S-Wave Site Amplification Factors from Observed Ground Motions in Japan: Validation of Delineated Velocity Structures and Proposal for Empirical Correction

We first derived site amplification factors (SAFs) from the observed strong motions by the Japanese nationwide networks, namely, K-NET and KiK-net of National Institute of Earthquake Research and Disaster Resilience and Shindokei (Instrumental Seismic Intensity) Network of Japan Meteorological Agency by using the so-called generalized spectral inversion technique. We can use these SAFs for strong motion prediction at these observation sites, however, we need at least observed weak motion or microtremor data to quantify SAF at an arbitrary site. So we tested the capability of the current velocity models in Japan whether they can reproduce or not the observed SAFs at the nearest grid of every 250 m as the one-dimensional theoretical transfer functions (TTF). We found that at about one-half of the sites the calculated 1D TTFs show more or less acceptable fit to the observed SAFs, however, the TTFs tend to underestimate the observed SAFs in general. Therefore, we propose a simple, empirical method to fill the gap between the observed SAFs and the calculated TTFs. Validation examples show that our proposed method effectively predict better SAFs than the direct substitute of TTFs at sites without observed data

Periodontal Tissue as a Biomaterial for Hard-Tissue Regeneration following bmp-2 Gene Transfer

The application of periodontal tissue in regenerative medicine has gained increasing interest since it has a high potential to induce hard-tissue regeneration, and is easy to handle and graft to other areas of the oral cavity or tissues. Additionally, bone morphogenetic protein-2 (BMP-2) has a high potential to induce the differentiation of mesenchymal stem cells into osteogenic cells. We previously developed a system for a gene transfer to the periodontal tissues in animal models. In this study, we aimed to reveal the potential and efficiency of periodontal tissue as a biomaterial for hard-tissue regeneration following a bmp-2 gene transfer. A non-viral expression vector carrying bmp-2 was injected into the palate of the periodontal tissues of Wistar rats, followed by electroporation. The periodontal tissues were analyzed through bone morphometric analyses, including mineral apposition rate (MAR) determination and collagen micro-arrangement, which is a bone quality parameter, before and after a gene transfer. The MAR was significantly higher 3–6 d after the gene transfer than that before the gene transfer. Collagen orientation was normally maintained even after the bmp-2 gene transfer, suggesting that the bmp-2 gene transfer has no adverse effects on bone quality. Our results suggest that periodontal tissue electroporated with bmp-2 could be a novel biomaterial candidate for hard-tissue regeneration therapy.Kawai M.Y., Ozasa R., Ishimoto T., et al. Periodontal Tissue as a Biomaterial for Hard-Tissue Regeneration following bmp-2 Gene Transfer. Materials, 15, 3, 993. https://doi.org/10.3390/ma15030993

EFFICACY OF INTERFERON THERAPY FOR CHRONIC HEPATITIS C ： A COOPERATIVE STUDY IN ELEVEN HOSPITALS

We investigated the influences of liver histology，serum levels of hepatitis C virus (HCV) and HCV genotypes on responsiveness to interferon (IFN) therapy in 342 patients with chronic hepatitis C. Either 9 million units (MU) of lymphoblastoid alpha IFN or 3 MU of recombinant IFN-alpha was administered daily for 2 weeks and then three times a week for 22 weeks. IFN responses were divided into three groups on the basis of the results of polymerase chain reaction (PCR) assay detecting HCV-RNA in serum. Complete response (CR) was defined as sustained elimination of HCV for at least 6 months after treatment，partial response (PR) as HCV elimination for a limited period，non-response (NR) as continuously positive for HCV-RNA in serum. Quantitation of pre-treament HCV-RNA amount in serum was determined by competitive PCR assay in 47 patients. HCV genotyping was performed in 114 patients by PCR with genotype-specific primers. CR was obtained in 97 patients (28.4%)，PR in 104 (30.4%) and NR in 141 (41.2%). IFN responses，represented by CR/PR/NR，were 15/18/11 in 44 patients with chronic persistent hepatitis (CPH)，72/65/73 in 210 patients with chronic aggressive hepatitis (CAH) 2a，and 10/21/57 in 88 patients with CAH2b. CR rate was lower in patients with CAH2b (11.4%) compared to those with CPH (34.1%) or CAH2a (34.3%). Averages of pre-treatment serum HCV-RNA amount (copies/50μl) were 10³·⁵⁵ in 13 CRs，10⁴·⁵⁶ in 17 PRs，and 10⁵·⁹⁵ in 17 NRs. There was a positive correlation between pre-treatment HCV-RNA levels and IFN unresponsiveness. HCV genotyping in 114 patients revealed that HCV type Ⅰ infection was observed in one，type Ⅱ in 94，type Ⅲ in 11，type Ⅳ in 6 and mixed (types Ⅱ and Ⅳ) in 2 patients，and their IFN responses (CR/PR/NR) were 0/0/1，28/26/40，3/5/3，1/3/2 and 0/1/1，respectively

Robot-directed speech detection using multimodal semantic confidence based on speech, image, and motion

ABSTRACT In this paper, we propose a novel method to detect robotdirected (RD) speech that adopts the Multimodal Semantic Confidence (MSC) measure. The MSC measure is used to decide whether the speech can be interpreted as a feasible action under the current physical situation in an object manipulation task. This measure is calculated by integrating speech, image, and motion confidence measures with weightings that are optimized by logistic regression. Experimental results show that, compared with a baseline method that uses speech confidence only, MSC achieved an absolute increase of 5% for clean speech and 12% for noisy speech in terms of average maximum F-measure

DsTau: Study of tau neutrino production with 400 GeV protons from the CERN-SPS

In the DsTau experiment at the CERN SPS, an independent and direct way to measure tau neutrino production following high energy proton interactions was proposed. As the main source of tau neutrinos is a decay of Ds mesons, produced in proton-nucleus interactions, the project aims at measuring a differential cross section of this reaction. The experimental method is based on a use of high resolution emulsion detectors for effective registration of events with short lived particle decays. Here we present the motivation of the study, details of the experimental technique, and the first results of the analysis of the data collected during test runs, which prove feasibility of the full scale study of the process in future

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

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron