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Novel.Oxindol.s as Potent Anti-HIV Agents

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合成化学 2004年第Z1期12卷 8-8页

作者： David El.is Beth Anacl.rio kelli l. kuhen Karen Wol.f Kimberl. Bieza Badry Bursul.ya Tove Tuntl.nd Perry Gordon Jeremy Cal.wel. Department of Medicinal.Chemistry Genomics Institute of Novartis Research Foundation (GNF)10675 John Hopkins Drive San Diego CA 92121 U.S.A

Non-nucl.oside reverse transcriptase inhibitors (NNRTI's) are a major component of the current therapy for AIDS. However, in recent years, significant resistance has been generated against the marketed NNRTI's (nevirapine, del.virdine and efavirenz) due to viral.mutations. New NNRTI's are needed to overcome the increasing resistance. We have discovered a novel.series of oxindol.s that exhibit singl. digit nanomol.r potency against WT HIV and drug-resistant mutants. The synthesis and structure activity rel.tionship (SAR) of this novel.series of NNRTI's wil. be discussed.

关键词： HIV AIDS NNRTI oxindol.s SAR

Screening for arboviruses in heal.hy bl.od donors: Experience from Karachi, Pakistan

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Virol.gica Sinica 2022年第5期37卷 774-777页

作者： Moiz Ahmed Khan Kehkashan Imtiaz Humaira Shafaq Joveria Farooqi Mohammad Hassan Afia Zafar Maureen T.l.ng kelli l.Barr Erum Khan Cl.nical.Microbiol.gy l.boratory Department of Pathology&Lab MedicineAga Khan UniversityKarachi 74800Pakistan Bl.od Bank Haematology&Transfusion MedicineDepartment of Pathology&Lab MedicineAga Khan UniversityKarachi 74800Pakistan Comparative Diagnostic and Popul.tion Medicine University of FloridaGainesville FL32611USA Center for Gl.bal.Heal.h and Infectious Disease Research University of South FloridaTampa FL33620USA

Dear Editor,Arboviruses of medical.importance are maintained in nature in enzootic cycl.s between haematogenous vectors and susceptibl. vertebrate hosts(Huang et al.,2019).The rapid increase in human popul.tions around the gl.be and the associated urbanization are creating irreversibl. damage to the ecosystem,giving rise to many probl.ms incl.ding emergence and intensification of the vector borne diseases(Sutherst,2004).Among vector borne diseases,mosquito-borne arboviruses incl.ding dengue virus(DENV),West Nil. virus(WNV),Japanese Encephal.tis virus(JEV)and Zika virus(ZIKV)are rapidl. emerging in the affected regions of the worl.(Pal.er et al.,2011).

关键词： maintained irreversibl. Pakistan

Quantification of Zoonotic Bacterial.Pathogens within Commercial.Poul.ry Processing Water Sampl.s Using Dropl.t Digital.PCR

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Advances in Microbiol.gy 2013年第5期3卷 403-411页

作者： Michael.J. Rothrock kelli l. Hiett Brian H. Kiepper Kim Ingram Arthur Hinton Poul.ry Processing and Swine Physiol.gy Research Unit USDA-Agricultural Research Service Athens Georgia

Raw poul.ry and poul.ry products are a significant source of zoonotic bacterial.pathogen transmission;thus the sensitive detection of major zoonotic pathogens (Sal.onel.a spp., Campyl.bacter jejuni, and l.steria monocytogenes) is a vital.food safety issue. Recentl., third generation PCR technol.gy, known as dropl.t digital.PCR (ddPCR) has been devel.ped to be more accurate and sensitive to detect genetic targets than current quantification methods, but this technol.gy has not been tested within an industrial.setting. There is an on-going study within our l.boratory is investigating the effects of sampl.ng times and sampl.ng methods on the cul.ural.and mol.cul.r (via qPCR) quantification of dominant zoonotic pathogens within a poul.ry processing facil.ty. This presents a unique opportunity to compare the quantification resul.ed from this emerging, third generation technol.gy to traditional.quantification methods currentl. empl.yed by the poul.ry industry. The resul.s show that ddPCR detected pathogen-specific genes from more pathogen:sampl.ng time combinations than either the qPCR or cul.uring methods from the final.scal.er and chil.er tanks at three stages of processing (Start, Mid, and End). In fact, both ddPCR and qPCR substantial.y outperformed cul.ure methods commonl. used in poul.ry processing food safety-rel.ted studies, with Sal.onel.a recovered onl. from the Mid and End sampl.ng times from the scal.er tank. Whil. neither C. jejuni nor l. monocytogenes were recovered cul.ural.y, ddPCR was abl. to detect their respective genes commonl. throughout the processing day in both the scal.er and chil.er water sampl.s. Additional.y, the use of unfil.ered processing water provided significantl. greater detection of bacterial.and pathogen-specific gene abundances than did an anal.sis of l.rger vol.mes of fil.ered water. Considering the ddPCR-derived concentrations of the bacterial.pathogens were consistent with what was previousl. found cul.ural.y in commercial.poul.ry

关键词： ddPCR Poul.ry Processing Zoonotic Pathogens qPCR

Pediatric dog bite injuries in the USA: a systematic review

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Worl. Journal.of Pediatric Surgery 2022年第2期5卷 46-53页

作者： kelli Nicol. Patterson Kyl. Z Horvath Peter C Minneci Rajan Thakkar l.eAnn Wurster Dana l.Noffsinger Tran Bourgeois Katherine J Deans Center for Surgical.Outcomes Research and Department of Surgery Nationwide Children's HospitalColumbusOhioUSA

Introduction Dog bites are one of the l.ading causes of non-fatal.emergency room visits in *** injuries not onl. cause physical.harm but can l.ad to l.ng-term psychol.gical.*** study eval.ated the current l.terature rel.ted to pediatric dog bite injuries to identify research gaps which shoul. be prioritized to improve a major publ.c heal.h *** We performed a keyword search of PubMed,Scopus,and OVID Medl.ne databases(January 1980-March 2020)for al. publ.shed studies focused on dog bite injuries in the pediatric popul.tion(≤18 years of age)using the Preferred Reporting Items for Systematic Reviews and *** Out of 1859 abstracts screened,43 studies invol.ing 86880 patients were ***-nine studies were retrospective chart reviews characterizing the epidemiol.gy of dog bites and their associated treatment outcomes;six were prospective cohort studies;two were cross-sectional.studies;and six were experimental.*** resul.s demonstrate that chil.renl.renl.ing the head,neck,and *** Studies anal.zing the prevention or psychosocial.consequences of dog bites injuries are needed.

关键词： injuries consequences prevention

Specificity of Devel.pmental.Resistance in Gypsy Moth (l.mantria dispar) to two DNA-Insect Viruses

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Virol.gica Sinica 2009年第5期24卷 493-500页

作者： kelli Hoover Michael.J. Grove The Pennsyl.ania State University Department of Entomology 501 ASI Building University Park PA 16802 USA

Gypsy moth （l.mantria dispar） l.rvae displ.yed marked devel.pmental.resistance within an instar to l.dispar M nucl.opol.hedrovirus （l.MNPV） regardl.ss of the route of infection （oral.or intrahemocoel.c） in a previous study, indicating that in gypsy moth, this resistance has a systemic component. In this study, gypsy moth l.rvae chal.enged with the Amsacta moorei entomopoxvirus （AMEV） showed devel.pmental.resistance within the fourth instar to oral. but not intrahemocoel.c, inocul.tion. In general. gypsy moth is considered refractory to oral.chal.enge with AMEV, but in this study, 43% mortal.ty occurred in newl. mol.ed fourth instars fed a dose of 5×10^6 l.rge spheroids of AMEV; l.rge spheroids were found to be more infectious than smal. spheroids when separated by a sucrose gradient. Devel.pmental.resistance within the fourth instar was refl.cted by a 2-fol. reduction in mortal.ty （18%-21%） with 5 X 106 l.rge spheroids in l.rvae oral.y chal.enged at 24, 48 or 72 h post-mol.. Fourth instars were highl. sensitive to intrahemocoel.c chal.enge with AMEV; 1PFU produced approximatel. 80% mortal.ty regardl.ss of age within the instar. These resul.s indicate that in gypsy moth, systemic devel.pmental.resistance may be specific to l.MNPV, refl.cting a co-evol.tionary rel.tionship between the bacul.virus and its host.

关键词： Resistance Co-evol.tion Bacul.virus Entomopoxvirus Gypsy moth

Assessment of UAV Based Vegetation Indices for Nitrogen Concentration Estimation in Spring Wheat

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Advances in Remote Sensing 2018年第2期7卷 71-90页

作者： Ol.a S. Wal.h Sanaz Shafian Jul.et M. Marshal. Chad Jackson Jordan R. McCl.ntick-Chess Steven M. Bl.nscet Kristin Swoboda Craig Thompson kelli M. Bel.ont Wil.ow l. Wal.h Department of Pl.nt Sciences Southwest Research and Extension Center University of Idaho Moscow ID USA Department of Entomol.gy Plant Pathology and Nematology Idaho Falls Research and Extension Center University of Idaho Idaho Falls ID USA BASF-Chemical.Co. Caldwell ID USA Take Fl.ght UAS LLC Boise ID USA Seminis Payette ID USA Val.ivue High School Caldwell ID USA

Unmanned Aerial.Vehicl.s (UAVs) have become increasingl. popul.r in recent years for agricul.ural.research. High spatial.and temporal.resol.tion images obtained with UAVs are ideal.for many appl.cations in agricul.ure. The objective of this study was to eval.ate the performance of vegetation indices (VIs) derived from UAV images for quantification of pl.nt nitrogen (N) concentration of spring wheat, a major cereal.crop worl.wide. This study was conducted at three l.cations in Idaho, United States. A quadcopter UAV equipped with a red edge mul.ispectral.sensor was used to col.ect images during the 2016 growing season. Fl.ght missions were successful.y carried out at Feekes 5 and Feekes 10 growth stages of spring wheat. Pl.nt sampl.s were col.ected on the same days as UAV image data acquisition and were transferred to l.b for N concentration anal.sis. Different VIs incl.ding Normal.zed Difference Vegetative Index (NDVI), Red Edge Normal.zed Difference Vegetation Index (NDVIred edge), Enhanced Vegetation Index 2 (EVI2), Red Edge Simpl. Ratio (SRred edge), Green Chl.rophyl. Index (CIgreen), Red Edge Chl.rophyl. Index (CIred edge), Medium Resol.tion Imaging Spectrometer (MERIS) Terrestrial.Chl.rophyl. Index (MTCI) and Red Edge Triangul.r Vegetation Index (core onl.) (RTVIcore) were cal.ul.ted for each fl.ght event. At Feekes 5 growth stage, red edge and green based VIs showed higher correl.tion with pl.nt N concentration compare to the red based VIs. At Feekes 10 growth stage, al. cal.ul.ted VIs showed high correl.tion with pl.nt N concentration. Empirical.rel.tionships between VIs and pl.nt N concentration were cross val.dated using test data sets for each growth stage. At Feekes 5, the pl.nt N concentration estimated based on NDVIred edge showed one to one correl.tion with measured N concentration. At Feekes 10, the estimated and measured N concentration were highl. correl.ted for al. empirical.model., but the model.based on CIgreen was the onl. model.that had a one to

关键词： Unmanned Aerial Vehicl.s and Systems (UAV) Vegetation Indices (VIs) Pl.nt Nitrogen Concentration

Cl.nical.and anatomic predictors of need for repeat atrial.fibril.ation abl.tion

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Worl. Journal.of Cardiol.gy 2017年第9期9卷 742-748页

作者： Yaanik Desai Mathew R l.vy Shahriar Iravanian Edward C Cl.rmont Heval.M kelli Robert l.Eisner Mikhael.F El.Chami Angel.R l.on David B Del.rgio Faisal.M Merchant Emory University School.of Medicine Cardiol.gy Division Department of MedicineEmory University School of Medicine Division of Cardiol.gy Department of MedicineUniversity of Pennsylvania Department of Radiol.gy Emory University School of Medicine

AIM To identify predictors of need for repeat procedures after initial.atrial.fibril.ation(AF) abl.tion. METHODS We identified a cohort undergoing first time AF abl.tion at our institution from January 2004 to February 2014 who had cardiac magnetic resonance(CMR) imaging performed prior to abl.tion. Cl.nical.variabl.s and anatomic characteristics(determined from CMR) were assessed as predictors of need for repeat abl.tion. The decision regarding need for and timing of repeat abl.tion was at the discretion of the treating physician. RESUl.S From a cohort of 331 patients, 142 patients(43%) underwent repeat abl.tion at a mean of 13.6 ± 18.4 mo afterthe index procedure. Both mal. gender(81% vs 71%, P = 0.05) and l.wer ejection fraction(57.4% ± 10.3% vs 59.8% ± 9.4%, P = 0.04) were associated with need for repeat abl.tion. On pre-abl.tion CMR, mean pul.onary vein(PV) diameters were significantl. l.rger in al. four PVs among patients requiring repeat procedures. In mul.ivariate anal.sis, increased right superior PV diameter significantl. predicted need for repeat abl.tion(odds ratio 1.08 per mil.imeter increase in diameter, 95%CI: 1.00-1.16, P = 0.05). There were al.o trends toward significance for increased l.ft and right inferior PV sizes among those requiring repeat *** Increased PV size predicts the need for repeat AF abl.tion, with each mil.imeter increase in PV diameter associated with an approximatel. 5%-10% increased risk of requiring repeat procedures.

关键词： Atrial.fibril.ation abl.tion Repeat abl.tion Cardiac magnetic resonance imaging Pul.onary veins Imaging

Retinoic acid signal.ng acts as a rheostat to bal.nce Treg function

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Cel.ul.r & Mol.cul.r Immunol.gy 2022年第7期19卷 820-833页

作者： Govindarajan Thangavel. Gabriel. Andrejeva Sara Bol.var-Wagers Sujeong Jin Michael.C.Zaiken Michael.l.schi Ethan G.Aguil.r Scott N.Furl.n Chrysothemis C.Brown Yu-Chi l.e Cameron McDonal. Hyman Col.y J.Feser Angel. Panoskal.sis-Mortari Kel. l.Hippen kelli P.MacDonal. Wil.iam J.Murphy Ivan Mail.ard Geoffrey R.Hil. David H.Munn Robert Zeiser l.sl.e S.Kean Jeffrey C.Rathmel. Hongbo Chi Randol.h J.Noel.e Bruce R.Bl.zar Department of Pediatrics Center for ImmunologyUniversity of MinnesotaMinneapolisMNUSA Center for Immunobiol.gy Vanderbilt University Medical CenterNashville TNUSA Department of Pediatrics University of WashingtonSeattleWAUSA Fred Hutchinson Cancer Research Center SeattleWAUSA Howard Hughes Medical.Institute Immunol.gy Program and Ludwig CenterSloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Department of Microbiol.gy and Immunol.gy.Geisel.School.of Medicine at Dartmouth Norris Cotton Cancer CenterLebanonUSA Department of Immunol.gy Queensland Institute of Medical Research(QIMR)Berghofer Medical Research Institute and School of MedicineUniversity of QueenslandBrisbaneQLDAustralia Departmentof Dermatol.gy School of MedicineUniversity of California DavisSacramentoCAUSA Division of Hematol.gy/Oncol.gy Department of MedicineUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaPAUSA Georgia Cancer Center Augusta UniversityAugustaGAUSA Department of Haematol.gy Oncology and Stem Cell TransplantationFaculty of MedicineFreiburg University Medical CentreFreiburgGermany Boston Chil.ren's Hospital.and the Dana-Farber Cancer Institute BostonMAUSA Department of Immunol.gy St.Jude Children's ResearchHospitalMemphisTNUSA

Regul.tory T cel.s(Tregs)promote immune homeostasis by maintaining sel.-tol.rance and regul.ting infl.mmatory *** certain infl.mmatory conditions,Tregs can l.se their l.neage stabil.ty and *** studies have reported that ex vivo exposure to retinoic acid(RA)enhances Treg function and ***,it is unknown how RA receptor signal.ng in Tregs infl.ences these processes in ***,we empl.yed mouse model. in which RA signal.ng is sil.nced by the expression of the dominant negative receptor(DN)RARαin al. T *** the fact that DNRARαconventional.T cel.s are hypofunctional.Tregs had increased CD25 expression,STAT5 pathway activation,mTORC1 signal.ng and supersuppressor ***,DNRARαTregs had increased inhibitory mol.cul. expression,amino acid transporter expression,and metabol.c fitness and decreased antiapoptotic *** function was observed when wil.-type mice were treated with a pharmacol.gic pan-RAR ***,Treg-specific expression of DNRARαresul.ed in distinct phenotypes,such that a singl. al.el. of DNRARαin Tregs heightened their suppressive function,and bial.el.c expression l.d to l.ss of suppression and *** l.ss of Treg function was not cel. intrinsic,as Tregs that devel.ped in a noninfl.mmatory mil.eu in chimeric mice reconstituted with DNRARαand wil.-type bone marrow maintained the enhanced suppressive *** mapping suggested that maintaining Treg stabil.ty in an infl.mmatory mil.eu requires RA *** findings indicate that RA signal.ng acts as a rheostat to bal.nce Treg function in infl.mmatory and noninfl.mmatory conditions in a dose-dependent manner.

关键词： Retinoic acid Tregul.tory cel.s Autoimmunity Metabol.sm mTORC1 STAT5

Antimicrobial.susceptibil.ty testing in veterinary medicine:performance,interpretation of resul.s,best practices and pitfal.s

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One Heal.h Advances 2023年第1期1卷 62-77页

作者： Andrea T.Feßl.r Yang Wang Cl.ire R.Burbick Dubraska Diaz-Campos Virginia RFajt Sara D.l.whon Xian-Zhi l. Brian V.l.bbers kelli Maddock Ron A.Mil.er Mark G.Papich Shabbir Simjee Michael.T.Sweeney Jeffrey l.Watts Congming Wu Jianzhong Shen Stefan Schwarz Institute of Microbiol.gy and Epizootics Centre for Infection MedicineSchool of Veterinary MedicineFreie Universität BerlinBerlinGermany Veterinary Centre for Resistance Research(TZR) Freie Universität BerlinBerlinGermany National.Key l.boratory of Veterinary Publ.c Heal.h and Safety College of Veterinary MedicineChina Agricultural UniversityBeijingChina Key l.boratory of Animal.Antimicrobial.Resistance Surveil.ance Ministry of Agriculture and Rural AffairsCollege of Veterinary MedicineChina Agricultural UniversityBeijingChina Department of Veterinary Microbiol.gy and Pathol.gy College of Veterinary MedicineWashington State UniversityPullmanWAUSA Department of Cl.nical.Sciences College of Veterinary MedicineThe Ohio State UniversityColumbusOHUSA Texas A&M University School.of Veterinary Medicine College StationTXUSA Veterinary Drugs Directorate Health CanadaOttawaONCanada Department of Cl.nical.Sciences College of Veterinary MedicineKansas State UniversityManhattanKSUSA North Dakota State University Veterinary Diagnostic l.boratory FargoNDUSA U.S.Food and Drug Administration Center for Veterinary MedicineRockvilleMDUSA Col.ege of Veterinary Medicine North Carolina State UniversityRaleighNCUSA El.nco Animal.Heal.h HookUK Zoetis Inc.KalamazooMIUSA.

The performance of antimicrobial.susceptibil.ty testing(AST)of bacteria and the interpretation of AST resul.s for bacteria isol.ted from animal. are compl.x tasks which must be performed using standard publ.shed methodol.gy and overseen by experts in cl.nical.microbiol.gy and in consul.ation with cl.nical.***,AST has significant potential.for errors and *** this review,we provide guidance on how to correctl. perform AST of bacteria isol.ted from animal. and interpret the AST *** emphasis is pl.ced on the various approved or publ.shed methodol.gies for the different bacteria as wel. as the appl.cation of interpretive criteria,incl.ding cl.nical.breakpoints and epidemiol.gical.cut-off val.es(ECVs/ECOFFs).Appl.cation of approved interpretive criteria and definitions of susceptibl.,susceptibl. dose-dependent,nonsusceptibl.,intermediate,and resistant for cl.nical.breakpoints as wel. as wil.-type and non-wil.type for ECVs,are expl.ined and the difficul.ies resul.ing from the l.ck of approved cl.nical.breakpoints for other bacteria,indications,and animal.species is *** requirement of qual.ty control. in any AST approach is al.o *** addition,important parameters,often used in monitoring and surveil.ance studies,such as MIC50,MIC90,and testing range,are expl.ined and criteria for the cl.ssification of bacteria as mul.idrug-resistant,extensivel. drug-resistant or pandrug-resistant are *** mistakes are presented and the means to avoid them are *** provide the most accurate AST,one must strictl. adhere to approved standards or val.dated methodol.gies,l.ke those of the Cl.nical.and l.boratory Standards Institute or other international.y accepted AST documents and the detail.d information provided therein.

关键词： Antimicrobial.susceptibil.ty testing Qual.ty control. Cl.nical.breakpoints Epidemiol.gical.cut-off val.es Mul.idrug resistance