1,726,014 research outputs found

    The role of poly (ADP-ribose) polymerase-1 in the celluar response to several marine-derived compounds:

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    PARP-1 is a multi-functional protein that is involved in many DNA-dependent genomic processes under normal and pathophysiological conditions. It is well characterized as a DNA damage detector and responds by catalytic production and attachment of polymers of ADP-ribose (PAR) to nuclear protein targets, facilitating the chromatin changes that are a prerequisite to DNA repair. In this study, we tested whether PARP-1 is involved in the cellular response to Yondelis®, Zalypsis®, PSL1, and PSL2, novel chemotherapeutic agents with putative DNA damage- and transcription-targeted activities. We observed a dose-dependent activation of PARP-1 catalytic activity following treatment with all four compounds, while PARP-1 protein levels remained unchanged. Interestingly, cells derived from PARP-1 null mice were significantly sensitized to the agents, yet, with respect to Yondelis®, only moderate DNA damage was observed which was repaired with equal efficiency by both PARP-1 wildtype and PARP-1 null cells. While the mechanism of sensitization is unclear, it is of interest to determine whether inhibition of PARP in human cells could sensitize cells to the four agents. Initial in vivo experiments testing this prediction using MX-1 breast carcinoma xenografts treated with Yondelis® alone or in combination with the PARP-1 inhibitor DIQ, demonstrate an additive effect between these two compounds with regard to tumor volume inhibition and tumor growth delay. However, corresponding in vitro experiments failed to corroborate this observation. The effects of PARP-1 on the transcription of genes impacting drug sensitivity, as well as the cyto-protective role of PARP-1 independent of its catalytic function are of interest to direct future efforts to clarify the mechanism of PARP-1-mediated sensitivity to the four agents. Taken together, these data suggest that PARP-1 plays an important role in the protection of cells to Yondelis®, Zalypsis®, PSL1, and PSL2, and suggest that PARP-1 status may determine the sensitivity or resistance of cells treated with these agents.M.S.Includes bibliographical references (p. 45-53)by Brijesh B. Pate

    Isabelle Files for Verifying Secure Speculation in Isabelle/HOL

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    Isabelle files for FM 2021 paper "Verifying Secure Speculation in Isabelle/HOL" by Matt Griffin and Brijesh Dongol

    Triconodont mammals from the Jurassic Kota Formation of India

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    Prasad, Guntupalli V. R., Manhas, Brijesh K. (2002): Triconodont mammals from the Jurassic Kota Formation of India. Geodiversitas 24 (2): 445-464, DOI: http://doi.org/10.5281/zenodo.537570

    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

    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

    Convolution algebras: Relational convolution, generalised modalities and incidence algebras

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    Convolution is a ubiquitous operation in mathematics and computing. The Kripke semantics for substructural and interval logics motivates its study for quantale-valued functions relative to ternary relations. The resulting notion of relational convolution leads to generalised binary and unary modal operators for qualitative and quantitative models, and to more conventional variants, when ternary relations arise from identities over partial semigroups. Convolution-based semantics for fragments of categorial, linear and incidence (segment or interval) logics are provided as qualitative applications. Quantitative examples include algebras of durations and mean values in the duration calculus
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