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Ephrin-B reverse signaling induces expression of wound healing associated genes in IEC-6 intestinal epithelial cells

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World Journal of Gastroenterology 2005年第29期11卷 4511-4518页

作者： Christian Hafner Stefanie Meyer Ilja Hagen Bernd Becker alexander Roesch michael Landthaler Thomas Vogt Department of Dermatology University Hospital of Regensburg Regensburg D-93042 Germany

AIM： Eph receptors and ephrin ligands play a pivotal role in development and tissue maintenance. Since previous data have indicated an involvement of ephrin-B2 in epithelial healing, we investigated the gene expression and downstream signaling pathways induced by ephrin-B mediated cell-cell signaling in intestinal epithelial cells. METHODS： Upon stimulation of ephrin-B pathways in IEC-6 cells with recombinant rat EphB1-Fc, gene expression was analyzed by Affymetrix rat genome 230 high density arrays at different time points. Differentially expressed genes were confirmed by real-time RT-PCR. In addition, MAP kinase pathways and focal adhesion kinase （FAK） activation downstream of ephrin-B were investigated by immunoblotting and fluorescence microscopy. RESULTS： Stimulation of the ephrin-B reverse signaling pathway in IEC-6 cells induces predominant expression of genes known to be involved into wound healing/cell migration, antiapoptotic pathways, host defense and inflammation. Cox-2, c-Fos, Egr-1, Egr-2, and MCP-1 were found among the most significantly regulated genes. Furthermore, we show that the expression of repair- related genes is also accompanied by activation of the ERKI/2 MAP kinase pathway and FAK, two key regulators of epithelial restitution. CONCLUSION： Stimulation of the ephrin-B reverse signaling pathway induces a phenotype characterized by upregulation of repair-related genes, which may partially be mediated by ERK1/2 pathways.

关键词： Ephrin-B IEC-6 Wound healing Gene expression c-Fos Egr-1/2 COX-2

Optimization of a novel three dimensional risk calculation model for software-based aneuploidy screening in early pregnancy

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Open Journal of Obstetrics and Gynecology 2011年第3期1卷 84-89页

作者： Cindy Hormansdorfer michael Golatta Bernhard Vaske alexander Scharf Peter Schmidt Klinikum Oldenburg gGmbH Department of General and Visceral SurgeryOldenburgGermany University of Heidelberg Department of Gynecology and ObstetricsHeidelbergGermany Medical University of Hannover Department of Medical Statistics and BiometryHannoverGermany Institute for Prenatal Health WolfenbuttelGermany

Introduction: A novel three dimensional approach for aneuploidy screening in the first trimester of pregnancy was developed in which risk assessment derives directly from comparing the plotted data of nuchal translucency, pregnancy associated plasma protein A (PAPP-A), and free β-human chorionic gonadotropin (fβ-hCG) of an examined fetus with similar coordinates of fetuses with already known health status. Under this approach, it is possible to utilize either a ‘box’ or a ‘sphere’ model. In either case, optimal volume sizes and the benefits of adopting a ‘minimum number of required fetuses’ (MNR) have not yet been investigated;and for the box model, two modifications, called ‘empty box results positive’ (EB+) and ‘simulation’ (SIM), provide additional options. It was the aim of this study to analyze which of the two models and their variants provides the best test performance. Methods: The study cohort was divided into a reference collective (n = 10,954) and a test collective (n = 4239). The test collective was examined repeatedly, with another model and modification used on each occasion. Test performances were compared by the area under curve (AUC) of receiver operating characteristics (ROC) curves. Results: The sphere model was inferior to the box model when optimal volumes were used with the latter and combined with the modifications EB+ and Sim. EB+ increased the number of assessable fetuses while Sim improved the test performance. MNR improved neither the box nor the sphere model. Conclusion: A new, optimized model in line with the obtained results should be developed and tested in further studies.

关键词： Aneuploidy Down Syndrome First Trimester Screening Nuchal Translucency Trisomy

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青藏高原东缘活动构造

矿物岩石 2006年第2期26卷 40-51页

作者：周荣军李勇 alexander L Densmore michael A Ellis 何玉林王凤林黎小刚四川省地震局工程地震研究所成都理工大学油气藏地质及开发工程国家重点实验室 Institute of Geology Department of Earth SciencesETH Zentrum CH-8092 ZürichSwitzerland Center for Earthquake Research and Information University of Memphis 3890 Central AvenueMemphisTN 38152USA

青藏高原东缘由岷山断块和龙门山构造带构成。以活动构造地貌学为主线,在解析该地区主干断裂晚第四纪以来活动的地质地貌表现的基础上,对一批断裂运动学和史前强震活动的定量数据进行分析研究,结果表明:在岷山断块中,虎牙断裂的平均左... 详细信息

青藏高原东缘由岷山断块和龙门山构造带构成。以活动构造地貌学为主线,在解析该地区主干断裂晚第四纪以来活动的地质地貌表现的基础上,对一批断裂运动学和史前强震活动的定量数据进行分析研究,结果表明:在岷山断块中,虎牙断裂的平均左旋滑动速率为1.4 mm/a,垂直滑动速率为0.3 mm/a。岷江断裂的平均垂直滑动速率介于0.37 mm/a^0.53 mm/a之间,左旋位错量与垂直位错量大致相当;在龙门山构造带中,茂汶-汶川断裂、北川-映秀断裂和彭县-灌县断裂的平均垂直滑动速率均在1 mm/a左右,且几条主干断裂的右旋位错量与垂直位错量相当。结合震源机制解结果和GPS测量资料,建立晚新生代以来青藏高原东缘向南东方向逸出的构造变形模式。

关键词：构造地貌滑动速率强震复发青藏高原东缘

Bioactive hydrogel microcapsules for guiding stem cell fate decisions by release and reloading of growth factors

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Bioactive Materials 2022年第9期7卷 1-14页

作者： Kihak Gwon Hye Jin Hong Alan M.Gonzalez-Suarez michael Q.Slama Daheui Choi Jinkee Hong Harihara Baskaran Gulnaz Stybayeva Quinn P.Peterson alexander Revzin Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMN55902USA Department of Chemical and Biomolecular Engineering Yonsei UniversitySeoul03722Republic of Korea Department of Chemical and Biomolecular Engineering Case Western Reserve UniversityClevelandOH44106USA

Human pluripotent stem cells(hPSC)hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver *** of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation *** this paper,we sought to address these challenges through the development of bioactive microcapsules.A co-axial flow focusing microfluidic device was used to encapsulate hPSCs in microcapsules comprised of an aqueous core and a hydrogel ***,the shell contained heparin moieties for growth factor(GF)binding and *** aqueous core enabled rapid aggregation of hPSCs into 3D spheroids while the bioactive hydrogel shell was used to load inductive cues driving pluripotency maintenance and endodermal ***,we demonstrated that one-time,1 h long loading of pluripotency signals,fibroblast growth factor(FGF)-2 and transforming growth factor(TGF)-β1,into bioactive microcapsules was sufficient to induce and maintain pluripotency of hPSCs over the course of 5 days at levels similar to or better than a standard protocol with soluble ***,stem cell-carrying microcapsules that previously contained pluripotency signals could be reloaded with an endodermal cue,Nodal,resulting in higher levels of endodermal markers compared to stem cells differentiated in a standard ***,bioactive heparin-containing core-shell microcapsules decreased GF usage five-fold while improving stem cell phenotype and are well suited for 3D cultivation of hPSCs.

关键词： Droplet microfluidics Bioactive core-shell microcapsule Growth factor release 3D stem cell culture Stem cell differentiation

Signaling pathways involved in the inhibition of epidermal growth factor receptor by erlotinib in hepatocellular cancer

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World Journal of Gastroenterology 2006年第32期12卷 5160-5167页

作者： alexander Huether michael Hpfner Andreas P Sutter Viola Baradari Detlef Schuppan Hans Scherübl Charité-Universittsmedizin Berlin Campus Benjamin Franklin Medical Clinic ⅠGastroenterology/Infectious Diseases/RheumatologyBerlinGermany Harvard Medical School Beth Israel Deaconess Medical Center Division of Gastroenterology and HepatologyBostonUnited States

AIM： To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma （HCC）. METHODS： Erlotinib-induced alterations in gene expression were evaluated using cDNA array technology; changes in protein expression and/or protein activation due to erlotinib treatment as well as IGF-1-induced EGFR transactivation were investigated using Western blotting. RESULTS： Erlotinib treatment inhibited the mitogen activated protein （MAP）-kinase pathway and signal transducer of activation and transcription （STAT）- mediated signaling which led to an altered expression of apoptosis and cell cycle regulating genes as demonstrated by cDNA array technology. Overexpression of proapoptotic factors like caspases and gadds associated with a down-regulation of antiapoptotic factors like Bcl-2, Bcl-XL or jun D accounted for erlotinib＇s potency to induce apoptosis. Downregulation of cell cycle regulators promoting the G1/S-transition and overexpression of cyclin-dependent kinase inhibitors and gadds contributed to the induction of a G1/G0-arrest in response to erlotinib. Furthermore, we displayed the transactivation of EGFR-mediated signaling by the IGF-1-receptor and showed erlotinib＇s inhibitory effects on the receptor-receptor cross talk. CONCLUSION： Our study sheds light on the understanding of the mechanisms of action of EGFR-TK- inhibition in HCC-cells and thus might facilitate the design of combination therapies that act additively or synergistically. Moreover, our data on the pathways responding to erlotinib treatment could be helpful in predicting the responsiveness of tumors to EGFR-TKIs in the future.

关键词： Epidermal growth factor receptor Insulinlike growth factor receptor Tarceva^TM Signal transducerof activation and transcription Extracellular regulatedkinase Gene expression

Role of the endothelium in inflammatory bowel diseases

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World Journal of Gastroenterology 2011年第5期17卷 578-593页

作者： Walter E Cromer J michael Mathis Daniel N Granger Ganta V Chaitanya J Steven alexander Department of Cellular Biology and Anatomy LSU Health Sciences Center-Shreveport1501 Kings HighwayShreveportLA 71130-3932United States Department of Cellular and Molecular Physiology LSU Health Sciences Center-Shreveport1501 Kings HighwayShreveportLA 71130-3932United States

Inflammatory bowel diseases(IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the *** the core of these alterations are endothelial cells,whose continual adjustments in structure and function coordinate vascular supply,immune cell emigration,and regulation of the tissue *** of the endothelium in IBD(angiogenesis),mediated by inflammatory growth factors,cytokines and chemokines,is a hallmark of active gut disease and is closely related to disease *** endothelium in newly formed or inflamed vessels differs from that in normal vessels in the production of and response to inflammatory cytokines,growth factors,and adhesion molecules,altering coagulant capacity,barrier function and blood cell recruitment in *** review examines the roles of the endothelium in the initiation and propagation of IBD pathology and distinctive features of the intestinal endothelium contributing to these conditions.

关键词： Microvasculature Endothelium Inflamma-tion Nitric oxide Adhesion molecules Crohn's disease Ulcerative colitis Cytokines Chemokines Growth factors

Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds

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Bioactive Materials 2022年第3期7卷 358-372页

作者： Chia-Chen Hsu Julian H.George Sharlayne Waller Cyril Besnard David A Nagel Eric J Hill michael D.Coleman alexander M.Korsunsky Zhanfeng Cui Hua Ye Institute of Biomedical Engineering Department of Engineering ScienceUniversity of OxfordOX37DQUK MBLEM Department of Engineering ScienceUniversity of OxfordParks RoadOxfordOX13PJUK School of Biosciences College of Health and Life SciencesAston UniversityBirminghamB47ETUK Translational Medicine Research Group Aston Medical SchoolCollege of Health and Life SciencesAston UniversityBirminghamB47ETUK

To reflect human development,it is critical to create a substrate that can support long-term cell survival,differentiation,and *** are promising materials for 3D ***,a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell ***,granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell(hiPSC)-derived neural networks.A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel *** and hydrogel granules were combined using a weaker secondary gelation step,forming self-supporting cell laden *** three and seven days,granular scaffolds supported higher cell viability compared to bulk hydrogels,whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions(65.52±11.59μm)after seven days compared to bulk hydrogels(22.90±4.70μm).Long-term(three-month)cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the *** approach is significant as it provides a simple,rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures.

关键词： Microgel Hydrogel Hyaluronan iPSC Neural tissue engineering 3D printing

Sulfidation and selenidation of nickel nanoparticles

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Carbon Energy 2021年第4期3卷 582-589页

作者： Brian B.Lynch Andrew P.Kelliher Bryan D.Anderson alexander Japit michael A.Spencer Mehedi H.Rizvi Mehmet F.Sarac Veronica Augustyn Joseph B.Tracy Department of Materials Science and Engineering North Carolina State UniversityRaleighNorth CarolinaUSA

NPs using elemental sulfur,1-hexadecanthiol,thiourea,trioctylphosphine sulfide,elemental selenium,and *** maintaining mole ratios of 2 mmol sulfur/selenium precursor:mmol Ni,products with phases of Ni_(3)S_(2),Ni_(9)S_(8),NiS,NiSO_(4)·6H_(2)O,Ni_(3)S_(4),Ni_(3)Se_(2),and NiSe have been *** products have voids that form through the Kirkendall effect during *** relating the chemical properties of the precursors to the phases of the products have been *** some precursors contained phosphorus,there was no significant incorporation of phosphorus in any of the *** increase of the NP size during sulfidation and selenidation is consistent with *** application of Ni sulfide and selenide NPs as electrocatalysts for the hydrogen evolution reaction is also demonstrated.

关键词： conversion chemistry electrocatalysis nanoparticles nickel selenide sulfide

Chapter 5 Dark Matter and New Physics Beyond the Standard Model with LHAASO

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Chinese Physics C 2022年第3期46卷 126-138页

作者： Xiao-Jun Bi Andrea Addazi Konstantin Belotsky Vitaly Beylin Marco Cirelli Arman Esmaili Nicolao Fornengo Qing-Yu Gan michael Kachekriess Maxim Khlopov Vladimir Korchagin alexander Korochkin Vladimir Kuksa Antonino Marciano Andrei Neronov Paolo Panci Roman Pasechnick alexander Sakharov Filippo Sala Giuseppe Di Sciascio Dimiri Semikoz Pasquale Dario Serpico Nikolay Volchanskiy Peng-Fei Yin Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Center for Theoretical Physics College of Physics Science and TechnologySichuan UniversityChengdu 610065China Laboratori Nazionali di Frascati INFN Frasacati(Rome)ItalyEU National Research Nuclear University MEPHI(Moscow State Engineering Physics Institute) 31 Kashirskoe chausseeMoscow 115409Russia Institute of Physics Southern Federal University Stachki 194Rostov on Don 344090Russia LPTHE CNRS and Sorbonne Universit′e4 Place JussieuF-75252ParisFrance Departamento de Fisica Pontificia Universidade Catolica do Rio de JaneiroRio de Janeiro 22452-970Brazil Dipartimento di Fisica Universita di TorinoVia P.Giuria 110125 TorinoItaly Istituto Nazionale di Fisica Nucleare Sezione di TorinoVia P.Giuria 110125TorinoItaly Institutt for fysikk NTNU7491 TrondheimNorway Universite de Paris CNRSAstroparticule et CosmologieF-75013 ParisFrance Department of Physics and Center for Field Theory and Particle Physics Fudan UniversityShanghai 200433China Astronomy Department University of GeneveCh.d’Ecogia 161290VersolxSwitzerland Dipartimento di Fisica Universita di Pisa and INFNSezione di Pisa Largo Pontecorvo 356127 PisaItaly Department of Astronomy and Theoretical Physics Lund University22100 LundSwedenEU Experimental Physics Department CERNGeneva 23 CH 1211Switzerland Department of Physics New York UniversityNew York NY United States of America INFN sezione Roma Tor Vergata I-00133 RomeItaly LAPTh Univ.Grenoble AlpesUSMBCNRSF-74000 AnnecyFrance Bogoliubov Laboratory of Theoretical Pjysics JINRDubnaRussia

In order to reveal the nature of dark matter,it is crucial to detect its non-gravitational interactions with the standard model *** traditional dark matter searches focused on the so-called weakly interacting massive ***,this paradigm is strongly constrained by the null results of current experiments with high *** there is a renewed interest of searches for heavy dark matter particles above TeV *** Large High Altitude Air Shower Observatory(LHAASO)with large effective area and strong background rejection power is very suitable to investigate the gamma-ray signals induced by dark matter annihilation or decay above TeV *** this document,we review the theoretical motivations and background of heavy dark *** review the prospects of searching for the gamma-ray signals resulted from dark matter in the dwarf spheroidal satellites and Galactic halo for LHAASO,and present the projected *** also review the prospects of searching for the axion-like particles,which are a kind of well motivated light pseudo-scalars,through the LHAASO measurement of the very high energy gamma-ray spectra of astrophysical sources.

关键词： dark matter gamma-ray axion-like particle