2,233 research outputs found

    Reclaiming literacies: competing textual practices in a digital higher education

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    This essay examines the implications of the ubiquitous use of the term ‘digital literacies’ in higher education and its increasing alignment with institutional and organisational imperatives. It suggests that the term has been stripped of its provenance and association with disciplinary knowledge production and textual practice. Instead it is called into service rhetorically in order to promote competency based agendas both in and outside the academy. The piece also points to a tendency to position teachers in deficit with regard to their technological capabilities and pay scant attention to their own disciplinary and scholarly practices in a digital world. It concludes that there is a case for building on established theoretical and conceptual frameworks from literacy studies if we wish to integrate advantages of the digital landscape with thoughtful teaching practice

    Fragment-based discovery of a regulatory site in thioredoxin glutathione reductase acting as "doorstop" for NADPH entry

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    Members of the FAD/NAD-linked reductase family are recognized as crucial targets in drug development for cancers, inflammatory disorders, and infectious diseases. However, individual FAD/NAD reductases are difficult to inhibit in a selective manner with off target inhibition reducing usefulness of identified compounds. Thioredoxin glutathione reductase (TGR), a high molecular weight thioredoxin reductase-like enzyme, has emerged as a promising drug target for the treatment of schistosomiasis, a parasitosis afflicting more than 200 million people. Taking advantage of small molecules selected from a high-throughput screen and using X-ray crystallography, functional assays, and docking studies, we identify a critical secondary site of the enzyme. Compounds binding at this site interfere with well-known and conserved conformational changes associated with NADPH reduction, acting as a doorstop for cofactor entry. They selectivity inhibit TGR from Schistosoma mansoni and are active against parasites in culture. Since many members of the FAD/NAD-linked reductase family have similar catalytic mechanisms the unique mechanism of inhibition identified in this study for TGR broadly opens new routes to selectively inhibit homologous enzymes of central importance in numerous diseases

    SOFIA/FORCAST and Spitzer/IRAC Imaging of the Ultra Compact H II Region W3(OH) and Associated Protostars in W3

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    We present infrared observations of the ultra-compact H II region W3(OH) made by the FORCAST instrument aboard SOFIA and by Spitzer/IRAC. We contribute new wavelength data to the spectral energy distribution, which constrains the optical depth, grain size distribution, and temperature gradient of the dusty shell surrounding the H II region. We model the dust component as a spherical shell containing an inner cavity with radius ~ 600 AU, irradiated by a central star of type O9 and temperature ~ 31,000 K. The total luminosity of this system is 71,000 L_solar. An observed excess of 2.2 - 4.5 microns emission in the SED can be explained by our viewing a cavity opening or clumpiness in the shell structure whereby radiation from the warm interior of the shell can escape. We claim to detect the nearby water maser source W3 (H2O) at 31.4 and 37.1 microns using beam deconvolution of the FORCAST images. We constrain the flux densities of this object at 19.7 - 37.1 microns. Additionally, we present in situ observations of four young stellar and protostellar objects in the SOFIA field, presumably associated with the W3 molecular cloud. Results from the model SED fitting tool of Robitaille et al. (2006, 2007} suggest that two objects (2MASS J02270352+6152357 and 2MASS J02270824+6152281) are intermediate-luminosity (~ 236 - 432 L_solar) protostars; one object (2MASS J02270887+6152344) is either a high-mass protostar with luminosity 3000 L_solar or a less massive young star with a substantial circumstellar disk but depleted envelope; and one object (2MASS J02270743+6152281) is an intermediate-luminosity (~ 768 L_solar) protostar nearing the end of its envelope accretion phase or a young star surrounded by a circumstellar disk with no appreciable circumstellar envelope.Comment: 12 pages, 8 figures, 2 tables, accepted by Ap

    Skillful long-range prediction of European and North American winters

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    This is the final version. Available from AGU via the DOI in this recordUntil recently, long-range forecast systems showed only modest levels of skill in predicting surface winter climate around the Atlantic Basin and associated fluctuations in the North Atlantic Oscillation at seasonal lead times. Here we use a new forecast system to assess seasonal predictability of winter North Atlantic climate. We demonstrate that key aspects of European and North American winter climate and the surface North Atlantic Oscillation are highly predictable months ahead. We demonstrate high levels of prediction skill in retrospective forecasts of the surface North Atlantic Oscillation, winter storminess, near-surface temperature, and wind speed, all of which have high value for planning and adaptation to extreme winter conditions. Analysis of forecast ensembles suggests that while useful levels of seasonal forecast skill have now been achieved, key sources of predictability are still only partially represented and there is further untapped predictability. Key Points The winter NAO can be skilfully predicted months ahead The signal-to-noise ratio of the predictable signal is anomalously low Predictions of the risk of regional winter extremes are possibleThis work was supported by the Joint DECC/Defra Met Office Hadley Centre Climate Programme (GA01101), the UK Public Weather Service research program, and the European Union Framework 7 SPECS project. Leon Hermanson was funded as part of his Research Fellowship by Willis as part of Willis Research Network (WRN)

    INFN What Next: Ultra-relativistic Heavy-Ion Collisions

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    This document was prepared by the community that is active in Italy, within INFN (Istituto Nazionale di Fisica Nucleare), in the field of ultra-relativistic heavy-ion collisions. The experimental study of the phase diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP) deconfined state will proceed, in the next 10-15 years, along two directions: the high-energy regime at RHIC and at the LHC, and the low-energy regime at FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the present and future programme of the ALICE experiment, the upgrade of which will open, in the 2020s, a new phase of high-precision characterisation of the QGP properties at the LHC. As a complement of this main activity, there is a growing interest in a possible future experiment at the SPS, which would target the search for the onset of deconfinement using dimuon measurements. On a longer timescale, the community looks with interest at the ongoing studies and discussions on a possible fixed-target programme using the LHC ion beams and on the Future Circular Collider.Comment: 99 pages, 56 figure

    Coralline algal Barium as indicator for 20th century northwestern North Atlantic surface ocean freshwater variability

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    During the past decades climate and freshwater dynamics in the northwestern North Atlantic have undergone major changes. Large-scale freshening episodes, related to polar freshwater pulses, have had a strong influence on ocean variability in this climatically important region. However, little is known about variability before 1950, mainly due to the lack of long-term high-resolution marine proxy archives. Here we present the first multidecadal-length records of annually resolved Ba/Ca variations from Northwest Atlantic coralline algae. We observe positive relationships between algal Ba/Ca ratios from two Newfoundland sites and salinity observations back to 1950. Both records capture episodical multi-year freshening events during the 20th century. Variability in algal Ba/Ca is sensitive to freshwater-induced changes in upper ocean stratification, which affect the transport of cold, Ba-enriched deep waters onto the shelf (highly stratified equals less Ba/Ca). Algal Ba/Ca ratios therefore may serve as a new resource for reconstructing past surface ocean freshwater changes

    Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

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    INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma
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