47 research outputs found

    Teach Me How to Improve My Argumentation Skills: A Survey on Feedback in Argumentation

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    The use of argumentation in education has been shown to improve critical thinking skills for end-users such as students, and computational models for argumentation have been developed to assist in this process. Although these models are useful for evaluating the quality of an argument, they oftentimes cannot explain why a particular argument is considered poor or not, which makes it difficult to provide constructive feedback to users to strengthen their critical thinking skills. In this survey, we aim to explore the different dimensions of feedback (Richness, Visualization, Interactivity, and Personalization) provided by the current computational models for argumentation, and the possibility of enhancing the power of explanations of such models, ultimately helping learners improve their critical thinking skills.Comment: 14 pages, 4 figure

    DOCK2 is involved in the host genetics and biology of severe COVID-19

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    「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

    The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

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    「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

    AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells

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    Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-beta 1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-beta signaling pathway. Our findings regarding the effects of AM251 on the TGF-beta signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis

    Metabolic Alkalosis due to Feeding Chicks in Breeding Adélie Penguins Pygoscelis adeliae under Natural Conditions

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    Prolonged abnormal vomiting causes metabolic alkalosis. Many seabirds are known to feed their chicks by regurgitation. We hypothesized that metabolic alkalosis occurs in seabirds even under natural conditions during the breeding season. Adélie penguins Pygoscelis adeliae feed their chicks by regurgitating food for 50-60 d until the chicks fledge. In this study, the concentrations of Cl-, HCO3-, Na+, K+, pH, and in the blood of breeding Adélie penguins were measured throughout the chick-rearing season. The pH of penguin venous blood shifted from 7.54 in the guarding period to 7.47 in the crèche period. Decreasing Cl- and increasing HCO3- blood concentrations in parents were associated with increasing mass of their brood in the guarding period, the early phase of the rearing season, indicating that regurgitating to feed chicks causes loss of gastric acid and results in relative metabolic alkalosis. The inverse trend was observed during the crèche period, the latter phase of the rearing season, when parents spent more time at sea and have fewer opportunities for gastric acid loss. This was assumed to be the recovery phase. These results indicate that regurgitation might cause metabolic alkalosis in breeding Adélie penguins. To our knowledge, this is the first report to indicate that seabirds exhibit metabolic alkalosis due to regurgitation to feed chicks under natural conditions

    Stabilization of vertical plasma position in the PHiX tokamak with saddle coils

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    Saddle coils (SCs) are proposed as coils with a stabilizing effect of a vertical plasma position. This effect comes from an average magnetic field along a magnetic field line. Magnetic field line tracing was performed to investigate the structure and the quantitative values of the averaged magnetic field generated by SCs and toroidal magnetic field coils (TFCs). Experiments to stabilize the vertical position of the plasma were also carried out in a small tokamak device, PHiX. It was experimentally demonstrated that the averaged magnetic field generated with SCs and TFCs could stabilize the vertically unstable plasmas. In addition, three-dimensional equilibrium calculation using VMEC suggested that the plasmas were vertically elongated on the toroidal average when the vertical positions were stabilized by SCs. From the above results, it was shown that the non-axisymmetric magnetic fields generated by SCs could realize the plasmas with stable vertical position and an elongated cross-section
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