Canonical Equivalence between Super D-string and Type IIB Superstring

We show that the super D-string action is canonically equivalent to the type IIB superstring action with a world-sheet gauge field. Canonical transformation to the type IIB theory with dynamical tension is also constructed to establish the SL(2,Z) covariance beyond the semi-classical approximations.Comment: Latex, 11 page

Pathologic stage I non–small cell lung cancer with high levels of preoperative serum carcinoembryonic antigen: Clinicopathologic characteristics and prognosis

ObjectiveSurgery alone remains the standard therapy for patients with stage I non–small cell lung cancer. Although the preoperative serum level of carcinoembryonic antigen has been shown to be an independent prognostic factor, it has not yet been included in the staging system and does not alter the treatment strategy, especially in the selection of patients for adjuvant chemotherapy.MethodsFrom 1986 to 2003, preoperative and postoperative serum carcinoembryonic antigen levels were measured in 455 patients with completely resected pathologic stage I non–small cell lung cancer. We compared the clinicopathologic characteristics and outcomes among patients who had preoperative serum carcinoembryonic antigen levels within the normal range (N group, n = 323), patients who had high carcinoembryonic antigen levels before surgery but normal levels after surgery (HN group, n = 112), and patients who had high carcinoembryonic antigen levels before and after surgery (HH group, n = 20).ResultsThe significant characteristics of the HN group included the male sex, greater age, smoking, squamous cell histology, T2 status, lymphatic invasion, vascular invasion, and pleural invasion. Adenocarcinomas in patients of the HN group were more likely to be moderately to poorly differentiated. The 5-year survivals in the HN and HH groups were significantly lower (56.2% and 43.1%, respectively) than those in the N group (85.9%). Multivariate analysis revealed that greater age, non-adenocarcinoma histology, pleural invasion, and the carcinoembryonic antigen in the HN and HH groups were independent prognostic factors.ConclusionPatients with resected pathologic stage I non–small cell lung cancer and high preoperative serum carcinoembryonic antigen levels are a subgroup with a distinctly poor prognosis who display smoking-related clinicopathologic characteristics

Transcellular transport of West Nile virus-like particles across human endothelial cells depends on residues 156 and 159 of envelope protein

<p>Abstract</p> <p>Background</p> <p>West Nile virus (WNV) causes viremia after invasion to the hosts by mosquito bite. Endothelial cells could play an important role in WNV spread from the blood stream into the central nervous system and peripheral tissues. Here, we analyzed the capacity of virus-like particles (VLPs) of the highly virulent NY99 6-LP strain (6-LP VLPs) and the low virulence Eg101 strain (Eg VLPs) to cross cultured human endothelial cells.</p> <p>Results</p> <p>6-LP VLPs were transported from the apical to basolateral side of endothelial cells, whereas Eg VLPs were hardly transported. The localization of tight junction marker ZO-1 and the integrity of tight junctions were not impaired during the transport of 6-LP VLPs. The transport of 6-LP VLPs was inhibited by treatment with filipin, which prevents the formation of cholesterol-dependent membrane rafts, suggesting the involvement of raft-associated membrane transport. To determine the amino acid residues responsible for the transport of VLPs, we produced mutant VLPs, in which residues of E protein were exchanged between the 6-LP and Eg strains. Double amino acid substitution of the residues 156 and 159 greatly impaired the transport of VLPs.</p> <p>Conclusion</p> <p>Our results suggest that a transcellular pathway is associated with 6-LP VLPs transport. We also showed that the combination of the residues 156 and 159 plays an important role in the transport of VLPs across endothelial cells.</p

A Study of the Efficacy of Lectures Incorporating the Handicap Simulation Activities in the Department of Education

本稿では，教育学部において実施した障害シミュレーションを中心とした授業の有効性について検討を行った。視覚障害，聴覚障害，肢体不自由の各領域でシミュレーションを中心とした授業を実施し，障害に対する受講前後の考えおよび自分にできると思う取り組みについて受講生にアンケートを実施した。その結果，障害に対する考えについては，自分自身の態度や行動に関する4項目および障害者に対する肯定的，積極的意見に関する4項目においてシミュレーション後の得点が有意に増加した。自分にできると思う取り組みについては，［持続的な学びと関わり］［具体的支援］［障害への配慮］のカテゴリーグループが抽出された。シミュレーションを通じて自身の意見をまとめたり，他者の意見を聞いたりすることによって知識の幅を広げたことが，自身の態度や行動に関する項目および障害者に対する肯定的，積極的な意見に関する項目の得点増加につながったと考えられるなど，一定の効果が見られた。しかし，より障害理解を促すための授業内容について引き続き検討することなどが課題として挙げられた。In the present study, the effectiveness of the class that centered on the handicap simulation executed to the students of Department of Education was examined. The class that centered on the simulation in each area of visual impairment, hearing impairment, and physical disability was executed. Afterwards, the questionnaire of the idea before and after the class to handicaps and of the approach that they would be able to do for handicaps was executed to the participant. As a result, for the idea to handicaps, the score after the simulation has increased significantly about four items concerning their attitudes and action, and four items concerning an affirmative, positive opinion to people with handicaps. On the other hand, for the approach that they would be able to do, the category group of “Continued learning and participation”, “Concrete support”, and “Consideration to handicaps” has been extracted. It was thought that having expanded the width of knowledge by integrating their own opinions through the simulation, and hearing others’ opinions led to a score increase about items concerning their attitudes and action, and an affirmative, positive opinion to people with handicaps. However, it is necessary to continue to examine the course content that can urge understanding about handicaps more

Chondroitin sulfate N-acetylgalactosaminyltransferase-1 is required for normal cartilage development

CS (chondroitin sulfate) is a glycosaminoglycan species that is widely distributed in the extracellular matrix. To understand the physiological roles of enzymes involved in CS synthesis, we produced CSGalNAcT1 (CS N-acetylgalactosaminyltransferase 1)-null mice. CS production was reduced by approximately half in CSGalNAcT1-null mice, and the amount of short-chain CS was also reduced. Moreover, the cartilage of the null mice was significantly smaller than that of wild-type mice. Additionally, type-II collagen fibres in developing cartilage were abnormally aggregated and disarranged in the homozygous mutant mice. These results suggest that CSGalNAcT1 is required for normal CS production in developing cartilage

New Approach to Teaching Japanese Pronunciation in the Digital Era - Challenges and Practices

Pronunciation has been a black hole in the L2 Japanese classroom on account of a lack of class time, teacher\u2019s confidence, and consciousness of the need to teach pronunciation, among other reasons. The absence of pronunciation instruction is reported to result in fossilized pronunciation errors, communication problems, and learner frustration. With an intention of making a contribution to improve such circumstances, this paper aims at three goals. First, it discusses the importance, necessity, and e ectiveness of teaching prosodic aspects of Japanese pronunciation from an early stage in acquisition. Second, it shows that Japanese prosody is challenging because of its typological rareness, regardless of the L1 backgrounds of learners. Third and finally, it introduces a new approach to teaching L2 pronunciation with the goal of developing L2 comprehensibility by focusing on essential prosodic features, which is followed by discussions on key issues concerning how to implement the new approach both inside and outside the classroom in the digital era

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

「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

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

「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