ガス雲の分裂と銀河星団の質量函数

京都大学0048新制・課程博士理学博士理博第110号新制||理||73(附属図書館)1575京都大学大学院理学研究科原子核理学専攻(主査)教授 林 忠四郎, 教授 小林 稔, 教授 長谷川 博一学位規則第5条第1項該当Kyoto UniversityDA

Mechanism of Magnetic Flux Loss in Molecular Clouds

We investigate the detailed processes working in the drift of magnetic fields in molecular clouds. To the frictional force, whereby the magnetic force is transmitted to neutral molecules, ions contribute more than half only at cloud densities $n_{\rm H} < 10^4 {\rm cm}^{-3}$, and charged grains contribute more than 90% at $n_{\rm H} > 10^6 {\rm cm}^{-3}$. Thus grains play a decisive role in the process of magnetic flux loss. Approximating the flux loss time $t_B$ by a power law $t_B \propto B^{-\gamma}$, where $B$ is the mean field strength in the cloud, we find $\gamma \approx 2$, characteristic to ambipolar diffusion, only at $n_{\rm H} < 10^7 {\rm cm}^{-3}$. At higher densities, $\gamma$ decreases steeply with $n_{\rm H}$, and finally at $n_{\rm H} \approx n_{\rm dec} \approx {\rm a few} \times 10^{11} {\rm cm}^{-3}$, where magnetic fields effectively decouple from the gas, $\gamma << 1$ is attained, reminiscent of Ohmic dissipation, though flux loss occurs about 10 times faster than by Ohmic dissipation. Ohmic dissipation is dominant only at $n_{\rm H} > 1 \times 10^{12} {\rm cm}^{-3}$. While ions and electrons drift in the direction of magnetic force at all densities, grains of opposite charges drift in opposite directions at high densities, where grains are major contributors to the frictional force. Although magnetic flux loss occurs significantly faster than by Ohmic dissipation even at very high densities as $n_{\rm H} \approx n_{\rm dec}$, the process going on at high densities is quite different from ambipolar diffusion in which particles of opposite charges are supposed to drift as one unit.Comment: 34 pages including 9 postscript figures, LaTex, accepted by Astrophysical Journal (vol.573, No.1, July 1, 2002

Magnetorotational Instability in Protoplanetary Disks. II. Ionization State and Unstable Regions

We investigate where in protoplanetary disks magnetorotational instability operates, which can cause angular momentum transport in the disks. We investigate the spatial distribution of various charged particles and the unstable regions for a variety of models for protoplanetary disks taking into account the recombination of ions and electrons at grain surfaces, which is an important process in most parts of the disks. We find that for all the models there is an inner region which is magnetorotationally stable due to ohmic dissipation. This must make the accretion onto the central star non-steady. For the model of the minimum-mass solar nebula, the critical radius, inside of which the disk is stable, is about 20 AU, and the mass accretion rate just outside the critical radius is 10^{-7} - 10^{-6} M_{\odot} yr^{-1}. The stable region is smaller in a disk of lower column density. Dust grains in protoplanetary disks may grow by mutual sticking and may sediment toward the midplane of the disks. We find that the stable region shrinks as the grain size increases or the sedimentation proceeds. Therefore in the late evolutionary stages, protoplanetary disks can be magnetorotationally unstable even in the inner regions.Comment: 23 pages + 16 figures + 3 tables, accepted for publication in Ap

Evolution of Molecular Abundance in Protoplanetary Disks

We investigate the evolution of molecular abundance in quiescent protoplanetary disks which are presumed to be around weak-line T Tauri stars. In the region of surface density less than $10^2$ g cm$^{-2}$ (distance from the star $\gtrsim 10$ AU in the minimum- mass solar nebula), cosmic rays are barely attenuated even in the midplane of the disk and produce chemically active ions such as He$^+$ and H$_{3}^+$. Through reactions with these ions CO and N$_2$ are finally transformed into CO$_2$, NH$_3$, and HCN. In the region where the temperature is low enough for these products to freeze onto grains, considerable amount of carbon and nitrogen is locked up in the ice mantle and is depleted from the gas phase in a time scale $\lesssim 3\times 10^6$ yr. Oxidized (CO$_2$) ice and reduced (NH$_3$ and hydrocarbon) ice naturally coexist in this part of the disk. The molecular abundance both in the gas phase and in ice mantle varies significantly with the distance from the central star.Comment: 7 pages latex file (using aas2pp4.sty), 3 figures (ps file), to appear in the Astrophysical Journal Letter

Stent-Related Adverse Events as Related to Dual Antiplatelet Therapy in First- vs Second-Generation Drug-Eluting Stents

[Background] There are limited data on the long-term stent-related adverse events as related to the duration of dual antiplatelet therapy (DAPT) in second-generation (G2) drug-eluting stents (DES) compared with first-generation (G1) DES. [Objectives] This study sought to compare the long-term stent-related outcomes of G2-DES with those of G1-DES. [Methods] The study group consisted of 15, 009 patients who underwent their first coronary revascularization with DES from the CREDO-Kyoto PCI/CABG (Coronary Revascularization Demonstrating Outcome Study in Kyoto Percutaneous Coronary Intervention/Coronary Artery Bypass Grafting) Registry Cohort-2 (first-generation drug-eluting stent [G1-DES] period; n = 5, 382) and Cohort-3 (second-generation drug eluting stent [G2-DES] period; n = 9, 627). The primary outcome measures were definite stent thrombosis (ST) and target vessel revascularization (TVR). [Results] The cumulative 5-year incidences of definite ST and TVR were significantly lower in the G2-DES group than in the G1-DES group (0.7% vs 1.4%; P < 0.001; and 16.2% vs 22.1%; P < 0.001, respectively). The lower adjusted risk of G2-DES relative to G1-DES for definite ST and TVR remained significant (HR: 0.53; 95% CI: 0.37-0.76; P < 0.001; and HR: 0.74; 95% CI: 0.68-0.81; P < 0.001, respectively). In the landmark analysis that was based on the DAPT status at 1 year, the lower adjusted risk of on-DAPT status relative to off-DAPT was significant for definite ST beyond 1 year in the G1-DES stratum (HR: 0.42; 95% CI: 0.24-0.76; P = 0.004) but not in the G2-DES stratum (HR: 0.66; 95% CI: 0.26-1.68; P = 0.38) (Pinteraction = 0.14). [Conclusions] G2-DES compared with G1-DES were associated with a significantly lower risk for stent-related adverse events, including definite ST and TVR. DAPT beyond 1 year was associated with a significantly lower risk for very late ST of G1-DES but not for that of G2-DES

Effect of Heart Failure on Long‐Term Clinical Outcomes After Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Severe Coronary Artery Disease

[Background] Heart failure might be an important determinant in choosing coronary revascularization modalities. There was no previous study evaluating the effect of heart failure on long‐term clinical outcomes after percutaneous coronary intervention (PCI) relative to coronary artery bypass grafting (CABG). [Methods and Results] Among 14 867 consecutive patients undergoing first coronary revascularization with PCI or isolated CABG between January 2011 and December 2013 in the CREDO‐Kyoto PCI/CABG registry Cohort‐3, we identified the current study population of 3380 patients with three‐vessel or left main coronary artery disease, and compared clinical outcomes between PCI and CABG stratified by the subgroup based on the status of heart failure. There were 827 patients with heart failure (PCI: N=511, and CABG: N=316), and 2553 patients without heart failure (PCI: N=1619, and CABG: N=934). In patients with heart failure, the PCI group compared with the CABG group more often had advanced age, severe frailty, acute and severe heart failure, and elevated inflammatory markers. During a median 5.9 years of follow‐up, there was a significant interaction between heart failure and the mortality risk of PCI relative to CABG (interaction P=0.009), with excess mortality risk of PCI relative to CABG in patients with heart failure (HR, 1.75; 95% CI, 1.28–2.42; P<0.001) and no excess mortality risk in patients without heart failure (HR, 1.04; 95% CI, 0.80–1.34; P=0.77). [Conclusions] There was a significant interaction between heart failure and the mortality risk of PCI relative to CABG with excess risk in patients with heart failure and neutral risk in patients without heart failure

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