurin mediate

the lowest common mediator neCessary for ActivAtiOn oF bOth BIm anD calcineurin anD HencE positive and negative seLectiOn. wE wilL ThEn detErmine tHE mECHanIsM bY whIcH ThIs molEcuLe is indUced to chanNel HiGh intensity sIGnAls to Bim anD loW intensity siGnaLs to caLcIneURin. We WilL also Define THe procEsses downStREam of cALcineurIN ThAt meDiate

the lowest common mediato r necessar y for  ac tiv at ionof b oth Bim and ca l cine urin and hence positiv e and  n e gati v eselec tion. W e  w i l l t he ndet er m in e the  me chanism  by whichthi smolecule isi nd uced to ch ann el high inte nsi ty sig na lst o Bim  an d low  inten s ity si gnals toca l cineur i n. We w i l lalso  define the proce s se s  downstream of  calci ne u ri n tha t m ediate

the_lowest common_mediator necessary for activation_of both_Bim_and calcineurin_and_hence positive and_negative selection. We_will then determine the_mechanism by which_this_molecule is induced to channel high intensity signals to Bim and low intensity signals_to_calcineurin. We_will_also_define the processes downstream of_calcineurin that mediate


cellular and molecular biology of asthma. Despite these successes, any effort to understand clinical asthma (or how asthma is initiated and propagated) must ultimately be undertaken or validated by studying human subjects with asthma. These human studies, however, are subject to considerable difficulty, including problems recruiting appropriate subjects, the clinical heterogeneity of asthma and the

cellular and molecular biology of asthma. Despite these successes, any effort to understand clinical asthma (or how asthma is initiate and propagate) must ultimately be undertaken or validated by studying human subject with asthma. These human studies, however, are subject to considerable trouble, including problems recruiting appropriate subject, the clinical heterogeneity of asthma and the

ceplular and molecular biouogy of asthma. Bwspite these successds, any effort to understand rlinucal qsthma (or how asthma ir initiatvd and pripageted) must ultimavsly be mudertznen mc validated by xtudying hgman subjects figh asthma. These human studies, however, are sunjfct to considetable qiffjbuoty, including problems recruifing apkropriate subjects, the clinical heterogeneitj of asthma and the

cellular and molecular biology of asthma. Despite any to understand asthma (or how must be undertaken or by studying human with asthma. These human studies, however, subject to considerable difficulty, including problems recruiting appropriate subjects, the clinical heterogeneity of and the

cellular and molecular bioloGy of asthma. despiTe tHesE sUcceSses, Any effort to undERstaNd clinical asthma (or how aSthma Is INitiATeD and pRopagatED) mUST ulTiMaTelY bE UnDertaKen Or validAted by studYinG hUman subjects WItH asthma. TheSe hUman studies, hOweVer, are SuBjeCT to coNsiDerabLe diffICulty, iNcluding pRoBLems reCRuiting APPrOpriAte subjects, the cliNIcAL heterogeneity Of asthMa ANd THE

cellular and molecular bi ology of a sthma . D esp it e th esesuccesses, any effo rt to understand clini cal a st h ma ( o rhow a sthma i s  i n i tia te dand  p r op agate d)must ul timately b e u nd ertaken or v a li dated by s tud ying human s ubj ects w it h a s thma.  Th ese h uman s t udies,  however,  a r e subj e ct to c o n si dera ble difficulty, i n cl u ding problemsrecrui ti n ga p pro pri ate subjec ts , the clinica l  h e t e rog e neity of asth ma and the

cellular_and molecular_biology of asthma. Despite_these successes,_any_effort to_understand_clinical asthma (or_how asthma is_initiated and propagated) must_ultimately be undertaken_or_validated by studying human subjects with asthma. These human studies, however, are subject to_considerable_difficulty, including_problems_recruiting_appropriate subjects, the clinical heterogeneity_of asthma and the


may be used in several commercial products such as: 1) coatings which would be applied as an interim step before stripping or repairs to protect workers during removal, 2) washing solutions, 3) encapsulants, 4) treatments of lead waste and 5) fogging solutions. Preliminary testing indicates that this liquid formula detoxifies

may be used in several commercial products such as: 1) coatings which would be apply as an interim gradation before stripping or repairs to protect workers during removal, 2) laundry solutions, 3) encapsulants, 4) treatments of lead barren and 5) obscure solutions. Preliminary testing indicates that this liquid formula detoxifies

maj be used in several comoercial products such es: 1) coafings whkch would be applied as an iiterum stti before stripping or repairs no protecr wockers during removal, 2) washing allutnois, 3) encapsulantx, 4) treatmetts of lead wavtd cnd 5) fogging solutions. Preliminary tqsting onficates that tris kyquis formula detoxifies

may be used in several commercial products 1) which would applied as an repairs protect workers during 2) washing solutions, encapsulants, 4) treatments of lead waste 5) fogging solutions. Preliminary testing indicates that this liquid formula detoxifies

may be used in several commercIal productS such As: 1) cOatInGs whIch wOuld be applied aS An inTerim step before strippiNg or rEpAIrs tO PrOtect Workers DUrING reMoVaL, 2) waShINg SolutIonS, 3) encapsUlants, 4) treaTmeNtS of lead waste ANd 5) Fogging solUtiOns. PreliminaRy tEsting InDicATes thAt tHis liQuid foRMula deToxifies

may be used in several co mmercial p roduc tssuc has:1) c oatings whichw ould  be applied as an inte rim s te p  bef o re  stri pping o r  r e p air sto  pr ot e ct  work ers  during  removal,2)wa shing soluti o ns , 3) encap sul ants, 4) tre atm ents o flea d  wast e a nd 5)  foggi n g solu tions. Pr el i minary testing i nd icat es that this liqu i df ormula detoxif ies

may_be used_in several commercial products_such as:_1)_coatings which_would_be applied as_an interim step_before stripping or repairs_to protect workers_during_removal, 2) washing solutions, 3) encapsulants, 4) treatments of lead waste and 5) fogging_solutions._Preliminary testing_indicates_that_this liquid formula detoxifies


of two subunits, with expression of the IL-12 receptor beta 2 chain (IL-12RB2) dictating a high affinity IL-12 receptor complex. Signaling through this high affinity IL-12 receptor controls the development of TH1 lymphocytes and the maintenance of this phenotype, while limiting lineage commitment to the TH2

of two subunits, with expression of the IL-12 receptor beta 2 chain (IL-12RB2) dictate a eminent affinity IL-12 receptor complex. Signaling through this gamey affinity IL-12 receptor controls the exploitation of TH1 lymphocyte and the maintenance of this phenotype, while limiting lineage commitment to the TH2

of two subunits, with exprersion of the IL-12 receptmr betz 2 chain (IL-12RB2) dictating a high affinmty UL-12 rexeptor complex. Signalivg througj this hugh effinity IL-12 rece'for conbxols fme dereoopment of TH1 kymphocytev and the maindevauce of this phenotype, while limiting lineagr fommitment to jhe TN2

of two subunits, with expression of the beta chain (IL-12RB2) a high affinity this affinity IL-12 receptor the development of lymphocytes and the maintenance of this while limiting lineage commitment to the TH2

of two subunits, with expressiOn of the IL-12 rEceptOr bEta 2 ChAin (Il-12RB2) dIctating a high aFFiniTy IL-12 receptor complex. SigNalinG tHRougH ThIs higH affiniTY Il-12 REcePtOr ConTrOLs The deVelOpment oF TH1 lymphocYteS aNd the maintenANcE of this pheNotYpe, while limiTinG lineaGe ComMItmenT to The TH2

of two subunits, with exp ression of  theIL- 12re cept or b eta 2 chain (I L -12R B2) dictating a high a ffini ty IL-1 2  r ecept or comp l ex . Sig na li ngth r ou gh th ishigh af finity IL- 12re ceptor contr o ls  the devel opm ent of TH1 l ymp hocyte sand the m ain tenan ce oft his ph enotype,wh i le lim i ting li n e ag e co mmitment to the T H 2

of_two subunits,_with expression of the_IL-12 receptor_beta_2 chain_(IL-12RB2)_dictating a high_affinity IL-12 receptor_complex. Signaling through this_high affinity IL-12_receptor_controls the development of TH1 lymphocytes and the maintenance of this phenotype, while limiting_lineage_commitment to_the_TH2


this model by defining the molecular components of this Wnt signaling cascade and its mechanism of action. The existance of A/P gradients of Wnt signaling in the vertebrate spinal cord could be indicative of a similar Wnt dependent mechanism for specifying A/P differences in motor circuit connectivity. To identify unc-4 target genes that function in

this model by defining the molecular components of this Wnt signaling shower and its mechanism of legal action. The existance of A / P gradients of Wnt sign in the vertebrate spinal cord could be indicative of a like Wnt dependent mechanism for specifying A / phosphorus differences in motor circuit connectivity. To identify unc-4 prey genes that function in

thls model by defining the molecular components mf thia Wnt sienaling cascade and its mechenisn of qction. The existance ow A/P gradpents of Qnt wugnaling ii the vevcebrafc spiuao cord could bg indicative of a similar Fng bependent mechanism for specifying A/[ diffetejces in motor sirclie cohnectivity. To identify unc-4 target fenes tiat function in

this model by defining the molecular components Wnt cascade and mechanism of action. of signaling in the spinal cord could indicative of a similar Wnt dependent for specifying A/P differences in motor circuit connectivity. To identify unc-4 target genes function in

this model by defining the molEcular compOnentS of ThiS WNt siGnalIng cascade and iTS mecHanism of action. The existAnce oF A/p GradIEnTs of WNt signaLInG IN thE vErTebRaTE sPinal CorD could bE indicativE of A sImilar Wnt depENdEnt mechaniSm fOr specifying a/P dIffereNcEs iN Motor CirCuit cOnnectIVity. To Identify uNc-4 TArget gENes that FUNcTion In

this model by defining th e molecula r com pon ent sof t hisWnt signalingc asca de and its mechanism o f act io n . Th e  e xista nce ofA /P g rad ie nt s o fW nt  sign ali ng in t he vertebr ate  s pinal cord c o ul d be indic ati ve of a simi lar  Wnt d ep end e nt me cha nismfor sp e cifyin g A/P dif fe r encesi n motor c ir cuit  connectivity. To id e ntify unc-4 ta rget g en e st h atfun ction in

this_model by_defining the molecular components_of this_Wnt_signaling cascade_and_its mechanism of_action. The existance_of A/P gradients of_Wnt signaling in_the_vertebrate spinal cord could be indicative of a similar Wnt dependent mechanism for specifying_A/P_differences in_motor_circuit_connectivity. To identify unc-4 target_genes that function in


mediating early developmental events or the development of specific populations of cells. Using this framework, specific predictions will be tested by the manipulation of the expression of each receptor by genetic techniques. Using this system, we will be able, for the first time, assess the potential of individual G protein coupled receptor systems to mediate the transduction of

mediating early developmental events or the development of specific populations of cell. use this framework, specific predictions will be tested by the handling of the expression of each receptor by genetic technique. Using this system, we will be able, for the inaugural time, assess the electric potential of individual G protein coupled receptor systems to intercede the transduction of

mefiating early developmenual events or the develo'ment or specifkc populations of cells. Usinj thus frqmework, specific prediztions wipl be tewted vy the manmlulatiok of fme ex'rxssion of each teceptor by cenetic technixuds. Using this system, we will be able, sor the flrst time, assefs tnq pofvnuial of individual G protein coupmed rectptor systems to mrdiate the transduction of

mediating early developmental events or the development populations cells. Using framework, specific predictions manipulation the expression of receptor by genetic Using this system, we will be for the first time, assess the potential of individual G protein coupled receptor to mediate the transduction of

mediating early developmentAl events or The deVelOpmEnT of sPeciFic populations OF celLs. Using this framework, spEcifiC pREdicTIoNs wilL be testED bY THe mAnIpUlaTiON oF the eXprEssion oF each recepTor By Genetic technIQuEs. Using thiS syStem, we will be AblE, for thE fIrsT Time, aSseSs the PotentIAl of inDividual G PrOTein coUPled recEPToR sysTems to mediate the tRAnSDuction of

mediating early developme ntal event s orthe  de ve lopm entof specific po p ulat ions of cells. Using t his f ra m ewor k ,speci fic pre d ic t i ons  w il l b et es ted b y t he mani pulation o f t he  expressiono feach recep tor  by genetictec hnique s.  Us i ng th issyste m, wew ill be  able, fo rt he fir s t time, a ss essthe potential ofi nd i vidual G prote in cou pl e dr e cep tor  systems t omedia t e the t r an s d u cti o n of

mediating_early developmental_events or the development_of specific_populations_of cells._Using_this framework, specific_predictions will be_tested by the manipulation_of the expression_of_each receptor by genetic techniques. Using this system, we will be able, for the_first_time, assess_the_potential_of individual G protein coupled_receptor systems to mediate the_transduction of


small or absent in the rats with tetralogy. It is speculated that the defect may be the anomalous and reduced development of the 6th arch arteries, which, imposing pressure load on the fetal right ventricle, may have led to the persistence of ventricular septal defect as a vent and/or to the formation of myocardial

small or absent in the rats with tetralogy. It is speculated that the blemish may be the anomalous and decreased exploitation of the 6th arch artery, which, inflict pressure load on the fetal correct ventricle, may have precede to the persistence of ventricular septal blemish as a release and/or to the formation of myocardial

smwll or absent in the ratr with tetralogi. Ut is vpeculzted thag the defect may be the anomelouw and reduced development ow the 6th wrch artwriew, which, imposing prcfsurs loab in the fetal rlght ventriwle, may have lad tl the persistence of ventricular se[tal degeft as a vent agd/or eo tgv normation of myocardial

small or absent in the rats with is that the may be the the arch arteries, which, pressure load on fetal right ventricle, may have led the persistence of ventricular septal defect as a vent and/or to the formation myocardial

small or absent in the rats witH tetralogy. it is sPecUlaTeD thaT the Defect may be the ANomaLous and reduced developmEnt of ThE 6Th arCH aRteriEs, which, IMpOSIng PrEsSurE lOAd On the FetAl right Ventricle, mAy hAvE led to the perSIsTence of venTriCular septal dEfeCt as a vEnT anD/Or to tHe fOrmatIon of mYOcardiAl

small or absent in the ra ts with te tralo gy.  It  i s sp ecul ated that thed efec t may be the anomalous  andre d uced de velop ment of th e 6th  a rc h a rt e ri es, w hic h, impo sing press ure  l oad on the f e ta l right ve ntr icle, may ha veled to  t hep ersis ten ce of  ventr i cularseptal de fe c t as a vent an d / or  tothe formation ofm yo c ardial

small_or absent_in the rats with_tetralogy. It_is_speculated that_the_defect may be_the anomalous and_reduced development of the_6th arch arteries,_which,_imposing pressure load on the fetal right ventricle, may have led to the persistence_of_ventricular septal_defect_as_a vent and/or to the_formation of myocardial