351 research outputs found

    A Bootstrapped Modularised method of Global Sensitivity Analysis applied to Probabilistic Seismic Hazard Assessment

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    Probabilistic Seismic Hazard Assessment (PSHA) evaluates the probability of exceedance of a given earthquake intensity threshold like the Peak Ground Acceleration, at a target site for a given exposure time. The stochasticity of the occurrence of seismic events is modelled by stochastic processes and the propagation of the earthquake wave in the soil is typically evaluated by empirical relationships called Ground Motion Prediction Equations. The large uncertainty affecting PSHA is quantified by defining alternative model settings and/or model parametri-zations. In this work, we propose a novel Bootstrapped Modularised Global Sensitivity Analysis (BMGSA) method for identifying the model parameters most important for the uncertainty in PSHA, that consists in generating alternative artificial datasets by bootstrapping an available input-output dataset and aggregating the individual rankings obtained with the modularized method from each of those.The proposed method is tested on a realistic PSHA case study in Italy. The results are compared with a standard variance-based Global Sensitivity Analysis (GSA) method of literature. The novelty and strength of the proposed BMGSA method are both in the fact that its application only requires input-output data and not the use of a PSHA code for repeated calculations

    Faf1 is expressed during neurodevelopment and is involved in Apaf1-dependent caspase-3 activation in proneural cell

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    Fas-associated factor 1 (Faf1) has been described as a Fas-binding pro-apoptotic protein and as a component of the death-inducing signaling complex (DISC) in Fas-mediated apoptosis. Faf1 is able to potentiate Fas-induced apoptosis in several cell lines, although its specific functions are still not clear. Here we show that Faf1 is highly expressed in several areas of the developing telencephalon. Its expression pattern appears to be dynamic at different embryonic stages and to be progressively confined within limited territories. To decipher the specific role of Faf1 in developing brain, we used cDNA over-expression and mRNA down-regulation experiments to modulate Faf1 expression in telencephalic neural precursor cells, and we showed that in neural cell death Faf1 acts as a Fas-independent apoptotic enhancer. Moreover, we found that Faf1 protein level is down-regulated during apoptosis in a caspase- and Apaf1-dependent manner

    Role of PKC in the Regulation of the Human Kidney Chloride Channel ClC-Ka

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    The physiological role of the renal ClC-Ka/ClC-K1 channels is to confer a high Cl- permeability to the thin Ascending Limb of Henle (tAL), which in turn is essential for establishing the high osmolarity of the renal medulla that drives water reabsorption from collecting ducts. Here, we investigated by whole-cell patch-clamp measurements on HEK293 cells co-expressing ClC-Ka (tagged with GFP) and the accessory subunit barttin (tagged with m-Cherry) the effect of a natural diuretic extract from roots of Dandelion (DRE), and other compounds activating PKC, such as ATP, on ClC-Ka activity and its membrane localization. Treatment with 400 µg/ml DRE significantly inhibited Cl- currents time-dependently within several minutes. Of note, the same effect on Cl- currents was obtained upon treatment with 100 µM ATP. Pretreatment of cells with either the intracellular Ca2+ chelator BAPTA-AM (30 μM) or the PKC inhibitor Calphostin C (100 nM) reduced the inhibitory effect of DRE. Conversely, 1 µM of phorbol meristate acetate (PMA), a specific PKC activator, mimicked the inhibitory effect of DRE on ClC-Ka. Finally, we found that pretreatment with 30 µM Heclin, an E3 ubiquitin ligase inhibitor, did not revert DRE-induced Cl- current inhibition. In agreement with this, live-cell confocal analysis showed that DRE treatment did not induce ClC-Ka internalization. In conclusion, we demonstrate for the first time that the activity of ClC-Ka in renal cells could be significantly inhibited by the activation of PKC elicited by classical maneuvers, such as activation of purinergic receptors, or by exposure to herbal extracts that activates a PKC-dependent pathway. Overall, we provide both new information regarding the regulation of ClC-Ka and a proof-of-concept study for the use of DRE as new diuretic

    Failure modes detection of nuclear systems using machine learning

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    © 2018 IEEE. Early detection of the failure of a nuclear system is an important topic in nuclear energy. This paper proposes three machine learning methodologies to detect the failure modes (FM) of the Lead-Bismuth Eutectic eXperimental Accelerator Driven System (LBE-XADS) nuclear system after the first 10%, 50% and 90% time periods of the 3000 seconds mission time of the LBEXADS. The first methodology detects the FM of the LBE-XADS after the first 10% time period and consists of two Gaussian mixture-based (GM-based) classifiers. The second methodology detects the FM of the LBE-XADS after the first 50% time period and consists of a GM-based classifier and a neural network MLP1. The third methodology detects the failure mode of the LBE-XADS after the first 90% time period and consists of a GM-based classifier and a neural network MLP2. The three proposed methodologies outperformed the fuzzy similarity approach of the previous work

    Selective autophagy maintains centrosome integrity and accurate mitosis by turnover of centriolar satellites

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    The centrosome is the master orchestrator of mitotic spindle formation and chromosome segregation in animal cells. Centrosome abnormalities are frequently observed in cancer, but little is known of their origin and about pathways affecting centrosome homeostasis. Here we show that autophagy preserves centrosome organization and stability through selective turnover of centriolar satellite components, a process we termed doryphagy. Autophagy targets the satellite organizer PCM1 by interacting with GABARAPs via a C-terminal LIR motif. Accordingly, autophagy deficiency results in accumulation of large abnormal centriolar satellites and a resultant dysregulation of centrosome composition. These alterations have critical impact on centrosome stability and lead to mitotic centrosome fragmentation and unbalanced chromosome segregation. Our findings identify doryphagy as an important centrosome-regulating pathway and bring mechanistic insights to the link between autophagy dysfunction and chromosomal instability. In addition, we highlight the vital role of centriolar satellites in maintaining centrosome integrity

    Multi-source statistics:Basic situations and methods

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    Many National Statistical Institutes (NSIs), especially in Europe, are moving from single‐source statistics to multi‐source statistics. By combining data sources, NSIs can produce more detailed and more timely statistics and respond more quickly to events in society. By combining survey data with already available administrative data and Big Data, NSIs can save data collection and processing costs and reduce the burden on respondents. However, multi‐source statistics come with new problems that need to be overcome before the resulting output quality is sufficiently high and before those statistics can be produced efficiently. What complicates the production of multi‐source statistics is that they come in many different varieties as data sets can be combined in many different ways. Given the rapidly increasing importance of producing multi‐source statistics in Official Statistics, there has been considerable research activity in this area over the last few years, and some frameworks have been developed for multi‐source statistics. Useful as these frameworks are, they generally do not give guidelines to which method could be applied in a certain situation arising in practice. In this paper, we aim to fill that gap, structure the world of multi‐source statistics and its problems and provide some guidance to suitable methods for these problems
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