111 research outputs found
Word Sense Disambiguation of Corpus of Historical Japanese Using Japanese BERT Trained with Contemporary Texts
application/pdfTokyo University of Agriculture and TechnologyTokyo University of Agriculture and TechnologyNational Institute for Japanese Language and Linguisticshttps://aclanthology.org/2022.paclic-1.49/journal articl
Effects of solute and vacancy segregation on antiphase boundary migration in stoichiometric and Al-rich Fe₃Al: a phase-field simulation study
Effects of segregation of solute atoms and vacancies on migration of antiphase boundaries (APBs) in stoichiometric (Fe-25 at%Al) and Al-rich (Fe-28 at%Al) Fe₃Al at 673 K have been studied using a phase-field method in which local vacancy concentration is taken into account [Koizumi Y, Allen SM, Minamino Y. Acta Mater 2008;56:5861, ibid. 2009;57:3039]. Boundary mobility (M) of APBs having different phase-shift vectors of a/4 and a/2 (hereafter denoted as B2-APB and D0₃-APB, respectively) was evaluated by measuring the boundary velocity of shrinking circular APBs. Similar effects of the segregation on the migration of B2-APBs were observed in both compositions. Vacancies segregated and Al-atoms were depleted at B2-APBs in both compositions. Vacancy concentration at B2-APBs was up to 80% higher than that in the bulk. As a result, the migration of B2-APBs was greatly enhanced by the vacancy segregation. In contrast, the segregation to D0₃-APBs showed a marked composition dependence. Vacancies were depleted and Al-atoms segregated at D0₃-APBs in the Al-rich Fe₃Al, whereas vacancies segregated and Al-atoms were depleted at D0₃-APB in the stoichiometric Fe₃Al. The Al segregation in the Al-rich Fe3Al decreased M of D0₃-APBs much more significantly than the Al-depletion in the stoichiometric Fe₃Al. As the APDs shrank, D0₃-APBs broke away from the segregation atmospheres and the M increased rapidly in both compositions. A greater increase in the M due to the breakaway was observed in the Al-rich Fe₃Al than in Fe₃Al with the stoichiometric composition.Iketani Science and Technology Promotion Foundatio
Therapeutic benefits of factors derived from stem cells from human exfoliated deciduous teeth for radiation-induced mouse xerostomia
Radiation therapy for head and neck cancers is frequently associated with adverse effects on the surrounding normal tissue. Irreversible damage to radiation-sensitive acinar cells in the salivary gland (SG) causes severe radiation-induced xerostomia (RIX). Currently, there are no effective drugs for treating RIX. We investigated the efficacy of treatment with conditioned medium derived from stem cells from human exfoliated deciduous teeth (SHED-CM) in a mouse RIX model. Intravenous administration of SHED-CM, but not fibroblast-CM (Fibro-CM), prevented radiation-induced cutaneous ulcer formation (p < 0.0001) and maintained SG function (p < 0.0001). SHED-CM treatment enhanced the expression of multiple antioxidant genes in mouse RIX and human acinar cells and strongly suppressed radiation-induced oxidative stress. The therapeutic effects of SHED-CM were abolished by the superoxide dismutase inhibitor diethyldithiocarbamate (p < 0.0001). Notably, quantitative liquid chromatography-tandem mass spectrometry shotgun proteomics of SHED-CM and Fibro-CM identified eight proteins activating the endogenous antioxidant system, which were more abundant in SHED-CM than in Fibro-CM (p < 0.0001). Neutralizing antibodies against those activators reduced antioxidant activity of SHED-CM (anti-PDGF-D; p = 0.0001, anti-HGF; p = 0.003). Our results suggest that SHED-CM may provide substantial therapeutic benefits for RIX primarily through the activation of multiple antioxidant enzyme genes in the target tissue
Hematopoietic reconstitution by multipotent adult progenitor cells: precursors to long-term hematopoietic stem cells
For decades, in vitro expansion of transplantable hematopoietic stem cells (HSCs) has been an elusive goal. Here, we demonstrate that multipotent adult progenitor cells (MAPCs), isolated from green fluorescent protein (GFP)-transgenic mice and expanded in vitro for >40–80 population doublings, are capable of multilineage hematopoietic engraftment of immunodeficient mice. Among MAPC-derived GFP+CD45.2+ cells in the bone marrow of engrafted mice, HSCs were present that could radioprotect and reconstitute multilineage hematopoiesis in secondary and tertiary recipients, as well as myeloid and lymphoid hematopoietic progenitor subsets and functional GFP+ MAPC-derived lymphocytes that were functional. Although hematopoietic contribution by MAPCs was comparable to control KTLS HSCs, approximately 103-fold more MAPCs were required for efficient engraftment. Because GFP+ host-derived CD45.1+ cells were not observed, fusion is not likely to account for the generation of HSCs by MAPCs
Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction
心房細動の遺伝的基盤を解明 --大規模ゲノムデータによる病態解明と遺伝的リスクスコア構築--. 京都大学プレスリリース. 2023-01-20.Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9, 826 cases among 150, 272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77, 690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications
Changes in expression levels of ERCC1, DPYD, and VEGFA mRNA after first-line chemotherapy of metastatic colorectal cancer: results of a multicenter study
Our previous study showed that administering oxaliplatin as first-line chemotherapy increased ERCC1 and DPD levels in liver colorectal cancers (CRCs) metastases. Second, whether the anti-VEGF monoclonal antibody bevacizumab alters tumoral VEGFA levels is unknown. We conducted this multicenter observational study to validate our previous findings on ERCC1 and DPD, and clarify the response of VEGFA expression to bavacizumab administration. 346 CRC patients with liver metastases were enrolled at 22 Japanese institutes. Resected liver metastases were available for 175 patients previously treated with oxaliplatin-based chemotherapy (chemotherapy group) and 171 receiving no previous chemotherapy (non-chemotherapy group). ERCC1, DPYD, and VEGFA mRNA levels were measured by real-time RT-PCR. ERCC1 mRNA expression was significantly higher in the chemotherapy group than in the non-chemotherapy group (P = 0.033), and were significantly correlated (Spearman\u27s correlation coefficient = 0.42; P < 0.0001). VEGFA expression level was higher in patients receiving bevacizumab (n = 51) than in those who did not (n = 251) (P = 0.007). This study confirmed that first-line oxaliplatin-based chemotherapy increases ERCC1 and DPYD expression levels, potentially enhancing chemosensitivity to subsequent therapy. We also found that bevacizumab induces VEGFA expression in tumor cells, suggesting a biologic rationale for extending bevacizumab treatment beyond first progression
Genomic landscape of colorectal cancer in Japan: clinical implications of comprehensive genomic sequencing for precision medicine
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