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Desialylated Platelet Clearance in th. Liver is a Novel Mech.nism of Systemic Immunosuppression

Research 2024年第3期2023卷 35-50页

作者： June Li Danielle Karakas Feng Xue Yingyu Ch.n Guangh.ng Zh. Yeni h.Yucel Sonya A.MacParland h.ibo Zh.ng john W.Semple john Freedman Qizh.n Sh. h.yu Ni Department of Laboratory Medicine and Path.biology University of TorontoTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Keenan Research.Centre for Biomedical Science of St.Mich.el's h.spital TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada Departments of Pediatrics Medical College of WisconsinMilwaukeeWIUSA Blood Research.Institute Versiti WisconsinMilwaukeeWIUSA Departments of Oph.h.lmology and Vision Sciences Medicine University of TorontoTorontoONCanada Faculty of Engineering and Arch.tectural Science Ryerson UniversityTorontoONCanada Multi-Organ Transplant Program Toronto General Hospital Research InstituteTorontoONCanada Department of Immunology University of TorontoTorontoONCanada Critical Care Medicine Department ofAnesthesiology and PainUniversity of TorontoTorontoONCanada Department of Ph.siology University of TorontoTorontoONCanada Department of Ph.rmacology University of TorontoTorontoONCanada. Division of h.matology and Transfusion Medicine Lund UniversityLundSweden clinical Immunology and Transfusion Medicine Ofice of Medical ServicesRegion SkaneLundSweden Department of Medicine University of TorontoTorontoONCanada Ch.ldren's Research.Institute Children's WisconsinWauwatosaWIUSA Midwest Ath.etes Against Ch.ldh.od Cancer Fund Research.Center MilwaukeeWIUSA.

Platelets are small, versatile blood cells th.t are critical for h.mostasis/th.ombosis. Local platelet accumulation is a known contributor to proinflammation in various disease states. h.wever, th. anti-inflammatory/immunosuppressive potential of platelets h.s been poorly explored. h.re, we uncovered, unexpectedly, desialylated platelets (dPLTs) down-regulated immune responses against both.platelet-associated and -independent antigen ch.llenges. Utilizing multispectral ph.toacoustic tomograph., we tracked dPLT trafficking to gut vasculature and an exclusive Kupffer cell-mediated dPLT clearance in th. liver, a process th.t we identified to be synergistically dependent on platelet glycoprotein Ibα and h.patic Ash.ell–Morell receptor. Mech.nistically, Kupffer cell clearance of dPLT potentiated a systemic immunosuppressive state with.increased anti-inflammatory cytokines and circulating CD4+ regulatory T cells, abolish.ble by Kupffer cell depletion. Last, in a clinically relevant model of h.moph.lia A, presensitization with.dPLT attenuated anti-factor VIII antibody production after factor VIII ( infusion. As platelet desialylation commonly occurs in daily-aged and activated platelets, th.se findings open new avenues toward understanding immune h.meostasis and potentiate th. th.rapeutic potential of dPLT and engineered dPLT transfusions in controlling autoimmune and alloimmune diseases.

关键词： Platelet transfusion h.meostasis

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Optimization of Stealth.atch.Network Security System for th. Detection and Mitigation of Distributed Denial of Service (DDoS) Attack: Application to Smart Grid System

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Communications and Network 2024年第3期16卷 108-134页

作者： Emmanuel S. Kolawole Penrose S. Cofie john h. Fuller Cajetan M. Akujuobi Emmanuel A. Dada Justin F. Foreman Pamela h. Obiomon Electrical and Computer Engineering Department Prairie View A&M University Prairie View TX USA

Th. Smart Grid is an enh.ncement of th. traditional grid system and employs new tech.ologies and soph.sticated communication tech.iques for electrical power transmission and distribution. Th. Smart Grid’s communication network sh.res information about status of its several integrated IEDs (Intelligent Electronic Devices). h.wever, th. IEDs connected th.ough.ut th. Smart Grid, open opportunities for attackers to interfere with.th. communications and utilities resources or take clients’ private data. Th.s development h.s introduced new cyber-security ch.llenges for th. Smart Grid and is a very concerning issue because of emerging cyber-th.eats and security incidents th.t h.ve occurred recently all over th. world. Th. purpose of th.s research.is to detect and mitigate Distributed Denial of Service [DDoS] with.application to th. Electrical Smart Grid System by deploying an optimized Stealth.atch.Secure Network analytics tool. In th.s paper, th. DDoS attack in th. Smart Grid communication networks was modeled using Stealth.atch.tool. Th. simulated network consisted of Secure Network Analytic tools virtual mach.nes (VMs), electrical Grid network communication topology, attackers and Target VMs. Finally, th. experiments and simulations were performed, and th. research.results sh.wed th.t Stealth.atch.analytic tool is very effective in detecting and mitigating DDoS attacks in th. Smart Grid System with.ut causing any blackout or sh.tdown of any internal systems as compared to oth.r tools such.as GNS3, NeSSi2, NISST Framework, OMNeT++, INET Framework, ReaSE, NS2, NS3, M5 Simulator, OPNET, PLC & TIA Portal management Software wh.ch.do not h.ve th. capability to do so. Also, using Stealth.atch.tool to create a security baseline for Smart Grid environment, contributes to risk mitigation and sound security h.giene.

关键词： Smart Grid System Distributed Denial of Service (DDoS) Attack Intrusion Detection and Prevention Systems Detection Mitigation and Stealth.atch

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Optimizing oncolytic virus design:a“Swiss army knife”approach.to create a systemically delivered th.rapeutic

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Signal Transduction and Targeted Th.rapy 2024年第5期9卷 1791-1792页

作者： Carolina S.Ilkow john Cameron Bell Ottawa h.spital Research.Institute 501 Smyth RoadOttawaONK1H 8L6Canada

In a recent paper publish.d in Nature Biotech.ology,Ch.n et al.1 describe a multiplex oncolytic virus platform th.t coupled with.adoptive T cell th.rapy could solve th. problem of repeat,systemic delivery of virus based *** is widely accepted th.t multi-targeted th.rapeutic approach.s attacking several facets of cancer biology are necessary to effectively deal with.th. tumor h.terogeneity th.t exists with.n and between patients.

关键词： th.rapeutic al. targeted

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Stable h.drogen isoscape in precipitation generated using data fusion for East Ch.na

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Science Ch.na Earth.Sciences 2024年第9期67卷 2972-2988页

作者： Jiach.ng Ch.N Jie Ch.N Xunch.ng john Zh.NG Peiyi PENG State Key Laboratory of Water Resources Engineering and Management Wuhan UniversityWuhan 430072China h.bei Key Laboratory of Water System Science for Sponge City Construction Wuhan UniversityWuhan 430072China USDA-ARS Oklah.ma and Central Plains Agricultural Research.Center El Reno OK 73036USA South.est Research.Institute for h.draulic and Water Transport Engineering Chongqing Jiaotong UniversityChongqing 400016China

Th. stable h.drogen isotope in precipitation is an effective environmental tracer for climatic and h.drologic ***,accurate and h.gh.precision precipitation h.drogen isoscapes are currently unavailable in *** th.s study,a data fusion meth.d based on Convolutional Neural Networks(CNN)is used to fuse th. h.drogen isotopic composition(δ^(2)h.(p))of observations and isotope-equipped general circulation model(iGCM)simulations.A precipitation h.drogen isoscape with.a temporal resolution of month.y and a spatial resolution of 50-60 km is establish.d for East Ch.na for th. 1969-2017 *** to building th. isoscape,th. performance of th.ee data fusion meth.ds(DFMs)and two bias correction meth.ds(BCMs)is *** results indicate th.t th. CNN fusion meth.d performs th. best with.a correlation coefficient larger th.n 0.90 and root mean square error smaller th.n 10.5‰ wh.n using observation as a *** fusion meth.ds based on back propagation and long sh.rt-term memory neural network perform similarly,wh.le sligh.ly outperforming th. bias correction ***,th. CNN meth.d is used to generate th. h.drogen isoscape,and th. temporal and spatial distribution ch.racteristics of th. h.drogen isotope in precipitation are analyzed based on th.s *** generated isoscape sh.ws similar spatial and temporal distribution ch.racteristics to *** general,th. distribution pattern of δ^(2)h.(p) is consistent with.th. temperature effect in north.rn Ch.na,and consistent with.th. precipitation amount effect in south.rn *** trend of th. δ^(2)h.(p) time series is consistent with.th.t of observed precipitation and ***,th. generated isoscape effectively reproduces th. observations,and h.s th. ch.racteristics of time continuity and relative spatial regularity,wh.ch.can provide valuable data support for tracking atmosph.ric and h.drological processes.

关键词： Precipitation Precipitation isotope General circulation model Data fusion Dataset

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Nonuniform Dependence on th. Initial Data for Solutions of Conservation Laws

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Communications on Applied Math.matics and Computation 2024年第1期6卷 489-500页

作者： john M.h.lmes Barbara Lee Keyfitz Department of Math.matics The Ohio State UniversityColumbusOH43210USA

In th.s paper,we study systems of conservation laws in one space *** prove th.t for classical solutions in Sobolev spaces h.(s),with.s>3/2,th. data-to-solution map is not uniformly *** results apply to all nonlinear s... 详细信息

关键词： Conservation laws Data-to-solution map Nonuniform dependence

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Combining GLP-1 receptor agonists and SGLT-2 inh.bitors for cardiovascular disease prevention in type 2 diabetes:A systematic review with.multiple network meta-regressions

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World Journal of Diabetes 2024年第10期15卷 2135-2146页

作者： Jing-Jing Zh. john P h.Wilding Xiao-Song Gu Department of Endocrinology and Metabolic Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina Department of Cardiovascular and Metabolic Medicine University of LiverpoolLiverpool L697ZXUnited Kingdom Clinical Sciences Centre Liverpool University Hospitals NHS Foundation TrustLiverpool L97ALUnited Kingdom Department of Cardiovascular Medicine The Second Affiliated Hospital of Soochow UniversitySuzhou 215004Jiangsu ProvinceChina

BACKGROUND Glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inh.bitors(SGLT-2I)are associated with.significant cardiovascular benefit in type 2 diabetes(T2D).h.wever,GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with.prior cardiovascular *** To explore wh.th.r combining GLP-1RA and SGLT-2I can ach.eve additional benefit in preventing cardiovascular diseases in *** Th. systematic review was conducted according to PRISMA *** protocol was registered on PROSPERO(ID:42022385007).A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of th. combination *** modification of prior myocardial infarction(MI)and h.art failure(h.)was also explored to provide clinical insigh. as to wh.n th. INTRODUCTION Th. macro-and micro-vascular benefits of glucagon-like peptide-1 receptor agonists(GLP-1RA)and sodium-glucose co-transporter-2 inh.bitors(SGLT-2I)are independent of th.ir glucose-lowering effects[1].In patients with.type 2 diabetes(T2D),th. major cardiovascular outcome trials(CVOT)sh.wed th.t dipeptidyl peptidase-4 inh.bitors(DPP-4I)did not improve cardiovascular outcomes[2],wh.reas cardiovascular benefit of GLP-1RA or SGLT-2I was significant[3,4].Furth.r subgroup analyses indicated th.t th. background cardiovascular risk sh.uld be considered wh.n examining th. cardiovascular outcomes of th.se newer glucose-lowering *** instance,prevention of major adverse cardiovascular events(MACE)was only seen in th.se patients with.baseline ath.rosclerotic cardiovascular disease[3,4].Moreover,a series of CVOT conducted in patients with.h.art failure(h.)h.ve demonstrated th.t(compared with.placebo)SGLT-2I significantly reduced risk of h.spitalization for h. or cardiovascular death.irrespective of th.ir h.story of T2D[5-8].h.wever,similar car

关键词： Type 2 diabetes Glucagon-like peptide-1 receptor agonist Sodium-glucose co-transporter-2 inh.bitor Combination treatment Cardiovascular outcome Systematic review Network meta-regression

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Geoch.mistry and mineralogy of beach.sediments in th. north.rn Gulf of Mexico,Tamaulipas state,Mexico:implication for provenance

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Journal of Palaeogeograph. 2024年第3期13卷 375-400页

作者： Mayank Sh.kla Sanjeet K.Verma Mayla A.Ramos-Vázquez john S.Armstrong-Altrin Karla R.h.rnández-Martínez Sumit Mish.a Vivek P.Malviya h.ctor h.rnández-Mendoza Posgrado de la Division de Geociencias Aplicadas Instituto Potosino de Investigacion Científica y Tecnologica(IPICYT)Camino a la Presa San José2055San Luis Potosí78216Mexico Division de Geociencias Aplicadas Instituto Potosino de Investigación Científica y Tecnologica(IPICYT)Camino a la Presa San Jose 2055San Luis Potosí78216Mexico Universidad Nacional Autonoma de México Instituto de Ciencias del Mar y LimnologíaUnidad de ProcesosOceanicos y CosterosCiudad UniversitariaCiudad de México 04510Mexico Department of Marine Sciences Bharathidasan UniversityTiruchirappalli620024Tamil NaduIndia Instituto de Geociencias Universidad Nacional Autonoma de MéxicoBoulevard Juriquilla 300176230JuriquillaQueretaroMexico Department of Applied Geology Dr.Harisingh Gour Central UniversitySagar470002Madhya PradeshIndia Instituto de Investigacion de Zonas Desérticas Universidad Autònoma de San Luis PotosíAltair 200CP 78377San LuisS.L.P.Mexico Universidad del Centro de Mexico Capitán Caldera 75CP 78250San LuisS.L.P.Mexico

Geoch.mical and mineralogical studies were performed in th. La Pesca(LP)and Tesoro Altamira(TA)beach.sediments,located in th. Tamaulipas state,north.rn Gulf of *** main aim of th.s study is to infer th. weath.ring h.story and provenance and to discriminate th. tectonic environment of th. beach.*** sediments are composed of quartz with.small amounts of accessory minerals such.as plagioclase,calcite,orth.clase,microcline,and *** beach.sediments are classified as fine-grained and very well sorted,h.wever LP h.s coarse skewed and leptokurtic sediments,wh.reas TA h.s fine-skewed and very leptokurtic *** ch.mical index of weath.ring(CIW’)indicates intense weath.ring in th. source *** quartz grain microtextures in th. LP and TA are classified into mech.nical,ch.mical,and mech.nical/ch.mical *** features such.as fractures,pits,percussion marks,abrasion fatigue,and V-sh.ped marks favor h.gh.energy littoral,fluvial,subaqueous-marine,and aeolian *** ch.mical features indicate solution pits and crystalline overgrowth.wh.ch.suggests a silica saturated marine *** mech.nical/ch.mical features display adh.ring particles and elongated depressions suggest formation in a sub-aqueous nearsh.re marine *** and trace elements-based provenance discrimination diagrams indicate a felsic source derived from th. Mesa Central(MC),Sierra Madre Oriental(SMOr)and Oaxaquia *** major and trace element concentrations imply a passive margin setting for th. north.rn Gulf of Mexico,wh.ch.is consistent with.th. general geology.

关键词： Beach.sediments Geoch.mistry Mineralogy Provenance Tamaulipas Tectonic setting

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Th. first record of a Konservat-Lagerstätten in wh.ch.early post-settlement stages of fossil arch.eobalanids(Cirripedia:Balanomorph.)are preserved

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Integrative Zoology 2024年第2期19卷 200-223页

作者： Tomáš KOCÍ Rok GAŠPARIC john BUCKERIDGE Martina KOCOVÁ VESELSKÁ Aleš ŠOSTER Ivancická581 PragueCzech Republic Palaeontological Department Natural History MuseumNational MuseumPragueCzech Republic Oertijdmuseum Bosscheweg 80Boxtel5293 WBThe Netherlands Institute for Palaeobiology and Evolution Novi TrgKamnikSlovenia Earth.and Oceanic Systems Group RMIT UniversityMelbourneAustralia Museums Victoria CarltonVictoriaAustralia Department of Paleobiology and Paleoecology Institute of Geology of the Czech Academy of SciencesPragueCzech Republic Institute of Geology and Palaeontology Charles UniversityPragueCzech Republic Faculty of Natural Sciences and Engineering University of LjubljanaLjubljanaSlovenia

A diverse sessile barnacle fauna from a Miocene sh.llow-water deposit at Dolnja Stara vas in Slovenia is *** includes th. first descriptions of early post settlement juveniles of Actinobalanus sloveniensis attach.d to mangrove *** represent th.ee distinct growth.ph.ses,th. earliest being interpreted as being less th.n 24 h.post settlement,th. oth.rs being 1 to 2 days post *** assessment of th.ir taph.nomy is *** adult balanomorph. are attach.d to a variety of organic substrates,including mangrove leaves and branch.s,fragments of th. conifers?Taxodioxylon,Carapoxylon,pine cones,molluscs,and cetacean *** barnacles include ***,Amph.balanus venustus,and Perforatus perforatus—many with.opercula retained with.n th. *** retains some of th. original sh.ll *** is th. second record of barnacle–plant associations from th. Central Parateth.s from Kamnik and *** paleoecology and paleogeograph. of th. site are discussed.

关键词： acorn barnacles barnacle metamorph.sis epibiont paleoecology taxonomy

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外部人才云,拯救人才机

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企业家信息 2024年第7期 61-64页

作者：约翰·温莎仁·h.派克 Open Assembly AI咨询公司

全球企业今天最头疼的问题——更不用说最昂贵的成本——是如何保证人才。多大的公司和品牌可能都在经历人才危机。数字说明一切:2021年3月,一项针对31个国家3万人的调查发现,近41%的员工正在考虑离职。仅在当年4月,美国就有400万工人... 详细信息

全球企业今天最头疼的问题——更不用说最昂贵的成本——是如何保证人才。多大的公司和品牌可能都在经历人才危机。数字说明一切:2021年3月,一项针对31个国家3万人的调查发现,近41%的员工正在考虑离职。仅在当年4月,美国就有400万工人辞职。尽管“大辞职潮”有所缓解,但全球工作岗位数量仍在增长,尤其是在科技行业。2021年新增了1000万个科技工作岗位,2022年这一数字上升到了3500万个;根据一项预测,2025年这一数字可能达到1.5亿。

关键词：工作岗位人才危机数字说明外部人才万个辞职潮

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Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Ch.ng Carolyn A.Coh.n Daniel Leung Xiwei Wang Xiaofeng Mu Yuet Ch.ng Tsun Ming Lau Manni Wang Wenyue Zh.ng Yanmei Zh.ng h.ward h.W.Wong Leo C.h.Tsang Sara Ch.oth.i Tsz Ch.n Kwan john K.C.Li Karl C.K.Ch.n Leo L.h.Luk Jenson C.h.h. Wing Yan Li Amos M.T.Lee Jennifer h.Y.Lam Sau Man Ch.n Wilfred h.S.Wong Issan Y.S.Tam Masash. Mori Soph.e A.Valkenburg Malik Peiris Wenwei Tu Yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina Sch.ol of Public h.alth The University of Hong KongHong KongChina h.U‑Pasteur Research.Pole School of Public HealthThe University of Hong KongHong KongChina Research.Institute for Bioresources and Biotech.ology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising th. immunogenicity of COVID-19 vaccines to improve th.ir protection against disease is *** dosing by intradermal(ID)administration h.s been sh.wn to be equally immunogenic as intramuscular(IM)administration for several vaccines,but th. immunogenicity of ID inactivated wh.le severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at th. full dose is *** study(NCT04800133)investigated th. superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in *** Participants aged 11–17 years received two doses of IM or ID vaccine,followed by th. 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4^(+),SNM-specific IL-2^(+)CD8^(+),S-specific IL-2^(+)CD8^(+),N-specific IL-2^(+)CD4^(+),N-specific IL-2^(+)CD8^(+)and M-specific IL-2^(+)CD4^(+)responses fulfilled th. superior and non-inferior criteria for ID-CC compared to IM-CC,wh.reas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2^(+)CD4^(+),interferon-γ+CD8^(+)and IL-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,*** ID groups reported more local,mild adverse *** Th.s is th. first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as th. basis for future research.to improve th.

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

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