521 research outputs found

    AI for Zero-Touch Management of Satellite Networks in B5G and 6G Infrastructures

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    Satellite Communication (SatCom) networks are become more and more integrated with the terrestrial telecommunication infrastructure. In this paper, we shows the current status of the still ongoing European Space Agency (ESA) project”Data-driven Network Controller Orchestration for Real time Network Management-ANChOR”. In particular, we propose a Long Short-Term Memory (LSTM)based methodology to drive the dynamic selection of the optimal satellite gateway station, which will be performed by combining different kinds of information (i.e. traffic profile, network and weather conditions). Some preliminary results on the real world dataset shows the effectiveness of the proposed approach

    Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease

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    Background & Aims: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered. Methods: To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine aminotransferase at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants with liver fat content in 8930 participants in whom liver fat measurement was available, and replicated 2 genetic variants in 3 independent cohorts comprising 2621 individuals with available liver biopsy. Results: We identified 190 genetic variants independently associated with alanine aminotransferase after correcting for multiple testing with Bonferroni method. The majority of these variants were not previously associated with this trait. Among those associated, there was a striking enrichment of genetic variants influencing lipid metabolism. We identified the variants rs2792751 in GPAM/GPAT1, the gene encoding glycerol-3-phosphate acyltransferase, mitochondrial, and rs429358 in APOE, the gene encoding apolipoprotein E, as robustly associated with liver fat content and liver disease after adjusting for multiple testing. Both genes affect lipid metabolism in the liver. Conclusions: We identified 2 novel genetic variants in GPAM and APOE that are robustly associated with steatosis and liver damage. These findings may help to better elucidate the genetic susceptibility to FLD onset and progression

    IL32 downregulation lowers triglycerides and type I collagen in di-lineage human primary liver organoids

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    Steatotic liver disease (SLD) prevails as the most common chronic liver disease yet lack approved treatments due to incomplete understanding of pathogenesis. Recently, elevated hepatic and circulating interleukin 32 (IL-32) levels were found in individuals with severe SLD. However, the mechanistic link between IL-32 and intracellular triglyceride metabolism remains to be elucidated. We demonstrate in vitro that incubation with IL-32ÎČ protein leads to an increase in intracellular triglyceride synthesis, while downregulation of IL32 by small interfering RNA leads to lower triglyceride synthesis and secretion in organoids from human primary hepatocytes. This reduction requires the upregulation of Phospholipase A2 group IIA (PLA2G2A). Furthermore, downregulation of IL32 results in lower intracellular type I collagen levels in di-lineage human primary hepatic organoids. Finally, we identify a genetic variant of IL32 (rs76580947) associated with lower circulating IL-32 and protection against SLD measured by non-invasive tests. These data suggest that IL32 downregulation may be beneficial against SLD

    Rare ATG7 genetic variants predispose patients to severe fatty liver disease

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    Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants. Methods: We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level. Results: In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; OR 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-related 7 (ATG7), which we characterized as a loss-of-function, vs. the general population, and an enrichment in rare variants affecting the catalytic domain (OR 13.9; 95% CI 1.9-612; p = 0.002). In the UK Biobank cohort, loss-of-function ATG7 variants increased the risk of cirrhosis and hepatocellular carcinoma (OR 3.30; 95% CI 1.1-7.5 and OR 12.30, 95% CI 2.6-36, respectively; p <0.001 for both). The low-frequency loss-of-function p.V471A variant (rs36117895 T>C) was also associated with severe NAFLD in the clinical cohort (OR 1.7; 95% CI 1.2-2.5; p = 0.003), predisposed to hepatocellular ballooning (p = 0.007) evolving to fibrosis in a Liver biopsy cohort (n = 2,268), and was associated with liver injury in the UK Biobank (aspartate aminotransferase levels, p <0.001), with a larger effect in severely obese individuals in whom it was linked to hepatocellular carcinoma (p = 0.009). ATG7 protein localized to periportal hepatocytes, particularly in the presence of ballooning. In the Liver Transcriptomic cohort (n = 125), ATG7 expression correlated with suppression of the TNFα pathway, which was conversely upregulated in p.V471A carriers. Conclusions: We identified rare and low-frequency ATG7 loss-of-function variants that promote NAFLD progression by impairing autophagy and facilitating ballooning and inflammation. Lay summary: We found that rare mutations in a gene called autophagy-related 7 (ATG7) increase the risk of developing severe liver disease in individuals with dysmetabolism. These mutations cause an alteration in protein function and impairment of self-renewal of cellular content, leading to liver damage and inflammation

    Measurement of the multi-TeV neutrino cross section with IceCube using Earth absorption

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    Neutrinos interact only very weakly, so they are extremely penetrating. However, the theoretical neutrino-nucleon interaction cross section rises with energy such that, at energies above 40 TeV, neutrinos are expected to be absorbed as they pass through the Earth. Experimentally, the cross section has been measured only at the relatively low energies (below 400 GeV) available at neutrino beams from accelerators \cite{Agashe:2014kda, Formaggio:2013kya}. Here we report the first measurement of neutrino absorption in the Earth, using a sample of 10,784 energetic upward-going neutrino-induced muons observed with the IceCube Neutrino Observatory. The flux of high-energy neutrinos transiting long paths through the Earth is attenuated compared to a reference sample that follows shorter trajectories through the Earth. Using a fit to the two-dimensional distribution of muon energy and zenith angle, we determine the cross section for neutrino energies between 6.3 TeV and 980 TeV, more than an order of magnitude higher in energy than previous measurements. The measured cross section is 1.30−0.19+0.211.30^{+0.21}_{-0.19} (stat.) −0.43+0.39^{+0.39}_{-0.43} (syst.) times the prediction of the Standard Model \cite{CooperSarkar:2011pa}, consistent with the expectation for charged and neutral current interactions. We do not observe a dramatic increase in the cross section, expected in some speculative models, including those invoking new compact dimensions \cite{AlvarezMuniz:2002ga} or the production of leptoquarks \cite{Romero:2009vu}.Comment: Preprint version of Nature paper 10.1038/nature2445

    Search for astrophysical sources of neutrinos using cascade events in IceCube

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    The IceCube neutrino observatory has established the existence of a flux of high-energy astrophysical neutrinos inconsistent with the expectation from atmospheric backgrounds at a significance greater than 5σ5\sigma. This flux has been observed in analyses of both track events from muon neutrino interactions and cascade events from interactions of all neutrino flavors. Searches for astrophysical neutrino sources have focused on track events due to the significantly better angular resolution of track reconstructions. To date, no such sources have been confirmed. Here we present the first search for astrophysical neutrino sources using cascades interacting in IceCube with deposited energies as small as 1 TeV. No significant clustering was observed in a selection of 263 cascades collected from May 2010 to May 2012. We show that compared to the classic approach using tracks, this statistically-independent search offers improved sensitivity to sources in the southern sky, especially if the emission is spatially extended or follows a soft energy spectrum. This enhancement is due to the low background from atmospheric neutrinos forming cascade events and the additional veto of atmospheric neutrinos at declinations â‰Č−30∘\lesssim-30^\circ.Comment: 14 pages, 9 figures, 1 tabl

    Search for astrophysical sources of neutrinos using cascade events in IceCube

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    The IceCube neutrino observatory has established the existence of a flux of high-energy astrophysical neutrinos inconsistent with the expectation from atmospheric backgrounds at a significance greater than 5σ5\sigma. This flux has been observed in analyses of both track events from muon neutrino interactions and cascade events from interactions of all neutrino flavors. Searches for astrophysical neutrino sources have focused on track events due to the significantly better angular resolution of track reconstructions. To date, no such sources have been confirmed. Here we present the first search for astrophysical neutrino sources using cascades interacting in IceCube with deposited energies as small as 1 TeV. No significant clustering was observed in a selection of 263 cascades collected from May 2010 to May 2012. We show that compared to the classic approach using tracks, this statistically-independent search offers improved sensitivity to sources in the southern sky, especially if the emission is spatially extended or follows a soft energy spectrum. This enhancement is due to the low background from atmospheric neutrinos forming cascade events and the additional veto of atmospheric neutrinos at declinations â‰Č−30∘\lesssim-30^\circ.Comment: 14 pages, 9 figures, 1 tabl
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