31 research outputs found

    The S₄ and Few-Group Diffusion Calculations of Fast Reactors

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    To economize a large amount of numerical work in the calculation of fast breeders, the present work has been done in the hope that few-group diffusion theory might give acceptable results in some cases. A hypothetic 233TJ-232Th system with large core size (~670/) as well as a hypothetic 239Pu-238U fast reactor with small core size (~50l) are adopted. These systems are assumed to be of spherically symmetric geometry. One dimensional calculations are applied to obtain the static characteristics of the systems. The results from few-group S4 and diffusion method are investigated. These results seem to indicate that fouror three-group diffusion calculation might at least be used in place of three-group S4 computation for both large and small fast reactors. A new convergence criterion imposed upon the static parameters is proposed. The leakage rate of neutrons from the blanket is selected as the sensitive measure of convergence. This rate is estimated in two ways, i.e. with the aid of neutron current and by neutron inventory. The sufficiently converged state can be reached when these two values coincide with each other. One is also able to infer the necessary number of spatial mesh points by comparing these two values

    Alternative-ingredient Recommendation Based on Co-occurrence Relation on Recipe Database

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    AbstractThis paper proposes a recommendation method of alternative-ingredients based on co-occurrence relation on recipe database. Currently, dishes are often cooked with reference to recipes on Website. Convenience to access so many and varied recipes encourages beginners to cook. Recipe on Website list ingredients used for a dish. However, for some reason, some of the listed ingredients cannot be used for the cooking; this paper defines such ingredient as “exchange-ingredient.” To cook a dish, it should alternate exchange-ingredient and another one (i.e., alternative-ingredient). This paper proposes two algorithms to recommend alternative-ingredient. Through the cooking and tasting experiments, it was confirmed that the each of the proposed methods were effective for each intended purpose

    Continuous Health Interface Event Retrieval

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    Knowing the state of our health at every moment in time is critical for advances in health science. Using data obtained outside an episodic clinical setting is the first step towards building a continuous health estimation system. In this paper, we explore a system that allows users to combine events and data streams from different sources to retrieve complex biological events, such as cardiovascular volume overload. These complex events, which have been explored in biomedical literature and which we call interface events, have a direct causal impact on relevant biological systems. They are the interface through which the lifestyle events influence our health. We retrieve the interface events from existing events and data streams by encoding domain knowledge using an event operator language.Comment: ACM International Conference on Multimedia Retrieval 2020 (ICMR 2020), held in Dublin, Ireland from June 8-11, 202

    Constitutive Expression of Insulin Receptor Substrate (IRS)-1 Inhibits Myogenic Differentiation through Nuclear Exclusion of Foxo1 in L6 Myoblasts

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    Insulin-like growth factors (IGFs) are well known to play essential roles in enhancement of myogenic differentiation. In this report we showed that initial IGF-I signal activation but long-term IGF-1 signal termination are required for myogenic differentiation. L6 myoblast stably transfected with myc-epitope tagged insulin receptor substrate-1, myc-IRS-1 (L6-mIRS1) was unable to differentiate into myotubes, indicating that IRS-1 constitutive expression inhibited myogenesis. To elucidate the molecular mechanisms underlying myogenic inhibition, IGF-I signaling was examined. IGF-I treatment of control L6 cells for 18 h resulted in a marked suppression of IGF-I stimulated IRS-1 association with the p85 PI 3-kinase and suppression of activation of Akt that correlated with a down regulation of IRS-1 protein. L6-mIRS1 cells, in contrast, had sustained high levels of IRS-1 protein following 18 h of IGF-I treatment with persistent p85 PI 3-kinase association with IRS-1, Akt phosphorylation and phosphorylation of the downstream Akt substrate, Foxo1. Consistent with Foxo1 phosphorylation, Foxo1 protein was excluded from the nuclei in L6-mIRS1 cells, whereas Foxo1 was localized in the nuclei in control L6 cells during induction of differentiation. In addition, L6 cells stably expressing a dominant-interfering form of Foxo1, Δ256Foxo1 (L6-Δ256Foxo1) were unable to differentiate into myotubes. Together, these data demonstrate that IGF-I regulation of Foxo1 nuclear localization is essential for the myogenic program in L6 cells but that persistent activation of IGF-1 signaling pathways results in a negative feedback to prevent myogenesis

    Evidence for an Essential Deglycosylation-Independent Activity of PNGase in Drosophila melanogaster

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    BACKGROUND: Peptide:N-glycanase (PNGase) is an enzyme which releases N-linked glycans from glycopeptides/glycoproteins. This enzyme plays a role in the ER-associated degradation (ERAD) pathway in yeast and mice, but the biological importance of this activity remains unknown. PRINCIPAL FINDINGS: In this study, we characterized the ortholog of cytoplasmic PNGases, PNGase-like (Pngl), in Drosophila melanogaster. Pngl was found to have a molecular weight of approximately 74K and was mainly localized in the cytosol. Pngl lacks a CXXC motif that is critical for enzymatic activity in other species and accordingly did not appear to possess PNGase activity, though it still retains carbohydrate-binding activity. We generated microdeletions in the Pngl locus in order to investigate the functional importance of this protein in vivo. Elimination of Pngl led to a serious developmental delay or arrest during the larval and pupal stages, and surviving mutant adult males and females were frequently sterile. Most importantly, these phenotypes were rescued by ubiquitous expression of Pngl, clearly indicating that those phenotypic consequences were indeed due to the lack of functional Pngl. Interestingly, a putative "catalytic-inactive" mutant could not rescue the growth-delay phenotype, indicating that a biochemical activity of this protein is important for its biological function. CONCLUSION: Pngl was shown to be inevitable for the proper developmental transition and the biochemical properties other than deglycosylation activity is important for its biological function

    Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment

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    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
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