69 research outputs found

    CASS FRACTURE TESTS USING FLAT PLATE SPECIMENS WITH A SURFACE FLAW

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    ABSTRACT JSME rules for fitness for service have flaw acceptance rules for cast austenitic stainless steel (CASS) pipes. They allow applying two-parameter and elastic-plastic fracture mechanics methods using Z-factor. However they do not clearly describe whether limit load method is applicable for the case of no or low thermal aging condition. The authors performed tensile fracture tests using flat plate specimens with a surface flaw and confirmed that limit load method is applicable in the conditions of no thermal aging and even fully saturated thermal aging with high ferrite number. Also the plate with a shallow flaw ruptured at the critical stress defined by nominal stress at rupture-flaw depth curve in the code case which was determined by the similar flat plate tests of stainless steel or nickel alloy specimens. These results will be reflected to the revision of the code

    Determining the structure of a benzene7.2-silicalite-1 zeolite using a single-crystal X-ray method

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    An orthorhombic benzene-silicalite-1 single crystal was obtained from a monoclinic twin crystal, and the structure was determined by a single-crystal method for the first time

    Potential association of bystander-patient relationship with bystander response and patient survival in daytime out-of-hospital cardiac arrest

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    Aim: To investigate whether the bystander-patient relationship affects bystander response to out-of-hospital cardiac arrest (OHCA) and patient outcomes depending on the time of day. Methods: This population-based observational study in Japan involving 139,265 bystander-witnessed OHCAs (90,426 family members, 10,479 friends/colleagues, and 38,360 others) without prehospital physician involvement was conducted from 2005 to 2009. Factors associated with better bystander response [early emergency call and bystander cardiopulmonary resuscitation (BCPR)] and 1-month neurologically favourable survival were assessed. Results: The rates of dispatcher-assisted CPR during daytime (7:00-18:59) and nighttime (19:00-6:59) were highest in family members (45.6% and 46.1%, respectively, for family members; 28.7% and 29.2%, respectively, for friends/colleagues; and 28.1% and 25.3%, respectively, for others). However, the BCPR rates were lowest in family members (35.5% and 37.8%, respectively, for family members; 43.7% and 37.8%, respectively, for friends/colleagues; and 59.3% and 50.0%, respectively, for others). Large delays (≥5. min) in placing emergency calls and initiating BCPR were most frequent in family members. The overall survival rate was lowest (2.7%) for family members and highest (9.1%) for friends/colleagues during daytime. Logistic regression analysis revealed that the effect of bystander relationship on survival was significant only during daytime [adjusted odds ratios (95% CI) for survival from daytime OHCAs with family as reference were 1.51 (1.36-1.68) for friends/colleagues and 1.23 (1.13-1.34) for others]. Conclusions: Family members are least likely to perform BCPR and OHCAs witnessed by family members are least likely to survive during daytime. Different strategies are required for family-witnessed OHCAs

    Functional regulation of the DNA damage-recognition factor DDB2 by ubiquitination and interaction with xeroderma pigmentosum group C protein

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    In mammalian nucleotide excision repair, the DDB1-DDB2 complex recognizes UV-induced DNA photolesions and facilitates recruitment of the XPC complex. Upon binding to damaged DNA, the Cullin 4 ubiquitin ligase associated with DDB1-DDB2 is activated and ubiquitinates DDB2 and XPC. The structurally disordered N-terminal tail of DDB2 contains seven lysines identified as major sites for ubiquitination that target the protein for proteasomal degradation; however, the precise biological functions of these modifications remained unknown. By exogenous expression of mutant DDB2 proteins in normal human fibroblasts, here we show that the N-terminal tail of DDB2 is involved in regulation of cellular responses to UV. By striking contrast with behaviors of exogenous DDB2, the endogenous DDB2 protein was stabilized even after UV irradiation as a function of the XPC expression level. Furthermore, XPC competitively suppressed ubiquitination of DDB2 in vitro, and this effect was significantly promoted by centrin-2, which augments the DNA damage-recognition activity of XPC. Based on these findings, we propose that in cells exposed to UV, DDB2 is protected by XPC from ubiquitination and degradation in a stochastic manner; thus XPC allows DDB2 to initiate multiple rounds of repair events, thereby contributing to the persistence of cellular DNA repair capacit

    Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature

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    Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL

    A deeply branching thermophilic bacterium with an ancient acetyl-CoA pathway dominates a subsurface ecosystem

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    <div><p>A nearly complete genome sequence of <em>Candidatus</em> ‘Acetothermum autotrophicum’, a presently uncultivated bacterium in candidate division OP1, was revealed by metagenomic analysis of a subsurface thermophilic microbial mat community. Phylogenetic analysis based on the concatenated sequences of proteins common among 367 prokaryotes suggests that <em>Ca.</em> ‘A. autotrophicum’ is one of the earliest diverging bacterial lineages. It possesses a folate-dependent Wood-Ljungdahl (acetyl-CoA) pathway of CO<sub>2</sub> fixation, is predicted to have an acetogenic lifestyle, and possesses the newly discovered archaeal-autotrophic type of bifunctional fructose 1,6-bisphosphate aldolase/phosphatase. A phylogenetic analysis of the core gene cluster of the acethyl-CoA pathway, shared by acetogens, methanogens, some sulfur- and iron-reducers and dechlorinators, supports the hypothesis that the core gene cluster of <em>Ca.</em> ‘A. autotrophicum’ is a particularly ancient bacterial pathway. The habitat, physiology and phylogenetic position of <em>Ca.</em> ‘A. autotrophicum’ support the view that the first bacterial and archaeal lineages were H<sub>2</sub>-dependent acetogens and methanogenes living in hydrothermal environments.</p> </div

    SUMOylation of xeroderma pigmentosum group C protein regulates DNA damage recognition during nucleotide excision repair

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    The xeroderma pigmentosum group C (XPC) protein complex is a key factor that detects DNA damage and initiates nucleotide excision repair (NER) in mammalian cells. Although biochemical and structural studies have elucidated the interaction of XPC with damaged DNA, the mechanism of its regulation in vivo remains to be understood in more details. Here, we show that the XPC protein undergoes modification by small ubiquitin-related modifier (SUMO) proteins and the lack of this modification compromises the repair of UV-induced DNA photolesions. In the absence of SUMOylation, XPC is normally recruited to the sites with photolesions, but then immobilized profoundly by the UV-damaged DNA-binding protein (UV-DDB) complex. Since the absence of UV-DDB alleviates the NER defect caused by impaired SUMOylation of XPC, we propose that this modification is critical for functional interactions of XPC with UV-DDB, which facilitate the efficient damage handover between the two damage recognition factors and subsequent initiation of NER

    DOCK2 is involved in the host genetics and biology of severe COVID-19

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    「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

    都市部の妊娠期・出産後の女性の喫煙と食生活および生活習慣との関連

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    都市部に在住する乳児の母親を対象として,妊娠前後の喫煙の現状と食・生活習慣との関連を明らかにすることを目的に,無記名自記式アンケート調査を実施した。対象は,平成14年11月の1ヶ月間に,京都市内14ヶ所の保健所・支所にて,生後4ヶ月児健診を受診した991名の乳児の母親である。喫煙や食・生活習慣に関する調査紙を手渡し,回答が得られた466名(回収率47.0%)を解析対象とした。その結果,妊娠前喫煙率は28.5%で,年齢が若いほど喫煙率が高かった。妊娠を契機に74.4%が禁煙し,妊娠中喫煙率は7.3%であったが,出産後喫煙率は10.9%に増加していた。喫煙者は非喫煙者と比較して,食・生活習慣,授乳,喫煙に関する知識の欠如などの健康課題を有しており,小児期からの喫煙防止教育等,総合的な保健対策が望まれる
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