130,522 research outputs found

    The cystatin M/E-cathepsin L balance is essential for tissue homeostasis in epidermis, hair follicles, and cornea

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    Cystatin M/E (CST6) is a nonredundant, epithelium-specific protease inhibitor with a presumed role in epidermal differentiation and tumor suppression. We have previously reported that cystatin M/E deficiency in Cst6(-)(/)(-) mice causes neonatal lethality because of excessive transepidermal water loss. Biochemical evidence suggests that cystatin M/E controls the activity of legumain, cathepsin L, cathepsin V, and transglutaminase-3. Using a genetic approach we sought to define the role of cystatin M/E in epithelial biology by identification of its target proteases and their downstream functions. Ablation of cathepsin L in a Cst6(-)(/)(-) background (Cst6(-)(/)(-)Ctsl(-)(/)(-) double-knockout mice) restored viability and resulted in normalization of stratum corneum morphology. Ablation of legumain or transglutaminase-3 in Cst6(-)(/)(-) mice, however, did not rescue the lethal phenotype. Intriguingly, both Cst6(-)(/)(-)Ctsl(-)(/)(-) and Cst6(-)(/)(-)Ctsl(+)(/)(-) mice were viable, but the absence of cystatin M/E caused scarring alopecia in adult animals. In the cornea of Cst6(-)(/)(-)Ctsl(+)(/)(-) mice, we observed keratitis, hyperplasia, and transition to a cornified epithelium. Evidence is provided that activation of cathepsin D and transglutaminase-1 are downstream events, dependent of cathepsin L activity. We conclude that a tightly regulated balance between cathepsin L and cystatin M/E is essential for tissue integrity in epidermis, hair follicles, and corneal epithelium.-Zeeuwen, P.L.J.M., van Vlijmen-Willems, I.M.J.J., Cheng, T., Rodijk-Olthuis, D., Hitomi, K., Hara-Nishimura, I., John, S., Smyth, N., Reinheckel, T., Hendriks, W.J.A.J., Schalkwijk, J. The cystatin M/E-cathepsin L balance is essential for tissue homeostasis in epidermis, hair follicles and cornea

    MeSH term explosion and author rank improve expert recommendations

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    Information overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    "Closing the R&D Gap, Evaluating the Sources of R&D Spending"

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    Both spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.

    A. D. Fricke, author

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    Black and white photograph of author, A. D. Fricke

    The Approach to Social Theory: Hazards and Benefits

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    Introduction -- On the idea of worldview and its relation to philosophy / Albert M Wolters -- On worldviews / James H. Olthuis -- On worldviews and philosophy: a response to Wolters and Olthuis / Nicholas Wolterstorff -- The approach to social theory: hazards and benefits / Sander Griffioen -- Sociology and progress: a worldview analysis of the crisis of modern society / Jan Verhoogt -- Worldview and the meaning of work / P.J.D. Drenth -- Society after the subject, philosophy after the worldview / William Rowe -- Epilogue: On faith and social science / Paul Marshal

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Scholarly Communication and Publishing Lunch and Learn Talk #11: The ULS Open Access Author Fee Fund

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    At the May 2014 talk, you will learn about the ULS Open Access Author Fee Fund--what it is, why we do it, how it works, and how the program is going so far

    The R&D Tax Incentives

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    This article sets out some background information and reflections of the author on the R&D tax incentive schemes included in the Common Corporate Tax Base (CCTB) Proposal. In particular the author analyzes the stimulus to private R&D through ad hoc tax incentives included in the CCTB Proposal and dives into the actual provisions included in the Proposal highlighting the most relevant issues connected with their design and interpretation. Moreover, the author explores the interaction between the CCTB Proposal and the granting by Member States of domestic R&D tax incentives

    sj-docx-2-eso-10.1177_23969873231220464 – Supplemental material for Cost-effectiveness of endovascular treatment after 6–24 h in ischaemic stroke patients with collateral flow on CT-angiography: A model-based economic evaluation of the MR CLEAN-LATE trial

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    Supplemental material, sj-docx-2-eso-10.1177_23969873231220464 for Cost-effectiveness of endovascular treatment after 6–24 h in ischaemic stroke patients with collateral flow on CT-angiography: A model-based economic evaluation of the MR CLEAN-LATE trial by Florentina ME Pinckaers, Silvia MAA Evers, Susanne GH Olthuis, Hieronymus D Boogaarts, Alida A Postma, Robert J van Oostenbrugge, Wim H van Zwam and Janneke PC Grutters in European Stroke Journal</p
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