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A 3D Human Liver Model of Nonalcoholic Steatohepatitis

Journal of Clinical and Translational Hepatology 2020年第4期8卷 359-370页

作者： marion duriez Agnes Jacquet Lucile Hoet Sandrine Roche Marie-Dominique Bock Corinne Rocher Gilles Haussy Xavier Vigé Zsolt Bocskei Tamara Slavnic Valérie Martin Jean-Claude Guillemot Michel Didier Aimo Kannt Cécile Orsini Vincent Mikol Anne-Céline Le Fèvre Translational Sciences Sanofi1 Avenue Pierre BrossoletteChilly-MazarinFrance IT&M STATS Groupe IT&MNeuilly-sur-SeineFrance Non Clinical Biostatistics SanofiVitry sur SeineFrance Diabetes and Cardiovascular Research SanofiIndustriepark HöchstFrankfurtGermany Institute of Experimental Pharmacology Medical Faculty MannheimUniversity of HeidelbergMannheimGermany

Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the devel-opment of an in vitro 3D model to mimic liver architecture and the NASH environment. Methods:We have developed an in vitro preclinical 3D NASH model by coculturing primary hu-man hepatocytes, human stellate cells, liver endothelial cells and Kupffer cells embedded in a hydrogel of rat collagen on a 96-well plate. A NASH-like environment was induced by ad-dition of medium containing free fatty acids and tumor ne-crosis factor-α. This model was then characterized by biochemical, imaging and transcriptomics analyses. Results:We succeeded in defining suitable culture conditions to main-tain the 3D coculture for up to 10 days in vitro, with the lowest level of steatosis and reproducible low level of inflammation and fibrosis. NASH disease was induced with a custom me-dium mimicking NASH features. The cell model exhibited the key NASH disease phenotypes of hepatocyte injury, steatosis, inflammation, and fibrosis. Hepatocyte injury was highlighted by a decrease of CYP3A4 expression and activity, without loss of viability up to day 10. Moreover, the model was able to stimulate a stable inflammatory and early fibrotic environ-ment, with expression and secretion of several cytokines. A global gene expression analysis confirmed the NASH induc-tion. Conclusions:This is a new in vitro model of NASH dis-ease consisting of four human primary cell-types that exhibits most features of the disease. The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.

关键词： 3D liver model Human primary cells Key features of NASH

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Laser-induced plasma formation in water with up to 400 mJ double-pulse LIBS

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Plasma Science and Technology 2024年第1期26卷 93-100页

作者： marion HENKEL Michelle SIEMENS Ralf METHLING Benjamin EMDE Jörg HERMSDORF Steffen FRANKE Diego GONZALEZ Leibniz Institute for Plasma Science and Technology(INP) Felix-Hausdorff-Straße 2Greifswald 17489Germany Laser Zentrum Hannover e.V.(LZH) Hollerithallee 8Hannover 30419Germany

Double-pulse LIBS is a promising technique for deep-sea *** measurements in shallow water with up to 400 mJ each pulse were done to select laser parameters which promote optimized spectral line emission from plasma even at elevated pressures,where line broadening until loss of most of the spectral information can *** emission spectroscopy,using a Czerny-Turner spectrometer,has been applied to investigate the dependence of the emitted radiation on laser parameters and hydrostatic *** has been found,that higher laser pulse energies,especially with short pulse delay as required in high water pressure,can also have an adverse effect on the measured spectrum.

关键词： double-pulse LIBS underwater plasma formation emission spectrosocpy

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Key technologies for wireless network digital twin towards smart railways

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High-Speed Railway 2024年第1期2卷 1-10页

作者： Ke Guan Xinghai Guo Danping He Philipp Svoboda marion Berbineau Stephen Wang Bo Ai Zhangdui Zhong Markus Rupp State Key Laboratory of Advanced Rail Autonomous Operation Beijing Jiaotong UniversityBeijing 100044China School of Electronic and Information Engineering Beijing Jiaotong UniversityBeijing 100044China Christian Doppler Laboratory for Digital Twin Assisted AI for Sustainable Radio Access Networks Institute of TelecommunicationsTU WienVienna 1040Austria UniversitéGustave Eiffel COSYSLEOSTVilleneuve d′Ascq 59650France VIAVI Marconi Labs VIAVI SolutionsStevenage SG12ANUK Institute of Telecommunications TU WienVienna 1040Austria

An emerging railway technology called smart railway promises to deliver higher transportation efficiency,enhanced comfort in services,and greater *** smart railway is expected to integrate fifth-generation mobile communication(5G),Artificial Intelligence(AI),and other technologies,which poses new problems in the construction,operation and maintenance of railway wireless *** Digital Twins(DTs),which have recently emerged as a new paradigm for the design of wireless networks,can address these problems and enable the whole lifecycle management of railway wireless ***,there are still many scientific issues and challenges for railway-oriented wireless *** key technologies to solve these problems are introduced and described,including characterization of materials'physical-EM properties,autonomous reconstruction of Three-dimensional(3D)environment model,AI-empowered environmental cognition,Ray-Tracing(RT),model-based and AIbased RT acceleration,and generation of multi-spectra sensing ***,this paper presents our research results for each key technology and describes the wireless network planning and optimization system based on highperformance RT developed by our *** paper outlines the framework for realizing the wireless DT of smart railways,providing the direction for future research.

关键词： Digital twin Smart railways Ray tracing Channel characterization

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Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children:results from the French pediatric national registry

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World Journal of Pediatrics 2024年第6期20卷 611-620页

作者： Marguerite Lockhart-Bouron Noemie Vanel Michael Levy Anais R.Briant Etienne Javouhey Sophie Breinig Julia Dina marion Caseris Francois Angoulvant Stephane Leteurtre Morgan Recher David W.Brossier Univ.Lille CHU LilleULR 2694-METRICS:Evaluation Des Technologies de Sante Et Des Pratiques Medicales59000LilleFrance Pediatric Intensive Care Unit CHU de MarseilleMarseilleFrance Pediatric Intensive Care Unit CHU Robert-DebreAssistance Publique Hopitaux de ParisParisFrance UniversitéParis-Cite ParisFrance Biostatistics and Clinical Research Unit CHU de Caen Normandie14000CaenFrance Pediatric Intensive Care Hospices Civils de LyonLyonFrance Neonatal andPediatric IntensiveCare Unit Children's HospitalToulouseFrance Virology Department INSERM U1311 DynamicureUniv CAEN NormandieCHU de Caen14000 CaenFrance Medical School Universite Caen Normandie14000 CaenFrance Department of Pediatrics CHU Robert-DebréAssistance Publique Hopitaux de ParisParisFrance Department Women-Mother-Child Service of PediatricsLausanne University Hospital(CHUV)LausanneSwitzerland Pediatric Intensive Care Unit Réanimation Et Soins Intensifs PéediatriquesCHU de CAENAvenue de La Cote de Nacre14000 CaenFrance CHU Sainte Justine Research Center MontréalCanada

Background Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)is responsible for an important mortality rate *** aimed to evaluate the actual imputability of SARS-CoV-2 on the mortality rate associated with SARS-CoV-2-related illnesses in the pediatric intensive care unit(PICU).Secondary objectives were to identify risk factors for *** This national multicenter comparative study comprised all patients under 18 years old with positive SARS-CoV-2 polymerase chain reactions(PCRs)[acute corona virus disease 2019(COVID-19)or incidental SARS-CoV-2 infection]and/or pediatric inflammatory multisystem syndrome(PIMS)recorded in the French PICU registry(PICURe)between September 1,2021,and August 31,*** patients were classified and compared according to their living status at the end of their PICU *** patients were evaluated by four experts in the field of pediatric infectiology and/or pediatric intensive *** imputability of SARS-CoV-2 as the cause of death was classified into four categories:certain,very probable,possible,or unlikely,and was defined by any of the first three *** There were 948 patients included of which 43 died(4.5%).From this,26 deaths(67%)could be attributed to SARS-CoV-2 infection,with an overall mortality rate of 2.8%.The imputability of death to SARS-CoV-2 was considered certain in only one case(O.1%).Deceased patients suffered more often from comorbidities,especially heart disease,neurological disorders,hematological disease,cancer,and *** of the deceased patients were admitted for pediatric inflam-matory multisystem syndrome(PIMS).Mortality risk factors were male gender,cardiac comorbidities,cancer,and acute respiratorydistress *** SARS-CoV-2 mortality in the French pediatric population was *** though the imputability of SARS-Cov-2 on mortality was considered in almost two-thirds of cases,this imputability was considered certain in only one case.

关键词： Death Pediatric intensive care unit SARS-CoV-2

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A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis

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International Journal of Oral Science 2024年第2期16卷 265-279页

作者： Alfredo Torres M.Angélica Michea Ákos Végvári marion Arce Valentina Pérez Marcela Alcota Alicia Morales Rolando Vernal Mauricio Budini Roman A.Zubarev Fermín E.González Laboratory of Experimental Immunology&Cancer Faculty of DentistryUniversity of ChileSantiagoChile Department of Conservative Dentistry Faculty of DentistryUniversity of ChileSantiagoChile Division of Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden Periodontal Biology Laboratory Faculty of DentistryUniversidad de ChileSantiagoChile Laboratory of Cellular and Molecular Pathology Institute for Research in Dental SciencesFaculty of DentistryUniversity of ChileSantiagoChile

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases,yet its association with progressive periodontitis remains *** investigate the involvement and significance of ferroptosis in periodontitis progression,we assessed sixteen periodontitis-diagnosed *** progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid(GCF)collection was performed for further *** metrics,proteomic data,in silico methods,and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with *** western blot analyses validated key ***,a single-cell RNA sequencing(scRNA-seq)dataset(GSE164241)for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis *** progression was identified as occurring at a faster rate than traditionally *** samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic *** addition,specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins,including SNCA,CA1,HBB,SLC4A1,and ANK1 was strongly associated with the clinical progression status of ***,we found specific proteins-drivers or suppressors-associated with ferroptosis(SNCA,FTH1,HSPB1,CD44,and GCLC),revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of ***,the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to *** analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients,which offer new insights into the molecular mechanisms of progressive periodontal *** findings may le

关键词： finding progression faster

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Abnormal ACT in a Patient with Prekallikrein Deficiency Undergoing Cardiopulmonary Bypass

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Open Journal of Anesthesiology 2024年第5期14卷 145-149页

作者： Maria R. Fuertes Naila Ahmad Orlando Perez-Franco Andrew Oster marion Svendrowski Pin Yue Department of Anesthesiology and Critical Care Saint Louis University School of Medicine St. Louis MO USA

Prekallikrein deficiency is a disorder that often remains undiagnosed. Prekallikrein activates factor XII, which initiates the intrinsic coagulation pathway. Prekallikrein deficiency results in prolonged Partial Thromboplastin Time and Activated Clotting Time in absence of anticoagulants or active bleeding. This case report describes the anesthesia management of a patient with Prekallikrein deficiency who underwent cardiac surgery with Cardiopulmonary Bypass for correction of a congenital cardiac malformation. We highlight the importance of understanding the different tests available for the diagnosis of coagulation factors deficiency during administration of heparin in the setting of cardiovascular procedures under general anesthesia.

关键词： Prekallikrein Deficiency Fletcher Factor Deficiency Cardiopulmonary Bypass Congenital Cardiac Malformation

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Selection Principles and Sierpinski Sets

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Acta Mathematica Sinica,English Series 2007年第7期23卷 1153-1162页

作者： marion SCHEEPERS Department of Mathematics Boise State University

We show that a set of real numbers is a Sierpinski set if, and only if, it satisfies a selection property similar to the familiar Menger property.

关键词： Sierpinski set selection principle infinite game partition relation L-space

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Ion emission from warm dense matter produced by irradiation with a soft x-ray free-electron laser

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Matter and Radiation at Extremes 2024年第1期9卷 71-84页

作者： Josef Krása Tomás Burian Vera Hájková Jaromír Chalupský Šimon Jelínek Katerina Frantálová Michal Krupka Zuzana Kuglerová Sushil Kumar Singh Vojtech Vozda Ludek Vysín MichalŠmíd Pablo Perez-Martin marion Kühlman Juan Pintor Jakub Cikhardt Matthias Dreimann Dennis Eckermann Felix Rosenthal Sam M.Vinko Alessandro Forte Thomas Gawne Thomas Campbell Shenyuan Ren YuanFeng Shi Trevor Hutchinson Oliver Humphries Thomas Preston Mikako Makita Motoaki Nakatsutsumi Xiayun Pan Alexander Köhler marion Harmand Sven Toleikis Katerina Falk Libor Juha Department of Radiation and Chemical Physics Institute of PhysicsCzech Academy of SciencesNa Slovance 218221 Prague 8Czech Republic Laser Plasma Department Institute of Plasma PhysicsCzech Academy of SciencesZa Slovankou 318200 Prague 8Czech Republic Department of Surface and Plasma Science Faculty of Mathematics and PhysicsCharles University in PragueV Holesovi ckách 218000 Prague 8Czech Republic Department of Physical Electronics Faculty of Nuclear Science and Engineering PhysicsCzech Technical University in PragueV Holesovi ckách 218000 Prague 8Czech Republic Helmholtz-Zentrum Dresden-Rossendorf Bautzner Landstraße 40001328 DresdenGermany DESY Photon Science Notkestraße 85D-22607 HamburgGermany Institut de Minéralogie de Physique des Matériaux et de CosmochimieUMR 7590–UPMC/CNRS/IRD/MNHNSorbonne Université4 place Jussieu75005 ParisFrance Department of Physics Faculty of Electrical EngineeringCzech Technical University in PragueTechnická216627 Prague 6Czech Republic Center for Soft Nanoscience University of MünsterBusso-Peus-Straße 10D-48149 MünsterGermany Department of Physics Clarendon LaboratoryUniversity of OxfordParks RoadOxford OX13PUUnited Kingdom Central Laser Facility STFC Rutherford Appleton LaboratoryDidcot OX110QXUnited Kingdom Lawrence Livermore National Laboratory 7000 East AvenueLivermoreCalifornia 94550USA European XFEL GmbH Holzkoppel 4D-22869 SchenefeldGermany Technische Universität Dresden 01062 DresdenGermany

We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric *** the experiment,we focus on study of the ions emitted during the soft x-ray ablation process using time-of-flight electron multipliers and a shifted Maxwell–Boltzmann velocity distribution *** find that most emitted ions are thermal,but that some impurities chemisorbed on the target surface,such as protons,are accelerated by the electrostatic field created in the plasma by escaped *** morphology of the complex crater structure indicates the presence of several ion groups with varying *** find that the ion sound velocity is controlled by the ion temperature and show how the ion yield depends on the FEL radiation attenuation length in different materials.

关键词： electrostatic emitted chemi

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Investigation of Influencing Parameters for Tribological Conditions in Dry Forming Processes

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Acta Metallurgica Sinica(English Letters) 2015年第12期28卷 1435-1441页

作者： Jennifer Steiner marion Merklein Institute of Manufacturing Technology Friedrich-Alexander-Universitat Erlangen-Nürnberg

Environmental awareness and a growing demand for efficient resource utilization encourage the realization of lubricant-free forming processes. A first step in accomplishing dry sheet metal forming is to gain knowledge about the changing tribological conditions and to identify the relevant influencing parameters. The commonly used flat strip drawing test was selected to investigate the tribological conditions in the flange area of deep drawing processes. The influencing factors of contact pressure and varying drawing velocities were analyzed under dry and lubricated conditions. Additionally,the tool and workpiece surfaces were characterized. Besides lubrication, the contact pressure mainly determines the tribological conditions. In lubricated tests higher normal pressure reduces friction, whereas without lubrication higher pressure results in slightly increasing friction. A changing drawing velocity affects the friction when lubricant is applied. In dry experiments, no influence of velocity was found. Results of surface characterization reveal adhesion as main wear mechanism under dry conditions. Based on the investigated influence of the process parameters, an increase in process understanding for dry forming operations is derived.

关键词： Deep drawing Tribology Friction Dry forming

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Thermal response of steel framing members in open car park fires

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Frontiers of Structural and Civil Engineering 2022年第9期16卷 1071-1088页

作者： Xia YAN marion CHARLIER Thomas GERNAY Department of Civil and Systems Engineering Johns Hopkins UniversityBaltimoreMD 21218USA ArcelorMittal Steligence Esch-sur-Alzette 4221Luxembourg

For open car park structures,adopting a performance-based structural fire design is often justified and allowed because the fire does not reach ***,this design approach requires an accurate assessment of temperatures in structural members exposed to car *** paper describes a numerical study on the thermal exposure on steel framing members in open car park *** temperatures are computed by the coupling of computational fluid dynamics and finite element modeling,and by analytical models from the *** addition,the influence of galvanization on the steel temperature evolution is *** show that temperatures in unprotected beams and columns are influenced by the section geometry,car fire scenario,modeling approach,and use of *** slightly delays and reduces peak *** the different models,CFD-FEM(CFD:computational fluid dynamics,FEM:finite-element method)coupled models predict lower temperatures than the Hasemi model,because the latter conservatively assumes that the fire flame continuously touches the ***,the Hasemi model cannot account for the effect of reduced emissivity from galvanization on the absorbed heat *** temperature distributions obtained in the steel members can be used to complete efficient structural fire designs based on the member sections,structure layout,and use of galvanization.

关键词： open car park localized fire steel frame numerical modeling computational fluid dynamics

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