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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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Emerging insights into the function of very long chain fatty acids at cerebellar synapses

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Neural Regeneration Research 2025年第6期20卷 1709-1710页

作者： martin-Paul Agbaga Mohiuddin Ahmad Department of Cell Biology and Ophthalmology University of Oklahoma Health Sciences Centerand Dean McGee Eye InstituteOklahoma CityOKUSA

Very long chain-saturated and-polyunsaturated fatty acids(VLC-SFA and VLC-PUFA, respectively) are a functionally important class of fatty acids containing 28 carbons or more in their acyl chain. They are synthesized by the elongation of very long fatty acids-4(ELOVL4) enzyme, expressed mainly in the brain, retina, skin, testes, and meibomian gland, where these fatty acids are found(Agbaga et al., 2008). Further, these organs exhibit tissuespecific VLC-PUFA and VLC-SFA biosynthesis and incorporation into complex lipids for specific functions. In the brain, skin, and Meibomian glands, the ELOVL4 mainly makes VLC-SFA, which are incorporated into complex sphingolipids. In the retina, the ELOVL4 makes VLC-PUFA that are incorporated into phosphatidylcholine, that are critical for visual function, while in testes and sperm, the VLC-PUFA are incorporated into sphingolipids that are critical for fertility(Yeboah et al., 2021).

关键词： functions function insight

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Soil moisture content as a predictor of soil disturbance caused by wheeled forest harvesting machines on soils of the Western Carpathians

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Journal of Forestry Research 2017年第2期28卷 283-289页

作者： Michal Allman martin Jankovsk valéria Messingerov Zuzana Allmanov Department of Forest Harvesting Logistics and AmeliorationsFaculty of ForestryTechnical University in ZvolenT.G.Masaryka 24960 53 ZvolenSlovakia

Limiting surface soil disturbance caused by forest harvesting machines is an important task and is influenced by the selection of efficient and reliable predictors of such disturbance. Our objective was to determine whether soil moisture content affects soil load bearing capacity and the formation of ruts. Measurements were conducted in six forest stands where various machines operated. We measured the formation of ruts along skid trails in connection with varying soil moisture content. Soil moisture content was determined through the gravimetric sampling method. Our results showed that severe（rut depth16–25 cm） to very severe disturbance（rut depth [26 cm）occurred in forest stands where the instantaneous soil moisture exceeded its plasticity limits defined through Atterberg limits. Atterberg limits of soil plasticity ranged from 26 to 32 % in individual stands. Regression and correlation analysis confirmed a moderately strong relationship（R = 0.52; p ／ 0.05） between soil moisture content and average rut depth. This confirmed that soil moisture is a suitable and effective predictor of soil disturbance.

关键词： disturbance moisture machines stands plasticity harvesting predictor moderately operated limits

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Alternative Strategy for Development of Dielectric Calcium Copper Titanate‑Based Electrolytes for Low‑Temperature Solid Oxide Fuel Cells

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Nano-Micro Letters 2025年第1期17卷 310-332页

作者： Sajid Rauf Muhammad Bilal Hanif Zuhra Tayyab Matej Veis MAKYousaf Shah Naveed Mushtaq Dmitry Medvedev Yibin Tian Chen Xia martin Motola Bin Zhu College of Mechatronics and Control Engineering Shenzhen UniversityShenzhen 518060People’s Republic of China Department of Inorganic Chemistry Faculty of Natural SciencesComenius University BratislavaIlkovicova684215 BratislavaSlovakia Energy Storage Joint Research Center School of Energy and EnvironmentSoutheast UniversityNanjing 210096People’s Republic of China Hydrogen Energy Laboratory Ural Federal University620002 EkaterinburgRussia Laboratory of Electrochemical Devices Based on Solid Oxide Proton Electrolytes Institute of High Temperature Electrochemistry620066 EkaterinburgRussia School of Microelectronics Hubei UniversityWuhan 430062People’s Republic of China

The development of low-temperature solid oxide fuel cells(LT-SOFCs)is of significant importance for realizing the widespread application of *** has stimulated a substantial materials research effort in developing high oxide-ion conductivity in the electrolyte layer of *** this context,for the first time,a dielectric material,CaCu_(3)Ti_(4)O_(12)(CCTO)is designed for LT-SOFCs electrolyte application in this *** individual CCTO and its heterostructure materials with a p-type Ni_(0.8)Co_(0.15)Al_(0.05)LiO_(2−δ)(NCAL)semiconductor are evaluated as alternative electrolytes in LT-SOFC at 450–550℃.The single cell with the individual CCTO electrolyte exhibits a power output of approximately 263 mW cm^(-2) and an open-circuit voltage(OCV)of 0.95 V at 550℃,while the cell with the CCTO–NCAL heterostructure electrolyte capably delivers an improved power output of approximately 605 mW cm^(-2) along with a higher OCV over 1.0 V,which indicates the introduction of high hole-conducting NCAL into the CCTO could enhance the cell performance rather than inducing any potential short-circuiting *** is found that these promising outcomes are due to the interplay of the dielectric material,its structure,and overall properties that led to improve electrochemical mechanism in CCTO–***,density functional theory calculations provide the detailed information about the electronic and structural properties of the CCTO and NCAL and their heterostructure CCTO–*** study thus provides a new approach for developing new advanced electrolytes for LT-SOFCs.

关键词： LT-SOFCs Dielectric CaCu_(3)Ti_(4)O_(12) Semiconductor Ni_(0.8)Co_(0.15)Al_(0.05)LiO_(2−δ) Ionic conductivity Heterostructure electrolyte

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Movement analysis in the diagnosis and management of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 485-486页

作者： Johannes Burtscher Nicolas Bourdillon Jules MJanssen Daalen Aurélien Patoz Julien FBally martin Kopp Davide Malatesta Bastiaan RBloem Institute of Sport Sciences University of LausanneLausanneSwitzerland Radboud University Medical Center Department of NeurologyDonders Institute for BrainCognition and BehaviorCenter of Expertise for Parkinson and Movement DisordersNijmegenThe Netherlands Radboud University Medical Center Department of Medical BioSciencesNijmegenThe Netherlands Research and Development Department Volodalen Swiss Sport LabAigleSwitzerland Service of Neurology Department of Clinical NeurosciencesLausanne University Hospital(CHUV)and University of Lausanne(UNIL)LausanneSwitzerland Department of Sport Science University of InnsbruckInnsbruckAustria

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall ***,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses *** biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).

关键词： diagnosis Clinical eventually

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Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of Methodology 2025年第1期15卷 20-25页

作者： Nadeesha R Samarasinghe Taniya S Nagpal Michele L Barbeau Charys M martin Division of General Surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada Department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary *** investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(MSK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving MSK anatomy knowledge,PA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of MSK concepts(90.0%)and activity levels(97.7%).Many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in PA based interventions to supplement MSK course *** with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： Medical education Musculoskeletal Anatomy Exercise Online learning

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The martin moving grate technology

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Waste Disposal and Sustainable Energy 2023年第3期5卷 283-293页

作者： Ralf Koralewska Ulrich martin Max Schönsteiner martin GmbH für Umwelt-und Energietechnik Leopoldstrasse 24680807MunichGermany

The thermal treatment of waste using grate-based systems has gained global acceptance as the preferred method for sustainable management of residual *** is because the energy content of the waste is utilized and quality products and residues are *** Waste-to-Energy(WtE)plants are extremely *** knowledge of“fuel”waste and its effects on the design and operation of WtE plants is crucial for the successful planning and operation of these *** respond to new challenges and/or priorities,developing and implementing innovative technologies is *** long-term global partnerships and innovative grate and combustion technologies,martin guarantees that in future,residual waste will be treated following ecological and economic constraints and in compliance with international legal requirements.

关键词： Waste-to-Energy Combustion Grate technologies Heating value Developing countries

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Anatomically realistic multiscale models of normal and abnormal gastrointestinal electrical activity

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World Journal of Gastroenterology 2007年第9期13卷 1378-1383页

作者： Leo K Cheng rie Komuro Travis M Austin martin L Buist Andrew J Pullan Bioengineering Institute The University of Auckland Private Bag 92019 Auckland 1142 New Zealand Division of Bioengineering National University of SingaporeSingapore Bioengineering Institute The University of Auckland Private Bag 92019 Auckland 1142 New ZealandDepartment of Engineering Science The University of Auckland

One of the major aims of the International Union of Physiological Sciences (IUPS) Physiome Project is to develop multiscale mathematical and computer models that can be used to help understand human health. We present here a small facet of this broad plan that applies to the gastrointestinal system. Specifically, we present an anatomically and physiologically based modelling framework that is capable of simulating normal and pathological electrical activity within the stomach and small intestine. The continuum models used within this framework have been created using anatomical information derived from common medical imaging modalities and data from the Visible Human Project. These models explicitly incorporate the various smooth muscle layers and networks of interstitial cells of Cajal (ICC) that are known to exist within the walls of the stomach and small bowel. Electrical activity within individual ICCs and smooth muscle cells is simulated using a previously published simplified representation of the cell level electrical activity. This simulated cell level activity is incorporated into a bidomain representation of the tissue, allowing electrical activity of the entire stomach or intestine to be simulated in the anatomically derived models. This electrical modelling framework successfully replicates many of the qualitative features of the slow wave activity within the stomach and intestine and has also been used to investigate activity associated with functional uncoupling of the stomach.

关键词： Model Bidomain Simulation Interstitial cells of Cajal Physiome GIOIE

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JET and the Physics Basis of ITER

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Plasma Science and Technology 2004年第1期6卷 2109-2122页

作者： martin Keilhacker Kapellengartenstr. 11 D-81247 Mimchen Germany Director of JET Joint Undertaking from 1992- 1999

JET has made unique contributions to the physics basis of ITER by virtue ofits ITER-like geometry, large plasma size and D-T capability. The paper discusses recent JET resultsand their implications for ITER in the areas of standard ELMy H-mode, D-T operation and advancedtokamak modes. In ELMy H-mode the separation of plasma energy into core and pedestal contributionsshows that core confinement scales like gyroBohm transport. High triangularity has a beneficialeffect on confinement and leads to an integrated plasma performance exceeding the ITER Q =10reference case. A revised type I ELM scaling predicts acceptable ELM energy losses for ITER, whileprogress in physics understanding of NTMs shows how to control them in ITER. The D-T experiments of1997 have validated ICRF scenarios for heating ITER/a reactor and identified ion minority schemes(e.g. (~3He)DT) with strong ion heating. They also show that the slowing down of alpha particles isclassical so that the self-heating by fusion alphas should cause no unexpected problems. With thePellet Enhanced Performance mode of 1988, JET has produced the first advanced tokamak mode, withpeaked pressure profiles sustained by reversed magnetic shear and strongly reduced transport. Morerecently, LHCD has provided easy tuning of reversed shear and reliable access to ITBs. Improvedphysics understanding shows that rational g-surfaces play a key role in the formation anddevelopment of ITBs. The demonstration of real time feedback control of plasma current and pressureprofiles opens the path towards fully controlled steady-state tokamak plasmas.

关键词： fusion experiment JET high confinement regime ELMy H-mode advanced tokamakscenario D-T experiments physics basis of ITER

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Nodal, zonal, or uniform electricity pricing： how to deal withnetwork congestion

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Frontiers in Energy 2017年第2期11卷 210-232页

作者： martin WEIBELZAHI Friedrich-Alexander-University Erlangen-Nuremberg Discrete Optimi-zation Cauerstr. 11 91058 Erlangen Germany Energy CampusNuremberg Ffirther Str. 250 90429 Nuremberg Germany

In this paper, the main contributions to congestion management and electricity pricing, i.e., nodal, zonal, and uniform electricity pricing, are surveyed. The key electricity market concepts are structured and a formal model framework is proposed for electricity transportation, production, and consumption in the context of limited transmission networks and competitive, welfare maximizing electricity markets. In addition, the main results of existing short-run and long-run congestion management studies are explicitly summarized. In particular, the important interconnection between short-run network management approaches and optimal long-run investments in both generation facilities and network lines are highlighted.

关键词： nodal pricing zonal pricing uniform pricing competitive electricity markets welfare maximization redispatch optimization models

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