Search for heavy neutral lepton production in K+ decays

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 |Uμ4| 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 |Uμ4|2

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

中国书法是中国传统文化中的瑰宝，它既是一门艺术，又有着深厚的文化内涵。我国普通高校开设公共书法教学是与目前倡导的素质教育，培养创新型人才，提倡人的全面和谐发展的高等教育理念相一致的。加强高校公共书法教育，是全面推进素质教育的有效途径之一，也是提高当代大学生人文素质的重要手段。它对促进大学生人格完善、创造力培养以及民族文化的传承等有着不可低估的作用。本文主要针对我国普通高等院校公共书法教学现状进行分析，并由此比较借鉴日本高校中实施书法教学的成功经验提出对我国高校公共书法教学改革的具体建议和措施，设计并实践一种具备学科视野的、以学生为主体的公共书法教学的新模式。论文共分为五部分。引言扼要介绍论文写...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...学位：文学硕士院系专业：艺术教育学院美术系_美术学学号：20042201

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

A study of the dynamics of the rare decay $K^\pm\to\pi^\pm\gamma\gamma$ has been performed on a sample of 232 decay candidates, with an estimated background of $17.4\pm1.1$ 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 $z=(m_{\gamma\gamma}/m_K)^2>0.2$ is ${\cal B}_{\rm MI}(z>0.2) = (0.965 \pm 0.063) \times 10^{-6}$, and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is ${\cal B}(K_{\pi\gamma\gamma}) = (1.003 \pm 0.056) \times 10^{-6}$. A detailed comparison of the results with the previous measurements is performed.A study of the dynamics of the rare decay $K^\pm\to\pi^\pm\gamma\gamma$ has been performed on a sample of 232 decay candidates, with an estimated background of $17.4\pm1.1$ 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 $z=(m_{\gamma\gamma}/m_K)^2>0.2$ is ${\cal B}_{\rm MI}(z>0.2) = (0.965 \pm 0.063) \times 10^{-6}$, and the combined branching ratio in the full kinematic range assuming a Chiral Perturbation Theory description is ${\cal B}(K_{\pi\gamma\gamma}) = (1.003 \pm 0.056) \times 10^{-6}$. A detailed comparison of the results with the previous measurements is performed.A study of the dynamics of the rare decay K±→π±γγ 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(Kπγγ)=(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

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

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

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

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