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国外畜牧学（猪与禽） 2024年第1期44卷 12-13页

作者： Katia Pedrosa kathrin buehler Jan Dirk Van der Klis 张相鑫(译) 王晶晶(校) 孟祥光(制图) 不详

维生素D是一种重要的营养物质,母猪在妊娠后期和哺乳期对其需要量非常高。本文概述了维生素D对母猪分娩的影响,提出可以在常规添加维生素D之外补充1,25-二羟基维生素D3糖苷,以缩短分娩时间,减少分娩过程中的人为干预,减少死胎数。

关键词：维生素D 1 25-二羟基维生素D3糖苷分娩

Conception of a new 4-quadrant hydrogen compressed air energy storage power plant with an integrated electrolyzer

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Energy Reviews 2024年第3期3卷 92-101页

作者： Hans-Peter Beck Ann-kathrin Klaas Christoph Klaas Research Center Energy Storage Technologies Clausthal University of TechnologyAm Stollen 19A38640GoslarGermany Institute of Electrical Power Engineering and Energy Systems Clausthal University of TechnologyLeibnizstraße 2838678Clausthal-ZellerfeldGermany

A hydrogen compressed air energy storage power plant with an integrated electrolyzer is ideal for large-scale,long-term energy storage because of the emission-free operation and the possibility to offer multiple ancillary services on the German energy *** paper defines analyzes such a storage concept and conducts an extensive comparison with four additional storage concepts based on various *** results show that the combination of storing compressed air and hydrogen offers a higher efficiency than storing only hydrogen and lower specific investment costs than storing only compressed *** result is confirmed with analysis of the optimal sizing of each power plant component for simultaneous participation on multiple energy markets with a linear optimization dispatch *** hydrogen compressed air energy storage(HCAES)power plant can utilize more revenue possibilities than a hydrogen energy storage because of the higher round-trip efficiency and the combination of the air compressor and the integrated electrolyzer during charging *** integration of the electrolyzer,however,offers a couple of challenges itself because of the highly flexible operation mode.A new concept for the controllable 24-pulse diode-thyristor rectifier of the electrolyzer is presented,that uses mostly common components while offering little to no grid harmonics and a long *** flexible integrated electrolyzer allows for the 4-quadrant operation of the storage power plant.

关键词： Long-term energy storage Hydrogen energy storage Compressed air energy storage Mixed-integer linear programming Electrolyzer 24-Pulse thyristor rectifier

Network analyses:Inhibition of androgen receptor signaling reduces inflammation in the lung through AR-MAF-IL6 signaling axes

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Genes & Diseases 2024年第3期11卷 140-143页

作者： Albert R.Wang Andrew M.Baschnagel Zijian Ni Sean R.Brennan Hypatia K.Newton Darya buehler Christina Kendziorski Randall J.Kimple Gopal lyer Department of Human Oncology University of Wisconsin School of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA Department of Biomedical Engineering University of Wisconsin-MadisonMadisonWI 53705USA University of Wisconsin Carbone Cancer Center MadisonWI 53705USA Department of Biostatistics and Medical Informatics University of Wisconsin-MadisonMadisonWI 53706USA Department of Biology Tufts UniversityMedfordMA 02155USA Department of Pathology and Laboratory Medicine University of Wisconsin School of Medicine and Public HealthUniversity of WisconsinMadisonWI 53705USA

Androgen receptor(AR)is a major transcription factor that plays a role in inflammatory response including interleukin-6(IL6)signaling.1 While AR regulation through paracrine loop signaling in prostate tissue is well-studied,its impact through an IL6 autocrine loop in the lung has not been wellstudied despite the organ's response to respiratory viral *** inhibition and RNA knockdown of AR identified a bZIP transcription factor MAF to be a common target of inflammation using these perturbations in lung cells.

关键词： inflammation lung respiratory

Ca^(2+) binding to the C_(2)E domain of otoferlin is required for hair cell exocytosis and hearing

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Protein & Cell 2024年第4期15卷 305-312页

作者： Han Chen Mehar Monga Qinghua Fang Loujin Slitin Jakob Neef Shashank S.Chepurwar Regina Célia Mingroni Netto Karina Lezirovitz Alfredo Tabith,Jr. Fritz Benseler Nils Brose kathrin Kusch Carolin Wichmann Nicola Strenzke Barbara Vona Julia Preobraschenski Tobias Moser Institute for Auditory Neuroscience and InnerEarLab University Medical Center Göttingen37075 GöttingenGermany Collaborative Research Center 889 University of Göttingen37075 GöttingenGermany Auditory Neuroscience and Synaptic Nanophysiology Group Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Göttingen Graduate Center for Neurosciences Biophysics and Molecular BiosciencesUniversity of Göttingen37075 GöttingenGermany Biochemistry of Membrane Dynamics Group Institute for Auditory NeuroscienceUniversity Medical Center Göttingen37075 GöttingenGermany Molecular Architecture of Synapses Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Center for Biostructural Imaging of Neurodegeneration University Medical Center Göttingen37075 GöttingenGermany Auditory Systems Physiology Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Departamento de Genética e Biologia Evolutiva Centro de Pesquisas sobre o Genoma Humano e Células-TroncoInstituto de BiociênciasUniversidade de São PauloSão Paulo 05508-220Brazil Laboratório de Otorrinolaringologia/LIM32 Faculdade de MedicinaHospital das ClínicasUniversidade de São PauloSão PauloSP 05508-220Brazil DERDIC Pontifícia Universidade Católica de São PauloSão Paulo 05508-220Brazil Department of Molecular Neurobiology Max Planck Institute for Multidisciplinary Sciences37075 GöttingenGermany Multiscale Bioimaging Cluster of Excellence(MBExC) University of Göttingen37075 GöttingenGermany Functional Auditory Genomics Group Auditory Neuroscience and Optogenetics LaboratoryGerman Primate Center37077 GöttingenGermany Hearing Genomics Group Institute for Auditory Neuroscience and InnerEarLabUniversity Medical Center Göttingen37075 GöttingenGermany Institute of Human Genetics University Medical Center Göttingen37075 GöttingenGermany

Dear Editor,Afferent synapses of cochlear inner hair cells(IHCs)employ a unique molecular machinery(see extended background in Supplementary Materials).Otoferlin is a key player in this machinery and its defects cause human auditory synaptopathy(Moser and Starr,2016).Otoferlin,a tail-anchored(Vogl et al.,2016)multi-C_(2)-domain protein(Fig.1Ai)specific to hair cells(Roux et al.,2006),is a member of the ferlin protein family involved in membrane trafficking and repair that are of major disease relevance(Pangršičet al.,2012),also see Supplementary *** is distributed broadly within IHCs(Fig.2Ai-Aiii;Pangrsic et al.,2010;Roux et al.,2006).

关键词： auditory hair

Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela Schulz Martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German Center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany Center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for Metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany Department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

MULTISCALE MECHANICS OF BIOLOGICAL AND BIOLOGICALLY INSPIRED MATERIALS AND STRUCTURES

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Acta Mechanica Solida Sinica 2010年第6期23卷 471-483页

作者： Markus J.buehler Laboratory for Atomistic and Molecular Mechanics Department of Civil and Environmental EngineeringMassachusetts Institute of Technology Center for Computational Engineering Massachusetts Institute of Technology Center for Materials Science and Engineering Massachusetts Institute of Technology

The world of natural materials and structures provides an abundance of applications in which mechanics is a critical issue for our understanding of functional material properties. In particular, the mechanical properties of biological materials and structures play an important role in virtually all physiological processes and at all scales, from the molecular and nanoscale to the macroscale, linking research fields as diverse as genetics to structural mechanics in an approach referred to as materiomics. Example cases that illustrate the importance of mechanics in biology include mechanical support provided by materials like bone, the facilitation of locomotion capabilities by muscle and tendon, or the protection against environmental impact by materials as the skin or armors. In this article we review recent progress and case studies, relevant for a variety of applications that range from medicine to civil engineering. We demonstrate the importance of fundamental mechanistic insight at multiple time- and length-scales to arrive at a systematic understanding of materials and structures in biology, in the context of both physiological and disease states and for the development of de novo biomaterials. Three particularly intriguing issues that will be discussed here include： First, the capacity of biological systems to turn weakness to strength through the utilization of multiple structural levels within the universality-diversity paradigm. Second, material breakdown in extreme and disease conditions. And third, we review an example where the hierarchical design paradigm found in natural protein materials has been applied in the development of a novel hiomaterial based on amyloid protein.

关键词： biological materials materiomics mechanics mechanical properties mutability,tunability deformation failure

Linking atomic structural defects to mesoscale properties in crystalline solids using graph neural networks

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npj Computational Materials 2022年第1期8卷 1886-1898页

作者： Zhenze Yang Markus J.buehler Laboratory for Atomistic and Molecular Mechanics(LAMM) Massachusetts Institute of Technology77 Massachusetts Ave.CambridgeMA02139USA Department of Materials Science and Engineering Massachusetts Institute of Technology77 Massachusetts Ave.CambridgeMA02139USA Center for Computational Science and Engineering Schwarzman College of ComputingMassachusetts Institute of Technology77 Massachusetts AveCambridgeMA02139USA Center for Materials Science and Engineering 77 Massachusetts Ave CambridgeMA02139USA

Structural defects are abundant in solids,and vital to the macroscopic materials ***,a defect-property linkage typically requires significant efforts from experiments or simulations,and often contains limited information due to the breadth of nanoscopic design *** we report a graph neural network(GNN)-based approach to achieve direct translation between mesoscale crystalline structures and atom-level properties,emphasizing the effects of structural *** end-to-end method offers great performance and generality in predicting both atomic stress and potential energy of multiple systems with different ***,the approach also precisely captures derivative properties which strictly observe physical laws and reproduces evolution of properties with varying boundary *** incorporating a genetic algorithm,we then design de novo atomic structures with optimum global properties and target local *** method would significantly enhance the efficiency of evaluating atomic behaviors given structural imperfections and accelerates the design process at the meso-level.

关键词： structural solids crystalline

Compressive deformation of ultralong amyloid fibrils

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Acta Mechanica Sinica 2010年第6期26卷 977-986页

作者： Raffaella Paparcone Steven Cranford Markus J.buehler Laboratory for Atomistic and Molecular Mechanics

Involved in various neurodegenerative diseases, amyloid fibrils and plaques feature a hierarchical structure, ranging from the atomistic to the micrometer *** the atomistic level,a dense and organized hydrogen bond network is resembled in a beta-sheet rich secondary structure, which drives a remarkable stiffness in the range of 10-20GPa,larger than many other biological nanofibrils, a result confirmed by both experiment and ***, the understanding of how these exceptional mechanical properties transfer from the atomistic to the nanoscale remains *** we report a multiscale analysis that, from the atomistic-level structure of a single fibril,extends to the mesoscale level,reaching size scales of hundreds of *** use parameters directly derived from full atomistic simulations of Aβ（1-40） amyloid fibrils to parameterize a mesoscopic coarse-grained model,which is used to reproduce the elastic properties of amyloid *** then apply our mesoscopic model in an analysis of the buckling behavior of amyloid fibrils with different lengths and report a comparison with predictions from continuum beam theory. An important implication of our results is a severe reduction of the effective modulus due to buckling,an effect that could be important to interpret experimental results of ultralong amyloid *** model represents a powerful tool to mechanically characterize molecular structures on the order of hundreds of nanometers to micrometers on the basis of the underlying atomistic *** work provides insight into structural and mechanical properties of amyloid fibrils and may enable further analysis of larger-scale assemblies such as amyloidogenic bundles or plaques as found in disease states.

关键词： Amyloid Coarse-grain Molecular simulation Nanomechanics Materiomics

The dynamical complexity of work-hardening:a large-scale molecular dynamics simulation

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Acta Mechanica Sinica 2005年第2期21卷 103-111页

作者： MarkusJ.buehler AlexanderHartmaier MarkA.Duchaineau FaridEAbraham HuajianGao MaxPlanckInstituteforMetalsResearch Heisenbergstrasse3D-70569StuttgartGermany CaliforniaInstituteofTechnology 1201EastCaliforniaBlvd.Pasadena91125CAUSA//MaxPlanckInstituteforMetalsResearchHeisenbergstrasse3D-70569StuttgartGermany LawrenceLivermoreNationalLaboratory 7000EastAve.LivermoreCA94550USA IBMAlmadenResearchCenter 650HarryRoadSanJoseCA95120USA

We analyze a large-scale molecular dynamics simulation of work hardening in a model system of a ductile solid. With tensile loading, we observe emission of thousands of dislocations from two sharp cracks. The dislocations interact in a complex way, revealing three fundamental mechanisms of work-hardening in this ductile material. These are (1) dislocation cutting processes, jog formation and generation of trails of point defects; (2) activation of secondary slip systems by Frank-Read and cross-slip mechanisms; and (3) formation of sessile dislocations such as Lomer-Cottrell locks. We report the discovery of a new class of point defects referred to as trail of partial point defects, which could play an important role in situations when partial dislocations dominate plasticity. Another important result of the present work is the rediscovery of the Fleischer-mechanism of cross-slip of partial dislocations that was theoretically proposed more than 50 years ago, and is now, for the first time, confirmed by atomistic simulation. On the typical time scale of molecular dynamics simulations, the dislocations self-organize into a complex sessile defect topology. Our analysis illustrates numerous mechanisms formerly only conjectured in textbooks and observed indirectly in experiments. It is the first time that such a rich set of fundamental phenomena have been revealed in a single computer simulation, and its dynamical evolution has been studied. The present study exemplifies the simulation and analysis of the complex nonlinear dynamics of a many-particle system during failure using ultra-large scale computing.

关键词： Work-hardening Large-scale atomistic simulation Dislocation junction Cross-slip

Computational and theoretical modeling of intermediate filament networks:Structure,mechanics and disease

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Acta Mechanica Sinica 2012年第4期28卷 941-950页

作者： Zhao Qin Markus J. buehler Laboratory for Atomistic and Molecular Mechanics (LAMM) Department of Civil and Environmental Engineering 77 Massachusetts Ave. Massachusetts Institute of Technology Room 1-235 A&B Cambridge 02139 MA USA Center for Computational Engineering Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA Center for Materials Science and Engineering Massachusetts Institute of Technology77 Massachusetts Ave. Cambridge MA 02139 USA

Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cells, intermediate filament proteins play key roles to reinforce cells subjected to large-deformation, and that they participate in signal transduction, and it was proposed that their nanome- chanical properties are critical to perform those functions. However, it is still poorly understood how the nanoscopic structure, as well as the combination of chemical composition, molecular structure and interfacial properties of these protein molecules contribute to the biomechanical properties of filaments and filament networks. Here we review recent progress in computational and theoretical studies of the intermediate filaments network at various levels in the protein＇s structure. A multiple scale method is discussed, used to couple molecular modeling with atomistic detail to larger-scale material properties of the networked material. It is shown that a finer-trains-coarser method- ology as discussed here provides a useful tool in understanding the biomechanical property and disease mechanism of intermediate filaments, coupling experiment and simulation. It further allows us to improve the understanding of associated disease mechanisms and lays the foundation for engineering the mechanical properties of biomaterials.

关键词： Intermediate filament network - Multiple scale method Nanoscopic structure Mechanics Disease mechanism Molecular mechanics