1,580 research outputs found

    Evaluation of SCRAN subscription to Scottish public libraries

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    This report commissioned by the Scottish Library and Information Council evaluates the year-long Scottish Executive-funded project to give all public libraries in Scotland access to the SCRAN service. The implementation of the project was supported by a Project Steering Group with both SLIC and SCRAN representation, and a wider steering group with membership from Heads of Service, Scottish Executive, and SCRAN and chaired by Elaine Fulton of SLIC

    An indefensible frontier: the Claustra Alpium Iuliarum

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    It has been long maintained that the system of barrier walls and fortlets in the Julian Alps dates to the early 4th century and that it was a fortification line used to defend Italy during times of civil war. Reviewing the historical, archaeological and topographic evidence, it is here argued that its military importance has been much exaggerated; one role may well have been to regulate traffic and perhaps to exact taxes from the civilians using the imperial road system, or crossing from Illyricum into Italy. Its date cannot be yet established for certain but the most likely context is the very end of the 4th century AD, not long before the system was abandoned at some point during the first decade of the 5th century. Contrary to received wisdom, it was incapable of repulsing any major force coming from the East, whether they were Goths or Romans. Regulation and taxation, however, do not require the erection of barrier walls. There must have been additional reasons for their construction even though the walls were unable to deal with anything more than a low intensity threat. What the percieived danger was, it is impossible to determin for certain,except that there were a series of problems facing the Western Empire c. 390-400 which could warrant the construction of a 'frontier' in the Julian Alps; an influx of refugees from Illyricum, Gothic war bands from Thrace, raiding parties from across the Danube and the endemic danger posed by local bandits. Any one of these, or more likely a combination of several factors, precipitated the decision to regulate, but not seriously to defend the routes which led west from Illyricum and into the Italian peninsular

    Farnesyl diphosphate synthetase: molecular cloning, sequence, and expression of an essential gene from Saccharomyces cerevisiae

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    Journal ArticleFarnesyl diphosphate (FPP) synthetase is a key enzyme in isoprenoid biosynthesis which supplies C15 precursors for several classes of essential metabolites including sterols, dolichols, and ubiquinones. The structural gene for FPP synthetase was isolated on a 4.5-kilobase EcoRI genomic restriction fragment from the yeast Saccharomyces cerevisiae. The clone encodes a 40,483-dalton polypeptide of 342 amino acids with a high degree of similarity to the protein encoded by a putative rat liver clone of FPP synthetase (Clarke, C. F., Tanaka, R. D., Svenson, K., Wamsley, M., Fogelman, A. M., and Edwards, P. A. (1987) Mol. Cell Biol. 7, 3138-3146) and to an active site protein fragment from avian liver FPP synthetase (Brems, D. N., Bruenger, E., and Rilling, H. C. (1981) Biochemistry 20, 3711-3718). When cloned into the yeast shuttle vector YRp17, the 4.5-kilobase EcoRI fragment directed a 2-3-fold over-expression of FPP synthetase activity in transformed yeast cells. The levels of expression were independent of culture growth phase and orientation of the insert, indicative of a functional promoter in the clone. Disruption of the FPP synthetase gene from a diploid yeast strain, followed by dissection and analysis of tetrads, demonstrates that the gene is an essential, single copy number gene in yeast. The gene for FPP synthetase resides on chromosome XI as judged from Southern blots of separated yeast chromosomes

    The actin binding proteins cortactin and HS1 are dispensable for platelet actin nodule and megakaryocyte podosome formation

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    A dynamic, properly organised actin cytoskeleton is critical for the production and haemostatic function of platelets. The Wiskott Aldrich Syndrome protein (WASp) and Actin-Related Proteins 2 & 3 Complex (Arp2/3 complex) are critical mediators of actin polymerisation and organisation in many cell types. In platelets and megakaryocytes, these proteins have been shown to be important for proper platelet production and function. The cortactin family of proteins (Cttn & HS1) are known to regulate WASp-Arp2/3-mediated actin polymerisation in other cell types and so here we address the role of these proteins in platelets using knockout mouse models. We generated mice lacking Cttn and HS1 in the megakaryocyte/platelet lineage. These mice had normal platelet production, with platelet number, size and surface receptor profile comparable to controls. Platelet function was also unaffected by loss of Cttn/HS1 with no differences observed in a range of platelet function assays including aggregation, secretion, spreading, clot retraction or tyrosine phosphorylation. No effect on tail bleeding time or in thrombosis models was observed. In addition, platelet actin nodules, and megakaryocyte podosomes, actin-based structures known to be dependent on WASp and the Arp2/3 complex, formed normally. We conclude that despite the importance of WASp and the Arp2/3 complex in regulating F-actin dynamics in many cells types, the role of cortactin in their regulation appears to be fulfilled by other proteins in platelets

    Energy gap of the bimodal two-dimensional Ising spin glass

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    An exact algorithm is used to compute the degeneracies of the excited states of the bimodal Ising spin glass in two dimensions. It is found that the specific heat at arbitrary low temperature is not a self-averaging quantity and has a distribution that is neither normal or lognormal. Nevertheless, it is possible to estimate the most likely value and this is found to scale as L^3 T^(-2) exp(-4J/kT), for a L*L lattice. Our analysis also explains, for the first time, why a correlation length \xi ~ exp(2J/kT) is consistent with an energy gap of 2J. Our method allows us to obtain results for up to 10^5 disorder realizations with L <= 64. Distributions of second and third excitations are also shown.Comment: 4 pages, 4 figure

    CRP 2020 Reviews: Grain Legumes and Dryland Cereals (GLDC)

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    The primary purpose of the review is to assess the extent to which the GLDC is delivering quality of science and demonstrating effectiveness in relation to its theories of change (ToCs) in the approved proposal. Its objectives are to fulfill CGIAR’s obligations for accountability and donor support for international agricultural research; assess the effectiveness and evolution of research program’s work; and provide an opportunity for GLDC to generate insights, including lessons for future CGIAR research modalities

    Suppression of piriform cortex activity in rat by corticotropin-releasing factor 1 and serotonin 2A/C receptors

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    The piriform cortex (PC) is richly innervated by Corticotropin-releasing factor (CRF) and Serotonin (5-HT) containing axons arising from central amygdala and Raphe nucleus. CRFR1 and 5-HT2A/2CRs have been shown to interact in manner where CRFR activation subsequently potentiates the activity of 5-HT2A/2CRs. The purpose of this study was to determine how the activation of CRFR1 and/or 5-HT2Rs modulates PC activity at both the circuit and cellular level. Voltage sensitive dye imaging showed that CRF acting through CRFR1 dampened activation of the layer II of PC and interneurons of endopiriform nucleus. Application of the selective 5-HT2A/CR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) following CRFR1 activation potentiated this effect. Blocking the interaction between CRFR1 and 5-HT2R with a Tat-CRFR1-CT peptide abolished this potentiation. Application of forskolin did not mimic CRFR1 activity but instead blocked it, while a protein kinase A antagonist had no effect. However, activation and antagonism of protein kinase C (PKC) either mimicked or blocked CRF modulation respectively. DOI had no effect when applied alone indicating that the prior activation of CRFR1 receptors was critical for DOI to show significant effects similar to CRF. Patch clamp recordings showed that both CRF and DOI reduced the synaptic responsiveness of layer II pyramidal neurons. CRF had highly variable effects on interneurons within layer III, both increasing and decreasing their excitability, but DOI had no effect on the excitability of this group of neurons. These data show that CRF and serotonin, acting through both CRFR1 and 5-HT2A/CRs, reduce the activation of the PC. This modulation may be an important blunting mechanism of stressor behaviours mediated through the olfactory cortex

    An indefensible frontier: the Claustra Alpium Iuliarum

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    It has been long maintained that the system of barrier walls and fortlets in the Julian Alps dates to the early 4th century and that it was a fortification line used to defend Italy during times of civil war. Reviewing the historical, archaeological and topographic evidence, it is here argued that its military importance has been much exaggerated; one role may well have been to regulate traffic and perhaps to exact taxes from the civilians using the imperial road system, or crossing from Illyricum into Italy. Its date cannot be yet established for certain but the most likely context is the very end of the 4th century AD, not long before the system was abandoned at some point during the first decade of the 5th century. Contrary to received wisdom, it was incapable of repulsing any major force coming from the East, whether they were Goths or Romans. Regulation and taxation, however, do not require the erection of barrier walls. There must have been additional reasons for their construction even though the walls were unable to deal with anything more than a low intensity threat. What the percieived danger was, it is impossible to determin for certain,except that there were a series of problems facing the Western Empire c. 390-400 which could warrant the construction of a 'frontier' in the Julian Alps; an influx of refugees from Illyricum, Gothic war bands from Thrace, raiding parties from across the Danube and the endemic danger posed by local bandits. Any one of these, or more likely a combination of several factors, precipitated the decision to regulate, but not seriously to defend the routes which led west from Illyricum and into the Italian peninsular

    A "superstorm": When moral panic and new risk discourses converge in the media

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    This is an Author's Accepted Manuscript of an article published in Health, Risk and Society, 15(6), 681-698, 2013, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/13698575.2013.851180.There has been a proliferation of risk discourses in recent decades but studies of these have been polarised, drawing either on moral panic or new risk frameworks to analyse journalistic discourses. This article opens the theoretical possibility that the two may co-exist and converge in the same scare. I do this by bringing together more recent developments in moral panic thesis, with new risk theory and the concept of media logic. I then apply this theoretical approach to an empirical analysis of how and with what consequences moral panic and new risk type discourses converged in the editorials of four newspaper campaigns against GM food policy in Britain in the late 1990s. The article analyses 112 editorials published between January 1998 and December 2000, supplemented with news stories where these were needed for contextual clarity. This analysis shows that not only did this novel food generate intense media and public reactions; these developed in the absence of the type of concrete details journalists usually look for in risk stories. Media logic is important in understanding how journalists were able to engage and hence how a major scare could be constructed around convergent moral panic and new risk type discourses. The result was a media ‘superstorm’ of sustained coverage in which both types of discourse converged in highly emotive mutually reinforcing ways that resonated in a highly sensitised context. The consequence was acute anxiety, social volatility and the potential for the disruption of policy and social change

    Estimation of individual beneficial and adverse effects of intensive glucose control for patients with type 2 diabetes

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    AIMS/HYPOTHESIS: Intensive glucose control reduces the risk of vascular complications while increasing the risk of severe hypoglycaemia at a group level. We sought to estimate individual beneficial and adverse effects of intensive glucose control in patients with type 2 diabetes. METHODS: We performed a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, a randomised controlled trial evaluating standard vs intensive glucose control (HbA1c target ≀6.5% [48 mmol/mol]). In 11,140 participants, we estimated the individual 5 year absolute risk reduction (ARR) for the composite outcome of major micro- and macrovascular events and absolute risk increase (ARI) for severe hypoglycaemia for intensive vs standard glucose control. Predictions were based on competing risks models including clinical characteristics and randomised treatment. RESULTS: Based on these models, 76% of patients had a substantial estimated 5 year ARR for major vascular events (>1%, 5 year number-needed-to-benefit [NNTB5] 200). Similarly, 36% of patients had a substantial estimated ARI for severe hypoglycaemia (5 year number-needed-to-harm [NNTH5] 200). When assigning similar or half the weight to severe hypoglycaemia compared with a major vascular event, net benefit was positive in 85% or 99% of patients, respectively. Limiting intensive treatment to the 85% patient subgroup had no significant effect on the overall incidence of major vascular events and severe hypoglycaemia compared with treating all patients. CONCLUSIONS/INTERPRETATION: Taking account of the effects of intensive glucose control on major micro- and macrovascular events and severe hypoglycaemia for individual patients, the estimated net benefit was positive in the majority of the participants in the ADVANCE trial. The estimated individual effects can inform treatment decisions once individual weights assigned to positive and adverse effects have been specified. TRIAL REGISTRATION: ClinicalTrials.gov NCT00145925
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