128 research outputs found

    The physics of higher-order interactions in complex systems

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    Complex networks have become the main paradigm for modelling the dynamics of interacting systems. However, networks are intrinsically limited to describing pairwise interactions, whereas real-world systems are often characterized by higher-order interactions involving groups of three or more units. Higher-order structures, such as hypergraphs and simplicial complexes, are therefore a better tool to map the real organization of many social, biological and man-made systems. Here, we highlight recent evidence of collective behaviours induced by higher-order interactions, and we outline three key challenges for the physics of higher-order systems

    Search for heavy neutral lepton production in K+ decays

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    A search for heavy neutral lepton production in K + decays using a data sample collected with a minimum bias trigger by the NA62 experiment at CERN in 2015 is reported. Upper limits at the 10−7 to 10−6 level are established on the elements of the extended neutrino mixing matrix |Ue4| 2 and |UÎŒ4| 2 for heavy neutral lepton mass in the ranges 170–448 MeV/c2 and 250–373 MeV/c2, respectively. This improves on the previous limits from HNL production searches over the whole mass range considered for |Ue4|2 and above 300 MeV/c2 for |UÎŒ4|2

    A Probe into the Reform of Public Calligraphy Course in Chinese Colleges and Universities

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    äž­ć›œäčŠæł•æ˜Żäž­ć›œäŒ ç»Ÿæ–‡ćŒ–äž­çš„ç‘°ćźïŒŒćźƒæ—ąæ˜Żäž€é—šè‰șæœŻïŒŒćˆæœ‰ç€æ·±ćŽšçš„æ–‡ćŒ–ć†…æ¶”ă€‚æˆ‘ć›œæ™źé€šé«˜æ ĄćŒ€èźŸć…Źć…±äčŠæł•æ•™ć­Šæ˜ŻäžŽç›źć‰ć€ĄćŻŒçš„玠莚教è‚ČćŸčć…»ćˆ›æ–°ćž‹äșșæ‰ïŒŒæć€Ąäșșçš„ć…šéąć’Œè°ć‘ć±•çš„é«˜ç­‰æ•™è‚Čç†ćż”ç›žäž€è‡Žçš„ă€‚ćŠ ćŒșé«˜æ Ąć…Źć…±äčŠæł•æ•™è‚ČïŒŒæ˜Żć…šéąæŽšèż›çŽ èŽšæ•™è‚Čçš„æœ‰æ•ˆé€”ćŸ„äč‹äž€ïŒŒäčŸæ˜Żæé«˜ćœ“ä»Łć€§ć­Šç”Ÿäșșæ–‡çŽ èŽšçš„é‡èŠæ‰‹æź”ă€‚ćźƒćŻčäżƒèż›ć€§ć­Šç”Ÿäșșæ ŒćźŒć–„ă€ćˆ›é€ ćŠ›ćŸčć…»ä»„ćŠæ°‘æ—æ–‡ćŒ–çš„äŒ æ‰żç­‰æœ‰ç€äžćŻäœŽäŒ°çš„äœœç”šă€‚æœŹæ–‡äž»èŠé’ˆćŻčæˆ‘ć›œæ™źé€šé«˜ç­‰é™ąæ Ąć…Źć…±äčŠæł•æ•™ć­ŠçŽ°çŠ¶èż›èĄŒćˆ†æžïŒŒćč¶ç”±æ­€æŻ”èŸƒć€Ÿé‰Žæ—„æœŹé«˜æ Ąäž­ćźžæ–œäčŠæł•æ•™ć­Šçš„æˆćŠŸç»éȘŒæć‡șćŻčæˆ‘ć›œé«˜æ Ąć…Źć…±äčŠæł•æ•™ć­Šæ”čé©çš„ć…·äœ“ć»șèźźć’ŒæŽȘæ–œïŒŒèźŸèźĄćč¶ćźžè·”äž€ç§ć…·ć€‡ć­Šç§‘è§†é‡Žçš„ă€ä»„ć­Šç”Ÿäžșäž»äœ“çš„ć…Źć…±äčŠæł•æ•™ć­Šçš„æ–°æšĄćŒă€‚èźșæ–‡ć…±ćˆ†äžșäș”éƒšćˆ†ă€‚ćŒ•èš€æ‰ŒèŠä»‹ç»èźșæ–‡ć†™...Chinese calligraphy is a treasure of Chinese traditional culture. It not only is an art, but also has profound culture contents. Opening the public calligraphy course to the university students is in accordance with the concept that advocated by the current quality- oriented education, which aims to cultivate the students’ creative talent and comprehensive development. This paper concentrates on a...ć­ŠäœïŒšæ–‡ć­ŠçĄ•ćŁ«é™ąçł»äž“äžšïŒšè‰șæœŻæ•™è‚Čć­Šé™ąçŸŽæœŻçł»_çŸŽæœŻć­Šć­Šć·ïŒš20042201

    Study of the K+- to pi+- gamma gamma decay by the NA62 experiment

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    A study of the dynamics of the rare decay KÂ±â†’Ï€Â±ÎłÎłK^\pm\to\pi^\pm\gamma\gamma has been performed on a sample of 232 decay candidates, with an estimated background of 17.4±1.117.4\pm1.1 events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 collaboration at CERN. The combined model-independent branching ratio in the kinematic range z=(mγγ/mK)2>0.2z=(m_{\gamma\gamma}/m_K)^2>0.2 is BMI(z>0.2)=(0.965±0.063)×10−6{\cal B}_{\rm MI}(z>0.2) = (0.965 \pm 0.063) \times 10^{-6}, and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is B(KÏ€ÎłÎł)=(1.003±0.056)×10−6{\cal B}(K_{\pi\gamma\gamma}) = (1.003 \pm 0.056) \times 10^{-6}. A detailed comparison of the results with the previous measurements is performed.A study of the dynamics of the rare decay KÂ±â†’Ï€Â±ÎłÎłK^\pm\to\pi^\pm\gamma\gamma has been performed on a sample of 232 decay candidates, with an estimated background of 17.4±1.117.4\pm1.1 events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 collaboration at CERN. The combined model-independent branching ratio in the kinematic range z=(mγγ/mK)2>0.2z=(m_{\gamma\gamma}/m_K)^2>0.2 is BMI(z>0.2)=(0.965±0.063)×10−6{\cal B}_{\rm MI}(z>0.2) = (0.965 \pm 0.063) \times 10^{-6}, and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is B(KÏ€ÎłÎł)=(1.003±0.056)×10−6{\cal B}(K_{\pi\gamma\gamma}) = (1.003 \pm 0.056) \times 10^{-6}. A detailed comparison of the results with the previous measurements is performed.A study of the dynamics of the rare decay KÂ±â†’Ï€Â±ÎłÎł has been performed on a sample of 232 decay candidates, with an estimated background of 17.4±1.1 events, collected by the NA62 experiment at CERN in 2007. The results are combined with those from a measurement conducted by the NA48/2 Collaboration at CERN. The combined model-independent branching ratio in the kinematic range z=(mγγ/mK)2>0.2 is BMI(z>0.2)=(0.965±0.063)×10−6 , and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is B(KÏ€ÎłÎł)=(1.003±0.056)×10−6 . A detailed comparison of the results with the previous measurements is performed

    An explainable model of host genetic interactions linked to COVID-19 severity

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    We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

    Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

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    Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

    A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

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    : The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

    Pathogen-sugar interactions revealed by universal saturation transfer analysis

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    Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an “end-on” manner. uSTA-guided modeling and a high-resolution cryo–electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

    The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

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    The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways. Abbreviations: AP: autophagosome; AUC: area under the curve; BafA1: bafilomycin A1; COVID-19: coronavirus disease-2019; HCQ: hydroxychloroquine; RAP: rapamycin; ROC: receiver operating characteristic; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; TLR: toll like receptor; TNF/TNF-α: tumor necrosis factor

    LHCb calorimeters: Technical Design Report

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