1,762 research outputs found

    Du fragment dans le discours esthétique. L’Histoire de la peinture en Italie de Stendhal

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    Dans l’Histoire de la peinture en Italie, Stendhal privilégie la forme fragmentaire : il morcèle sa mise en page et sa syntaxe, cultive la discontinuité, l’ellipse, l’enthymème et l’ironie. La fragmentation de son discours lui permet de renouveler le genre du traité sur les arts et surtout de rester au plus près de l’émotion esthétique

    Advances in genome-wide RNAi cellular screens: a case study using the Drosophila JAK/STAT pathway

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    BACKGROUND: Genome-scale RNA-interference (RNAi) screens are becoming ever more common gene discovery tools. However, whilst every screen identifies interacting genes, less attention has been given to how factors such as library design and post-screening bioinformatics may be effecting the data generated. RESULTS: Here we present a new genome-wide RNAi screen of the Drosophila JAK/STAT signalling pathway undertaken in the Sheffield RNAi Screening Facility (SRSF). This screen was carried out using a second-generation, computationally optimised dsRNA library and analysed using current methods and bioinformatic tools. To examine advances in RNAi screening technology, we compare this screen to a biologically very similar screen undertaken in 2005 with a first-generation library. Both screens used the same cell line, reporters and experimental design, with the SRSF screen identifying 42 putative regulators of JAK/STAT signalling, 22 of which verified in a secondary screen and 16 verified with an independent probe design. Following reanalysis of the original screen data, comparisons of the two gene lists allows us to make estimates of false discovery rates in the SRSF data and to conduct an assessment of off-target effects (OTEs) associated with both libraries. We discuss the differences and similarities between the resulting data sets and examine the relative improvements in gene discovery protocols. CONCLUSIONS: Our work represents one of the first direct comparisons between first- and second-generation libraries and shows that modern library designs together with methodological advances have had a significant influence on genome-scale RNAi screens

    Inter-study reproducibility of arterial spin labelling magnetic resonance imaging for measurement of renal perfusion in healthy volunteers at 3 Tesla

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    Background: Measurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers.<p></p> Methods: ASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning.<p></p> Results: 12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 ± 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 ± 15.1 ml/min/1.73 m2. Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 ± 25.5 cm3, and 156.7 ± 28.9 cm3 respectively. Mean kidney perfusion was 229 ± 41 ml/min/100 g and mean cortical perfusion was 327 ± 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 ± 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%.<p></p> Conclusions: ASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers.<p></p&gt

    On the prediction of topology and local properties for optimal trussed structures

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    A new formulation is presented for mathematical modelling to predict the distribution of material, material properties, and topology for the optimal design of trussed structures. The design problem is cast in a form to minimize a measure of generalized compliance , which is calculated as a sum over the structure of weighted displacement. Member stiffnesses appear as design variables and, starting with a given ground structure, the solution predicts the optimal layout and distribution of stiffness. The isoperimetric constraint in the reformulated problem measures total cost in generalized form , based on independently specified unit relative cost factors for each truss element. One or another form of optimal design is generated via a process where designated elements in the unit relative cost field are adjusted systematically at each cycle. The generalized cost feature provides as well for the introduction of certain technical constraints into the design problem, e.g. the facility to design around obstacles. Results for each cycle of an algorithm for computational treatment are identified as the solution to a properly posed optimization problem. Computational procedures are demonstrated by the prediction of optimal designs for a variety of truss problems in 2D.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46074/1/158_2005_Article_BF01197558.pd

    La personnalité de l’artiste

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    A l’époque romantique, Michel-Ange quitte sa dépouille d’individu réel pour devenir un « homme fabuleux ». Le véritable objet esthétique n’est plus la création, mais la sensibilité de l’artiste

    NICE guidance on long-term sickness and incapacity

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    Long-term sickness absence and incapacity benefits (disability pension) rates have increased across industrialised countries. Effective measures are needed to support return to work. The recommendations of this guidance were informed by the most appropriate available evidence of effectiveness and cost-effectiveness. Public health evidence was provided by research using a variety of study designs that attempted to determine the outcome of a particular intervention by evaluating status before and after the intervention had been effected, and was not limited to randomised control trials. Where the evidence base was depleted or underdeveloped, expert witnesses were called to give their opinion on the best available evidence and emerging interventions. The process enabled challenge and contestability from stakeholder groups at different points as the guidance was developed. Forty-five heterogeneous studies were included in the review of interventions to reduce long-term sickness absence and transitions from short-term to long-term absence (mainly covering the former and also mainly examining musculoskeletal conditions). The analysis of evidence was restricted to descriptive synthesis. Three general themes emerged from an analysis of the studies that were more likely to report positive results: early interventions; multidisciplinary approaches; and interventions with a workplace component. Two further reviews were undertaken, one on interventions to reduce the re-occurrence of sickness absence, which identified seven studies on lower back pain, and concluded that early intervention and direct workplace input are important factors. The final evidence review focused on six studies of interventions for those in receipt of incapacity benefit. The evidence was that work-focused interviews coupled with access to tailored support are effective and cost-effective interventions. Practitioners should consider the impact of interventions and management options on work ability for patients of working age. Work ability should be considered a key outcome for future intervention studies

    ‘Green’ on the ground but not in the air: Pro-environmental attitudes are related to household behaviours but not discretionary air travel

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    The rise in greenhouse gas emissions from air travel could be reduced by individuals voluntarily abstaining from, or reducing, flights for leisure and recreational purposes. In theory, we might expect that people with pro-environmental value orientations and concerns about the risks of climate change, and those who engage in more pro-environmental household behaviours, would also be more likely to abstain from such voluntary air travel, or at least to fly less far. Analysis of two large datasets from the United Kingdom, weighted to be representative of the whole population, tested these associations. Using zero-inflated Poisson regression models, we found that, after accounting for potential confounders, there was no association between individuals’ environmental attitudes, concern over climate change, or their routine pro-environmental household behaviours, and either their propensity to take non-work related flights, or the distances flown by those who do so. These findings contrasted with those for pro-environmental household behaviours, where associations with environmental attitudes and concern were observed. Our results offer little encouragement for policies aiming to reduce discretionary air travel through pro-environmental advocacy, or through ‘spill-over’ from interventions to improve environmental impacts of household routines

    Search for Possible Variation of the Fine Structure Constant

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    Determination of the fine structure constant alpha and search for its possible variation are considered. We focus on a role of the fine structure constant in modern physics and discuss precision tests of quantum electrodynamics. Different methods of a search for possible variations of fundamental constants are compared and those related to optical measurements are considered in detail.Comment: An invited talk at HYPER symposium (Paris, 2002

    Applying spatial reasoning to topographical data with a grounded geographical ontology

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    Grounding an ontology upon geographical data has been pro- posed as a method of handling the vagueness in the domain more effectively. In order to do this, we require methods of reasoning about the spatial relations between the regions within the data. This stage can be computationally expensive, as we require information on the location of points in relation to each other. This paper illustrates how using knowledge about regions allows us to reduce the computation required in an efficient and easy to understand manner. Further, we show how this system can be implemented in co-ordination with segmented data to reason abou
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