Theoretical and experimental investigation of the atomic and electronic structures at the 4H-SiC(0001)/SiO2 interface

Density functional theory calculations are carried out to investigate the atomic and electronic structures of the 4H-SiC(0001)/SiO2 interface. We find two characteristic interface atomic structures in scanning transmission electron microscopy images: One is an interface in which the density of atoms at the first interfacial SiC bilayer is greater than that in the SiC substrate, while the other is an interface where the density of atoms at the first interfacial SiC bilayer is lower. Density functional theory calculations reveal that the difference in the scanning transmission electron microscopy images is a reflection of the atomic structures of these two interfaces. In addition, it has been reported that the floating states, which appear at the conduction band edge of a 4H-SiC(0001)/SiO2 interface, affect the electronic structure of the interface and cause marked scattering of the electrons flowing along the interface [S. Iwase, C. J. Kirkham, and T. Ono, Phys. Rev. B 95, 041302(R) (2017)]. Interestingly, we find that the floating states do not appear at the conduction band edge of one of the two interfaces. These results provide physical insights into understanding and controlling the electronic structure and carrier mobility of electronic devices using wide-band-gap semiconductors

Molecular tumorigenesis of the skin

Skin tumors are supposed to develop through accumulations of genetic and/or epigenetic events in normal cells of the skin. Among them, we focus on common skin tumors, including benign, seborrheic keratosis, and malignant, squamous cell carcinoma and melanoma. Many important molecules have been detected on the molecular tumorigenesis of each of them to date, and some drugs targeted for their molecules have been already developed. We review updates on the molecular tumorigenesis of these tumors with our current works

Preliminary Design Study of the TMT Telescope Structure System: Overview

We present an overview of the preliminary design of the Telescope Structure System (STR) of Thirty Meter Telescope (TMT). NAOJ was given responsibility for the TMT STR in early 2012 and engaged Mitsubishi Electric Corporation (MELCO) to take over the preliminary design work. MELCO performed a comprehensive preliminary design study in 2012 and 2013 and the design successfully passed its Preliminary Design Review (PDR) in November 2013 and April 2014. Design optimizations were pursued to better meet the design requirements and improvements were made in the designs of many of the telescope subsystems as follows: 1. 6-legged Top End configuration to support secondary mirror (M2) in order to reduce deformation of the Top End and to keep the same 4% blockage of the full aperture as the previous STR design. 2. “Double Lower Tube” of the elevation (EL) structure to reduce the required stroke of the primary mirror (M1) actuators to compensate the primary mirror cell (M1 Cell) deformation caused during the EL angle change in accordance with the requirements. 3. M1 Segment Handling System (SHS) to be able to make removing and installing 10 Mirror Segment Assemblies per day safely and with ease over M1 area where access of personnel is extremely difficult. This requires semi-automatic sequence operation and a robotic Segment Lifting Fixture (SLF) designed based on the Compliance Control System, developed for controlling industrial robots, with a mechanism to enable precise control within the six degrees of freedom of position control. 4. CO2 snow cleaning system to clean M1 every few weeks that is similar to the mechanical system that has been used at Subaru Telescope. 5. Seismic isolation and restraint systems with respect to safety; the maximum acceleration allowed for M1, M2, tertiary mirror (M3), LGSF, and science instruments in 1,000 year return period earthquakes are defined in the requirements. The Seismic requirements apply to any EL angle, regardless of the operational status of Hydro Static Bearing (HSB) system and stow lock pins. In order to find a practical solution, design optimization study for seismic risk mitigation was carried out extensively, including the performing of dynamic response analyses of the STR system under the time dependent acceleration profile of seven major earthquakes. The work is now moving to the final design phase from April 2014 for two years

Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia

Due to the considerable success of cancer immunotherapy for leukemia, the tumor immune environment has become a focus of intense research; however, there are few reports on the dynamics of the tumor immune environment in leukemia. Here, we analyzed the tumor immune environment in pediatric B cell precursor acute lymphoblastic leukemia by analyzing serial bone marrow samples from nine patients with primary and recurrent disease by mass cytometry using 39 immunophenotype markers, and transcriptome analysis. High-dimensional single-cell mass cytometry analysis elucidated a dynamic shift of T cells from naïve to effector subsets, and clarified that, during relapse, the tumor immune environment comprised a T helper 1-polarized immune profile, together with an increased number of effector regulatory T cells. These results were confirmed in a validation cohort using conventional flow cytometry. Furthermore, RNA transcriptome analysis identified the upregulation of immune-related pathways in B cell precursor acute lymphoblastic leukemia cells during relapse, suggesting interaction with the surrounding environment. In conclusion, a tumor immune environment characterized by a T helper 1-polarized immune profile, with an increased number of effector regulatory T cells, could contribute to the pathophysiology of recurrent B cell precursor acute lymphoblastic leukemia. This information could contribute to the development of effective immunotherapeutic approaches against B cell precursor acute lymphoblastic leukemia relapse

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

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

Essential cellular modules for the proliferation of the primitive cell

Bacteria appeared early in the evolution of cellular life on planet Earth, and therefore the universally essential genes or biological pathways found across bacterial domains may represent fundamental genetic or cellular systems used in early life. The essential genes and the minimal gene set required to support bacterial life have recently been experimentally and computationally identified. It is, however, still hard to estimate the ancient genes present in primitive cells compared to the essential genes in contemporary bacteria, because we do not know how ancestral primitive cells lived and proliferated, and therefore cannot directly evaluate the essentiality of the genes in ancestral primitive cells. The cell wall is normally essential for bacterial proliferation and cellular division of walled bacterial cells is normally highly controlled by the essential FtsZ cell division machinery. But, bacteria are capable of reverting to their cell wall deficient ancestral form, called the “L-form”. Unlike “normal” cells, L-forms divide by a simple physical mechanism based on the effects of membrane dynamics, suggesting a mode of primitive proliferation before the appearance of the cell wall. In this review, we summarize the experimental and computational investigations of minimal gene sets and discuss the minimal cellular modules required to support the proliferation of primitive cells, based on L-form proliferation. Keywords: L-form, Essential genes, Minimal gene set, KEGG module, Bacteri