Use of automatic radiosonde launchers to measure temperature and humidity profiles from the GRUAN perspective

In the last two decades, technological progress has not only seen improvements to the quality of atmospheric upper-air observations but also provided the opportunity to design and implement automated systems able to replace measurement procedures typically performed manually. Radiosoundings, which remain one of the primary data sources for weather and climate applications, are still largely performed around the world manually, although increasingly fully automated upper-air observations are used, from urban areas to the remotest locations, which minimize operating costs and challenges in performing radiosounding launches. This analysis presents a first step to demonstrating the reliability of the automatic radiosonde launchers (ARLs) provided by Vaisala, Meteomodem and Meisei. The metadata and datasets collected by a few existing ARLs operated by the Global Climate Observing System (GCOS) Reference Upper-Air Network (GRUAN) certified or candidate sites (Sodankylä, Payerne, Trappes, Potenza) have been investigated and a comparative analysis of the technical performance (i.e. manual versus ARL) is reported. The performance of ARLs is evaluated as being similar or superior to those achieved with the traditional manual launches in terms of percentage of successful launches, balloon burst and ascent speed. For both temperature and relative humidity, the ground-check comparisons showed a negative bias of a few tenths of a degree and % RH, respectively. Two datasets of parallel soundings between manual and ARL-based measurements, using identical sonde models, provided by Sodankylä and Faa'a stations, showed mean differences between the ARL and manual launches smaller than ±0.2 K up to 10 hPa for the temperature profiles. For relative humidity, differences were smaller than 1 % RH for the Sodankylä dataset up to 300 hPa, while they were smaller than 0.7 % RH for Faa'a station. Finally, the observation-minus-background (O–B) mean and root mean square (rms) statistics for German RS92 and RS41 stations, which operate a mix of manual and ARL launch protocols, calculated using the European Centre for Medium-Range Weather Forecasts (ECMWF) forecast model, are very similar, although RS41 shows larger rms(O–B) differences for ARL stations, in particular for temperature and wind. A discussion of the potential next steps proposed by GRUAN community and other parties is provided, with the aim to lay the basis for the elaboration of a strategy to fully demonstrate the value of ARLs and guarantee that the provided products are traceable and suitable for the creation of GRUAN data products

Periductal Induction of High Endothelial Venule-Like Vessels in Type 1 Autoimmune Pancreatitis

信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第946号）・丸山 雅史This is a non-final version of an article published in final form in PANCREAS. 42(1):53-59 (2013).Objectives: Type 1 autoimmune pancreatitis (AIP) is histologically characterized by dense lymphoplasmacytic infiltration and marked storiform fibrosis, manifestations associated with pancreatic ducts. Such periductal lymphocyte recruitment is thought to be elicited by dysregulation of mechanisms governing physiological lymphocyte homing. The present study was undertaken to determine whether vascular addressins including peripheral lymph node addressin and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) play a role in type 1 AIP histogenesis. Methods: Tissue sections of type 1 AIP and tumor-associated non-AIP chronic pancreatitis, as well as normal pancreas, were subjected to immunohistochemical analysis using vascular addressin-related antibodies. Results: The number of periductal mouse endothelial cell antigen 79-positive high endothelial venule (HEV)-like vessels was increased in type 1 AIP relative to that seen in non-AIP chronic pancreatitis, whereas the number of MAdCAM-1-positive HEV-like vessels did not differ between the 2 conditions. Mouse endothelial cell antigen 79 antigens are expressed on duct-forming epithelial cells not only in pancreas but also in salivary glands, which often harbor extrapancreatic lesions in type 1 AIP. Conclusions: Type 1 AIP can be characterized by periductal induction of MECA-79-positive HEV-like vessels. MECA-79-positive 6-sulfo sialyl Lewis X-related carbohydrate antigens expressed on duct-forming epithelial cells could be associated with type 1 AIP pathogenesis.ArticlePANCREAS. 42(1):53-59 (2013)journal articl

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

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

E3ユビキチンリガーゼWWP1が脂肪細胞機能に及ぼす影響の検討

東京理科大学201

Comparison of GRUAN data products for Meisei iMS-100 and Vaisala RS92 radiosondes at Tateno, Japan

A total of 99 dual soundings with Meisei iMS-100 radiosonde and Vaisala RS92 radiosondes were carried out at the Aerological Observatory of the Japan Meteorological Agency, known as Tateno (36.06∘ N, 140.13∘ E, 25.2 m; the World Meteorological Organization, WMO, station number 47646), from September 2017 to January 2020. Global Climate Observing System (GCOS) Reference Upper-Air Network (GRUAN) data products (GDPs) from both sets of radiosonde data for 59 flights were subsequently created using a documented processing programme along with the provision of optimal estimates for measurement uncertainty. Differences in radiosonde performance were then quantified using these GDPs. For daytime observations, the iMS-100 temperature is around 0.5 K cooler than RS92-GDP in the stratosphere, with significant differences in the upper troposphere and lower stratosphere in consideration of combined uncertainties. For nighttime observations, the difference is around −0.1 K, and data are mostly in agreement. For relative humidity (RH), iMS-100 is around 1 % RH–2 % RH higher in the troposphere and 1 % RH smaller in the stratosphere than RS92, but both GDPs are in agreement for most of the profile. The mean pressure difference is ≤0.1 hPa, the wind speed difference is from −0.04 to +0.14 m s−1, the wind direction difference is , and the root mean square vector difference (RMSVD) for wind is ≤1.04 m s−1