3,744 research outputs found

    To ensure the continued life of the industry: The public relations campaign of the Ontario brewers during WWII

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    The Second World War witnessed the resurgence of the temperance movement in Canada. In an effort to keep prohibition a thing of the past, the brewers of Ontario undertook a public relations campaign to convince Canadians that brewing and beer drinking were beneficial to the war effort. This paper examines the evolution of that campaign in order to add to our understanding of “the ethos of advocacy.” The paper argues that during the war public relations became a subtle form of lobbying as the brewers attempted to improve their public image so as to achieve severa

    Increased Efficacy of Histone Methyltransferase G9a Inhibitors Against <i>MYCN</i>-Amplified Neuroblastoma.

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    Targeted inhibition of proteins modulating epigenetic changes is an increasingly important priority in cancer therapeutics, and many small molecule inhibitors are currently being developed. In the case of neuroblastoma (NB), a pediatric solid tumor with a paucity of intragenic mutations, epigenetic deregulation may be especially important. In this study we validate the histone methyltransferase G9a/EHMT2 as being associated with indicators of poor prognosis in NB. Immunological analysis of G9a protein shows it to be more highly expressed in NB cell-lines with MYCN amplification, which is a primary determinant of dismal outcome in NB patients. Furthermore, G9a protein in primary tumors is expressed at higher levels in poorly differentiated/undifferentiated NB, and correlates with high EZH2 expression, a known co-operative oncoprotein in NB. Our functional analyses demonstrate that siRNA-mediated G9a depletion inhibits cell growth in all NB cell lines, but, strikingly, only triggers apoptosis in NB cells with MYCN amplification, suggesting a synthetic lethal relationship between G9a and MYCN. This pattern of sensitivity is also evident when using small molecule inhibitors of G9a, UNC0638, and UNC0642. The increased efficacy of G9a inhibition in the presence of MYCN-overexpression is also demonstrated in the SHEP-21N isogenic model with tet-regulatable MYCN. Finally, using RNA sequencing, we identify several potential tumor suppressor genes that are reactivated by G9a inhibition in NB, including the CLU, FLCN, AMHR2, and AKR1C1-3. Together, our study underlines the under-appreciated role of G9a in NB, especially in MYCN-amplified tumors

    Cognitive representations of disability behaviours in people with mobility limitations : consistency with theoretical constructs

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    Disability is conceptualised as behaviour by psychological theory and as a result of bodily impairment by medical models. However, how people with disabilities conceptualise those disabilities is unclear. The purpose of this study was to examine disability representations in people with mobility disabilities. Thirteen people with mobility disabilities completed personal repertory grids (using the method of triads) applied to activities used to measure disabilities. Ten judges with expertise in health psychology then examined the correspondence between the elicited disability constructs and psychological and medical models of disability. Participants with mobility disabilities generated 73 personal constructs ofdisability. These constructs were judged consistent with the content of two psychological models, namely the theory of planned behaviour and social cognitive theory and with the main medical model of disability, the International Classification of Functioning Disability and Health.Individuals with activity limitations conceptualise activities in a manner that is compatible with both psychological and medical models. This ensures adequate communication in contexts where the medical model is relevant, e.g. clinical contexts, as well as in everyday conversation about activities and behaviours. Finally, integrated models of disability may be of value for theory driven interdisciplinary approaches to disability and rehabilitation

    Variability of M giant stars based on Kepler photometry: general characteristics

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    M giants are among the longest-period pulsating stars which is why their studies were traditionally restricted to analyses of low-precision visual observations, and more recently, accurate ground-based data. Here we present an overview of M giant variability on a wide range of time-scales (hours to years), based on analysis of thirteen quarters of Kepler long-cadence observations (one point per every 29.4 minutes), with a total time-span of over 1000 days. About two-thirds of the sample stars have been selected from the ASAS-North survey of the Kepler field, with the rest supplemented from a randomly chosen M giant control sample. We first describe the correction of the light curves from different quarters, which was found to be essential. We use Fourier analysis to calculate multiple frequencies for all stars in the sample. Over 50 stars show a relatively strong signal with a period equal to the Kepler-year and a characteristic phase dependence across the whole field-of-view. We interpret this as a so far unidentified systematic effect in the Kepler data. We discuss the presence of regular patterns in the distribution of multiple periodicities and amplitudes. In the period-amplitude plane we find that it is possible to distinguish between solar-like oscillations and larger amplitude pulsations which are characteristic for Mira/SR stars. This may indicate the region of the transition between two types of oscillations as we move upward along the giant branch.Comment: 12 pages, 13 figures, accepted for publication in MNRAS. The normalized light curves are available upon reques

    Correlations between three ELISA protocols measurements of RTS,S/AS01-induced anti-CSP IgG antibodies

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    Background RTS,S/AS01 induced anti-circumsporozoite protein (CSP) IgG antibodies are associated with the vaccine efficacy. There is currently no international standardisation of the assays used in the measurement of anti-CSP IgG antibody concentrations for use in evaluations of the vaccine’s immunogenicity and/or efficacy. Here, we compared the levels of RTS,S/AS01 induced anti-CSP IgG antibodies measured using three different enzyme-Linked ImmunoSorbent Assays (ELISA). Methods 196 plasma samples were randomly selected from the 447 samples collected during the RTS,S/AS01 phase IIb trial in 2007 from Kenyan children aged between 5–17 months. The vaccine-induced anti-CSP IgG antibodies were then measured using two independently developed ELISA protocols (‘Kilifi-RTS,S’ and ‘Oxford-R21’) and compared to the results from the reference ‘Ghent-RTS,S’ protocol for the same participants. For each pair of protocols, a deming regression model was fitted. Linear equations were then derived to aid in conversions into equivalent ELISA units. The agreement was assessed using Bland and Altman method. Findings The anti-CSP IgG antibodies measured from the three ELISA protocols were in agreement, and were positively and linearly correlated; ‘Oxford’ and ‘Kilifi’ r = 0.93 (95% CI 0.91–0.95), ‘Oxford’ and ‘Ghent’ r = 0.94 (95% CI: 0.92–0.96), and ‘Kilifi’ and ‘Ghent’ r = 0.97 (95% CI: 0.96–0.98), p<0.0001 for all correlations. Conclusions With the linearity, agreement and correlations established between the assays, conversion equations can be applied to convert results into equivalent units, enabling comparisons of immunogenicities across different vaccines of the same CSP antigens. This study highlights the need for the international harmonisation of anti-CSP antibody measurements

    Titanium and nitrogen interactions under laser additive manufacturing conditions

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    To understand how to make bulk titanium parts or coatings with desired levels of titanium nitrides, this paper investigates the dynamic interactions between titanium and nitrogen under representative laser-based additive manufacturing (AM) conditions. Under a set of gas environments containing different concentrations of nitrogen, the titanium and nitrogen reaction products—formed under typical Selective Laser Melting (SLM) and Laser Engineered Net Shaping (LENS) AM scanning conditions—are examined for compositions, phases, and microstructures. In-situ synchrotron X-ray diffraction (SXRD) test is performed to reveal the high temperature reaction steps between titanium and nitrogen

    Label-free electrochemical monitoring of DNA ligase activity

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    This study presents a simple, label-free electrochemical technique for the monitoring of DNA ligase activity. DNA ligases are enzymes that catalyze joining of breaks in the backbone of DNA and are of significant scientific interest due to their essential nature in DNA metabolism and their importance to a range of molecular biological methodologies. The electrochemical behavior of DNA at mercury and some amalgam electrodes is strongly influenced by its backbone structure, allowing a perfect discrimination between DNA molecules containing or lacking free ends. This variation in electrochemical behavior has been utilized previously for a sensitive detection of DNA damage involving the sugar-phosphate backbone breakage. Here we show that the same principle can be utilized for monitoring of a reverse process, i.e., the repair of strand breaks by action of the DNA ligases. We demonstrate applications of the electrochemical technique for a distinction between ligatable and unligatable breaks in plasmid DNA using T4 DNA ligase, as well as for studies of the DNA backbone-joining activity in recombinant fragments of E. coli DNA ligase

    Design and construction of new central and forward muon counters for CDF II

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    New scintillation counters have been designed and constructed for the CDF upgrade in order to complete the muon coverage of the central CDF detector, and to extend this coverage to larger pseudorapidity. A novel light collection technique using wavelength shifting fibers, together with high quality polystyrene-based scintillator resulted in compact counters with good and stable light collection efficiency over lengths extending up to 320 cm. Their design and construction is described and results of their initial performance are reported.Comment: 20 pages, 15 figure

    A Survey of Current Prescribing Practices of Anti-Inflammatory and Urate Lowering Drugs in Gouty Arthritis in New South Wales and Queensland

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    We recently have conducted a cross-sectional survey to determine the prescribing practices of rheumatologists and a random sample of general practitioners in New South Wales and Queensland. While in general there was agreement as to the preferred management of gout, several important differences were noted between the two groups of doctors. In particular, general practitioners were more liberal than were rheumatologists in their use of allopurinol. However, they were less likely to cover the introduction of allopurinol with anti-inflammatory agents, to titrate the dose against the serum uric acid level or to adjust the dose according to the serum creatinine level. A small number of doctors continued to use urate-lowering drugs as a routine in the treatment of entirely asymptomatic hyperuricaemia. The data indicate a continuing need to disseminate information regarding the preferred management of hyperuricaemic states

    Assessing the influence of the Responsibility to Protect on the UN Security Council during the Arab Spring

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    This article challenges those perspectives which assert first, that the Security Council’s engagement with the Responsibility to Protect (R2P) during the Arab Spring evidences a generally positive trend, and second, that the response to the Arab Spring, particularly Syria, highlights the need for veto restraint. With respect to the first point, the evidence presented in this article suggests that the manner in which R2P has been employed by the Security Council during this period evidences three key trends: first, a willingness to invoke R2P only in the context of Pillar I; second, a pronounced lack of consensus surrounding Pillar III; and third, the persistent prioritisation of national interests over humanitarian concerns. With respect to veto restraint, this article argues that there is no evidence that this idea will have any significant impact on decision-making at the Security Council; the Council’s response to the Arab Spring suggests that national interests continue to trump humanitarian need
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