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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech frank tim. beil Michael Amling Johannes Keller Anita Ignatius tim.r A.Yorgan tim.Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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大陆集团总部

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现代装饰 2024年第3期 32-41页

作者： Arsen Aliverdiev(设计) Michael Bertram(设计) Kerstin El-Khawad(设计) Gunter Fleitz(设计) Eva Perez Fons(设计) Lisa Holler(设计) Leticia Hutchings(设计) Peter Ippolito(设计) Christiane Klinner(设计) Susann Kreplin(设计) frank Lakmann(设计) tim.Lessmann(设计) Eleonora Mannisi(设计) Thomas Mura(设计) Maria Cristina Orizzonte(设计) Jana Stumpe(设计) Bradley Wheeler(设计) Elisabed Zautashvili(设计) Werner Huthmacher(摄影) Ippolito Fleitz Group(摄影) 不详

“The Future in Motion”是大陆集团的座右铭,而大陆集团的品牌“Continental”则代表着面向未来、可持续发展和团结协作的理念。由于原集团总部的面积不再能满足公司的未来发展,大陆集团决定在德国汉诺威毗邻城市森林的位置新建一座... 详细信息

“The Future in Motion”是大陆集团的座右铭,而大陆集团的品牌“Continental”则代表着面向未来、可持续发展和团结协作的理念。由于原集团总部的面积不再能满足公司的未来发展,大陆集团决定在德国汉诺威毗邻城市森林的位置新建一座总部。新总部的设计以共享办公为概念,可为多达2400名员工提供工作场所。新楼经过五年建设,于2023年12月投入使用。

关键词：集团总部德国汉诺威可持续发展团结协作大陆座右铭

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Electrical properties and microstructure formation of V/Al-based n-contacts on high Al mole fraction n-AlGaN layers

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Photonics Research 2020年第8期8卷 1381-1387页

作者： LUCA SULMONI frank MEHNKE ANNA MOGILATENKO MARTIN GUTTMANN tim.WERNICKE MICHAEL KNEISSL Institut für Festkorperphysik Technische Universitat Berlin10623 BerlinGermany Ferdinand-Braun-Institut Leibniz-Institut fur Höchstfrequenztechnik12489 BerlinGermany Institut für Physik Humboldt Universität zu Berlin12489 BerlinGermany

The electrical and structural properties of V/Al-based n-contacts on n‐AlxGa1−xN with an Al mole fraction x ranging from x=0.75 to x=0.95 are *** n-contacts are obtained up to x=0.75 with a contact resistivity of 5.7×10^−4Ω·cm^2 whereas for higher Al mole fraction the IV characteristics are *** electron microscopy reveals a thin crystalline AlN layer formed at the metal/semiconductor interface upon thermal *** analysis confirmed an Al enrichment at the *** interfacial nitride-based layer in n-contacts on n‐Al0.9Ga0.1N is partly amorphous and heavily contaminated by *** role and resulting limitations of Al in the metal stack for n-contacts on n-AlGaN with very high Al mole fraction are ***,ultraviolet C(UVC)LEDs grown on n‐Al0.87Ga0.13N and emitting at 232 nm are fabricated with an operating voltage of 7.3 V and an emission power of 120μW at 20 mA in cw operation.

关键词： AlGaN fraction properties

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SARS-CoV-2 inhibition and specific targeting of infected cells by VSV particles carrying the ACE2 receptor

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Signal Transduction and Targeted Therapy 2023年第6期8卷 2463-2466页

作者： Fabian Zech Stefanie Weber Hanna Dietenberger Linyun Zhang Sabrina Noettger Meta Volcic tim.Bergner Clarissa Read Konstantin M.J.Sparrer Thomas F.E.Barth frank Kirchhoff Institute of Molecular Virology Ulm University Medical CenterUlmGermany Institute of Pathology Ulm UniversityUlmGermany Central Facility for Electron Microscopy Ulm UniversityUlmGermany

Dear Editor Effective vaccines and some antiviral agents against SARS-CoV-2,the causative agent of coronavirus disease 2019(COVID-19),have been ***,additional therapeutics are needed since emerging SARS-CoV-2 variants evade immunity induced by vaccination or previous infection and are resistant to therapeutic antibodies and fusion inhibitors.^(1)In addition,many patients experience prolonged post-acute sequelae of SARS-CoV-2.

关键词： ACE2 immunity acute

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Therapeutic targeting of epidermal growth factor receptor in human cancer: successes and limitations

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Chinese Journal of Cancer 2011年第1期30卷 5-12页

作者： Jill Wykosky tim.Fenton frank Furnari Webster K. Cavenee Ludwig Institute for Cancer Research University of California San Diego Department of Medicine University of California San Diego

Epidermal growth fac tor receptor (EGFR) is one of the most commonly altered genes in human cancer by way of over-expression, amplification, and mutation. Targeted inhibition of EGFR activity suppresses signal transduction pathways which control tumor cell growth, proliferation, and resistance to apoptosis. Small molecule tyrosine kinase inhibitors and monoclonal antibodies are among the most common EGFR-targeting agents and have been used clinically for treating various malignancies. This review discusses the successes and challenges of targeting EGFR in human cancer. The genetic alterations of EGFR tend to occur more often in some solid tumors than others, as do the mechanisms of resistance to targeted inhibition. The clinical and basic science experiences with these agents thus far have important implications for the future of therapeutic targeting of EGFR.

关键词：表皮生长因子受体靶向治疗癌症人类酪氨酸激酶抑制剂信号转导通路恶性肿瘤临床治疗

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Electrical and optical characteristics of highly transparent MOVPE-grown AlGaN-based tunnel heterojunction LEDs emitting at 232 nm

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Photonics Research 2021年第6期9卷 1117-1123页

作者： frank MEHNKE CHRISTIAN KUHN MARTIN GUTTMANN LUCA SULMONI VERENA MONTAG JOHANNES GLAAB tim.WERNICKE MICHAEL KNEISSL Institute of Solid State Physics Technische Universität Berlin10623 BerlinGermany Ferdinand-Braun-Institut Leibniz-Institut für Höchstfrequenztechnik12489 BerlinGermany Current address:School of Electrical and Computer Engineering Georgia Institute of TechnologyAtlantaGeorgia 30332USA

We present the growth and electro-optical characteristics of highly transparent AlGaN-based tunnel heterojunction light-emitting diodes(LEDs)emitting at 232 nm entirely grown by metalorganic vapor phase epitaxy(MOVPE).A GaN:Si interlayer was embedded into a highly Mg-and Si-doped Al_(0.87)Ga_(0.13)N tunnel junction to enable polarization field enhanced *** LEDs exhibit an on-wafer integrated emission power of 77μWat 5 mA,which correlates to an external quantum efficiency(EQE)of 0.29%with 45μWemitted through the bottom sapphire substrate and 32μW emitted through the transparent top *** depositing a highly reflective aluminum reflector,a maximum emission power of 1.73 mW was achieved at 100 mA under pulsed mode operation with a maximum EQE of 0.35%as collected through the bottom substrate.

关键词： heterojunction MOVPE AlGaN

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Golimumab in real-world practice in patients with ulcerative colitis:Twelve-month results

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World Journal of Gastroenterology 2020年第21期26卷 2852-2863页

作者： Niels Teich Harald Grümmer Eric Jorgensen Thomas Liceni frank Holtkamp-Endemann tim.Fischer Susanne Hohenberger Internistische Gemeinschaftspraxis für Verdauungs-und Stoffwechselkrankheiten Leipzig und Schkeuditz Leipzig 04105Germany Praxis für Innere Medizin/Gastroenterologie Potsdam 14471Germany Magen-Darm-Zentrum Remscheid Remscheid 42859Germany MVZ für Gastroenterologie am Bayerischen Platz Berlin 10825Germany Gastroenterologische Gemeinschaftspraxis am Germania-Campus Münster 48159Germany Medical Affairs MSD Sharp and Dohme GmbHHaar 85540Germany

BACKGROUND The introduction of biologics has revolutionized the management of the chronic inflammatory bowel disease,ulcerative colitis(UC),with many patients experiencing significant improvements not only in their symptoms but in other outcomes relevant to individuals and society as a *** Germany,there are no prospective data>3 mo that assess the work productivity,daily activities and quality of life(QoL)of patients with moderate-to-severe UC treated with *** To assess change in work productivity,capacity for daily activities and QoL in UC patients treated with golimumab in *** The validated Work Productivity Activity Impairment(WPAI)Questionnaire was used to analyze the change in work productivity,the capacity for daily activities after three months(primary endpoint)and disease specific and health related QoL(HRQoL)up to 1 year(secondary endpoints).The changes in work productivity and activity impairment were evaluated every three months until month twelve compared to ***-specific and health-related QoL were assessed with the inflammatory bowel disease questionnaire and with the short-form 12 health survey questionnaire(SF-12).RESULTS This prospective non-interventional study included 287 *** analysis population was comprised of 282 patients who had completed at least two *** baseline,61%of patients had moderate UC and 18%had severe ***,75%of patients worked full-tim. or part-tim. at baseline.A total of 212 patients who were employed at the start of the study(employed population)were evaluated for the primary *** significantly reduced all WPAI sub-scores compared to baseline after three,six,nine and twelve months after the start of treatment(Ptim.s(P<0.0001 in each case vs baseline).CONCLUSION Treatment of moderate-to-severe UC with golimum

关键词： Ulcerative colitis Quality of life Work productivity Non-interventional study Golimumab Work Productivity Activity Impairment(WPAI)Questionnaire

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Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第20期12卷 3275-3282页

作者： Lars A Ormandy Anatol Frber Tobias Cantz Susanne Petrykowska Heiner Wedemeyer Monique Hrning frank Lehner Michael P Manns Firouzeh Korangy tim.F Greten Department of Gastroenterology Hepatology and Endocrinology Hannover Medical SchoolGermany Departments of Visceral and Transplantation Surgery Hannover Medical School Germany

瞄准：与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法：骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80， CD83， CD86 和 HLA... 详细信息

瞄准：与肝细胞癌(HCC ) 从病人分析树枝状的房间(DC ) 的显型和功能以便在这疾病理解他们的角色。方法：骨髓的的树枝状的房间在 HCC 病人的外部血被枚举。从外部血的天真、刺激的骨髓的的树枝状的房间上的 CD80， CD83， CD86 和 HLA 医生表示被分析。骨髓的的树枝状的房间从外部血被孤立，他们的功能被测试。吞噬作用用 FITC 葡聚糖祷告被分析，肽特殊刺激，在多形核白细胞 dI:dC 之上刺激 allogeneic T 房间和 cytokines 的分泌物的能力被测试。结果：骨髓的的树枝状的房间与 HCC 在病人被减少。在 CD80， CD83， CD86 和 HLA 医生表示的差别都没从 HCC 病人和健康控制在天真、刺激的骨髓的的树枝状的房间上被发现。肽 specific T 房间的正常吞噬作用或刺激与一个损害 allo-stim.latory 能力和减少的 IL-12 分泌物相对照被观察。结论：在病人的 mDCs 的损害 IL-12 生产能导致建议指导治疗可以提高的那 IL-12 的天真的 T 房间的一个损害 stim.latory 能力在 HCC 病人的肿瘤 specific 免疫者回答。

关键词：树状细胞肝细胞癌骨髓细胞外周血

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Process Window Expansion of Laser Chemical Machining by Using High Pressure

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Materials Sciences and Applications 2020年第5期11卷 296-304页

作者： Marcel Simons tim.Radel frank Vollertsen BIAS-Bremer Institut für Angewandte Strahltechnik Bremen Germany Faculty of Production Engineering-Mechanical Engineering & Process Engineering University of Bremen Bremen Germany

Laser Chemical Machining (LCM) is a non-conventional removal process, based on a precise thermal activation of heterogeneous chemical reactions between an electrolyte and a metallic surface. Due to local overheating during the process, boiling bubbles occur, which can impair the removal quality. In order to reduce the amount of bubbles, the laser chemical process is performed at different process pressures. Removal experiments were performed on Titanium Grade 1 using the electrolyte phosphoric acid at various process pressures, machining speeds and laser powers in order to determine the limit of the process window by evaluating the characteristics of the removal cavities. As a result, the process window for non-disturbed laser chemical machining is widened at higher process pressures. The process pressures have no influence on the geometric shape of the removal. The expansion of the process window is attributed to the fact that at higher process pressures the saturation temperature of the electrolyte rises, so that bubble boiling starts at a higher surface temperature on the workpiece induced by the laser power. The removal rate could be increased by a factor of 2.48 by increasing the process pressures from ambient pressure to 6 bar, thus taking an important step towards the economic efficiency of the laser chemical machining.

关键词： Micro Machining Laser Micro Machining Laser Chemical Removal Removal Rate Process Pressure

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Recombination mechanisms and thermal droop in AlGaN-based UV-B LEDs

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Photonics Research 2017年第2期5卷 44-51页

作者： CARLO DE SANTI MATTEO MENEGHINI DESIREE MONTI JOHANNES GLAAB MARTIN GUTTMANN JENS RASS SVEN EINFELDT frank MEHNKE JOHANNES ENSLIN tim.WERNICKE MICHAEL KNEISSL GAUDENZIO MENEGHESSO ENRICO ZANONI Department of Information Engineering University of Padova Ferdinand-Braun-Institut Leibniz-Institut fur Hochstfrequenztechnik Technische Universitat Berlin Institut für Festkorperphysik

This paper reports a comprehensive analysis of the origin of the electroluminescence(EL)peaks and of the thermal droop in UV-B AlGaN-based *** carrying out spectral measurements at several temperatures and currents,(i)we extract information on the physical origin of the various spectral bands,and(ii) we develop a novel closed-form model based on the Shockley–Read–Hall theory and on the ABC rate equation that is able to reproduce the experimental data on thermal droop caused by non-radiative recombination through deep *** the samples under test,the three EL bands are ascribed to the following processes:band-to-band recombination in the quantum wells(main EL peak),a parasitic intra-bandgap radiative transition in the quantum well barriers,and a second defect-related radiative process in the p-AlGaN superlattice.

关键词： Recombination mechanisms and thermal droop in AlGaN-based UV-B LEDs Ga AlGaN EBL SRH UV

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