2,157 research outputs found

    Integrative Gene Set Analysis: Application to Platinum Pharmacogenomics

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    Integrative genomics has the potential to uncover relevant loci, as clinical outcome and response to chemotherapies are most likely not due to a single gene (or data type) but rather a complex relationship involving genetic variation, mRNA, DNA methylation, and copy number variation. In addition to this complexity, many complex phenotypes are thought to be controlled by the interplay of multiple genes within the same molecular pathway or gene set (GS). To address these two challenges, we propose an integrative gene set analysis approach and apply this strategy to a cisplatin (CDDP) pharmacogenomics study involving lymphoblastoid cell lines for which genome-wide SNP and mRNA expression data was collected. Application of the integrative GS analysis implicated the role of the RNA binding and cytoskeletal part GSs. The genes LMNB1 and CENPF, within the cytoskeletal part GS, were functionally validated with siRNA knockdown experiments, where the knockdown of LMNB1 and CENPF resulted in CDDP resistance in multiple cancer cell lines. This study demonstrates the utility of an integrative GS analysis strategy for detecting novel genes associated with response to cancer therapies, moving closer to tailored therapy decisions for cancer patients.National Institutes of Health (U.S.) (NIH/NCI GM61388)National Institutes of Health (U.S.) (NIH/NCI CA140879)National Institutes of Health (U.S.) (NIH/NCI GM86689)National Institutes of Health (U.S.) (NIH/NCI CA130828)National Institutes of Health (U.S.) (NIH/NCI CA138461)National Institutes of Health (U.S.) (NIH/NCI CA102701)Mayo Foundation for Medical Education and Researc

    The Right Place at the Right Time: Creative Spaces in Libraries

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    Purpose This essay explores the recent trend in libraries: that of the establishment of spaces specifically set aside for creative work. The rise of these dedicated creative spaces is owed to a confluence of factors that happen to be finding their expression together in recent years. This essay examines the history of these spaces and explores the factors that gave rise to them and will fuel them moving forward. Design/Methodology/Approach A viewpoint piece, this essay combines historical research and historical/comparative analyses to examine the ways by which libraries have supported creative work in the past and how they may continue to do so into the 21st century. Findings The key threads brought together include a societal recognition of the value of creativity and related skills and attributes; the philosophies, values, and missions of libraries in both their longstanding forms and in recent evolutions; the rise of participatory culture as a result of inexpensive technologies; improved means to build community and share results of efforts; and library experience and historical practice in matters related to creativity. The chapter concludes with advice for those interested in the establishment of such spaces, grounding those reflections in the author’s experiences in developing a new creative space at Virginia Commonwealth University. Originality/value While a number of pieces have been written that discuss the practicalities of developing certain kinds of creative spaces, very little has been written that situates these spaces in larger social and library professional contexts; this essay begins to fill that gap

    #StopHateForProfit and the Ethics of Boycotting by Corporations

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    In July 2020, more than 1,000 companies that advertise on social media platforms withdrew their business, citing failures of the platforms (especially Facebook) to address the proliferation of harmful content. The #StopHateForProfit movement invites reflection on an understudied topic: the ethics of boycotting by corporations. Under what conditions is corporate boycotting permissible, required, supererogatory, or forbidden? Although value-driven consumerism has generated significant recent discussion in applied ethics, that discussion has focused almost exclusively on the consumption choices of individuals. As this article underscores, value-driven consumerism by business corporations complicates these issues and invites further examination. We propose principles for the ethics of boycotting by corporations, indicate how these principles relate to different CSR paradigms, and show how these insights can help assess recent instances of corporate boycotting

    Our Space: Being a Responsible Citizen of the Digital World

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    Our Space is a set of curricular materials designed to encourage high school students to reflect on the ethical dimensions of their participation in new media environments. Through role-playing activities and reflective exercises, students are asked to consider the ethical responsibilities of other people, and whether and how they behave ethically themselves online. These issues are raised in relation to five core themes that are highly relevant online: identity, privacy, authorship and ownership, credibility, and participation.Our Space was co-developed by The Good Play Project and Project New Media Literacies (established at MIT and now housed at University of Southern California's Annenberg School for Communications and Journalism). The Our Space collaboration grew out of a shared interest in fostering ethical thinking and conduct among young people when exercising new media skills

    A preliminary survey of avian mortality on power lines in the Overberg, South Africa

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    Avian mortality on power lines in South Africa is currently recorded on the Central Incident Register (CIR), which is a collation of incidentally reported cases. The true scale of the problem is unknown, so we report here on a survey of representative power lines in the Overberg region of the Western Cape. On the 199 km surveyed, 123 birds of at least 18 species were found. Collisions were more common than electrocutions, apparently killing 88% of the birds found on distribution lines. Large terrestrial birds were the most numerous victims, with large numbers of Blue Cranes Anthropoides paradiseus and Denham's Bustards Neotis denhami killed. In comparison with mortality rates from the CIR, we estimate that only 2.6% of power-line mortalities are reported, emphasising the importance of systematic surveys in quantifying mortality and directing mitigation. Our survey highlights the general hazard that power lines pose to avifauna, and the urgent need for further research into the population impacts of the high incidence of collisions

    SNAVI: Desktop application for analysis and visualization of large-scale signaling networks

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    <p>Abstract</p> <p>Background</p> <p>Studies of cellular signaling indicate that signal transduction pathways combine to form large networks of interactions. Viewing protein-protein and ligand-protein interactions as graphs (networks), where biomolecules are represented as nodes and their interactions are represented as links, is a promising approach for integrating experimental results from different sources to achieve a systematic understanding of the molecular mechanisms driving cell phenotype. The emergence of large-scale signaling networks provides an opportunity for topological statistical analysis while visualization of such networks represents a challenge.</p> <p>Results</p> <p>SNAVI is Windows-based desktop application that implements standard network analysis methods to compute the clustering, connectivity distribution, and detection of network motifs, as well as provides means to visualize networks and network motifs. SNAVI is capable of generating linked web pages from network datasets loaded in text format. SNAVI can also create networks from lists of gene or protein names.</p> <p>Conclusion</p> <p>SNAVI is a useful tool for analyzing, visualizing and sharing cell signaling data. SNAVI is open source free software. The installation may be downloaded from: <url>http://snavi.googlecode.com</url>. The source code can be accessed from: <url>http://snavi.googlecode.com/svn/trunk</url></p

    Digital archives, e-books and narrative space

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    In this paper we are concerned with the capacity of digital media to enable publics to tell their own environmental stories using digital broadcast archives (DBAs). We consider how digital media afford different ways of telling stories in relation to digital media archives. Central to this discussion is our experience of writing e‐books as part of the AHRC‐funded project “Earth in Vision: BBC coverage of environmental change 1960–2010”. The e‐book format has been adopted in order to explore some of the possibilities for writing environmental history and politics using DBAs
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