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Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function

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Cellular & Molecular Immunology 2021年第2期18卷 328-338页

作者： Juan Huang Jian Peng james alexander pearson Georgios Efthimiou Youjia Hu Ningwen Tai Yanpeng Xing Luyao Zhang Jianlei Gu Jianping Jiang Hongyu Zhao Zhiguang Zhou F.Susan Wong Li Wen National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology(Central South University)Ministry of Educationand Department of Metabolism and EndocrinologyThe Second Xiangya HospitalCentral South UniversityChangshaHunanChina Section of Endocrinology Department of Internal MedicineSchool of MedicineYale UniversityNew HavenCTUSA Division of Infection and Immunity School of MedicineCardiff UniversityCardiffUK Department of Microbiology University of HullHullUK Department of Gastrointestinal Surgery of the First Hospital of Jilin University ChangchunJilinChina Department of Biostatistics Data Science&GeneticsYale School of Public HealthNew HavenCTUSA

Innate immunity mediated by Toll-like receptors(TLRs),which can recognize pathogen molecular patterns,plays a critical role in type 1 diabetes ***7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells;however,its role in type 1 diabetes development remains *** our study,we discovered that Tlr7-deficient(Tlr7^(−/−))nonobese diabetic(NOD)mice,a model of human type 1 diabetes,exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient(Tlr7^(+/+))NOD *** investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin ***,Tlr7^(−/−)NOD B cells were found to suppress diabetogenic CD4^(+)T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T *** addition,we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8^(+)T-cell activation by downregulating the expression of both nonclassical and classical MHC class I(MHC-I)molecules on B *** data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T ***,therapeutically targeting TLR7 may prove beneficial for disease protection.

关键词： Type 1 diabetes Toll-like receptor 7 B cell

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New Opportunities for Neutrons in Environmental and Biological Sciences

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Frontiers of Environmental Science & Engineering 2024年第7期18卷 179-186页

作者： alexander Johs Shuo Qian Leighton Coates Brian H.Davison james G.Elkins Xin Gu Jennifer Morrell-Falvey Hugh O'Neill Jeffrey M.Warren Eric M.Pierce Kenneth Herwig Oak Ridge National Laboratory Oak RidgeTN37831USA

The use of neutron methods in environmental and biological sciences is rapidly emerging and accelerating with the development of new instruments at neutron user *** article,based on a workshop held at Oak Ridge National Laboratory(ORNL),offers insights into the application of neutron techniques in environmental and biological *** highlight recent advances and identify key challenges and potential future research *** include soil and rhizosphere processes,root water dynamics,plant-microbe interactions,structure and dynamics of biological systems,applications in synthetic biology and enzyme engineering,next-generation bioproducts,biomaterials and bioenergy,nanoscale structure,and fluid dynamics of porous materials in *** provide an outlook on emerging opportunities with an emphasis on new capabilities that will be enabled at the Spallation Neutron Source Second Target Station currently under design at *** mission of scientific neutron user facilities worldwide is to enable science using state-of-the-art neutron *** aim to encourage researchers in the environmental and biological research community to explore the unique capability afforded by neutrons at these facilities.

关键词： Neutrons Environment Biology Neutron imaging Neutron scattering Second Target Station(STS)

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An Automated,Highly Selective Reaction Monitoring Instrument Using Molecular Rotational Resonance Spectroscopy

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Precision Chemistry 2024年第2期2卷 57-62页

作者： Ann Adele Byars Khushi R.Kompally Emily Mechnick Reilly E.Sonstrom alexander Mikhonin Justin L.Neill Ruth Boetzel james MacGregor Courtney Talicska Jian Li Yizhou Liu BrightSpec Inc.CharlottesvilleVirginia 22903United States Pfizer R&D UK Limited Sandwich CT139NJUnited Kingdom Analytical Research and Development Pfizer Research and DevelopmentGrotonConnecticut 06340United States

Online monitoring of chemical reactions by using analytical chemistry tools is a powerful way to maximize control over these *** this paper,we demonstrate the use of molecular rotational resonance,an emerging and extraordinarily selective spectroscopic technique,to perform automated reaction monitoring *** interface using a six-port valve with a calibrated sample loop,coupled to a temperature controlled inlet for analyte volatilization,was developed and *** reactions were chosen for initial characterization:an amine-aldehyde condensation reaction to form an imine product and an isotopic exchange reaction of aβ-ketoester with keto-enol *** spectrometer was able to provide kinetic information about the reaction and determine reaction *** the future,this system can be extended to detect and quantify impurities and characterize reaction selectivity,in addition to the reaction progress.

关键词： molecular rotational resonance spectroscopy reaction monitoring reaction kinetics isotopes process analytical technology

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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal J.Goldschmidt-Clermont Aisha Khan George Jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera alexander J.P.Goldschmidt Damien D.Pearse W.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Otolaryngology residency program factors associated with female resident representation

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 7-11页

作者： Julia E.Canick james C.Campbell Charles R.Woodard Lars J.Grimm Alissa M.Collins Duke University School of Medicine DurhamNorth CarolinaUSA Department of Head and Neck Surgery&Communication Sciences Duke University School of MedicineDurhamNorth CarolinaUSA Department of Radiology Duke University School of MedicineDurhamNorth CarolinaUSA

Objective:Female representation in the field of otolaryngology is *** is the first point at which medical school graduates specialize in a chosen field and thus represents an opportunity to recruit and train more female *** study sought to identify program factors associated with greater female representation among resident ***:Departmental websites of all 124 otolaryngology residency programs in the United States and Puerto Rico were examined for a list of *** programs with a resident roster available,the genders of residents,faculty,program directors,and chairpersons were *** and city population for each program was also recorded,as was female resident *** were compared using pearson Chi‐squared univariate ***:1,632 residents and 2,605 faculty were included in the analysis of 109 *** median female resident representation was 40%.Programs with larger faculty sizes,more female faculty,and urban location were associated with an above‐median female resident *** with a larger residency cohort approached significance regarding above‐median female resident *** female faculty representation,program director gender,chairperson gender,and US region were not associated with variation in female resident ***:Greater female otolaryngology residency representation was associated with programs having an urban location and greater numbers of female and total *** was also likely that a larger resident cohort size may affect female resident *** proportions of female faculty,program director,and chairperson gender,as well as the US region,were not associated with variation in female resident gender representation.

关键词： gender program director recruitment residency training

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Ballistic tests on hot-rolled Ti-6Al-4V plates:Experiments and numerical approaches

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Defence Technology（防务技术） 2023年第8期26卷 39-53页

作者： alexander Janda Benjamin james Ralph Yael Demarty Marcel Sorger Stefan Ebenbauer Aude Prestl Ingo Siller Martin Stockinger Helmut Clemens Department of Materials Science Montanuniversitat LeobenFranz Josef-Straße 188700 LeobenAustria Department Product Engineering Montanuniversitat LeobenFranz Josef-Straße 188700 LeobenAustria French-German Research Institute of Saint-Louis 5 Rue du General Cassagnou68300 Saint-LouisFrance voestalpine BOEHLER Bleche GmbH&Co KG Boehler-Gasse 18680MürzzuschlagAustria

Superior ballistic performance and the lightweight character of Ti alloys are considered as main reasons for their use in armour applications against a broad spectrum of ballistic threats,***,fragment or blast *** dynamic loading caused by typical penetrators is characterized by high strain rates,only specific test methods allow a closer investigation of the respective material *** the present study,quasi-static and dynamic compression tests as well as ballistic tests were conducted on a twophase a+βalloy Ti-6Al-4V(in m%)manufactured by ***-deformation heat treatments,influencing microstructure and mechanical properties were applied in order to compare three different microstructural configurations:as-rolled,mill-annealed and ***,on the one hand,ballistic tests were employed for the determination of the ballistic limit velocity v_(50),compression tests,on the other hand,delivered essential input parameters for the application of the Johnson-Cook constitutive model in a finite element simulation of the impact *** comparison of experimental results to simulation results was supplemented by means of microstructural characterization of tested samples with the focus set on the prevalently observed deformation and damage mechanisms,as for example adiabatic shearing.

关键词： Ti-6Al-4V Ballistic performance Split Hopkinson pressure bar FE simulation Adiabatic shear bands Intermetallic phase

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When gastroenteritis isn't:a case report of a 20-year-old male with Boerhaave's syndrome complicated by intra-abdomimal hemorrhage

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World Journal of Emergency Medicine 2016年第4期7卷 303-306页

作者： james Baird alexander B.Norinsky Department of Emergency Medicine Rowan University SOM Kennedy University Hospital

Here we present the case of a 20-year-old male with a known history of an artificial mechanical aortic valve replacement at ages four and twelve,on chronic warfarin therapy,who presented to our community emergency department for the evaluation of vomiting,diarrhea,generalized malaise and abdominal *** was seen at a local urgent care for similar symptoms earlier in the day,subsequently discharged with a diagnosis of

关键词： When gastroenteritis isn’t case

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Wireless data management system for environmental monitoring in livestock buildings

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Information Processing in Agriculture 2017年第1期4卷 1-17页

作者： james Gray Thomas M.Banhazi alexander A.Kist Faculty of Health Engineering and SciencesUniversity of Southern Queensland(USQ)West StreetToowoombaQLD 4350Australia National Centre for Engineering in Agriculture(NCEA) University of Southern Queensland(USQ)West StreetToowoombaQLD 4350Australia

The impact of air quality on the health,welfare and productivity of livestock needs to be considered,especially when livestock are kept in enclosed *** monitoring of such environmental factors allows for the development of appropriate strategies to reduce detrimental effects of sub-optimal air quality on the respiratory health of both livestock and *** 2009,an environmental monitoring system was designed,developed and tested that allowed for the monitoring of a number of airborne *** limitation of the system was the manual collection of logged data from each *** paper identifies limitations of the current environmental monitoring system and suggests a range of networking technologies that can be used to increase *** is taken for the networking of environmental monitoring units,as well as the collection of recorded ***,the design and development of a software system that is used to collate and store recorded environmental data from multiple farms is *** order to design such a system,simplified software engineering processes and methodologies have been *** main steps taken in order to complete the project were requirements elicitation with clients,requirements analysis,system design,implementation and finally *** outcome of the project provided a potential prototype for improving the environmental monitoring system and analysis informing the benefit of the implementation.

关键词： Sensors Environmental monitoring Networking Software engineering

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A full-wave HTS flux pump using a feedback control system

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Superconductivity 2023年第4期8卷 26-33页

作者： james H.P.Rice Ben P.P.Mallett Dominic A.Moseley alexander Petrov Heng Zhang Steven Wray Rodney A.Badcock Paihau-Robinson Research Institute Victoria University of WellingtonLower Hutt 5012New Zealand UK Atomic Energy Authority Culham Science CentreAbingdon OX143DBUnited Kingdom

Transformer‐rectifier flux pumps are DC superconducting power supplies capable of charging superconducting magnets to high currents and stored magnetic ***,we demonstrate a full‐wave superconducting flux pump assembled from high‐temperature superconducting(HTS)wire that utilizes superconducting switches controlled by applied magnetic field.A negative DC offset occurs in the superconducting secondary of the circuit during operation which is related to the output load current.A feedback control system is proposed and demonstrated to account for the negative DC *** the primary current proportional to the load current during operation allowed for the maximum output of the flux pump to be increased from 35 A to more than 275 *** results are reproduced using a coupled electrical‐and magnetic–circuit model formulated in the MATLAB Simulink®package.

关键词： High‐temperature superconductor Flux pump Power supply Circuit modelling High current

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ABA signaling prevents phosphodegradation of the SR45 splicing factor to alleviate inhibition of early seedling development in Arabidopsis

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Plant Communications 2023年第2期4卷 272-285页

作者： Rui Albuquerque-Martins Dora Szakonyi james Rowe alexander M.Jones Paula Duque Instituto Gulbenkian de Ciencia 2780-156 OeirasPortugal Sainsbury Laboratory University of CambridgeCambridge B21LRUK

Serine/arginine-rich(SR)proteins are conserved splicing regulators that play important roles in plant stress responses,namely those mediated by the abscisic acid(ABA)*** Arabidopsis thaliana SR-like protein SR45 is a described negative regulator of the ABA pathway during early seedling *** the inhibition of growth by ABA signaling is counteracted to maintain plant development under stress conditions remains largely ***,we show that SR45 overexpression reduces Arabidopsis sensitivity to ABA during early seedling *** and confocal microscopy analyses of transgenic plants expressing fluorescently tagged SR45 revealed that exposure to ABA dephosphorylates the protein at multiple amino acid residues and leads to its accumulation,due to SR45 stabilization via reduced ubiquitination and proteasomal *** phosphomutant and phosphomimetic transgenic Arabidopsis lines,we demonstrate the functional relevance of ABA-mediated dephosphorylation of a single SR45 residue,T264,in antagonizing SR45 ubiquitination and degradation to promote its function as a repressor of seedling ABA *** results reveal a mechanism that negatively autoregulates ABA signaling and allows early plant growth under stress via posttranslational control of the SR45 splicing factor.

关键词： abscisic acid alternative splicing Arabidopsis thaliana protein phosphorylation SR proteins

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