原型炉のための技術基盤確立に向けた日本の取組

The establishment of technology bases required for the development of a fusion demonstration reactor (DEMO) has been discussed by a joint effort throughout the Japanese fusion community. The basic concept of DEMO premised for investigation has been identified and the structure of technological issues to ensure the feasibility of this DEMO concept has been examined. The Joint-Core Team, which was launched along with the request by the ministerial council, has compiled analyses in two reports to clarify technology which should be secured, maintained, and developed in Japan, to share the common targets among industry, government, and academia, and to activate actions under a framework for implementation throughout Japan. The reports have pointed out that DEMO should be aimed at steady power generation beyond several hundred thousand kilowatts, availability which must be extended to commercialization, and overall tritium breeding to fulfill self-sufficiency of fuels. The necessary technological activities, such as superconducting coils, blanket, divertor, and others, have been sorted out and arranged in the chart with the time line toward the decision on DEMO. Based upon these Joint-Core Team reports, related actions are emerging to deliberate the Japanese fusion roadmap

Development of Strategic Establishment of Technology Bases for a Fusion DEMO Reactor in Japan

The strategic establishment of technology bases required for the development of a fusion demonstration reactor (DEMO) has been discussed by joint endeavors throughout the Japanese fusion community. The mission of Fusion DEMO is to demonstrate the technological and economic feasibility of fusion energy. The basic concept of Fusion DEMO has been identified and the structure of technological issues to ensure the feasibility of this DEMO concept has been examined. The Joint-Core Team consisting of experts from the Japanese fusion community including industry has pointed out that DEMO should be aimed at steady power generation beyond several hundred thousand kilowatts, availability which must be extensible to commercialization, and overall tritium breeding sufficient to achieve fuel-cycle self-sufficiency. The necessary technological issues and activities have been sorted out along with 11 identified elements of DEMO, such as superconducting coils, blanket, divertor, and others. These will be arranged within a time line to lead to the Japanese fusion roadmap

A Model for the 3He(\vec d, p)4He Reaction at Intermediate Energies

Polarization correlation coefficients have been measured atRIKEN for the \vec 3He(\vec d,p)4He reaction at intermediate energies. We propose a model for the (\vec d, p) reaction mechanism using the pd elastic scattering amplitude which is rigorously determined by a Faddeev calculation and using modern NN forces. Our theoretical predictions for deuteron polarization observables A_y, A_{yy}, A_{xx} and A_{xz} at E_d=140, 200 and 270 MeV agree qualitatively in shape with the experimental data for the reaction 3He(\vec d,p)4He.Comment: 6 pages, 11 figures, 1 table, reference: http://www.phys.ntu.edu.tw/english/fb16/contribution/topic4/Uesaka_Tomohiro1. ps in Contribution for the XVIth IUPAP International Conference on Few-Body Problems in Physics, (Taipei, Taiwan 6-11, March 2000

The Blimp1–Bcl6 axis is critical to regulate osteoclast differentiation and bone homeostasis

Controlling osteoclastogenesis is critical to maintain physiological bone homeostasis and prevent skeletal disorders. Although signaling activating nuclear factor of activated T cells 1 (NFATc1), a transcription factor essential for osteoclastogenesis, has been intensively investigated, factors antagonistic to NFATc1 in osteoclasts have not been characterized. Here, we describe a novel pathway that maintains bone homeostasis via two transcriptional repressors, B cell lymphoma 6 (Bcl6) and B lymphocyte–induced maturation protein-1 (Blimp1). We show that Bcl6 directly targets ‘osteoclastic’ molecules such as NFATc1, cathepsin K, and dendritic cell-specific transmembrane protein (DC-STAMP), all of which are targets of NFATc1. Bcl6-overexpression inhibited osteoclastogenesis in vitro, whereas Bcl6-deficient mice showed accelerated osteoclast differentiation and severe osteoporosis. We report that Bcl6 is a direct target of Blimp1 and that mice lacking Blimp1 in osteoclasts exhibit osteopetrosis caused by impaired osteoclastogenesis resulting from Bcl6 up-regulation. Indeed, mice doubly mutant in Blimp1 and Bcl6 in osteoclasts exhibited decreased bone mass with increased osteoclastogenesis relative to osteoclast-specific Blimp1-deficient mice. These results reveal a Blimp1–Bcl6–osteoclastic molecule axis, which critically regulates bone homeostasis by controlling osteoclastogenesis and may provide a molecular basis for novel therapeutic strategies

Power Exhaust Concepts and Divertor Designs for Japanese and European DEMO Fusion Reactors

Concepts of the power exhaust and divertor design have been developed, with a high priority in the pre-conceptual design phase of the Japan-Europe Broader Approach DEMO Design Activity. A common critical issue is the large power exhaust and its fraction in the main plasma and divertor by the radiative cooling. Different exhaust concepts in the main plasma and divertor have been developed for JA and EU DEMOs. JA proposed a conventional closed divertor geometry to challenge large Psep/Rp handling of 30-35 MWm-1 in order to maintain the radiation fraction in the main plasma at the ITER-level (fradmain = Pradmain/Pheat ~0.4) and higher plasma performance. EU challenged both increasing fradmain to ~0.65 and handling the ITER-level Psep/Rp in the open divertor geometry. Power exhaust simulations have been performed by SONIC (JA) and SOLPS5.1 (EU) with corresponding Psep = 250-300 MW and 150-200 MW, respectively. Both results showed that large divertor radiation fraction (Praddiv/Psep 0.8) was required to reduce both peak qtarget ( 10MWm-2) and Te,idiv. In addition, the JA divertor performance with EU-reference Psep of 150MW showed benefit of the closed geometry to reduce the peak qtarget and Te,idiv near the separatrix, and to produce the partial detachment. Integrated designs of the water cooled divertor target, cassette and coolant pipe routing have been developed in both EU and JA, based on the tungsten (W) monoblock concept with Cu-alloy pipe. For year-long operation, DEMO-specific risks such as radiation embrittlement of Cu-interlayers and Cu-alloy cooling pipe were recognized, and both foresee higher water temperature (130-200 °C) compared to that for ITER. At the same time, several improved technologies of high heat flux components have been developed in EU, and different heat sink design, i.e. Cu-alloy cooling pipes for targets and RAFM steel ones for the baffle, dome and cassette, was proposed in JA. The two approaches provide important case-studies of the DEMO divertor, and will significantly contribute to both DEMO designs

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