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Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF–RANKL signaling

Bone Research 2018年第1期6卷 50-59页

作者： Alexander Bartelt Friederike Behler-Janbeck F.Timo Beil Till Koehne Brigitte Müller tobias schmidt Markus Heine Laura Ochs Tayfun Yilmaz Martin Dietrich Jan P.Tuckermann Michael Amling Joachim Herz Thorsten Schinke Joerg Heeren Andreas Niemeier Department of Orthopaedics University Medical Center Hamburg-EppendorfMartinistr.5220246 HamburgGermany Department of Biochemistry and Molecular Cell Biology University Medical Center Hamburg-EppendorfMartinistr.5220246 HamburgGermany Department of Osteology and Biomechanics University Medical Center Hamburg-EppendorfMartinistr5220246 HamburgGermany Department of Orthodontics University Medical Center Hamburg-EppendorfMartinistr52 20246 HamburgGermany Department of Anatomy and Experimental Morphology University Medical Center Hamburg-EppendorfMartinistr.5220246 HamburgGermany Department of Molecular Genetics University of Texas Southwestern Medical CenterDallasTX 75390USA Institute for Comparative Molecular Endocrinology University of UlmUlmGermany Correspondence:Andreas Niemeier Department of Genetics and Complex Diseases&Sabriülker Center Harvard T.H.Chan School of Public Health665 Huntington AvenueBostonMA 02115USA

Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1(Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone *** lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1 limited receptor activator of NF-κB ligand(RANKL) expression in vivo and in vitro through attenuation of platelet-derived growth factor(PDGF-BB) signaling. In co-culture, Lrp1-deficient osteoblasts stimulated osteoclastogenesis in a PDGFRβ-dependent manner and in vivo treatment with the PDGFR tyrosine kinase inhibitor imatinib mesylate limited RANKL production and led to complete remission of the osteoporotic phenotype. These results identify osteoblast Lrp1 as a key regulator of osteoblast-to-osteoclast communication and bone mass through a PDGF–RANKL signaling axis in osteoblasts and open perspectives to further explore the potential of PDGF signaling inhibitors in counteracting bone loss as well as to evaluate the importance of functional LRP1 gene variants in the control of bone mass in humans.

关键词： PDGFRβ RANKL activator receptor imatinib axis gene vivo

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Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3223-3224页

作者： Tong Zhang Martina schmidt Department of Molecular Pharmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands School of Pharmacy Tianjin Medical UniversityTianjinChina

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and *** the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

关键词： Alzheimer impaired Aβ

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3D particle tracking velocimetry for the determination of temporally resolved particle trajectories within laser powder bed fusion of metals

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International Journal of Extreme Manufacturing 2019年第3期1卷 96-105页

作者： Eric Eschner tobias Staudt Michael schmidt Institute of Photonic Technologies Friedrich-Alexander-Universität Erlangen-NürnbergKonrad-Zuse-Str.3/5D-91052ErlangenGermany Graduate School in Advanced Optical Technologies Friedrich-Alexander-Universität Erlangen-NürnbergPaul-Gordan-Str.6D-91052ErlangenGermany

Within this work,we present a system for the measurement of the three-dimensional(3D)trajectories of spatters and entrained particles during laser powder bed fusion(L-PBF)of *** is comprised of two ultrahigh-speed cameras and a reconstruction task specific processing reconstruction *** system enables an automated determination of 3D measures from the trajectories of a large number of tracked *** evolving from an underdetermined geometrical situation induced by a two-camera setup is resolved within the tracking using a priori knowledge of L-PBF of *** processing steps were optimized to run on a graphics processing unit to allow the processing of large amounts of data within an appropriate time *** overall approach was validated by a comparison of the measurement results to synthetic images with a known 3D ground truth.

关键词： powder bed fusion laser image processing additive manufacturing high-speed imaging 3D particle velocimetry

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Transfer learning from synthetic data for open-circuit voltage curve reconstruction and state of health estimation of lithium-ion batteries from partial charging segments

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Energy and AI 2024年第3期17卷 80-97页

作者： tobias Hofmann Jacob Hamar Bastian Mager Simon Erhard Jan Philipp schmidt Chair of Systems Engineering for Electrical Energy Storage University of BayreuthWeiherstraße 26Bayreuth95448BavariaGermany BMW Group Petuelring 130Munich80809BavariaGermany

Data-driven models for battery state estimation require extensive experimental training data,which may not be available or suitable for specific tasks like open-circuit voltage(OCV)reconstruction and subsequent state of health(SOH)*** study addresses this issue by developing a transfer-learning-based OCV reconstruction model using a temporal convolutional long short-term memory(TCN-LSTM)network trained on synthetic data from an automotive nickel cobalt aluminium oxide(NCA)cell generated through a mechanistic model *** data consists of voltage curves at constant temperature,C-rates between C/30 to 1C,and a SOH-range from 70%to 100%.The model is refined via Bayesian optimization and then applied to four use cases with reduced experimental nickel manganese cobalt oxide(NMC)cell training data for higher use *** TL models’performances are compared with models trained solely on experimental data,focusing on different C-rates and voltage *** results demonstrate that the OCV reconstruction mean absolute error(MAE)within the average battery electric vehicle(BEV)home charging window(30%to 85%state of charge(SOC))is less than 22 mV for the first three use cases across all *** SOH estimated from the reconstructed OCV exhibits an mean absolute percentage error(MAPE)below 2.2%for these *** study further investigates the impact of the source domain on TL by incorporating two additional synthetic datasets,a lithium iron phosphate(LFP)cell and an entirely artificial,non-existing,cell,showing that solely the shifting and scaling of gradient changes in the charging curve suffice to transfer knowledge,even between different cell chemistries.A key limitation with respect to extrapolation capability is identified and evidenced in our fourth use case,where the absence of such comprehensive data hindered the TL process.

关键词： Lithium-ion battery State of health estimation Transfer learning OCV curve Partial charging Synthetic data

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Organ transplantation scandal influencing corneal donation rate

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International Journal of Ophthalmology(English edition) 2017年第6期10卷 1001-1003页

作者： tobias R?ck Matthias Bramkamp Karl Ulrich Bartz-schmidt Daniel R?ck Department of Ophthalmology Eberhard-Karls University Tiibingen Tiibingen 72076 Germany Department of General Medicine Ruhr-University Bochum Bochum 44801 Germany

~ In the majority of countries, there is a shortage of donor corneas for corneal transplantations. This study investigated the impact of organ transplantation scandals on corneal donation rate at the University Hospital T/ibingen. Each deceased patient was considered as a potential corneal donor. An ophthalmic resident handled with stable methods of procedures the corneal donor procurement from 2009 to 2015. The rates of corneal donation were examined and analyzed. Among the 5712 hospital deaths, consent for corneal donation was obtained in 711 cases. The mean annual corneal donation rate was 12.4%. Since 2009, the donation rate per year could be increased with exception of 2013 and 2015. In the end of 2012 and 2014 two huge organ donation scandals were known in Germany. In the following years 2013 and 2015 corneal donation rate decreased significantly （P=0.0181 and P=0.0006）. We concluded that transplantation scandals have a significant impact on corneal donation rate. Improving professional＇s performance through full transparency and honesty is very important to earn trust of potential donors and their families.

关键词： cornea corneal donation tissue procurement transplantation scandal public trust

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Role of histone deacetylases in pancreas: Implications for pathogenesis and therapy

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World Journal of Gastrointestinal Oncology 2015年第12期7卷 473-483页

作者： Eckhard Klieser Stefan Swierczynski Christian Mayr Johanna schmidt Daniel Neureiter tobias Kiesslich Romana Illig Institute of Pathology Paracelsus Medical UniversitySalzburger Landeskliniken (SALK) 5020 Salzburg Austria Department of Surgery Paracelsus Medical University Salzburger Landeskliniken (SALK) 5020 SalzburgAustria Department of Internal Medicine I Paracelsus Medical University Salzburger Landes- kliniken (SALK) 5020 Salzburg Austria Laboratory for Tumour Biology and Experimental Therapies (TREAT) Institute of Physiology and Pathophysiology Paracelsus Medical University

In the last years, our knowledge of the pathogenesis in acute and chronic pancreatitis(AP/CP) as well as in pancreatic cancerogenesis has significantly diversified. Nevertheless, the medicinal therapeutic options are still limited and therapeutic success and patient outcome are poor. Epigenetic deregulation of gene expression is known to contribute to development and progression of AP and CP as well as of pancreatic cancer. Therefore, the selective inhibition of aberrantly active epigenetic regulators can be an effective option for future thera-pies. Histone deacetylases(HDACs) are enzymes that remove an acetyl group from histone tails, thereby causing chromatin compaction and repression of transcri-ption. In this review we present an overview of the currently available literature addressing the role of HDACs in the pancreas and in pancreatic diseases. In pancreatic cancerogenesis, HDACs play a role in the important process of epithelial-mesenchymal-transition, ubiquitin-proteasome pathway and, hypoxia-inducible-factor-1-angiogenesis. Finally, we focus on HDACs as potential therapeutic targets by summarizing currently available histone deacetylase inhibitors.

关键词： Pancreatitis Pancreatic cancer Epigenetics Histone

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Modelling of particle layer detachment—Role of transient kinetic effects

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Particuology 2009年第1期7卷 45-51页

作者： Eberhard schmidt Faculty D-Safety Engineering/Environmental Protection University of WuppertalBuilding FFRainer-Gruenter-StrasseD-42119 WuppertalGermany

Particle layers tend to build up on wails in many filtration and separation processes, calling for periodic removal in order to keep the apparatus running. Important factors are the adhesion of the layer on the substrate and the cohesion of the particles in the layer. Models describing such layer detachment generally assume constant and homogeneous conditions for the forces acting on the layer. But in reality detachment is extremely non-stationary concerning place and time, primarily due to changing conditions of the detaching forces on the one hand and changes in the particle layer morphology on the other. This paper describes a model and a simulation based on this model considering such transient kinetic effects, for which some computing results are presented and discussed.

关键词： Adhesive forces Filter cleanability Dust cake discharge Patchy cleaning

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Quantification of particle separation using electrostatically charged spray mist in a dust chamber

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Particuology 2021年第5期19卷 92-98页

作者： Marcel Zillgitt Eberhard schmidt Institute of Particle Technology Rainer Gruenter StraBeBuilding FFCampusFreudenbergBergische Universitat Wuppertal42119 WuppertalGermany

In order to improve the efficiency of reducing fine dust emissions from diffuse sources,the commonly used water mist can be electrostatically ***,the attraction between particles and droplets increases due to electrostatic field *** the experimental investigations carried out,an electrostatic two-fluid nozzle was used to generate a charged spray mist according to the principle of charging by *** a chamber,dispersed dust was precipitated with the spray mist,while detecting the laser light *** means of comparative measurements it could be shown that faster sedimentation and separation takes place through electrostatic *** variations regarding the use of compressed air and water were investigated and the sedimentation time of the particle-droplet mixture in the chamber was shown.A size distribution was then calculated from the laser light attenuation,which shows that the proportion of small particles decreases with spray ***,the influence of the polarity of droplets and solid particles on the reduction measure was determined.

关键词： Dust separation Spray mist Electrostatic Dust chamber Laser light attenuation Charging by induction

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Navigation sensors and systems in GNSS degraded and denied environments

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Chinese Journal of Aeronautics 2015年第1期28卷 1-10页

作者： George T.schmidt IEEE Aerospace and Electronic Systems Society

Position, velocity, and timing（PVT） signals from the Global Positioning System（GPS）are used throughout the world but the availability and reliability of these signals in all environments has become a subject of concern for both civilian and military applications. This presentation summarizes recent advances in navigation sensor technology, including GPS, inertial, and other navigation aids that address these concerns. Also addressed are developments in sensor integration technology with several examples described, including the Bluefin-21 system mechanization.

关键词： navigation inertial GNSS environments receiver degraded military addressed presentation advances

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Machine learning guided high-throughput search of non-oxide garnets

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npj Computational Materials 2023年第1期9卷 1717-1725页

作者： Jonathan schmidt Hai-Chen Wang Georg schmidt Miguel A.L.Marques Institut für Physik Martin-Luther-Universität Halle-WittenbergD-06099 HalleGermany

Garnets have found important applications in modern technologies including magnetorestriction,spintronics,lithium batteries,*** overwhelming majority of experimentally known garnets are oxides,while explorations(experimental or theoretical)for the rest of the chemical space have been limited in scope.A key issue is that the garnet structure has a large primitive unit cell,requiring a substantial amount of computational *** perform a comprehensive search of the complete chemical space for new garnets,we combine recent progress in graph neural networks with high-throughput *** apply the machine learning model to identify the potentially(meta-)stable garnet systems before performing systematic density-functional calculations to validate the *** discover more than 600 ternary garnets with distances to the convex hull below 100 meV⋅atom−*** includes sulfide,nitride,and halide *** analyze their electronic structure and discuss the connection between the value of the electronic band gap and charge balance.

关键词： structure sulfide oxides

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