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Safety,immunogenicity,and protection provided by unadjuvanted and adjuvanted formulations of a recombinant plant-derived virus-like particle vaccine candidate for COVID-19 in nonhuman primates

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Cellular & Molecular Immunology 2022年第2期19卷 222-233页

作者： Stéphane Pillet Prabhu SArunachalam Guadalupe Andreani Nadia Golden jane Fontenot Pyone Pyone Aye Katharina Röltgen Gabrielle Lehmicke Philipe Gobeil Charlotte Dubé Sonia Trépanier Nathalie Charland Marc-AndréD’Aoust Kasi Russell-Lodrigue Christopher Monjure Robert V.Blair Scott D.Boyd Rudolf P.Bohm jay Rappaport François Villinger Nathalie Landry Bali Pulendran brian j.ward Medicago Inc. QuébecQCCanada. Institute for Immunity Transplantation and InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA. Tulane National Primate Research Center CovingtonLAUSA. New Iberia Research Center University of Louisiana at LafayetteNew IberiaLAUSA. Department of Pathology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Department of Microbiology and Immunology Tulane University School of MedicineNew OrleansLAUSA. Department of Microbiology and Immunology Stanford University School of MedicineStanford UniversityStanfordCAUSA. Institute for Immunity Transplantation&InfectionStanford University School of MedicineStanford UniversityStanfordCAUSA Research Institute of the McGill University Health Centre MontrealQCCanada.

Although antivirals are important tools to control severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,effective vaccines are essential to control the current coronavirus disease 2019(COVID-19)***-derived virus-like particle(VLP)vaccine candidates have previously demonstrated immunogenicity and efficacy against ***,we report the immunogenicity and protection induced in rhesus macaques by intramuscular injections of a VLP bearing a SARS-CoV-2 spike protein(CoVLP)vaccine candidate formulated with or without Adjuvant System 03(AS03)or cytidine-phospho-guanosine(CpG)*** a single dose of the unadjuvanted CoVLP vaccine candidate stimulated humoral and cell-mediated immune responses,booster immunization(at 28 days after priming)and adjuvant administration significantly improved both responses,with higher immunogenicity and protection provided by the AS03-adjuvanted *** micrograms of CoVLP adjuvanted with AS03 induced a polyfunctional interleukin-2(IL-2)-driven response and IL-4 expression in CD4 T *** were challenged by multiple routes(i.e.,intratracheal,intranasal,and ocular)with a total viral dose of 106 plaque-forming units of *** viral replication in nasal swabs and bronchoalveolar lavage fluid(BALF)as well as fewer SARS-CoV-2-infected cells and immune cell infiltrates in the lungs concomitant with reduced levels of proinflammatory cytokines and chemotactic factors in the BALF were observed in animals immunized with the CoVLP adjuvanted with *** clinical,pathologic,or virologic evidence of vaccineassociated enhanced disease was observed in vaccinated *** CoVLP adjuvanted with AS03 was therefore selected for vaccine development and clinical trials.

关键词： SARS-CoV-2 Virus-like particles Non-humane primates AS03 CpG1018

Angling of hybrid sunfish from a hatchery pond with potential implications for community fisheries

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Aquaculture and Fisheries 2023年第1期8卷 91-95页

作者： brian G.Blackwell Matthew j.ward Todd M.Kaufman South Dakota Department of Game Fish and Parks603 East 8th AvenueWebsterSD57274USA South Dakota Department of Game Fish and Parks44437139A StreetWaubaySD57273USA

Hatcheries are frequently called upon to produce catchable-sized fish for stocking community fishing *** attributes of fish selected for stocking into community ponds are that they are easy to produce in a hatchery system to sizes anglers are interested in catching and they provide anglers with high catch rates once *** sunfish[male Bluegill(Lepomis macrochirus)×female Green Sunfish(***)]have attributes that potentially make them attractive for use in community fishing *** assessed initial angler catch rates of 100 stocked hybrid sunfish in a 0.12-ha hatchery pond and after being subjected to angling(four,1-hr catch-and-release fishing events with five anglers).We also investigated whether catch rates would change following a supplemental stocking of an additional 100 hybrid sunfish(four,1-hr catch-and-release fishing events with five anglers).The anal fin of each fish in the second stocking was hole punched to differentiate them from those of the first stocking and fish caught by anglers were hole punched in the caudal fin each time they were caught before being released back into the *** catch rates were highest during initial fishing events that followed stocking(9.2 fish/angler hr and 18.0 fish/angler hr)and substantially declined in subsequent events(≤3.4 fish/angler hr).Catches of the newly stocked fish and previously stocked fish contributed to the high catch following the supplemental ***(80%)of the fish were caught in the first 30 min of each event and 45%were caught during the first 10 *** were able to catch 88%of the fish from the first stocking and 67%from the second stocking at least *** mortality occurred during the study as all fish were recovered when the pond was *** results suggest that hybrid sunfish will potentially provide high initial catch rates following stocking into community ponds,but managers should expect reduced catch rates following initial fishing even without h

关键词： Hybrid sunfish Angling Community fishing ponds

Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis

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Cellular & Molecular Immunology 2024年第1期21卷 33-46页

作者： Anja Meyer Stephanie R.Zack Wes Nijim Adel Burgos Vishwa Patel brian Zanotti Michael V.Volin M.Asif Amin Myles j.Lewis Costantino Pitzalis Shiva Arami joseph A.Karam Nadera j.Sweiss Shiva Shahrara jesse Brown VA Medical Center ChicagoILUSA Department of Medicine Division of RheumatologyThe University of Illinois at ChicagoChicagoILUSA Department of Microbiology and Immunology Midwestern UniversityDowners GroveILUSA Division of Rheumatology and Clinical Autoimmunity Center of Excellence University of MichiganAnn ArborMIUSA Centre for Experimental Medicine and Rheumatology William Harvey Research InstituteBarts and The London School of Medicine and DentistryQueen Mary University of LondonLondonUnited Kingdom Centre for Experimental Medicine&Rheumatology William Harvey Research InstituteQueen Mary University of London and Barts NIHR BRC&NHS TrustLondonUK Department of Biomedical Sciences Humanitas Universityand Humanitas Research HospitalMilanItaly Department of Orthopedic Surgery the University of Illinois at ChicagoChicagoILUSA

A novel rheumatoid arthritis(RA)synovial fluid protein,Syntenin-1,and its receptor,Syndecan-1(SDC-1),are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes(FLS).Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9,IL-1β,IL-6,and CCL2 through SDC-1 ligation and HIF1α,or mTOR ***,Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR *** Syntenin-1 reprogrammed endothelial cells,the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors,AMPK,PGC-1α,citrate,and inactive oxidative ***,RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP *** enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 *** found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS,which are also represented in RA *** to RA explants,morphological and transcriptome studies authenticated the importance of VEGFR1/2,Notch1,RAPTOR,and HIF1αpathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient ***,dysregulation of SDC-1,mTOR,and HIF1αnegated Syntenin-1 inflammatory phenotype in RA explants,while inhibition of HIF1αimpaired synovial angiogenic imprint amplified by *** conclusion,since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood,targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

关键词： Syntenin-1 Syndecan-1 RA FLS RA explants immunometabolism

Fetal Head Compression: Its Possible Role in Neurologic Injury

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Open journal of Obstetrics and Gynecology 2024年第1期14卷 124-143页

作者： Barry S. Schifrin brian j. Koos Wayne R. Cohen Department of Obstetrics and Gynecology The Western University of Health Sciences Pomona USA The David Geffen School of Medicine at UCLA Los Angeles USA The University of Arizona College of Medicine Tucson USA

It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

关键词： Fetal Brain Injury Fetal Head Compression Ischemic Encephalopathy Neonatal Encephalopathy

Aerosol jet printing of surface acoustic wave microfluidic devices

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Microsystems & Nanoengineering 2024年第1期10卷 231-242页

作者： joseph Rich brian Cole Teng Li Brandon Lu Hanyu Fu Brittany N.Smith jianping Xia Shujie Yang Ruoyu Zhong james L.Doherty Kanji Kaneko Hiroaki Suzuki Zhenhua Tian Aaron D.Franklin Tony jun Huang Department of Biomedical Engineering Duke UniversityDurhamNC 27708USA Department of Electrical and Computer Engineering Duke UniversityDurhamNC 27708USA Department of Mechanical Engineering Virginia Polytechnic Institute and State UniversityBlacksburgVA 24061USA Thomas Lord Department of Mechanical Engineering and Materials Science Duke UniversityDurhamNC 27708USA Deptartment of Precision Mechanics Faculty of Science and EngineeringChuo UniversityTokyo 112-8551Japan Department of Chemistry Duke UniversityDurhamNC 27708USA

The addition of surface acoustic wave(SAW)technologies to microfluidics has greatly advanced lab-on-a-chip applications due to their unique and powerful attributes,including high-precision manipulation,versatility,integrability,biocompatibility,contactless nature,and rapid ***,the development of SAW microfluidic devices is limited by complex and time-consuming micro/nanofabrication techniques and access to cleanroom facilities for multistep photolithography and vacuum-based *** simplify the fabrication of SAW microfluidic devices with customizable dimensions and functions,we utilized the additive manufacturing technique of aerosol jet *** successfully fabricated customized SAW microfluidic devices of varying materials,including silver nanowires,graphene,and poly(3,4-ethylenedioxythiophene)polystyrene sulfonate(PEDOT:PSS).To characterize and compare the acoustic actuation performance of these aerosol jet printed SAW microfluidic devices with their cleanroom-fabricated counterparts,the wave displacements and resonant frequencies of the different fabricated devices were directly measured through scanning laser Doppler ***,to exhibit the capability of the aerosol jet printed devices for lab-on-a-chip applications,we successfully conducted acoustic streaming and particle concentration ***,we demonstrated a novel solution-based,direct-write,single-step,cleanroom-free additive manufacturing technique to rapidly develop SAW microfluidic devices that shows viability for applications in the fields of biology,chemistry,engineering,and medicine.

关键词： printing wave fluid

Sequencing of high-efficacy disease-modifying therapies in multiple sclerosis： perspectives and approaches

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Neural Regeneration Research 2018年第11期13卷 1871-1874页

作者： Francois Grand'Maison Michael Yeung Sarah A. Morrow Liesly Lee Francois Emond brian j. ward Pierre Laneuville Robyn Schecter Neuro Rive-Sud Hospital Charles LeMoyne Greenfield Park Quebec Canada Clinical Neurosciences Foothills Medical Centre Calgary Alberta Canada London Health Sciences Center (LHSC) Western University London Ontario Canada Department of Neurology Sunnybrook Health Sciences Centre Toronto Ontario Canada Centre Hospitalier Universitaire de Quebec - hospital de l'Enfant-jesus Quebec City Quebec Canada Research Institute of the McGill University Health Centre Montreal Quebec Canada Department of Medicine McGill University Montreal Quebec Canada Novartis Pharmaceuticals Canada Inc. Dotal Quebec Canada

Multiple sclerosis（MS） is characterized by chronic inflammation in conjunction with neurodegeneration within the central nervous system. Most individuals with MS begin with a relapsing remitting course that later transitions to secondary progressive MS. Currently available disease-modifying therapies（DMTs） for relapsing MS have been demonstrated to reduce disease activity, however most patients require a change in therapy over the course of their disease. Treatment goals include the prevention of relapses and disability accumulation and to achieve this objective requires careful planning. Sequencing of DMTs for individual patients should be designed in such a way to maximize disease control and minimize risk based on the mechanism of action, pharmacokinetic and pharmacodynamic properties of each therapy. This includes the DMT patients are being switched from to those they are being switched to. The reversibility of immune system effects should be a key consideration for DMT sequence selection. This feature varies across DMTs and should factor more prominently in decision making as newer treatments become available for the prevention of disability accumulation in patients with progressive MS. In this short review, we discuss the landscape of existing therapies with an eye to the future when planning for optimal DMT sequencing. While no cure exists for MS, efforts are being directed toward research in neuroregeneration with the hope for positive outcomes.

关键词： relapsing multiple sclerosis high efficacy disease-modifying therapies treatment optimization treatment sequencing therapeutic inertia sub-optimal treatment progressive disease immune effects

Effect of Air Plasma Processing on the Adsorption Behaviour of Bovine Serum Albumin on Spin-Coated PMMA Surfaces

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journal of Bionic Engineering 2008年第3期5卷 204-214页

作者： Chaozong Liu brian j. Meenan Advanced Materials and Biomaterials Research Centre School of Engineering The Robert Gordon University Aberdeen ABIO 1FR UK Northern ireland Bioengineering Centre University of Ulster Newtownabbey BT37 OQB Northern Ireland UK

This paper reports the adsorption of Bovine Serum Albumin （BSA） onto Dielectric Barrier Discharge （DBD） processed Poly（methyl methacrylate）（PMMA） surfaces by a Quartz Crystal Microbalance with Dissipation monitoring （QCM-D） technique. The purpose is to study the influence of DBD processing on the nature and scale of BSA adsorption on PMMA surface in vitro. It was observed that DBD processing improves the surface wettability of PMMA film, a fact attributable to the changes in surface chemistry and topography. Exposure of the PMMA to Phosphate Buffed Saline （PBS） solution in the QCM-D system resulted in surface adsorption which reaches an equilibrium after about 30 minutes for pristine PMMA, and 90 minutes for processed PMMA surface. Subsequent injection of BSA in PBS indicated that the protein is immediately adsorbed onto the PMMA surface. It was revealed that adsorption behaviour of BSA on pristine PMMA differs from that on processed PMMA surface. A slower adsorption kinetics was observed for pristine PMMA surface, whilst a quick adsorption kinetics for processed PMMA. Moreover, the dissipation shift of protein adsorption suggested that BSA forms a more rigid structure on pristine PMMA surface that on processed surface. These data suggest that changes in wettability and attendant chemical properties and surface texture of the PMMA surface may play a significant role in BSA adsorption process.

关键词： in vitro test protein adsorption surface modification polymethylmethacrylate QCM-D

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一种新的筛板塔负荷系数关联式

化工装备技术 1990年第3期11卷 34-35页

作者： Thomas j.ward 倪翔

蒸馏塔和吸收塔塔径计算通常基于最大允许气速,而确定气速需要知道负荷系数C_F值。图1为负荷系数与气液动能参数F_(LV)的关联图,参变数是塔板间距t_o动能参数F_(LV)液体质量流速LM_L、气体质量流速VM_v(单位为磅/秒)以及两者的流体密度... 详细信息

蒸馏塔和吸收塔塔径计算通常基于最大允许气速,而确定气速需要知道负荷系数C_F值。图1为负荷系数与气液动能参数F_(LV)的关联图,参变数是塔板间距t_o动能参数F_(LV)液体质量流速LM_L、气体质量流速VM_v(单位为磅/秒)以及两者的流体密度ρ_L、ρ_V有关。

关键词：筛板塔负荷系数关联式

Psychiatric comorbidities in epilepsy:population co-occurrence,genetic correlations and causal effects

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General Psychiatry 2024年第1期37卷 103-111页

作者： Viktor H Ahlqvist Christina Dardani Paul Madley-Dowd Harriet Forbes jessica Rast Caichen Zhong Renee M Gardner Christina Dalman Kristen Lyal cRAIG Newschaffer Torbjorn Tomson Michael Lundberg Daniel Berglind Neil M Davies brian K Lee Cecilia Magnusson Dheeraj Rai Department of Global Public Health Karolinska InstitutetStockholmSweden Medical Research Council Integrative Epidemiology Unit Bristol Medical SchoolUniversity of BristolBristolUK Centre for Academic Mental Health Population Health SciencesBristol Medical SchoolUniversity of BristolBristolUK Faculty of Epidemiology and Population Health London School of Hygiene and Tropical MedicineLondonUK A.j.Drexel Autism Institute Drexel UniversityPhiladelphiaPAUSA Department of Epidemiology and Biostatistics School of Public HealthDrexel UniversityPhiladelphiaPAUSA College of Health and Human Development Pennsylvania State UniversityState CollegePAUSA Department of Clinical Neuroscience Karolinska InstitutetStockholmSweden Centre for Epidemiology and Community Medicine Region StockholmStockholmSweden K.G jebsen Center for Genetic Epidemiology Department of Public Health and NursingNorwegian University of Science and TechnologyTrondheimNorway Division of Psychiatry University Collge LondonLondonUK Department of Statistical Sciences University Cllge LondonLondonK NIHR Biomedical Research Centre University of BristoBristolUK Avon and Wiltshire Partnership NHS Mental Health TrustBristolUK

Background Psychiatric comorbidities are common in patients with *** for the co-occurrence of psychiatric conditions and epilepsy remain poorly *** We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these *** Using nationwide Swedish health registries,we quantified the lifetime prevalence of psychiatric disorders in patients with *** then used summarydata from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score ***,we assessed the potential bidirectional relationships using two-sample Mendelian *** In a cohort of 7628495 individuals,we found that almost half of the 94435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime(adjusted lifetime prevalence,44.09%;95%confidence interval(Cl)43.78%to 44.39%).We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric *** example,we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder(r,=0.18,95%Cl 0.09 to 0.27,p<0.001)—a correlation that was more pronounced in focal epilepsy(r=0.23,95%CI 0.09 to 0.36,p<0.001).Findings from Mendelian randomisation using common genetic variants did not support bidirectional effects between epilepsy and neurodevelopmental or psychiatric *** Psychiatric comorbidities are common in patients with *** correlations may partially explain some comorbidities;however,there is little evidence of a bidirectional relationship between the genetic liability of epilepsy and psychiatric *** findings highlight the need to understand the role of environmental factors or rare genetic variations in the origins of psy

关键词： epilepsy Psychiat lifetime