45 research outputs found

    Adaptive data migration scheme with facilitator database and multi-tier distributed storage in LHD

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    Recent “data explosion” induces the demand for high flexibility of storage extension and data migration. The data amount of LHD plasma diagnostics has grown 4.6 times bigger than that of three years before. Frequent migration or replication between plenty of distributed storage becomes mandatory, and thus increases the human operational costs. To reduce them computationally, a new adaptive migration scheme has been developed on LHD’s multi-tier distributed storage. So-called the HSM (Hierarchical Storage Management) software usually adopts a low-level cache mechanism or simple watermarks for triggering the data stage-in and out between two storage devices. However, the new scheme can deal with a number of distributed storage by the facilitator database that manages the whole data locations with their access histories and retrieval priorities. Not only the inter-tier migration but also the intra-tier replication and moving are even manageable so that it can be a big help in extending or replacing storage equipment. The access history of each data object is also utilized to optimize the volume size of fast and costly RAID, in addition to a normal cache effect for frequently retrieved data. The new scheme has been verified its effectiveness so that LHD multi-tier distributed storage and other next-generation experiments can obtain such the flexible expandability

    Calreticulin and integrin alpha dissociation induces anti-inflammatory programming in animal models of inflammatory bowel disease

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    Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, is a chronic intestinal inflammatory condition initiated by integrins-mediated leukocyte adhesion to the activated colonic microvascular endothelium. Calreticulin (CRT), a calcium-binding chaperone, is known as a partner in the activation of integrin α subunits (ITGAs). The relationship between their interaction and the pathogenesis of IBD is largely unknown. Here we show that a small molecule, orally active ER-464195-01, inhibits the CRT binding to ITGAs, which suppresses the adhesiveness of both T cells and neutrophils. Transcriptome analysis on colon samples from dextran sodium sulfate-induced colitis mice reveals that the increased expression of pro-inflammatory genes is downregulated by ER-464195-01. Its prophylactic and therapeutic administration to IBD mouse models ameliorates the severity of their diseases. We propose that leukocytes infiltration via the binding of CRT to ITGAs is necessary for the onset and development of the colitis and the inhibition of this interaction may be a novel therapeutic strategy for the treatment of IBD

    Development of a Multi-Step Leukemogenesis Model of MLL-Rearranged Leukemia Using Humanized Mice

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    Mixed-lineage-leukemia (MLL) fusion oncogenes are intimately involved in acute leukemia and secondary therapy-related acute leukemia. To understand MLL-rearranged leukemia, several murine models for this disease have been established. However, the mouse leukemia derived from mouse hematopoietic stem cells (HSCs) may not be fully comparable with human leukemia. Here we developed a humanized mouse model for human leukemia by transplanting human cord blood-derived HSCs transduced with an MLL-AF10 oncogene into a supra-immunodeficient mouse strain, NOD/Shi-scid, IL-2Rγ−/− (NOG) mice. Injection of the MLL-AF10-transduced HSCs into the liver of NOG mice enhanced multilineage hematopoiesis, but did not induce leukemia. Because active mutations in ras genes are often found in MLL-related leukemia, we next transduced the gene for a constitutively active form of K-ras along with the MLL-AF10 oncogene. Eight weeks after transplantation, all the recipient mice had developed acute monoblastic leukemia (the M5 phenotype in French-American-British classification). We thus successfully established a human MLL-rearranged leukemia that was derived in vivo from human HSCs. In addition, since the enforced expression of the mutant K-ras alone was insufficient to induce leukemia, the present model may also be a useful experimental platform for the multi-step leukemogenesis model of human leukemia

    Three new species of the fairy shrimp Eubranchipus Verill, 1870 (Branchiopoda: Anostraca) from northern Japan and far Eastern Russia

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    Abstract Background Small crustaceans in the order Anostraca that lack a carapace are commonly referred to as fairy shrimps. Eubranchipus is an Anostracan genus distributed across the Holarctic region. E. uchidai has been recorded only in Japan and has been considered the only species of Eubranchipus in the region. Results We obtained fairy shrimps from three previously unsampled locations (Shiretoko and Chokai in Japan, and Khanka in Russia). Each specimen shares morphological similarities with E. uchidai, but can be discriminated by the second antenna of males and the genital morphology of females. Based on these specimens, we describe three new species of fairy shrimp: Eubranchipus asanumai n. sp. from the banks of the Shiretoko Five Lakes (Japan: Hokkaido), Eubranchipus hatanakai n. sp. from the base of Mt. Chokai (Japan: Yamagata) and Eubranchipus khankanus n. sp. from the banks of Lake Khanka (Russia: Primorsky). Phylogenetic analysis of mitochondrial DNA reveals significant differences from other known Eubranchipus species, including E. uchidai. Conclusion Both morphological and molecular analyses show that the three new species are similar to E. uchidai but constitute distinct species. Pronounced differences in female morphological features correspond to variability of the amplexus structure previously reported in the genus
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