24 research outputs found
Mechanisms of Coronary Artery Spasm
Recent clinical trials have highlighted that percutaneous coronary intervention in patients with stable angina provides limited additional benefits on top of optimal medical therapy. This has led to much more attention being paid to coronary vasomotion abnormalities regardless of obstructive or non-obstructive arterial segments. Coronary vasomotion is regulated by multiple mechanisms that include the endothelium, vascular smooth muscle cells (VSMCs), myocardial metabolic demand, autonomic nervous system and inflammation. Over the years, several animal models have been developed to explore the central mechanism of coronary artery spasm. This review summarises the landmark studies on the mechanisms of coronary vasospasm demonstrating the central role of Rho-kinase as a molecular switch of VSMC hypercontraction and the important role of coronary adventitial inflammation for Rho-kinase upregulation in VSMCs
Fundamental Parameters of the Milky Way Galaxy Based on VLBI astrometry
We present analyses to determine the fundamental parameters of the Galaxy
based on VLBI astrometry of 52 Galactic maser sources obtained with VERA, VLBA
and EVN. We model the Galaxy's structure with a set of parameters including the
Galaxy center distance R_0, the angular rotation velocity at the LSR Omega_0,
mean peculiar motion of the sources with respect to Galactic rotation (U_src,
V_src, W_src), rotation-curve shape index, and the V component of the Solar
peculiar motions V_sun. Based on a Markov chain Monte Carlo method, we find
that the Galaxy center distance is constrained at a 5% level to be R_0 = 8.05
+/- 0.45 kpc, where the error bar includes both statistical and systematic
errors. We also find that the two components of the source peculiar motion
U_src and W_src are fairly small compared to the Galactic rotation velocity,
being U_src = 1.0 +/- 1.5 km/s and W_src = -1.4 +/- 1.2 km/s. Also, the
rotation curve shape is found to be basically flat between Galacto-centric
radii of 4 and 13 kpc. On the other hand, we find a linear relation between
V_src and V_sun as V_src = V_sun -19 (+/- 2) km/s, suggesting that the value of
V_src is fully dependent on the adopted value of V_sun. Regarding the rotation
speed in the vicinity of the Sun, we also find a strong correlation between
Omega_0 and V_sun. We find that the angular velocity of the Sun, Omega_sun,
which is defined as Omega_sun = Omega_0 + V_sun/R_0, can be well constrained
with the best estimate of Omega_sun = 31.09 +/- 0.78 km/s/kpc. This corresponds
to Theta_0 = 238 +/- 14 km/s if one adopts the above value of R_0 and recent
determination of V_sun ~ 12 km/s.Comment: 14 pages, 6 figures, PASJ in pres
VLBI Astrometry of AGB Variables with VERA -- A Semiregular Variable S Crateris --
We present a distance measurement for the semiregular variable S Crateris (S
Crt) based on its annual parallax. With the unique dual beam system of the VLBI
Exploration for Radio Astrometry (VERA) telescopes, we measured the absolute
proper motion of a water maser spot associated with S Crt, referred to the
quasar J1147-0724 located at an angular separation of 1.23. In
observations spanning nearly two years, we have detected the maser spot at the
LSR velocity of 34.7 km s, for which we measured the annual parallax of
2.330.13 mas corresponding to a distance of 430 pc. This
measurement has an accuracy one order of magnitude better than the parallax
measurements of HIPPARCOS. The angular distribution and three-dimensional
velocity field of maser spots indicate a bipolar outflow with the flow axis
along northeast-southwest direction. Using the distance and photospheric
temperature, we estimate the stellar radius of S Crt and compare it with those
of Mira variables.Comment: 9 pages, 4 figures, accepted for publication in PASJ (Vol.60, No.5,
October 25, VERA special issue
Astrometry of HO Masers in Nearby Star-Forming Regions with VERA. III. IRAS 22198+6336 in L1204G
We present results of multi-epoch VLBI observations with VERA (VLBI
Exploration of Radio Astrometry) of the 22 GHz HO masers associated with
a young stellar object (YSO) IRAS 22198+6336 in a dark cloud L1204G. Based on
the phase-referencing VLBI astrometry, we derive an annual parallax of IRAS
22198+6336 to be 1.3090.047 mas, corresponding to the distance of
76427 pc from the Sun. Although the most principal error source of our
astrometry is attributed to the internal structure of the maser spots, we
successfully reduce the errors in the derived annual parallax by employing the
position measurements for all of the 26 detected maser spots. Based on this
result, we reanalyze the spectral energy distribution (SED) of IRAS 22198+6336
and find that the bolometric luminosity and total mass of IRAS 22198+6336 are
450 and 7, respectively. These values are consistent with
an intermediate-mass YSO deeply embedded in the dense dust core, which has been
proposed to be an intermediate-mass counterpart of a low-mass Class 0 source.
In addition, we obtain absolute proper motions of the HO masers for the
most blue-shifted components. We propose that the collimated jets aligned along
the east-west direction are the most plausible explanation for the origin of
the detected maser features.Comment: 15 pages, 7 figures, accepted for publication in PASJ (Vol.60, No.5,
October 25, VERA special issue
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
Adapting the Learning Rate of the Learning Rate in Hypergradient Descent
Gradient descent is a widely used optimization method. The adjustment of the learning rate is an important factor in improving its performance, and many researchers have investigated methods for automatically adjusting the learning rate. One such method, hypergradient descent, automatically adjusts the learning rate by using gradient descent. However, it introduces the “learning rate of the learning rate,” and an appropriate value for the learning rate of the learning rate must be chosen in order to effectively adjust the learning rate. We investigated the use of two datasets and two optimization methods for doing this and achieved an effective adjustment of the learning rate when the objective function was convex and L -smooth