A Sub-mW MPEG-4 Motion Estimation Processor Core for Mobile Video Application

This paper describes a sub-mW motion estimation processor core for MPEG-4 video encoding. It features a gradient descent search (GDS) algorithm that reduces required computational complexity to 15 MOPS. The GDS algorithm combined with a sub-block search method upgrades picture quality. The quality is almost equal to that of a full search method. An SIMD datapath architecture optimized for the algorithm decreases a clock frequency and supply voltage. A dedicated three-port SRAM macro for image data caches of the processor is newly designed to reduce power consumption. It has been fabricated with 0.18-/spl mu/m five-layer metal CMOS technology. The VLSI processing QCIF 15-f/s video consumes 0.4-mW power at 0.85-MHz clock frequency with 1.0-V supply voltage. It is applicable to mobile video applications

Suppression of Propionibacterium acnes

Purpose. Macrophages serve as sweepers of microbes and inflammation-derived wastes and regulators of inflammation. Some traditional Japanese medicines are reported to have adjuvant effects by modifying macrophages. Our aim was to characterize the actions of jumihaidokuto (JHT) for treatment of skin inflammations including acne vulgaris, in which Propionibacterium acnes has pathogenic roles. Methods. Dermatitis was induced in rat ears by intradermal injection of P. acnes. JHT or prednisolone (PDN) was given orally, and ear thickness and histology were evaluated. The effects of constituents and metabolites of JHT on monocytes were tested by cell-based assays using the human monocytic THP-1 cell. Results. JHT and PDN suppressed the ear thickness induced by P. acnes injection. Histological examinations revealed that JHT, but not PDN, promoted macrophage accumulation at 24 h after the injection. PDN suppressed the macrophage chemokine MCP-1 in the inflamed ears, while JHT did not affect it. The JHT constituents liquiritigenin and isoliquiritin increased expression of CD86 (type-1 macrophage marker) and CD192 (MCP-1 receptor) and enhanced phagocytosis by THP-1. Conclusions. JHT suppressed dermatitis, probably by enhancing type-1 macrophage functions, with an action different from PDN. JHT may be a beneficial drug in treatment of skin inflammation induced by P. acnes

Risk-adjusted therapy for pediatric non-T cell ALL improves outcomes for standard risk patients: results of JACLS ALL-02

This study was a second multicenter trial on childhood ALL by the Japan Childhood Leukemia Study Group (JACLS) to improve outcomes in non-T ALL. Between April 2002 and March 2008, 1138 children with non-T ALL were enrolled in the JACLS ALL-02 trial. Patients were stratified into three groups using age, white blood cell count, unfavorable genetic abnormalities, and treatment response: standard risk (SR), high risk (HR), and extremely high risk (ER). Prophylactic cranial radiation therapy (PCRT) was abolished except for CNS leukemia. Four-year event-free survival (4yr-EFS) and 4-year overall survival (4yr-OS) rates for all patients were 85.4% ± 1.1% and 91.2% ± 0.9%, respectively. Risk-adjusted therapy resulted in 4yr-EFS rates of 90.4% ± 1.4% for SR, 84.9% ± 1.6% for HR, and 66.5% ± 4.0% for ER. Based on NCI risk classification, 4yr-EFS rates were 88.2% in NCI-SR and 76.4% in NCI-HR patients, respectively. Compared to previous trial ALL-97, 4yr-EFS of NCI-SR patients was significantly improved (88.2% vs 81.2%, log rank p = 0.0004). The 4-year cumulative incidence of isolated (0.9%) and total (1.5%) CNS relapse were significantly lower than those reported previously. In conclusion, improved EFS in NCI-SR patients and abolish of PCRT was achieved in ALL-02

Sustained elevation of serum interleukin-18 and its association with hemophagocytic lymphohistiocytosis in XIAP deficiency

X-linked lymphoproliferative syndrome (XLP) is a rare primary immunodeficiency characterized by increased vulnerability to Epstein-Barr virus infection. XLP type 1 is caused by mutations in SH2D1A, whereas X-linked inhibitor of apoptosis (XIAP) encoded by XIAP/BIRC4 is mutated in XLP type 2. In XIAP deficiency, hemophagocytic lymphohistiocytosis (HLH) occurs more frequently and recurrence is common. However, the underlying mechanisms remain mostly unknown. We describe the characteristics of the cytokine profiles of serum samples from 10 XIAP-deficient patients. The concentration of interleukin (IL)-18 was strikingly elevated in the patients presented with HLH, and remained high after the recovery from HLH although levels of other pro-inflammatory cytokines approached the normal range. Longitudinal examination of two patients demonstrated marked exacerbation of IL-18 levels during every occasion of HLH. These findings may suggest the association between HLH susceptibility and high serum IL-18 levels in XIAP deficiency. © 2013 Elsevier Ltd. All rights reserved

Human AK2 links intracellular bioenergetic redistribution to the fate of hematopoietic progenitors

AK2 is an adenylate phosphotransferase that localizes at the intermembrane spaces of the mitochondria, and its mutations cause a severe combined immunodeficiency with neutrophil maturation arrest named reticular dysgenesis (RD). Although the dysfunction of hematopoietic stem cells (HSCs) has been implicated, earlier developmental events that affect the fate of HSCs and/or hematopoietic progenitors have not been reported. Here, we used RD-patient-derived induced pluripotent stem cells (iPSCs) as a model of AK2-deficient human cells. Hematopoietic differentiation from RD-iPSCs was profoundly impaired. RD-iPSC-derived hemoangiogenic progenitor cells (HAPCs) showed decreased ATP distribution in the nucleus and altered global transcriptional profiles. Thus, AK2 has a stage-specific role in maintaining the ATP supply to the nucleus during hematopoietic differentiation, which affects the transcriptional profiles necessary for controlling the fate of multipotential HAPCs. Our data suggest that maintaining the appropriate energy level of each organelle by the intracellular redistribution of ATP is important for controlling the fate of progenitor cells

Working report of the combined exercise program for geological and seismological surveys

海洋研究開発機構では高校を始めとする教育機関向けに地質学実習であるSand for Students(S4S)を2005年より実施してきた。一方で、近年推進している地震発生帯研究の成果についても教育機関や中高生向けにわかりやすく伝える機会や方法について模索してきた。そして、新たに地震探査実習を考案し（桑野他、本大会地殻構造セッションにてポスター発表）、今年度S4Sとともに実施することとした。本実習は、（独）科学技術振興機構が理科教育を推進するために運営しているサイエンス・パートナーシップ・プログラムの採択校である横浜高等学校向けに実施したものである。本発表では実際の実習内容とともにその教育的効果、および課題や今後の計画についても紹介する。 　実習プログラムは7月29日（月）?8月2日（金）に実施した。それぞれ２日間の地震学実習と地質学実習を経て、最終日に生徒のとりまとめたプレゼンテーション発表までの全５日間構成となっている。地震学実習では、１日目に屈折法地震探査の実験および実習を行い、２日目に「日本列島の形成」および「海洋プレート沈み込みに伴う海溝型地震研究」をテーマとした特別セミナー、様々な海洋調査機器の見学、実際に研究で使用されている地震計の原理を紹介し、地震計や海底地震計に触れてみる体験を盛り込んだ内容とした。地質学実習は、１日目に酒匂川（丹沢）周辺で地層の観察と鉱物の採取を行い、２日目に採取した鉱物を顕微鏡で観察する内容である。 　地震探査実習では、通常、地面に震動を与えることによって生じる地下を伝わる波を地震計で計測し、記録した後、研究室などに持ち帰りデータ処理、解析をすることが一般的であり、実際の研究で実施している作業プロセスと同じ内容を行うことが多い。今回の地震探査実習では、地震波計測により地下構造が明らかにできることを直感的に理解しやすくすることをねらいとし、地殻を模した寒天２層構造を用いた実験を考えた。この実験では模擬地殻物質が透明であるため光弾性を利用することで、弾性波の伝わる様子を可視化できる。さらに寒天の横波の伝播速度は数m/sと充分遅いため観察が容易になる。この実習では、地震波が伝わる様子をその場で一目で容易に観察でき、さらに観察の様子を録画し、そのデータを画像処理することで寒天模擬地殻表面の各点での振動波形を得ることもできる。この波形データは実際の屈折法地震探査データと同様に解析できるので、これを用いて寒天２層構造の速度構造を推定する演習を行う。演習を行いながら、地震探査を実施して地殻構造を推定することが、地震の発生メカニズムの解明にとって重要であることについて理解を促す。 　地質学実習では、身近な河川の砂を採取して観察することで河川流域の地質を把握するとともに、河川流域の地質の成り立ちを学ぶことで、日本列島形成の重要なメカニズムである付加体形成についての理解を促している。これは同時に、河川を通じて深海底に運ばれる陸源物質を探す作業でもあり、いわば地殻を構成する物質循環の基礎調査に相当する。 　本実習全体のねらいは、地震および地質調査研究に関する基礎的な科学知識・技能を普及させることである。特に、地震国である日本の地で生活する上で、身につけておいてほしい知識や技能の向上、問題の認識を目的としている。今回の実習では、講義、実験、演習、地質巡検を通じて、日本列島の形成や地震研究には地質学、地震学ともに必要であること、さらには様々な学問分野の知識が地球科学にとって重要であることを実感できるような構成とした。今回2日間で実施した地震学実習全体については、今後も実習プログラムの内容の改良、発展を加える上、地震探査実習については、実験レシピを作成して公開することも目指す。P1-36ポスター要旨, 日本地震学会2013年度秋季大会（2013年10月7日～9日, 神奈川県横浜市

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