Completion of the first ITER toroidal field coil structure

本論文は、日本が100%調達責任を有するITERのトロイダルコイル構造物の第1号機の完成を報告するものである。主な技術的な課題は、(i)極低温(4K)でも高い延性を持つ新規材料の開発、(ii)部分溶け込み溶接の適用、(iii)溶接変形対応、(iv)オーステナイトステンレス鋼溶接部の減衰効果を加味した超音波探傷試験法の開発、(v)巨大で複雑なD形状構造物の封止溶接開先の0.5mmオーダー公差での開先合わせ、などである。これらの各技術課題を解決し、ITER　TFコイル構造物第1号機は成功裏に完成することができた

Activation of ERK/IER3/PP2A-B56γ-positive feedback loop in lung adenocarcinoma by allelic deletion of B56γ gene

In order to investigate the involvement of the IER3/ PP2A-B56γ/ERK-positive feedback loop, which leads to sustained phosphorylation/activation of ERK in carcinogenesis, we immunohistochemically examined the expression of IER3 and phosphorylated ERK in lung tumor tissues. IER3 was overexpressed in all cases of adenocarcinomas examined, but was not overexpressed in squamous cell carcinomas. Phosphorylated ERK (pERK) was also overexpressed in almost all adenocarcinomas. EGFR and RAS, whose gene product is located upstream of ERK, were sequenced. Activating mutation of EGFR, which is a possible cause of overexpression of IER3 and pERK, was found only in 5 adenocarcinomas (42%). No mutation of RAS was found. We further examined the sequences of all exons of B56γ gene (PPP2R5C) and IER3, but no mutation was found. Using a single nucleotide insertion in intron 1 of PPP2R5C, which was found in the process of sequencing, allelic deletion of PPP2R5C was examined. Eight cases were informative (67%), and the deletion was found in 4 of them (50%). Three cases having deletion of PPP2R5C did not have EGFR mutation. Finally, PPP2R5C deletion or EGFR mutation that could be responsible for IER3/pERK overexpression was found in at least 8 cases (67% or more). This is the first report of a high incidence of deletion of PPP2R5C in human carcinomas.Embargo Period 12 month

Coronal Heating and Acceleration of the High/Low-Speed Solar Wind by Fast/Slow MHD Shock Trains

We investigate coronal heating and acceleration of the high- and low-speed solar wind in the open field region by dissipation of fast and slow magnetohydrodynamical (MHD) waves through MHD shocks. Linearly polarized \Alfven (fast MHD) waves and acoustic (slow MHD) waves travelling upwardly along with a magnetic field line eventually form fast switch-on shock trains and hydrodynamical shock trains (N-waves) respectively to heat and accelerate the plasma. We determine one dimensional structure of the corona from the bottom of the transition region (TR) to 1AU under the steady-state condition by solving evolutionary equations for the shock amplitudes simultaneously with the momentum and proton/electron energy equations. Our model reproduces the overall trend of the high-speed wind from the polar holes and the low-speed wind from the mid- to low-latitude streamer except the observed hot corona in the streamer. The heating from the slow waves is effective in the low corona to increase the density there, and plays an important role in the formation of the dense low-speed wind. On the other hand, the fast waves can carry a sizable energy to the upper level to heat the outer corona and accelerate the high-speed wind effectively. We also study dependency on field strength, $B_0$, at the bottom of the TR and non-radial expansion of a flow tube, $f_{\rm max}$, to find that large $B_0/f_{\rm max}\gtrsim 2$ but small $B_0\simeq 2$G are favorable for the high-speed wind and that small $B_0/f_{\rm max}\simeq 1$ is required for the low-speed wind.Comment: 13 pages, including 5 figures, in MNRAS style, MNRAS in pres

Solar Winds Driven by Nonlinear Low-Frequency Alfven Waves from the Photosphere : Parametric Study for Fast/Slow Winds and Disappearance of Solar Winds

(abridged) We investigate how the properties of the corona and solar wind in the open coronal holes depend on the properties of the magnetic fields and their footpoint motions at the surface, by perfoming 1D MHD simulations from the photosphere to 0.3 or 0.1AU. We impose low-frequency (<0.05Hz) transverse fluctuations of the field lines at the photosphere with various amplitude, spectrum, and polarization in the open flux tubes with different photospheric field strength, B, and super-radial expansion of the cross section, f_max. We find that a transonic solar wind is the universal consequence. The atmosphere is also stably heated up to >10^6K by the dissipation of the Alfven waves through compressive-wave generation and wave reflection in the case of the sufficient wave input with photospheric amplitude, > 0.7km/s. The density, and accordingly the mass flux, of solar winds show a quite sensitive dependence on because of an unstable aspect of the heating by the nonlinear Alfven waves. A case with =0.4km/s gives ~50 times smaller mass flux than the fiducial case for the fast wind with =0.7km/s; solar wind almost disappears only if becomes half. We also find that the solar wind speed has a positive correlation with B/f_max, which is consistent with recent observations. We finally show that both fast and slow solar winds can be explained by the single process, the dissipation of the low-frequency Alfven waves, with different sets of and B/f_max. Our simulations naturally explain the observed (i) anticorrelation of the solar wind speed and the coronal temperature and (ii) larger amplitude of the Alfvenic fluctuations in the fast winds. In Appendix, we also explain our implementation of the outgoing boundary condition of the MHD waves with some numerical tests.Comment: 27 pages, 16 figures embedded, accepted for publication in J. Geophys. Re

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

Fracture toughness and martensitic transformation in type 316LN austenitic stainless steel extra-thick plates at 4.2 K

The plane strain fracture toughness of type 316LN nitrogen-strengthened austenitic stainless steels depends on their stability at 4.2 K, which is characterized by the Md30 index. Deformation microstructures and martensite that developed at the crack tip of type 316LN steel extra-thick (535 mm) plates at 4.2 K were evaluated. Two kinds of type 316LN steel, LF and HF, represented low and high fracture toughness, respectively. The Md30 of the plates correlated well with their respective fracture toughness values, where a higher Md30 indicated lower fracture toughness. The plastic strains developed in austenite grains at the crack tip for the HF were higher and more homogeneous and extensive than those of the LF. The volume of alpha '-martensite detected in the HF was lower than that of the LF. Planar slip bands with the primary slip system and alpha '-martensite were dominant in the LF. In the HF, however, microslip bands with multiple slip systems, deformation twins, and alpha '-martensite formed. For the LF, extensive martensite leaves with multiple variants were formed at the crack tip. The martensite leaves grew along the high stress field at crack tip developed by the crack extension. For the HF, alpha '-martensite platelets were dispersed along {111} slip bands. Shear bands containing martensite were favored by low plastic strains and constituted a smaller fraction of their total density. Therefore, low plastic strains were responsible for an increase of alpha '-martensite formation at the crack tip. An alloy design having a higher Ni, Mn and Mo, and lower N content in its chemical composition would be favorable for type 316LN steel to provide a higher fracture toughness owing to higher stacking fault energy.Web of Science862art. no. 14412