1,721,695 research outputs found

    Single-shot, high resolution and in-depth quantification of endoplasmic reticulum stress in a human cell line

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    Endoplasmic reticulum (ER) stress is a convergence point in the cellular pathology of many diseases. In the case of type 2 diabetes and the metabolic syndrome, a major role of ER stress has been recognized in the pathogenic cellular alterations of the main districts involved, such as the adipose tissue, the pancreas and the liver. Mass spectrometry (MS) based shotgun proteomics is widely applied to characterize changes in the proteome between different cellular states and will become an invaluable tool in signal transduction and clinical studies. However, in-depth proteomics analysis has so far required elaborate fractionation and thus extensive MS analysis time or, alternatively, restriction to specific proteins of interest. We recently showed that the near complete yeast proteome can be mapped in single-shot fashion by combining the quadrupole Orbitrap (Q Exactive) with high performance and high resolution chromatography with long columns (Nagaraj et al. MCP 2012). Here we apply our single-shot platform to the dose dependent proteome changes induced in HeLa cells by treatment with tunicamycin. By using a simplified model in a human cell line, we give a comprehensive proteomic description of the dose-dependent features of ER stress. This study aims at revealing putative missing links between the unfolded protein response and cell recovery, the intervention of inflammation and innate immunity and apoptosis

    Single-shot, high resolution and in-depth quantification platform for mammalian cell proteomes enables rapid systems analysis of ER stress

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    Mass spectrometry (MS) based shotgun proteomics is widely applied to characterize changes in the proteome between different cellular states, providing a basis for systems biology. So far, in-depth proteomics analysis has required elaborate fractionation and thus extensive MS analysis time or alternatively restriction to specific proteins of interest. This is undesirable for unbiased (discovery type) biological studies that involve multiple samples and multiple time points. Recently we showed that the near complete yeast proteome can be mapped in single-shot fashion by combining the quadrupole Orbitrap (Q Exactive) with high performance and high resolution chromatography with long columns (Nagaraj et al. MCP 2012). Here we develop our single-shot platform towards systems biology studies in human cell lines. We use this platform to study the dose dependent proteome changes in HeLa cells upon ER stress induced by treatment with tunicamycin

    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

    On equivalences and standardization in a non-deterministic call-by-need lambda calculus

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    The goal of this report is to prove correctness of a considerable subset of transformations w.r.t. contextual equivalence in a an extended lambda-calculus with case, constructors, seq, let, and choice, with a simple set of reduction rules. Unfortunately, a direct proof appears to be impossible. The correctness proof is by defining another calculus comprising the complex variants of copy, case-reduction and seq-reductions that use variablebinding chains. This complex calculus has well-behaved diagrams and allows a proof that of correctness of transformations, and also that the simple calculus defines an equivalent contextual order

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Towards sharing in lazy computation systems

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    Work on proving congruence of bisimulation in functional programming languages often refers to [How89,How96], where Howe gave a highly general account on this topic in terms of so-called lazy computation systems . Particularly in implementations of lazy functional languages, sharing plays an eminent role. In this paper we will show how the original work of Howe can be extended to cope with sharing. Moreover, we will demonstrate the application of our approach to the call-by-need lambda-calculus lambda-ND which provides an erratic non-deterministic operator pick and a non-recursive let. A definition of a bisimulation is given, which has to be based on a further calculus named lambda-~, since the na1ve bisimulation definition is useless. The main result is that this bisimulation is a congruence and contained in the contextual equivalence. This might be a step towards defining useful bisimulation relations and proving them to be congruences in calculi that extend the lambda-ND-calculus
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