185 research outputs found

    Dynamic centrifuge testing to assess liquefaction potential

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    A set of centrifuge tests has been carried out at ISMGEO (Italy) laboratory on models of a liquefiable soil. A natural sand from the Emilia-Romagna region in Italy was used in the tests, in order to reproduce typical ground conditions where liquefaction occurred during the seismic sequence of 2012. The models were instrumented with miniaturised accelerometers and with pore pressure and displacement transducers. Spectrum-compatible acceleration time histories were applied at the base of the model. In this way triggering of the liquefaction was detected and post-liquefaction settlements were evaluated. The paper describes with the tests carried out on free-field models. Further tests are currently ongoing to assess the seismic response of simple model structures lying on liquefiable ground. The testing programme, funded within the H2020 research project LIQUEFACT, is aimed at an experimental verification of ground improvement techniques used to mitigate the liquefaction susceptibility of fully saturated loose sands

    Analysis of transient seepage through a river embankment by means of centrifuge modelling

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    Earthen river embankments are typically in unsaturated conditions during their lifetime and the degree of saturation within their bodies may vary significantly throughout the year, due to seasonalfluctuations of the river stage, as well as infiltrations of meteoric precipitation and evapotranspiration phenomena. Given the significant effects of partial saturation on the hydro-mechanical behaviour of soils, realistic assumptions on the actual water content distribution inside the embankments are essential forproperly modelling their response to hydraulic loadings. In this framework, centrifuge modelling is a useful tool to get insights into the evolution of saturation conditions of a water retaining structure during flood events. It allows for the direct observation of the groundwater flow process, which is hardly detectable at the prototype scale, enabling, at the same time, the validation and calibration of predictive numerical tools.In this paper, the results of a centrifuge test carried out on small-scale physical model of a compacted silty clayey sand embankment subjected to a simulated high-water event, at the enhanced gravity of 50-g, are presented and discussed. The physical model was carefully instrumented with potentiometers, miniaturized pore pressure transducers and tensiometers. Pore pressures and suctions measured during the experiment showed that the stationary flow conditions were reached only after an unrealistic hydrometric peak persistence. It therefore emerges that, for the design and/or the assessment of the safety conditions of a river embankment similar to the one tested, the simplified hypothesis of a steady-state seepage, in equilibrium with the maximum river stage expected could result, in many cases, an excessively conservative assumption

    Impact of treatment with dimethyl fumarate on sleep quality in patients with relapsing-remitting multiple sclerosis: A multicentre Italian wearable tracker study

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    BackgroundSleep disorders are common in patients with multiple sclerosis and have a bidirectional interplay with fatigue and depression. ObjectiveTo evaluate the effect of treatment with oral dimethyl fumarate on the quality of sleep in relapsing-remitting multiple sclerosis. MethodsThis was a multicentre observational study with 223 relapsing-remitting multiple sclerosis subjects starting treatment with dimethyl fumarate (n=177) or beta interferon (n=46). All patients underwent subjective (Pittsburgh Sleep Quality Index) and objective (wearable tracker) measurements of quality of sleep. Fatigue, depression, and quality of life were also investigated and physical activity was monitored. ResultsPatients treated with dimethyl fumarate had significant improvement in the quality of sleep as measured with the Pittsburgh Sleep Quality Index (p<0.001). At all-time points, no significant changes in Pittsburgh Sleep Quality Index score were observed in the interferon group. Total and deep sleep measured by wearable tracker decreased at week 12 with both treatments, then remained stable for the total study duration. Depression significantly improved in patients treated with dimethyl fumarate. No significant changes were observed in mobility, fatigue and quality of life. ConclusionIn patients with relapsing-remitting multiple sclerosis, the treatment with dimethyl fumarate was associated with improvements in patient-reported quality of sleep. Further randomised clinical trials are needed to confirm the benefits of long-term treatment with dimethyl fumarate

    Synaptic Proteins Linked to HIV-1 Infection and Immunoproteasome Induction: Proteomic Analysis of Human Synaptosomes

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    Infection of the central nervous system with human immunodeficiency virus type 1 (HIV-1) can produce morphological changes in the neocortical synaptodendritic arbor that are correlated with neurocognitive impairment. To determine whether HIV-1 infection influences the protein composition of human synapses, a proteomic study of isolated nerve endings was undertaken. Synaptosomes from frontal neocortex were isolated using isopyknic centrifugation from 19 human brain specimens. Purity and enrichment were assessed by measuring pre- and postsynaptic protein markers. Two-dimensional polyacrylamide gel electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to screen for proteins differentially expressed in HIV/AIDS. The concentrations of 31 candidate protein spots were potentially abnormal in HIV-infected decedents with HIV encephalitis and/or increased expression of immunoproteasome subunits. Immunoblots showed that the concentration of some of them was related to HIV-1 infection of the brain and immunoproteasome (IPS) induction. Synapsin 1b and stathmin were inversely related to brain HIV-1 load; 14-3-3ζ and 14-4-4ε proteins were higher in subjects with HIV-1 loads. Perturbed synaptosome proteins were linked with IPS subunit composition, and 14-3-3ζ was histologically colocalized with IPS subunits in stained neocortical neurons. Proteomics illustrates that certain human proteins within the synaptic compartment are involved with changes in the synaptodendritic arbor and neurocognitive impairment in HIV-1-infected people

    Combining Shapley value and statistics to the analysis of gene expression data in children exposed to air pollution

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    <p>Abstract</p> <p>Background</p> <p>In gene expression analysis, statistical tests for differential gene expression provide lists of candidate genes having, individually, a sufficiently low <it>p</it>-value. However, the interpretation of each single <it>p</it>-value within complex systems involving several interacting genes is problematic. In parallel, in the last sixty years, <it>game theory </it>has been applied to political and social problems to assess the power of interacting agents in forcing a decision and, more recently, to represent the relevance of genes in response to certain conditions.</p> <p>Results</p> <p>In this paper we introduce a Bootstrap procedure to test the null hypothesis that each gene has the same relevance between two conditions, where the relevance is represented by the Shapley value of a particular coalitional game defined on a microarray data-set. This method, which is called <it>Comparative Analysis of Shapley value </it>(shortly, CASh), is applied to data concerning the gene expression in children differentially exposed to air pollution. The results provided by CASh are compared with the results from a parametric statistical test for testing differential gene expression. Both lists of genes provided by CASh and t-test are informative enough to discriminate exposed subjects on the basis of their gene expression profiles. While many genes are selected in common by CASh and the parametric test, it turns out that the biological interpretation of the differences between these two selections is more interesting, suggesting a different interpretation of the main biological pathways in gene expression regulation for exposed individuals. A simulation study suggests that CASh offers more power than t-test for the detection of differential gene expression variability.</p> <p>Conclusion</p> <p>CASh is successfully applied to gene expression analysis of a data-set where the joint expression behavior of genes may be critical to characterize the expression response to air pollution. We demonstrate a synergistic effect between coalitional games and statistics that resulted in a selection of genes with a potential impact in the regulation of complex pathways.</p

    Tau association with synaptic vesicles causes presynaptic dysfunction

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    Tau is implicated in more than 20 neurodegenerative diseases, including Alzheimer's disease. Under pathological conditions, Tau dissociates from axonal microtubules and missorts to pre- and postsynaptic terminals. Patients suffer from early synaptic dysfunction prior to Tau aggregate formation, but the underlying mechanism is unclear. Here we show that pathogenic Tau binds to synaptic vesicles via its N-terminal domain and interferes with presynaptic functions, including synaptic vesicle mobility and release rate, lowering neurotransmission in fly and rat neurons. Pathological Tau mutants lacking the vesicle binding domain still localize to the presynaptic compartment but do not impair synaptic function in fly neurons. Moreover, an exogenously applied membrane-permeable peptide that competes for Tau-vesicle binding suppresses Tau-induced synaptic toxicity in rat neurons. Our work uncovers a presynaptic role of Tau that may be part of the early pathology in various Tauopathies and could be exploited therapeutically.status: publishe
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