272 research outputs found

    Evidence that LDL receptor-related protein 1 acts as an early injury detection receptor and activates c-Jun in Schwann cells.

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    Schwann cells (SCs) detect injury to peripheral nerves and transform phenotypically to respond to injury and facilitate repair. Cell-signaling pathways and changes in gene expression that drive SC phenotypic transformation in injury have been described; however, the SC receptors that detect peripheral nervous system (PNS) injury have not been identified. LDL receptor-related protein 1 (LRP1) is a receptor for numerous ligands, including intracellular proteins released by injured cells and protein components of degenerated myelin. In certain cell types, including SCs, LRP1 is a cell-signaling receptor. Here, we show that binding of the LRP1 ligand, tissue-type plasminogen activator (tPA), to cultured rat SCs induces c-Jun phosphorylation, a central event in activation of the SC repair program. The response to tPA was blocked by the LRP1 antagonist, receptor-associated protein. c-Jun phosphorylation was also observed when cultured rat SCs were treated with a recombinant derivative of matrix metalloproteinase-9 that contains the LRP1 recognition motif (PEX). The ability of LRP1 to induce c-Jun phosphorylation and ERK1/2 activation was confirmed using cultures of human SCs. When tPA or PEX was injected directly into crush-injured rat sciatic nerves, c-Jun phosphorylation and ERK1/2 activation were observed in SCs in vivo. The ability of LRP1 to bind proteins released in the earliest stages of PNS injury and to induce c-Jun phosphorylation support a model in which SC LRP1 functions as an injury-detection receptor in the PNS. © Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved

    Diphtheria-like disease caused by Toxigenic Corynebacterium ulcerans strain

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    Toxigenic Corynebacterium ulcerans is an increasingly reported cause of diphtheria in the United Kingdom and is often associated with a zoonotic origin (1,2). Here, we report a case of diphtheria caused by toxigenic C. ulcerans in a woman, 51 years of age, from Scotland, UK, who was admitted to a hospital in August 2013 with a swollen, sore throat and a gray-white membrane over the pharyngeal surface. The patient had returned from a 2-week family holiday in the state of Florida, United States, before the admission and also reported recent treatment of a pet dog for pharyngitis. The patient was believed to have been vaccinated against diphtheria during childhood. She was immediately admitted to an isolation ward and treated with a combination of clindamycin, penicillin, and metronidazole

    Three-Dimensional Numerical Investigation of an Improved Surface Plasmon Resonance Waveguide Sensor

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    A light-guiding structure is investigated to improve the performance of a surface plasmon resonance waveguide sensor using the three-dimensional beam-propagation method. The absorption strength at the resonance wavelength is examined in terms of the core width. Calculations show that a waveguide with a wide core supporting higher order modes leads to strong absorption comparable to the two-dimensional model. Besides, embedding the core in a substrate is quite effective in obtaining a sharp dip in the wavelength response, i.e., a full-width at half-minimum is reduced from ~11 to ~5 nm, when the core is embedded by 0.3 μm. This contributes to improved measurement precision

    Three-Dimensional Numerical Investigation of an Improved Surface Plasmon Resonance Waveguide Sensor

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    A light-guiding structure is investigated to improve the performance of a surface plasmon resonance waveguide sensor using the three-dimensional beam-propagation method. The absorption strength at the resonance wavelength is examined in terms of the core width. Calculations show that a waveguide with a wide core supporting higher order modes leads to strong absorption comparable to the two-dimensional model. Besides, embedding the core in a substrate is quite effective in obtaining a sharp dip in the wavelength response, i.e., a full-width at half-minimum is reduced from ~11 to ~5 nm, when the core is embedded by 0.3 μm. This contributes to improved measurement precision

    Abstract 5740: Aberration of (pro)renin receptor induces genomic instablity in human pancreatic ductal epithelial cells

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    Abstract Background: We have recently shown the potential contribution of (pro)renin receptor ((P)RR) to tumorigenesis of pancreatic ductal adenocarcinoma (PDAC) through an activation of Wnt/β-catenin signaling pathway (Sci. Rep., 2015). We also found that significant (P)RR expression was synchronized with an appearance of atypical nuclei in PanIN-2 of PDAC tissues. Furthermore, (P)RR knockdown reduced a total of DNA amount in human PDAC cell lines. Based on our findings, we have hypothesized that an aberration of (P)RR leads to a failure of genome homeostasis. Accordingly, we explored whether an aberrant expression of (P)RR induces genomic instability in human pancreatic ductal epithelial (HPDE) cells which are capable of developing to the PDAC. Methods: HPDE cells transfected by episomal vector inserted with ATP6ap2 encoding (P)RR were established. HPDE cells transfected by vector without the insertion of ATP6ap2 was noted as Mock. We also performed a comet assay to evaluate the defects of DNA repair capacity, flow-FISH to measure the length of telomere and western blotting to confirm the activation of DNA damage pathway by measuring protein levels of γ- H2AX and p53. Then, comparative analyses of human whole genome in Mock- expressing and (P)RR-expressing HPDE cells were examined. Furthermore, we implanted 14-passage HPDE cells expressed by either Mock or (P)RR into the renal subcapsules of immunodeficient mice to investigate whether (P)RR-expressing HPDE cells show a precancerous status in vivo. Results: (P)RR overexpression led to inactivation of γ-H2AX and p53 as the components of DNA damage pathway, which were associated with a disappearance of comet tail and shorten telomere length. Substantial structural variations, e.g., inter- and intra- chromosomal translocations throughout all the chromosomes were observed in HPDE cells expressed by (P)RR under the analysis by BreakDancer. Analyses with Bcftool showed that the number of all the somatic mutations was approximately 2-fold greater in HPDE cells expressed by (P)RR than those expressed by Mock (Mock: 124,579 vs. (P)RR: 239,080). (P)RR overexpression also significantly increased the number of somatic mutations in several genes which were commonly detected in PDAC tissues. The area occupied by (P)RR-expressing HPDE cell population remarkably expanded after the implantation to renal subcapsules of all the immunodeficient mice. However, there were no KRAS 12 codon mutations which are prevalent in PDAC patients. Conclusion: We have demonstrated that (P)RR overexpression induces genomic instability on global genome level in HPDE cells. These data are consistent with our hypothesis that (P)RR is essentially involved in the early carcinogenesis of PDAC. Citation Format: Yuki Shibayama, Jun Yasuda, Daisuke Yamazaki, Asadur Rahman, Shinichi Yachida, Akira Nishiyama. Aberration of (pro)renin receptor induces genomic instablity in human pancreatic ductal epithelial cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5740. doi:10.1158/1538-7445.AM2017-5740</jats:p

    Field Surveys of Recent Storm Surge Disasters

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    AbstractIn these ten years since 2004, there were more than ten big disasters in coastal area including six storm surge events and five tsunami events. The author performed post disaster surveys on all these events as the team leaders of survey teams. Based on those experiences, the author describes lessons of these events. Tsunami is now generally well known to coastal residents. Evacuation plans gradually become common for tsunami disasters. Storm surges arise more frequently due to strong storms but coastal residents are not well protected and not informed how to evacuate in case of surge emergency. From the field surveys conducted, it appeared that the damage depend on the geographical and social conditions of each of the areas that were visited by the author. It is now clear that such issues play important roles in disaster mechanisms. Therefore disaster risk management should carefully include local topography and social conditions of each area during the formulation of disaster prevention plans. In order to establish a reliable disaster prevention system, appropriate protection structures should be constructed, and these should be accompanied by a clear and concise evacuation plan for residents of a given area

    Understanding Cohesion in English

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    application/pdfDepartmental Bulletin PaperCohesion is Hasan's term. The concept of cohesion, however, is not well-formed and its mechanism is still to be studied. In this paper, the author says: 1. Both cohesion and a tie are semantic concepts. 2. Cohesion in a text is a set of ties between sentences. Based on the definitions, the author discusses the formal and lexicogrammatical factors which generate cohesion.departmental bulletin pape

    <Article>The Origins of Machiavelli's Thought : As Revealed by His Choice of Expressions

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    個人情報保護のため削除部分あり拙稿はとくにアメリカのブルックリンカレッジ Brooklyn College のマルチィン・フラィシャー Martin Fleisher 教授のマキァヴェリ Machiavelli 関係論著や、カナダのカルガリー大学 University of Calgary のアンソニー・パーレル Anthony parel 教授のマキァヴェリ論を参照しつつ、マキァヴェリ特有の意味を含む彼の常套語、たとえばアニモ Animo、アソビツィオーネambizione、インジェニョ ingegno、プルーデンツァ prudenza、インガーンノ inganno、ヴィルトゥ virtu、フォルトゥナ fortuna その他同意語や反意語あるいは玉虫色とも見える関連用語などを通じて、彼の複雑な思想の原点ーとくにその政治観や歴 史思想の局面を模索してみた。なおまた彼の思想に影響を及ぼした先人たちや当代の思想家と対比しつつ、彼の思想が現代に至る間にどのような曲折をたどって来たかについても、私なりに改めて再考した。The paper attempts to probe the origin of the complex thought of Niccolò Machiavelli--and specifically his political outlook and historical ideas--through the particular nuances with which he uses such common words as ànimo, ambizióne, ingégno, prudénza, inganno, virtù, and fortuna, and other synonyms and antonyms and related expressions that can take on a bewildering variety of colorations. Frequent reference is made to the works of prof. Martin Fleisher of Brooklyn College and to papers by Prof. Anthony Parel of the University of Calgary. Machiavelli's thinking is also contrasted with that of his predecessors and contemporaries who influenced him, and the author presents his own reappraisal of the varied course that Machiavelli's ideas have taken down to the present day

    Detailed computational modeling of crack patterns of silicon-based anode sheet in lithium-ion batteries upon mechanical stress

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    This article was originally published in Energy Materials and Devices. The version of record is available at: https://doi.org/10.26599/EMD.2025.9370054. © The Author(s) 2024. Published by Tsinghua University Press. The articles published in this open access journal are distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Silicon (Si)-based anodes, where Si serves as the active material, have garnered significant attention due to their potential to achieve high electric capacity in lithium-ion batteries (LIBs). A key challenge with Si-based anodes is their susceptibility to create in-plane cracks caused by stresses from the manufacturing process and cyclic charging, which ultimately shortens battery life and reduces the overall electrochemical capacity. To address this issue, a refined microstructural design of the active material layer is in pressing need to enhance both the performance and longevity of LIBs. We successfully applied the Oyane failure criterion, which models ductile failure under stress triaxiality, to simulate crack initiation and propagation in the binder matrix containing Si particles in the finite element modeling. Given the non-linear plastic deformation of the binder, this criterion was formulated based on cumulative strain increments. The computational results of microcrack formation within the active material layer under uniaxial tension were then validated by the experimental observations. Furthermore, we developed several models with varied particle arrangements, comparing each simulated crack path to actual microstructural images obtained via scanning electron microscopy. The findings confirm the accuracy of the model, underlying its promising application in optimizing the microstructure of Si-based anodes for enhanced LIB performance and durability. Graphical Abstract available at: https://doi.org/10.26599/EMD.2025.9370054.Akio Yonezu acknowledges the support of JSPS KAKENHI (Grant No. 21H01217) from the Japan Society for the Promotion of Science. Jun Xu acknowledges the support of the Startup funds from the University of Delaware
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