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Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S.pneumoniae

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Synthetic and Systems Biotechnology 2017年第1期2卷 49-58页

作者： Allison E.B.Turner Jonas E.gerson Helen Y.So Daniel J.Krasznai Adrienne J.St.Hilaire donald f.gerson Vaccine Research and Development PnuVax Incorporated Headquarters134 Albert St.KingstonOntarioK7L 3V2Canada Vaccine Research and Development PnuVax Incorporated Laboratories6000 Royalmount Ave.MontrealQuebecH4P 2T1Canada

Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing world.The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human vaccine development.The 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6B,7f,9V,14,18C,19A,19f,and 23f.Pneumococcal polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation methods.In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein.In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 days.Post-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable.Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2.As a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV development.The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.

关键词： Pneumonia Vaccine development PCV Pneumococcal conjugate vaccine Polysaccharide Carrier protein In vacuo glycation

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Mechanically Joined Extrusion Profiles for Battery Trays

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Automotive Innovation 2024年第1期7卷 182-193页

作者： florian Kneuper Stefan Neumann AndréSchulze Mortaza Otroshi A.Erman Tekkaya gerson Meschut Institute of forming Technology and Lightweight Components(IUL) TU Dortmund University44227 DortmundGermany Laboratory for Material and Joining Technology(LWf) Paderborn UniversityPaderbornGermany

In the context of electromobility,ensuring the leak tightness of assemblies is of paramount importance,particularly in bat-tery housings.Current battery housings,often featuring base assemblies crafted from extruded aluminum profiles,address the challenge of leak tightness at joints through methods like friction stir welding,a process known for its time and cost intensiveness.The aim of this study is to develop and implement a new type of extruded profile concept to produce tight base assemblies for battery housings by a longitudinal mechanical single stroke joining process.The geometry,the process and the properties of the aluminum profiles are investigated to get a joint that meets the tightness requirements and achieve high load-bearing capacities in agreement with the high homologation requirements set to vehicles with high-voltage systems.The joint is formed by means of a single stage press stroke,which eliminates the need for complex tool designs that are neces-sary for continuous joining(roll joining).flat steel contact surfaces are used as joining tools.To evaluate the joint quality,force curves from the joining process are analyzed and the resulting joint geometries are assessed using micrographs.The resulting leak tightness of the linear joints is measured by a helium sniffer leak detector and the load-bearing capacities are investigated by shear lap and bending tests and fatigue strength test.The study also explores whether a difference in strength between the two joining partners has a positive effect on the joint properties.

关键词： Joining by plastic deformation Aluminum Leak Tightness

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Global paleobiogeography of Albian—Cenomanian(mid-Cretaceous)marine ostracods

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Journal of Palaeogeography 2024年第2期13卷 212-236页

作者： Bernardo Vázquez-García Jorge Villegas-Martín gerson fauth Leonardo Borghi Aristóteles De Moraes Rios Netto Post-Graduate Program in Geology Unisinos UniversitySao LeopoldoRSBrazil Technological Institute of Paleoceanography and Climate Change-Itt Oceaneon Unisinos UniversitySao LeopoldoRSBrazil Laboratory of Sedimentary Geology(Lagesed) Department of GeologyInstitute of GeosciencesUFRJ-Federal Universityof Riode JaneiroBrazil Labmicro Department of GeologyInstitute of GeosciencesUFRJ-Federal University of Rio de JaneiroBrazil

Despite their potential for providing important information for paleobiogeography,studies using ostracod assemblages compiled from global datasets have been scarce so far.In this study,the paleogeographic implications of the relationship between different ostracod assemblages are analyzed and discussed for the Albian and Cenomanian.We compiled an ostracod dataset at the genus level,with 168 genera for the Albian and 174 for the Cenomanian,to which different multivariate statistical methods of grouping were applied.The affinity between different ostracod assemblages from different regions allowed for the delineation of 30 operational geographic units(OGUs)for the Albian,and 32 OGUs for the Cenomanian,grouped in three paleobiogeographic units(PBUs;Megatethys,Persia,and Austral)and one sub-unit(PBSU;Maghreb associated to the Megatethys).The Maghreb PBSU showed minor changes between the Albian and Cenomanian.The relationship among the OGUs grouped in each PBU is related to different factors,such as eustatic sea level events,similar climatic zones,and marine current circulation patterns.A relationship was observed between the Gabon and Nigeria OGUs with the Persia PBU,which suggests a direct east—west connection between them during the Cenomanian.The affinity observed in the Austral PBU between the South American,South African,and Australian regions during the Albian can be explained by their relative geographic isolation due to the Walvis Ridge barrier.The eventual flooding of this barrier led to the relationship observed between the SE Brazilian and Bolivian regions with the Austral PBU.finally,the data also suggested that the separation of the Indian subcontinent from the Austral PBU took place during the Cenomanian.

关键词： Operational geographic units Paleobiogeographic units Albian Cenomanian Marine ostracods

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Metabolic collaboration between cells in the tumor microenvironment has a negligible effect on tumor growth

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The Innovation 2024年第2期5卷 107-114页

作者： Johan Gustafsson fariba Roshanzamir Anders Hagnestål Sagar M.Patel Oseeyi I.Daudu donald f.Becker Jonathan L.Robinson Jens Nielsen Department of Life Sciences Chalmers University of TechnologySE-41296 GothenburgSweden Hagnesia AB SE-43854 HindåsSweden Department of Biochemistry and Redox Biology Center University of Nebraska-LincolnLincolnNE 68588USA BioInnovation Institute DK2200 CopenhagenDenmark

The tumor microenvironment is composed of a complex mixture of different cell types interacting under conditions of nutrient deprivation,but the metabolism therein is not fully understood due to difficulties in measuring metabolic fluxes and exchange of metabolites between different cell types in vivo.Genome-scale metabolic modeling enables estimation of such exchange fluxes as well as an opportunity to gain insight into the metabolic behavior of individual cell types.Here,we estimated the availability of nutrients and oxygen within the tumor microenvironment using concentration measurements from blood together with a metabolite diffusion model.In addition,we developed an approach to efficiently apply enzyme usage constraints in a comprehensive metabolic model of human cells.The combined modeling reproduced severe hypoxic conditions and the Warburg effect,and we found that limitations in enzymatic capacity contribute to cancer cells’preferential use of glutamine as a substrate to the citric acid cycle.furthermore,we investigated the common hypothesis that some stromal cells are exploited by cancer cells to produce metabolites useful for the cancer cells.We identified over 200 potential metabolites that could support collaboration between cancer cells and cancer-associated fibroblasts,but when limiting to metabolites previously identified to participate in such collaboration,no growth advantage was observed.Our work highlights the importance of enzymatic capacity limitations for cell behaviors and exemplifies the utility of enzyme-constrained models for accurate prediction of metabolism in cells and tumor microenvironments.

关键词： metabolism effect limitations

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Unimolecular Reactions of E-Glycolaldehyde Oxide and Its Reactions with One and Two Water Molecules

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Research 2024年第1期6卷 809-824页

作者： Yan Sun Bo Long donald G.Truhlar Department of Physics Guizhou UniversityGuiyang 550025China College of Materials Science and Engineering Guizhou Minzu UniversityGuiyang 550025China Department of Chemistry Chemical Theory Centerand Supercomputing InstituteUniversity of MinnesotaMinneapolisMN 55455-0431USA

The kinetics of Criegee intermediates are important for atmospheric modeling.However,the quantitative kinetics of Criegee intermediates are still very limited,especially for those with hydroxy groups.Here,we calculate rate constants for the unimolecular reaction of E-glycolaldehyde oxide[E-hydroxyethanal oxide,E-(CH_(2)OH)CHOO],for its reactions with H_(2)O and(H_(2)O)_(2),and for the reaction of the E-(CH_(2)OH)CHOO…H_(2)O complex with H_(2)O.for the highest level of electronic structure,we use W3X-L//CCSD(T)-f12a/cc-pVDZ-f12 for the unimolecular reaction and the reaction with water and W3X-L//Df-CCSD(T)-f12b/jun-cc-pVDZ for the reaction with 2 water molecules.for the dynamics,we use a dual-level strategy that combines conventional transition state theory with the highest level of electronic structure and multistructural canonical variational transition state theory with small-curvature tunneling with a validated density functional for the electronic structure.

关键词： structure kinetics molecular

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An unexpected cellular fountain of youth:platelets provide factors rejuvenating brain functions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 16-18页

作者： Harald f.Langer Department of Cardiology AngiologyHaemostaseology and Medical Intensive CareUniversity Medical Centre MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany German Centre for Cardiovascular Research(DZHK) Partner Site Heidelberg/MannheimMannheimGermany European Center for Angioscience Medical Faculty MannheimHeidelberg UniversityMannheimGermany Cardiovascular systems biology Medical Clinic IUniversity Heart Center LübeckLübeckGermany

In a recent manuscript published in Nature,Schroer et al.discovered that platelets and in particular platelet derived Pf-4(CXCL4)are a novel factor,which can rejuvenate the mammalian neuronal system.1 These findings have the potential to trigger an entire new field of research opening new platelet-derived candidate effector molecules for supporting regeneration.

关键词： supporting platelets finding

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Corn and Soybean Growth as Affected by Wastewater-Derived Struvite-Phosphorus Sources and Irrigation Water Types

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Agricultural Sciences 2024年第4期15卷 472-504页

作者： Machaela Morrison Kristofor R. Brye gerson Drescher Jennie Popp Lisa S. Wood Department of Crop Soil and Environmental Sciences University of Arkansas Fayetteville AR USA Department of Agricultural Economics & Agribusiness University of Arkansas Fayetteville AR USA

Struvite (MgNH4PO4·6H2O) produced synthetically from a stock solution of known phosphorus (P) and nitrogen (N) concentrations has been shown to be an effective, alternative fertilizer-P source for various crops, but little is known about the potential agronomic effectiveness of struvite created from an actual municipal wastewater source. The objective of this study was to evaluate the effects of soil [i.e., Creldon silt loam (Oxyaquic fragiudalf) and Calloway silt loam (Aquic fraglossudalf) series], fertilizer-P source [i.e., synthetically produced electrochemically precipitated struvite (ECSTsyn), real-wastewater-derived ECST (ECSTreal), chemically precipitated struvite (CPST), monoammonium phosphate (MAP), and an unamended control (UC)], and irrigation water type (i.e., tapwater and struvite-removed wastewater) on corn (Zea mays L.) and soybean [Glycine max (L.) Merr.] growth and N, P, and magnesium (Mg) uptake in a 60-day, greenhouse potted-plant study. Crop growth and N, P, and Mg uptakes for the struvite treatments (i.e., CPST, ECSTsyn, and ECSTreal) were generally similar to or at least 1.2 times greater than MAP. The ECSTsyn material commonly had up to five times greater N, P, and Mg uptake in corn and soybean than any other fertilizer-P source. Struvite-removed wastewater resulted in at least 1.3 times lower dry matter and N, P, and Mg uptake than tapwater. Similar corn and soybean results from the struvite fertilizers among the various soil-water type combinations compared to MAP suggest that struvite generates similar crop responses as at least one widely used, commercially available, multi-nutrient fertilizer-P source.

关键词： Arkansas Corn Production Soybean Production Struvite Recovered Nutrients

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Premature axon-oligodendrocyte interaction contributes to stalling of experimental axon regeneration after injury to the white matter

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Neural Regeneration Research 2024年第3期19卷 469-470页

作者： Ephraim f.Trakhtenberg Department of Neuroscience University of Connecticut School of MedicineFarmingtonCTUSA

Studies from nearly 3 decades ago suggested that,in the central nervous system(CNS),myelination of axons by oligodendrocytes not only helps improve axonal conductivity but also stabilizes circuitry(Colello and Schwab,1994).Over the years,myelin sheaths produced by oligodendrocytes have been found to contain multiple molecules that are inhibitory to axonal growth(e.g.,MAG,NogoA,OMgp,Semaphorins)(Yiu and He,2006;Silver et al.,2014).After white matter injury in the adult CNS,myelin debris from damaged axons and dead oligodendrocytes accumulates in the forming glial scar and exposes these myelin-associated axon growth-inhibitory molecules to the injured axonal stumps,thereby contributing to the inhibition of axonal regrowth.During development,CNS axons reach their postsynaptic targets and stop growing before oligodendrocytes appear and myelinate them(foran and Peterson,1992;Dangata et al.,1996).Therefore,myelin-associated axon growth-inhibitory molecules interacting with already grown axons during myelination were thought to block axons from promiscuous sprouting and miswiring,thereby stabilizing neural circuitry in the CNS(Colello and Schwab,1994).

关键词： thereby white injury

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Cognition and movement in neurodegenerative disorders:a dynamic duo

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Neural Regeneration Research 2024年第10期19卷 2101-2102页

作者： Marit f.L.Ruitenberg Department of Health Medical and NeuropsychologyLeiden UniversityLeidenthe Netherlands Leiden Institute for Brain and Cognition Leidenthe Netherlands

People with neurodegenerative disorders often experience problems across a variety of functional domains,including cognition,movement,and psychosocial functioning.The classification of these disorders is based on the phenotypical manifestations that represent the most prominent clinical features.for example,Parkinson's disease and Huntington's disease are typically regarded as movement disorders,whereas Alzheimer's disease(AD) and other dementias are regarded as cognitive disorders.

关键词： disorders Huntington degenerative

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Bolstering integrity in environmental data science and machine learning requires understanding socioecological inequity

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frontiers of Environmental Science & Engineering 2024年第5期18卷 171-179页

作者： Joe f.Bozeman III School of Civil and Environmental Engineering Georgia Institute of TechnologyAtlantaGA30332USA School of Public Policy Georgia Institute of TechnologyAtlantaGA30332USA

Socioecological inequity in environmental data science—such as inequities deriving from data-driven approaches and machine learning(ML)—are current issues subject to debate and evolution.There is growing consensus around embedding equity throughout all research and design domains—from inception to administration,while also addressing procedural,distributive,and recognitional factors.Yet,practically doing so may seem onerous or daunting to some.The current perspective helps to alleviate these types of concerns by providing substantiation for the connection between environmental data science and socioecological inequity,using the Systemic Equity framework,and provides the foundation for a paradigmatic shift toward normalizing the use of equity-centered approaches in environmental data science and ML settings.Bolstering the integrity of environmental data science and ML is just beginning from an equity-centered tool development and rigorous application standpoint.To this end,this perspective also provides relevant future directions and challenges by overviewing some meaningful tools and strategies—such as applying the Wells-Du Bois Protocol,employing fairness metrics,and systematically addressing irreproducibility;emerging needs and proposals—such as addressing data-proxy bias and supporting convergence research;and establishes a ten-step path forward.Afterall,the work that environmental scientists and engineers do ultimately affect the well-being of us all.

关键词： Equity Bias Machine Learning Data Science Justice Systemic Equity

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