1,720,982 research outputs found

    Pappulab/King-etal-Nucleoli: Version 2.0.0

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    <p>This is the public release of the data and code within the https://github.com/Pappulab/King-etal-Nucleoli repository for the manuscript:</p> <blockquote> <p><strong>King, Matthew R. and Ruff, Kiersten M. and Lin, Andrew Z. and Pant, Avnika and Farag, Mina and Lalmansingh, Jared and Wu, Tingting and Ouyang, Wei and Fossat, Martin J. and Lew, Matthew D. and Lundberg, Emma and Vahey, Michael D. and Pappu, Rohit</strong>, <em>Macromolecular Condensation Organizes Nucleolar Sub-Phases to Set Up a pH Gradient.</em> Available at SSRN: https://ssrn.com/abstract=4520791 or <a href="https://dx.doi.org/10.2139/ssrn.4520791">http://dx.doi.org/10.2139/ssrn.4520791</a></p> </blockquote&gt

    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

    Determining the Molecular Mechanisms of Huntington’s Disease through Multi-Scale Modeling

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    Huntington’s disease (HD) is associated with a mutational CAG repeat expansion within exon 1 of the huntingtin (Htt) gene. Post-transcriptional processing leads to the generation of N-terminal Htt protein fragments (Htt-NTFs), including those that encompass exon 1 (Httex1). Within Httex1, the CAG-repeat encoded polyglutamine (polyQ) tract is flanked N-terminally by a 17-residue amphipathic stretch (N17) and C-terminally by a 50-residue proline rich (PR) domain. Htt-NTFs, including Httex1, are among the smallest fragments that recapitulate HD pathology in mouse models. However, the direct link between Htt-NTFs with polyQ expansions and neurodegeneration that leads to HD remains unresolved. Despite being a monogenic disease, the onset and progression of HD are governed by an array of complex factors. Like other neurodegenerative diseases, HD too is characterized by deleterious changes across multiple length scales. These include, the length of the polyQ tract, the presence/absence of flanking sequences, the network of endogenous Htt-NTF interaction partners, the engagement of specific sub-cellular processes such as autophagy, and the cell-to-cell transfer of Htt-NTF aggregates. In this work, I have focused on uncovering the rich complexities of Htt-NTF conformations, interactions, and self-associations on the molecular length scales. Given the interplay amongst various length scales, the focus on the molecular scale will have a direct impact on understanding the onset and progression of HD across higher-order length scales. Importantly, all therapeutics will ultimately have to work on the molecular scale and so this scale is of direct biomedical relevance. This thesis pursues a multi-pronged strategy whereby a complete picture on the molecular scale emerges via integration of results obtained from multiple experimental techniques/assays and multi-scale computations. Specifically, this thesis work has uncovered key insights regarding the polyQ-length dependent “structure” of monomeric Httex1, the complexities of the aggregation landscape for different Htt-NTFs, an explanation of the role of flanking sequences as modulators of the aggregation landscape and Htt-NTF phase behavior, and a novel explanation for how ligand binding alters the phase behavior of Htt-NTFs. Along the way, I have developed novel computational methods that have enabled access to mesoscopic descriptions of higher-order aggregates formed by Htt-NTFs. Deployment of these methods highlight the direct connections between the sequence-encoded architectures of monomeric forms of Htt-NTFs and the driving forces for forming distinct types of higher-order morphologies and phases. Importantly, my work has unified the physics of Htt-NTF aggregation and phase separation with the physics of so-called “patchy- colloids”. The methods developed in this thesis have direct relevance for structural studies of various intrinsically disordered proteins, particularly those that encompass low complexity domains. Additionally, the physical principles and the methods developed here have direct bearing on the growing importance of the phase behavior of low complexity domains within cells. From a molecular perspective, we converge on the finding that the onset and progression of HD appears to be dependent on the interplay between gain-of-function hetero- and homo-typic interactions through the polyQ domain that grows in significance with the mutational expansion of this region. The findings in this thesis provide a more precise identification of molecular targets for therapeutic intervention in HD. The thesis also provides an evolutionary perspective regarding polar tracts and their sequence contexts in fifteen different model organisms. This perspective opens the door to uncovering how and why polar tracts are so common in a variety of proteins, especially those that have no known associations with neurodegenerative disorders

    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

    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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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