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A variant in IL6ST with a selective IL-11 signaling defect in human and mouse

Bone Research 2020年第2期8卷 157-168页

作者： Tobias Schwerd Freia Krause Stephen R.F.Twigg Dominik Aschenbrenner Yin-Huai Chen Uwe Borgmeyer Miryam Müller Santiago Manrique Neele Schumacher Steven A.Wall Jonathan Jung Timo Damm Claus-Christian Glüer Jürgen Scheller Stefan Rose-John E.Yvonne Jones Arian Laurence Andrew O.M.Wilkie dirk schmidt-arras Holm H.Uhlig Translational Gastroenterology Unit John Radcliffe HospitalUniversity of OxfordOxfordUK Department of Pediatrics Dr von Hauner Children’s HospitalLMU MunichMunichGermany Christian-Albrechts-University Kiel Institute of BiochemistryKielGermany Clinical Genetics Group MRC Weatherall Institute of Molecular MedicineUniversity of OxfordJohn Radcliffe HospitalOxfordUK Center for Molecular Neurobiology Hamburg(ZMNH) University Medical Center Hamburg-EppendorfHamburgGermany Division of Structural Biology Wellcome Trust Centre for Human GeneticsUniversity of OxfordOxfordUK Craniofacial Unit Department of Plastic and Reconstructive SurgeryOxford University Hospitals NHS Foundation TrustJohn Radcliffe HospitalOxfordUK Section Biomedical Imaging Department of Radiology and NeuroradiologyUniversity Medical Center Schleswig-HolsteinKielGermany Institute of Biochemistry and Molecular Biology Ⅱ Medical FacultyHeinrich-Heine-UniversityDüsseldorfGermany Department of Paediatrics University of OxfordOxfordUK NIHR Oxford Biomedical Research Centre OxfordUK The Beatson Institute for Cancer Research GlasgowUK School of Medicine University of GlasgowGlasgowUK

The GP130 cytokine receptor subunit encoded by IL6ST is the shared receptor for ten cytokines of the IL-6 family. We describe a homozygous non-synonymous variant in IL6 ST(p.R281 Q) in a patient with craniosynostosis and retained deciduous teeth. We characterize the impact of the variant on cytokine signaling in vitro using transfected cell lines as well as primary patient-derived cells and support these findings using a mouse model with the corresponding genome-edited variant Il6 st p.R279 Q. We show that human GP130 p.R281 Q is associated with selective loss of IL-11 signaling without affecting IL-6, IL-27, OSM, LIF, CT1, CLC, and CNTF signaling. In mice Il6 st p.R279 Q lowers litter size and causes facial synostosis and teeth abnormalities. The effect on IL-11 signaling caused by the GP130 variant shows incomplete penetrance but phenocopies aspects of IL11 RA deficiency in humans and mice. Our data show that a genetic variant in a pleiotropic cytokine receptor can have remarkably selective defects.

关键词： IL11 cytokine facial

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An Efficient Calculation of Photonic Crystal Band Structures Using Taylor Expansions

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Communications in Computational Physics 2014年第10期16卷 1355-1388页

作者： dirk Klindworth Kersten schmidt Research Center MATHEON TU BerlinDepartment of MathematicsStraße des 17.Juni 13610623 BerlinGermany.

In this paper we present an efficient algorithm for the calculation of photonic crystal band structures and band structures of photonic crystal *** method relies on the fact that the dispersion curves of the band structure are smooth functions of the quasi-momentum in the one-dimensional Brillouin *** show the derivation and computation of the group velocity,the group velocity dispersion,and any higher derivative of the dispersion *** derivatives are then employed in a Taylor expansion of the dispersion *** control the error of the Taylor expansion with the help of a residual estimate and introduce an adaptive scheme for the selection of nodes in the one-dimensional Brillouin zone at which we solve the underlying eigenvalue problem and compute the derivatives of the dispersion *** proposed algorithm is not only advantageous as it decreases the computational effort to compute the band structure but also because it allows for the identification of crossings and anti-crossings of dispersion curves,*** identification is not possible with the standard approach of solving the underlying eigenvalue problem at a discrete set of values of the quasi-momentum without taking the mode parity into account.

关键词： Photonic crystals band structure calculation group velocity Taylor expansion adaptivity

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Fulminant myocarditis in adults: a narrative review

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Journal of Geriatric Cardiology 2022年第2期19卷 137-151页

作者： Santiago Montero Darryl Abrams Enrico Ammirati Florent Huang dirk WDonker Guillaume Hekimian Cosme García-García Antoni Bayes-Genis Alain Combes Matthieu schmidt Acute Cardiovascular Care Unit Heart InstituteHospital Germans Trias i PujolDepartament de MedicinaUniversitat Autònoma de BarcelonaCIBERCVSpain Assistance Publique-Hôpitaux de Paris Pitié-Salpêtrière HospitalMedical Intensive Care UnitParisFrance Columbia University Vagelos College of Physicians&Surgeons/NewYork-Presbyterian Hospital New YorkUSA Center for Acute Respiratory Failure Columbia University Irving Medical CenterNew YorkUSA De Gasperis Cardio Center and Transplant Center Niguarda HospitalMilanoItaly Cardiology Hôpital FochSuresnesParisFrance Intensive Care Center University Medical Center UtrechtUtrechtthe Netherlands Cardiovascular and Respiratory Physiology TechMed CenterUniversity of TwenteEnschedethe Netherlands Sorbonne Université INSERM UMRS_1166-iCANInstitute of Cardiometabolism and NutritionParisFrance

Fulminant myocarditis(FM)is an uncommon syndrome characterized by sudden and severe hemodynamic compromise secondary to acute myocardial inflammation,often presenting as profound cardiogenic shock,life-threatening ventricular arrhythmias and/or electrical *** may be refractory to conventional therapies and require mechanical circulatory support(MCS).The immune system has been recognized as playing a pivotal role in the pathophysiology of myocarditis,leading to an increased focus on immunosuppressive treatment *** data have highlighted not only the fact that FM has significantly worse outcomes than non-FM,but that prognosis and management strategies of FM are heavily dependent on histological subtype,placing greater emphasis on the role of endomyocardial biopsy in *** impact of subtype on severity and prognosis will likewise influence how aggressively the myocarditis is managed,including whether MCS is *** patients with refractory cardiogenic shock secondary to FM end up requiring MCS,with venoarterial extracorporeal membrane oxygenation demonstrating favorable survival rates,particularly when initiated prior to the development of multiorgan *** the challenges facing the field are the need to more precisely identify immunopathophysiological pathways in order to develop targeted therapies,and the need to better optimize the timing and management of MCS to minimize complications and maximize outcomes.

关键词： myocarditis initiated storm

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Genomic landscape of pancreatic neuroendocrine tumors

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World Journal of Gastroenterology 2014年第46期20卷 17498-17506页

作者： Niklas Gebauer Christian schmidt-Werthern Veronica Bernard Alfred C Feller Tobias Keck Nehara Begum dirk Rades Hendrik Lehnert Georg Brabant Christoph Thorns Department of Pathology University Hospital of Schleswig-Holstein23538 LuebeckGermany Department of Surgery University Hospital of Schleswig-Holstein23538 LuebeckGermany Department of Radiation Oncology University Hospital of Schleswig-Holstein 23538 LuebeckGermany Department of Internal Medicine I University Hospital of Schleswig-Holstein23538 LuebeckGermany

AIM: To investigate the prognostic role of genomic stability and copy number alterations (CNAs) pancreatic neuroendocrine tumors (PanNETs).

关键词： Array comparative genomic hybridization Copy number alterations Chromosomal aberrations Pancreatic neuroendocrine tumors Prognosis

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Observation of a single protein by ultrafast X-ray diffraction

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Light(Science & Applications) 2024年第1期13卷 80-90页

作者： Tomas Ekeberg Dameli Assalauova Johan Bielecki Rebecca Boll Benedikt J.Daurer Lutz A.Eichacker Linda E.Franken Davide E.Galli Luca Gelisio Lars Gumprecht Laura H.Gunn Janos Hajdu Robert Hartmann dirk Hasse Alexandr Ignatenko Jayanath Koliyadu Olena Kulyk Ruslan Kurta Markus Kuster Wolfgang Lugmayr Jannik Lübke Adrian P.Mancuso Tommaso Mazza Carl Nettelblad Yevheniy Ovcharenko Daniel E.Rivas Max Rose Amit K.Samanta Philipp schmidt Egor Sobolev Nicusor Timneanu Sergey Usenko Daniel Westphal Tamme Wollweber Lena Worbs Paul Lourdu Xavier Hazem Yousef Kartik Ayyer Henry N.Chapman Jonas A.Sellberg Carolin Seuring Ivan A.Vartanyants Jochen Küpper Michael Meyer Filipe R.N.C.Maia Laboratory of Molecular Biophysics Department of Cell and Molecular BiologyUppsala UniversityHusargatan 3(Box 596)SE-75124 UppsalaSweden Deutsches Electronen-Synchrotron DESY Notkestrasse 8522607 HamburgGermany European XFEL Holzkoppel 422869 SchenefeldGermany Diamond Light Source Harwell Science&Innovation CampusDidcot OX110DEUK University of Stavanger Centre Organelle ResearchRichard-Johnsensgate 44021 StavangerNorway Leibniz Institute for Experimental Virology(HPI) Centre for Structural Systems BiologyNotkestraße 8522607 HamburgGermany Dipartimento di Fisica“Aldo Pontremoli” Universitàdegli Studi di Milanovia Celoria 1620133 MilanoItaly Center for Free-Electron Laser Science DESY22607 HamburgGermany Plant Biology Section School of Integrative Plant ScienceCornell UniversityIthacaNY 14853USA PNSensor GmbH Otto-Hahn-Ring 6D-81739 MünchenGermany Biomedical and X-Ray Physics Department of Applied PhysicsAlbaNova University CenterKTH Royal Institute of TechnologySE-10691 StockholmSweden ELI Beamlines/IoP Institute of Physics AS CR v.v.i.Na Slovance 218221 Prague 8Czech Republic Multi-User CryoEM Facility Centre for Structural Systems BiologyNotkestr.8522607 HamburgGermany University Medical Center Hamburg-Eppendorf(UKE) Martinistrasse 5220246 HamburgGermany The Hamburg Center for Ultrafast Imaging Universität HamburgLuruper Chaussee 14922761 HamburgGermany Department of Physics Universität HamburgLuruper Chaussee 14922761 HamburgGermany Department of Chemistry and Physics La Trobe Institute for Molecular ScienceLa Trobe UniversityMelbourneVIC 3086Australia Division of Scientific Computing Science for Life LaboratoryDepartment of Information TechnologyUppsala UniversityBox 337SE-75105 UppsalaSweden European Molecular Biology Laboratory c/o DESYNotkestrasse 8522607 HamburgGermany Department of Physics and Astronomy Uppsala UniversityBox 516SE-75120 UppsalaSweden Max Planck Institute for the Structure and Dynamics of Matter Luruper Chaussee 14922761 HamburgGe

The idea of using ultrashort X-ray pulses to obtain images of single proteins frozen in time has fascinated and inspired *** was one of the arguments for building X-ray free-electron *** to theory,the extremely intense pulses provide sufficient signal to dispense with using crystals as an amplifier,and the ultrashort pulse duration permits capturing the diffraction data before the sample inevitably *** was first demonstrated on biological samples a decade ago on the giant *** then,a large collaboration has been pushing the limit of the smallest sample that can be *** ability to capture snapshots on the timescale of atomic vibrations,while keeping the sample at room temperature,may allow probing the entire conformational phase space of *** we show the first observation of an X-ray diffraction pattern from a single protein,that of Escherichia coli GroEL which at 14 nm in diameter is the smallest biological sample ever imaged by X-rays,and demonstrate that the concept of diffraction before destruction extends to single *** the pattern,it is possible to determine the approximate orientation of the *** experiment demonstrates the feasibility of ultrafast imaging of single proteins,opening the way to single-molecule time-resolved studies on the femtosecond timescale.

关键词： smallest intense ultrafast

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寸金能买寸光阴——利用平面直接驱动装置节约装备时间和仓库费用

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现代制造 2003年第16期 28-31页

作者： dirk schmidt Andreas Zeiff

人们常说“寸金难买寸光阴”。这句话已经过时啦！因为如果你花钱买到效率和质量的同时,其实你就是买到了时间,并且“买一送一”,因此还节省了不少金钱。利用平面直接驱动装置节约装备时间和仓库费用,就是这种类似的好事。

关键词：平面直接驱动装置装备时间仓库费用夹具制造

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口服和静脉铁剂替代治疗对于炎性肠病患者肠道微生物和代谢组学的改变截然不同

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英国医学杂志中文版 2017年第9期20卷 416-416页

作者： Thomas Lee Thomas Clavel Kirill Smirnov Annemarie schmidt Ilias Lagkouvardos Aiesia Walker Marianna Lucio Bernhard Michalke Philippe Schmitt-Kopplin Richard Fedorak dirk Hailer 毛玲娜宋震亚不详浙江大学医学院附属第二医院全科医学科

目的缺铁是炎性肠病（IBD）患者常见的并发症，但口服铁剂治疗被认为可能加重IBD症状。我们进行一项开放临床研究，比较口服铁剂治疗与静脉铁剂治疗的作用。方法人选31例克罗恩病（CD）、22例溃疡性结肠炎（UC）和19例非炎性病变患者作... 详细信息

目的缺铁是炎性肠病（IBD）患者常见的并发症，但口服铁剂治疗被认为可能加重IBD症状。我们进行一项开放临床研究，比较口服铁剂治疗与静脉铁剂治疗的作用。方法人选31例克罗恩病（CD）、22例溃疡性结肠炎（UC）和19例非炎性病变患者作为对照。受试者随机接受口服硫酸亚铁治疗（PO）或者静脉注射蔗糖铁剂治疗（Iv）3个月，评价干预前后的临床指标、肠道菌群及代谢组学变化。结果口服和静脉治疗都能改善缺铁，静脉治疗后铁蛋白水平更高。疾病的活动度与铁剂治疗方法无关。IBD的肠道菌群有明显的个体间差异，梭菌属丰度和比例降低。代谢物分析也能明显区分CD、UC和对照组。约有一半的受试者在接受铁剂替代治疗后出现明显的细菌种属的多样性转变，其中CD者最为敏感。除铁剂替代治疗可导致个体．菌种属的特异性变化外，口服铁剂治疗还引起普氏粪杆菌、布氏瘤胃球菌、多利亚芽孢杆菌和产气柯氏杆菌属的操作分类单元（operationaltaxonomicunits，OTUs）丰度下降。代谢组学分析发现，Iv和PO治疗后胆固醇代谢相关的宿主底物水平有明显的改变。结论铁剂治疗可以导致IBD的肠道菌群结构和代谢产物改变。虽然临床结局类似，口服与静脉铁剂治疗对肠道菌群种属和代谢产物的改变有所不同。

关键词：静脉铁剂炎性肠病患者微生物肠道

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可快速安装的模块化采暖系统

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现代制造 2020年第4期 47-47页

作者： dirk schmidt 不详

物流大厅最好采用模块化结构的建筑方式来建造,它比砖砌建筑方式的建造速度要快70%,通常可以在6个月内完成物流大厅的建造。很短的建筑施工周期对建筑企业提出了很高的要求。预装的太阳能辐射采暖设备能够帮助用户轻松的完成物流大厅的... 详细信息

物流大厅最好采用模块化结构的建筑方式来建造,它比砖砌建筑方式的建造速度要快70%,通常可以在6个月内完成物流大厅的建造。很短的建筑施工周期对建筑企业提出了很高的要求。预装的太阳能辐射采暖设备能够帮助用户轻松的完成物流大厅的建筑施工任务。

关键词：太阳能辐射采暖设备采暖系统建筑施工模块化结构快速安装砖砌建筑物流

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