AIR-COOLED MAGNETIC ALLOY CAVITY FOR J-PARC DOUBLED REP.-RATE SCENARIO

Abstract The upgrade project of the J-PARC MR (Main Ring) based on doubled repetition-rate scenario is in progress to deliver the beam power of 750 kW. The present RF section will be occupied by 9 sets of new magnetic alloy, FT3L, cavities using the direct water cooling scheme. The direct water cooling is the efficient scheme to cool the magnetic alloy core although it requires dedicated high-quality cooling water which does not contain copper oxide and copper ions because copper ions may cause the severe corrosion damage on the magnetic alloy cores. These cavities will be used for the fundamental RF for acceleration which requires high duty operation. The second harmonic RF is necessary to increase the bunch length. This allows to enlarge the beam current because it relaxes the space charge effects during the injection. Thanks to the high impedance FT3L and low duty operation of the second harmonic RF, the power loss in the second harmonic RF system becomes moderate. The air cooled cavity is designed to fit in any locations in the MR where the dedicated high-quality water is not available. This paper reports the design of the second RF system, technical issues to produce the magnetic alloy cores to fit the air cooling, and construction of the system

PERFORMANCE OF MULTI-HARMONIC RF FEEDFORWARD SYSTEM FOR BEAM LOADING COMPENSATION IN THE J-PARC RCS

Abstract The beam loading compensation is a key part for acceleration of high intensity proton beams in the J-PARC RCS. In the wide-band MA-loaded RF cavity, the wake voltage consists of not only the accelerating harmonic component but also the higher harmonics. The higher harmonic components cause the RF bucket distortion. We employ the RF feedforward method to compensate the multi-harmonic beam loading. The full-digital feedforward system is developed, which compensates the first three harmonic components of the beam loading. We present the results of the beam test with a high intensity proton beam (2.5 × 10 13 ppp). The impedance seen by the beam is greatly reduced, the impedance of the fundamental accelerating harmonic is reduced to less than 25 Ω in a full accelerating cycle, while the shunt resistance of the cavity is in the order of 800 Ω. The performance of the feedforward system is promising for achievement of the design beam power, 1 MW, in the future

Exome-wide association study to identify rare variants influencing COVID-19 outcomes : Results from the Host Genetics Initiative

Publisher Copyright: Copyright: © 2022 Butler-Laporte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75–10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.Peer reviewe

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

Motion Estimation of a Moving Range Sensor by Image Sequences and Distorted Range Data

For a large scale object, scanning from the air is one of the most efficient methods of obtaining 3D data. In the case of large cultural heritage objects, there are some difficulties in scanning them with respect to safety and efficiency. To remedy these problems, we have been developing a novel 3D measurement system, the Floating Laser Range Sensor (FLRS) , in which a rage sensor is suspended beneath a balloon. The obtained data, however, have some distortion due to the intrascanning movement. In this paper, we propose a method to recover 3D range data obtained by a moving laser range sensor; this method is applicable not only to our FLRS, but also to a general moving range sensor. Using image sequences from a video camera mounted on the FLRS enables us to estimate the motion of the FLRS without any physical sensors such as gyros and GPS. At first, the initial values of camera motion parameters are estimated by perspective factorization. The next stage refines camera motion parameters using the relationships between camera images and the range data distortion. Finally, by using the refined parameter, the distorted range data are recovered. We applied this method to an actual scanning project and the results showed the effectiveness of our method