841 research outputs found

    Stress dependent thermal pressurization of a fluid-saturated rock

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    Temperature increase in saturated porous materials under undrained conditions leads to thermal pressurization of the pore fluid due to the discrepancy between the thermal expansion coefficients of the pore fluid and of the solid matrix. This increase in the pore fluid pressure induces a reduction of the effective mean stress and can lead to shear failure or hydraulic fracturing. The equations governing the phenomenon of thermal pressurization are presented and this phenomenon is studied experimentally for a saturated granular rock in an undrained heating test under constant isotropic stress. Careful analysis of the effect of mechanical and thermal deformation of the drainage and pressure measurement system is performed and a correction of the measured pore pressure is introduced. The test results are modelled using a non-linear thermo-poro-elastic constitutive model of the granular rock with emphasis on the stress-dependent character of the rock compressibility. The effects of stress and temperature on thermal pressurization observed in the tests are correctly reproduced by the model

    Releasing The Anti-inflammatory Potential of Paralysed Skeletal Muscle: The Circulating Cytokine Response to Voluntary Upper-limb Exercise With/Without The Addition of Functional Electrical Stimulation (FES)-evoked Lower-limb Contractions

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    Skeletal muscle is a rich store of inflammatory mediating ‘myokines’. Following release from contracting muscle, the myokine interleukin-6 (IL-6) promotes a circulating anti-inflammatory environment associated with a reduced risk of cardiovascular disease (CVD). The metabolic and functional consequences of lower-limb paralysis, including the gain in relative adiposity and physical inactivity, result in a high prevalence of CVD in individuals with a spinal cord injury (SCI). However, the magnitude of any contraction-induced myokine response in this population may be limited by the small active muscle mass of the upper-limb. The combination of voluntary, upper-limb exercise and involuntary, functional electrical stimulation (FES)-evoked lower-limb cycling termed ‘hybrid’ exercise, may augment the acute myokine response by activating a greater volume of muscle mass than upper-limb exercise alone. Five community-based individuals with motor complete, thoracic SCI (Age=44±15 years; Body mass=66.6±14.3 kg) and at least 3 months FES-evoked cycling experience volunteered to participate. On separate occasions, each participant performed 30 min of voluntary upper-limb, hand cycling exercise with (HYBRID) and without (ARM only) the addition of FES-evoked lower-limb cycling at a fixed workload. Blood samples were collected at rest, immediately post-exercise, and 1 and 2 h post-exercise. Plasma concentrations of IL-6, IL-10 and IL-1ra were subsequently determined by enzyme linked immunoassay. Estimated energy expenditure was significantly higher in HYBRID (154±25 kcal) than ARM (132±21 kcal) (P=0.01; ES=0.90). Plasma IL-6 concentrations were significantly elevated following HYBRID, with values 1 h and 2 h post-exercise significantly higher than rest and immediately post-exercise (P\u3c0.04). A small (~50%) non-significant increase in IL-6 was present 1 h and 2 h post-exercise following ARM, however concentrations were significantly higher in HYBRID than ARM at the same time points (P\u3c0.02). Plasma IL-10 concentrations were unaffected by exercise in ARM. Although not attaining statistical significance, there was a tendency for IL-10 concentrations to rise in HYBRID, with an 85% increase in IL-10 concentrations at 2 h post exercise. Plasma IL-1ra was unaffected by exercise in both trials. Initial findings suggest paralysed skeletal muscle releases the myokine IL-6 in response to electrically evoked contractions. Further, voluntary upper-limb exercise combined with involuntary lower-limb FES-evoked exercise had the tendency to elevate plasma concentrations of the anti-inflammatory cytokine IL-10; this effect was not present when performing arm exercise alone. Hybrid exercise may offer a method of maximising the anti-inflammatory potential of acute exercise in individuals with a SCI. The current findings require verification in a larger cohort

    Germline TERT promoter mutations are rare in familial melanoma.

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    Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57 T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers. The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte telomere length of a carrier was similar to wild-type cases. We provide evidence confirming that a rare promoter variant of TERT (c.-57 T>G) is associated with high penetrance, early onset melanoma and potentially other cancers, and explains <1 % of UK melanoma multicase families. The identification of POT1 and TERT germline mutations highlights the importance of telomere integrity in melanoma biology.The authors would like to thank the families for their willingness to participate; and Rajiv Kumar for the provision of mutation positive samples. The collection of samples in the UK population-ascertained sample set was funded by Cancer Research UK (awards C588/A19167 and C8216/A6129) and by the NIH (CA83115). The work of N.A.G. and R.v.D was supported by the Dutch Cancer Society (UL 2012-5489). D.J.A and C.D.R.E are supported by Cancer Research UK, ERC Combat Cancer and the Wellcome Trust. N.K.H is supported by a fellowship from the National Health and Medical Research Council of Australia. A.M.D. and K.A.P. were supported by CRUK grant (C8197/A16565) and The Isaac Newton Trust. K.M.B. is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10689-015-9841-

    Climate Change Effects on Slope Stability

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    Global warming is taking place and there is no doubt that the stability of natural and artificial slopes is influenced by climate change. In this context, the present study intends to show, as more quantitatively as possible, the effects of climate change on slopes stability. The analysis was developed considering a non-static approach suitable for meteorological phenomena which are expected to change in the next years. In the analysis a statistical method was combined with a mechanical one: the forecasts of the intensity growth of heavy precipitation were used, as well as the physical laws for describing the response of groundwater table to these rainfall events and the resulting slopes stability. A case study located in Monchiero (Cn), Italy, was used as a test for the analysis and the forecasts described above

    R&D Expenditures and Geographical Sales Diversification

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    This paper empirically examines the role of diversification in export markets on firm-level R&D activities taking account of the potential endogeneity in this relationship. We show that geographical sales diversification across different regions of the world induces UK firms to increase their R&D expenditures, as firms must innovate and develop new products to maintain a competitive edge over their rivals. This finding is robust to a battery of sensitivity checks. Furthermore, we find that R&D expenditures cause higher export sales but do not cause export sales diversification. Hence, the result that diversification causes higher R&D activity is not driven by reverse causality

    Warped Riemannian metrics for location-scale models

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    The present paper shows that warped Riemannian metrics, a class of Riemannian metrics which play a prominent role in Riemannian geometry, are also of fundamental importance in information geometry. Precisely, the paper features a new theorem, which states that the Rao-Fisher information metric of any location-scale model, defined on a Riemannian manifold, is a warped Riemannian metric, whenever this model is invariant under the action of some Lie group. This theorem is a valuable tool in finding the expression of the Rao-Fisher information metric of location-scale models defined on high-dimensional Riemannian manifolds. Indeed, a warped Riemannian metric is fully determined by only two functions of a single variable, irrespective of the dimension of the underlying Riemannian manifold. Starting from this theorem, several original contributions are made. The expression of the Rao-Fisher information metric of the Riemannian Gaussian model is provided, for the first time in the literature. A generalised definition of the Mahalanobis distance is introduced, which is applicable to any location-scale model defined on a Riemannian manifold. The solution of the geodesic equation is obtained, for any Rao-Fisher information metric defined in terms of warped Riemannian metrics. Finally, using a mixture of analytical and numerical computations, it is shown that the parameter space of the von Mises-Fisher model of nn-dimensional directional data, when equipped with its Rao-Fisher information metric, becomes a Hadamard manifold, a simply-connected complete Riemannian manifold of negative sectional curvature, for n=2,…,8n = 2,\ldots,8. Hopefully, in upcoming work, this will be proved for any value of nn.Comment: first version, before submissio

    Modeling Slope Instability as Shear Rupture Propagation in a Saturated Porous Medium

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    When a region of intense shear in a slope is much thinner than other relevant geometric lengths, this shear failure may be approximated as localized slip, as in faulting, with strength determined by frictional properties of the sediment and effective stress normal to the failure surface. Peak and residual frictional strengths of submarine sediments indicate critical slope angles well above those of most submarine slopes—in contradiction to abundant failures. Because deformation of sediments is governed by effective stress, processes affecting pore pressures are a means of strength reduction. However, common methods of exami ning slope stability neglect dynamically variable pore pressure during failure. We examine elastic-plastic models of the capped Drucker-Prager type and derive approximate equations governing pore pressure about a slip surface when the adjacent material may deform plastically. In the process we identify an elastic-plastic hydraulic diffusivity with an evolving permeability and plastic storage term analogous to the elastic term of traditional poroelasticity. We also examine their application to a dynamically propagating subsurface rupture and find indications of downslope directivity.Earth and Planetary SciencesEngineering and Applied Science
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