63 research outputs found

    Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

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    Peer reviewedPublisher PD

    Identification of Novel Genes and Pathways Regulating SREBP Transcriptional Activity

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    BACKGROUND: Lipid metabolism in mammals is orchestrated by a family of transcription factors called sterol regulatory element-binding proteins (SREBPs) that control the expression of genes required for the uptake and synthesis of cholesterol, fatty acids, and triglycerides. SREBPs are thus essential for insulin-induced lipogenesis and for cellular membrane homeostasis and biogenesis. Although multiple players have been identified that control the expression and activation of SREBPs, gaps remain in our understanding of how SREBPs are coordinated with other physiological pathways. METHODOLOGY: To identify novel regulators of SREBPs, we performed a genome-wide cDNA over-expression screen to identify proteins that might modulate the transcription of a luciferase gene driven from an SREBP-specific promoter. The results were verified through secondary biological assays and expression data were analyzed by a novel application of the Gene Set Enrichment Analysis (GSEA) method. CONCLUSIONS/SIGNIFICANCE: We screened 10,000 different cDNAs and identified a number of genes and pathways that have previously not been implicated in SREBP control and cellular cholesterol homeostasis. These findings further our understanding of lipid biology and should lead to new insights into lipid associated disorders

    Geographies of the Self: Space, Place, and Scale Revisited

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    Where do tendencies to exclude, discriminate, and dominate originate from? Why for many do harmful traits like these appear so characteristic of modern life? How might we move beyond this predicament to foster more sustainable and enriching relationships with one another and with Nature? In this paper, I explore the classic geographic concepts of space, place, and scale and apply them to a consideration of the body and of selfhood. In doing so, I trace out two markedly different ‘geographies of the self’. The first ‘self’ emerges from the basic tenet that space and matter are mutually exclusive, a premise that underpins the dominant episteme of objective rationality. This is the self as selfish, insular, and oppositional. The second ‘self’ emerges from the basic tenet that matter dynamically includes and is included in space, giving rise to the philosophy of ‘natural inclusionality’. The natural inclusional self is hence dynamically distinct but not definitively discrete, a vital inclusion of its natural neighbourhood. I consider some of the implications of these two versions of the self for society, contending that the first promotes a culture of exclusion and the second a culture of belonging. In finishing, I consider questions of method and praxis as they relate to the project of evolving inclusional selves

    All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

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    We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky
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