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SARS-CoV-2 RBD and Its Variants Can Induce Platelet Activation and Clearance:Implications for Antibody Therapy and Vaccinations against COVID-19

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Research 2024年第3期2023卷 1-15页

作者： Xiaoying Ma jady Liang Guangheng Zhu Preeti Bhoria Aron A.Shoara daniel T.MacKeigan Christopher j.Khoury Sladjana Slavkovicl Lisha Lin danielle Karakas Ziyan Chen Viktor Prifti Zhenze Liu Chuanbin Shen Yuchong Li Cheng Zhang jiayu Dou Zack Rousseau jiamin Zhang Tiffany Ni Xi Lei Pingguo Chen Xiaoyu Wu Hamed Shaykhalishahi Samira Mubareka Kim AConnelly Haibo Zhang Ori Rotstein Heyu Ni Department of Laboratory Medicine and Pathobiology University of TorontoTorontoONCanada Department of Laboratory Medicine Keenan Research Centre for Biomedical Science of St.Michael’s HospitalTorontoONCanada Toronto Platelet Immunobiology Group TorontoONCanada Department of Physiology University of TorontoTorontoONCanada CCOA Therapeutics Inc. TorontoONCanada Canadian Blood Services Centre for Innovation TorontoONCanada The State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Laboratory Medicine The Second Affliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina Advanced Pharmaceutics&Drug Delivery Laboratory Leslie Dan Faculty of PharmacyUniversity of TorontoTorontoONCanada Department of Medical Microbiology and Infectious Disease Sunnybrook Health Science CentreToronto ONCanada Department of Medicine University of TorontoTorontoONCanada Division of Cardiology.St.Michael's Hospital TorontoONCanada Department of Anesthesiology and Pain Medicine and Division of Critical Care Medicine University of TorontoTorontoONCanada interdepartmental Division of Critical Care Medicine University of TorontoTorontoONCanada Department of Surgery University of Toronto TorontoONCanada.

The COVID-19 pandemic caused by SARS-CoV-2 virus is an ongoing global health *** cases of COVID-19 and the rare cases of COVID-19 vaccine-induced-thrombotic-thrombocytopenia(VITT)are both associated with thrombosis and thrombocytopenia;however,the underlying mechanisms remain inadequately *** infection and vaccination utilize the spike protein receptor-binding domain(RBD)of *** found that intravenous injection of recombinant RBD caused significant platelet clearance in *** investigation revealed the RBD could bind platelets,cause platelet activation,and potentiate platelet aggregation,which was exacerbated in the Delta and Kappa *** RBD–platelet interaction was partially dependent on theβ3 integrin as binding was significantly reduced inβ3−/−***,RBD binding to human and mouse platelets was significantly reduced with relatedαIIbβ3 antagonists and mutation of the RGD(arginine-glycine-aspartate)integrin binding motif to RGE(arginine-glycine-glutamate).We developed anti-RBD polyclonal and several monoclonal antibodies(mAbs)and identified 4F2 and 4H12 for their potent dual inhibition of RBD-induced platelet activation,aggregation,and clearance in vivo,and SARS-CoV-2 infection and replication in Vero E6 *** data show that the RBD can bind platelets partially thoughαIIbβ3 and induce platelet activation and clearance,which may contribute to thrombosis and thrombocytopenia observed in COVID-19 and *** newly developed mAbs 4F2 and 4H12 have potential not only for diagnosis of SARS-CoV-2 virus antigen but also importantly for therapy against COVID-19.

关键词： Antibody diagnosis vaccine

Elucidating regulatory processes of intense physical activity by multi-omics analysis

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Military Medical Research 2024年第4期11卷 479-499页

作者： Ernesto S.Nakayasu Marina A.Gritsenko Young-Mo Kim jennifer E.Kyle Kelly G.Stratton Carrie D.Nicora Nathalie Munoz Kathleen M.Navarro daniel Claborne Yuqian Gao Karl K.Weitz Vanessa L.Paurus Kent j.Bloodsworth Kelsey A.Allen Lisa M.Bramer Fernando Montes Kathleen A.Clark Grant Tietje justin Teeguarden Kristin E.Burnum-johnson Biological Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Environmental and Molecular Sciences Division Pacific Northwest National LaboratoryRichlandWA 99352USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthWestern States DivisionDenverCO 80204USA Computational Analytics Division Pacific Northwest National LaboratoryRichlandWA 99352USA National Security Directorate Pacific Northwest National LaboratoryRichlandWA 99352USA Los Angeles County Fire Department Los AngelesCA 90063USA Centers for Disease Control and Prevention National Institute for Occupational Safety and HealthRespiratory Health DivisionMorgantownWV 26505USA Environmental and Molecular Toxicology Oregon State UniversityCorvallisOR 97331USA

Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work ***:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise *** profiles ***-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics ***:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of *** blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy *** urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid *** saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory ***:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

关键词： Multi-omics analysis Intense exercise Human performance Biofluids Metabolism Immunity

A new oxidative pathway of nitric oxide production from oximes in plants

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Molecular Plant 2024年第1期17卷 178-198页

作者： Pedro Lopez-Gomez javier Buezo Marina Urra Alfonso Cornejo Raquel Esteban jorge Fernandez de los Reyes Estibaliz Urarte Estefania Rodriguez-Dobreva Alejandro Chamizo-Ampudia Alejandro Eguaras Sebastian Wolf daniel Marino Victor Martinez-Merino jose F.Moran Institute for Multidisciplinary Research in Applied Biology(IMAB) Department of SciencesPublic University of Navarre(UPNA)Avda.de Pamplona 12331192 MutilvaSpain Institute for Advanced Materials and Mathematics(INAMAT2) Department of SciencesPublic University of Navarre(UPNA)Campus de Arosadia31006 PamplonaSpain Department of Plant Biology and Ecology University of the Basque Country(UPV/EHU)Sarriena s/nApdo.64448080 BilbaoSpain Center for Plant Molecular Biology(ZMBP) University of TubingenGeschwister-Scholl-Platz72074 TubingenGermany Institute of Natural Resources and Agrobiology of Salamanca(IRNASA) Department of Plant-Microorganism InteractionsSpanish National Research Council(CSIC)Cordel de Merinas40-5237008SalamancaSpain Department of Biochemistry Area of Molecular BiologyVeterinary FacultyUniversity of LeonCampus de Vegazanas/n.24071 LeonSpain

Nitric oxide(NO)is an essential reactive oxygen species and a signal molecule in *** several studies have proposed the occurrence of oxidative NO production,only reductive routes for NO production,such as the nitrate(NO_(3)^(-))-upper-reductase pathway,have been evidenced to date in land ***,plants grown axenically with ammonium as the sole source of nitrogen exhibit contents of nitrite and NO3−,evidencing the existence of a metabolic pathway for oxidative production of *** hypothesized that oximes,such as indole-3-acetaldoxime(IAOx),a precursor to indole-3-acetic acid,are intermediate oxidation products in NO *** detected the production of NO from IAOx and other oximes catalyzed by peroxidase(POD)enzyme using both 4-amino-5-methylamino-2′,7′-difluorescein fluorescence and *** stimulated the reaction,while superoxide dismutase inhibited ***,mouse NO synthase can also use IAOx to produce NO at a lower rate than *** provided a full mechanism for POD-dependent NO production from IAOx consistent with the experimental data and supported by density functional theory *** showed that the addition of IAOx to extracts from Medicago truncatula increased the in vitro production of NO,while in vivo supplementation of IAOx and other oximes increased the number of lateral roots,as shown for NO donors,and a more than 10-fold increase in IAOx dehydratase ***,we found that in vivo supplementation of IAOx increased NO production in Arabidopsis thaliana wild-type plants,while prx33-34 mutant plants,defective in POD33-34,had reduced *** data show that the release of NO by IAOx,as well as its auxinic effect,explain the superroot ***,our study reveals that plants produce NO utilizing diverse molecules such as oximes,POD,and flavins,which are widely distributed in the plant kingdom,thus introducing a long-awaited oxidative pathway to NO production in plants.T

关键词： ammonium oxidation auxin nitric oxide oxime peroxidase root phenotype

Numerical Models and Methods of Atmospheric Parameters Originating in the Formation of the Earth’s Climatic Cycle

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Atmospheric and Climate Sciences 2024年第2期14卷 277-286页

作者： Wend Dolean Arsène Ilboudo Kassoum Yamba Windé Nongué daniel Koumbem Issaka Ouédraogo Dé partement Energie Institut de Recherche en Sciences Appliqu&#233es et Technologies (IRSAT) Ouagadougou Burkina Faso Unité de Formation et de Recherche en Sciences Exactes et Appliqu&#233es Universit&#233 Joseph KI-ZERBO Ouagadougou Burkina Faso

Atmospheric models are physical equations based on the ideal gas law. Applied to the atmosphere, this law yields equations for water, vapor (gas), ice, air, humidity, dryness, fire, and heat, thus defining the model of key atmospheric parameters. The distribution of these parameters across the entire planet Earth is the origin of the formation of the climatic cycle, which is a normal climatic variation. To do this, the Earth is divided into eight (8) parts according to the number of key parameters to be defined in a physical representation of the model. Following this distribution, numerical models calculate the constants for the formation of water, vapor, ice, dryness, thermal energy (fire), heat, air, and humidity. These models vary in complexity depending on the indirect trigonometric direction and simplicity in the sum of neighboring models. Note that the constants obtained from the equations yield 275.156˚K (2.006˚C) for water, 273.1596˚K (0.00963˚C) for vapor, 273.1633˚K (0.0133˚C) for ice, 0.00365 in/s for atmospheric dryness, 1.996 in2/s for humidity, 2.993 in2/s for air, 1 j for thermal energy of fire, and 0.9963 j for heat. In summary, this study aims to define the main parameters and natural phenomena contributing to the modification of planetary climate. .

关键词： Atmospheric Parameter 1 Climatic Cycle 2 Numerical Models 3

Laser cut hole matrices in novel armour plate steel for appliqué battlefield vehicle protection

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Defence Technology（防务技术） 2016年第5期12卷 351-359页

作者： daniel j. THOMAS Engineering Manufacturing Centre College of Engineering Swansea University Swansea UK

During this research, experimental rolled homogeneous armour steel was cast, annealed and laser cut to form an appliqué plate. This Martensitic–Bainitic microstructure steel grade was used to test a novel means of engineering lightweight armour. It was determined that a laser cutting speed of 1200 mm/min produced optimum hole formations with limited distortion. The array of holes acts as a double-edged solution, in that they provide weight saving of 45%, providing a protective advantage and increasing the surface area. Data collected were used to generate laser cut-edge hole projections in order to identify the optimum cutting speed, edge condition, cost and deformation performance. These parameters resulted in the generation of a surface, with less stress raising features. This can result in a distribution of stress across the wider surface. Provided that appropriate process parameters are used to generate laser cut edges, then the hardness properties of the surface can be controlled. This is due to compressive residual stresses produced in the near edge region as a result of metallurgical transformations. This way the traverse cutting speed parameter can be adjusted to alter critical surface characteristics and microstructural properties in close proximity to the cut-edge. A relationship was identified between the width of the laser HAZ and the hardness of the cut edge. It is the thickness of the HAZ that is affected by the laser process parameters which can be manipulated with adjusting the traverse cutting speed.

关键词： Armour steels Defence systems Steel processing Armour engineering

Recent advances in the targeted fluorescent probes for the detection of metastatic bone cancer

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Science China Chemistry 2021年第8期64卷 1283-1296页

作者： Peng Wu daniel j.Siegwart Hu Xiong Research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular RecognitionCollege of ChemistryNankai UniversityTianjin300071China Department of Biochemistry Simmons Comprehensive Cancer CenterThe University of Texas Southwestern Medical CenterDallasTexas75390USA

Tumors of the breast,prostate,and lung are most likely to metastasize to the bone and typically indicates a poor cure and survival rate in cancer *** of metastatic bone cancer in early stage would save many lives and greatly improve patients’quality of ***,bone scintigraphy is often utilized to visualize bone metastases due to its relatively low cost and high ***,a growth number of analytical researches aimed at developing targeted fluorescent probes to noninvasively image bone metastases with improved spatial resolution and specificity has been *** this review,we will summarize and discuss the recent published fluorescent probes on the accurate detection of metastatic bone ***,the design principles of various targeted probes for imaging bone metastases will be presented,highlighting the signal moieties,targeting ligands,and physicochemical properties of the bone-specific ***,the up-to-date bone-targeting fluorescent probes will be summarized and ***,future perspectives and challenges confronting the researchers in this field will be *** believe this review will encourage novel ideas to develop smart targeted molecular probes for bone metastasis imaging,image-guided surgery,and therapeutic imaging materials.

关键词： bone metastasis targeted probes fluorescence imaging smart design bone-targeting moieties

The PACTUM model:Product analysis of cost and time using mathematics

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International journal of Modeling, Simulation, and Scientific Computing 2014年第S1期5卷 51-70页

作者： daniel j.Easters Department of Fashion Marketing Management&Communication School of Art&Design Nottingham Trent University Nottingham NG14BUUK

Establishing a mathematical supply-chain model is a proposition that has received attention due to its inherent benefits of evolving global supply-chain *** paper discusses the prevailing relationships found within apparel supply-chain environments,and contemplates the complex issues indicated for constituting a mathematical *** results identified within the data suggest,that the multifarious nature of global supply-chain activities require a degree of simplification in order to fully dilate the necessary factors which affect,each subsection of the ***,the research findings allowed the division of supply-chain components into subsections,which amassed a coherent method of product development ***,the supply-chain model was found to allow systematic mathematical formulae analysis,of cost and time,within the multiple contexts of each subsection *** paper indicates the supplychain model structure,the mathematics,and considers how product analysis of cost and time can improve the comprehension of product lifecycle management.

关键词： Fashion supply-chain mathematics

Corrigendum to“Towards a business model for second-life batteries:Barriers,opportunities,uncertainties,and technologies”[*** Chem.78(2023)507–525]

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journal of Energy Chemistry 2024年第4期91卷 684-684页

作者： Carlos Antônio Rufino júnior Eleonora Riva Sanseverino Pierluigi Gallo daniel Koch Yash Kotak Hans-Georg Schweiger Hudson Zanin Advanced Energy Storage Division New Energy Innovation CenterUniversity of Campinas(UNICAMP)Campinas 13083-852Brazil Engineering Department University of Palermo(UNIPA)Palermo 90128Italy Consorzio Nazionale Interuniversitario per le Telecomunicazioni(CNIT) Parma 43124Italy Technische Hochschule Ingolstadt Institute for ElectricConnected and Safe Mobility(C-ECOS)Ingolstadt 85049Germany

In the Acknowledgments Section,please replace“Shell oil”for“TotalEnergies”.The authors would like to apologise for any inconvenience *** the sake of clarity(“Shell oil”should be removed and in boldblack“TotalEn... 详细信息

关键词： please replace removed

Overcoming obstacles to implementation: addressing political,institutional and behavioral problems in earthquake hazard mitigation policies

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Earthquake Engineering and Engineering Vibration 2002年第1期1卷 152-158页

作者： daniel j.Alesch William j.Petak Department of Public and Environmental Affairs University of Wisconsin-Green BayGreen BayWisconsin54311USA Professor School of Policy Planning and DevelopmentUniversity of Southern California650 Childs WayRoom 201eLos AngelesCalifornia90089-0626USA Professor

This project is aimed at bridging the three planes,from basic research,through enabling processes,to engineered *** the basic research plane,we have been working to improve our collective understanding about obstacles to implementing mitigation practices,owner decision processes (in connection with other MCEER projects),and public policy *** the level of enabling processes,we have been seeking to develop an understanding of how obstacles to greater mitigation can be overcome by improved policy design and *** the engineered systems plane, our work is intended to result in practical guidelines for devising policies and programs with appropriate motivation and incentives for implementing policies and programs once *** phase of the research has been aimed,first,at a thorough,multidisciplinary review of the literature concerning obstacles to ***,the research has focused on advancing the state of the art by developing means for integrating the insights offered by diverse perspectives on the implementation process from the several social,behavioral,and decision *** research establishes a basis for testing our understanding of these processes in the case of hospital retrofit decisions.

关键词： earthquake mitigation earthquake mitigation policies earthquake losses