在宅訪問サービス拠点の地域配置に関する研究 一高齢者を支える地域的なサポート環境の構築にむけて-

名古屋大学Nagoya University博士(工学)名古屋大学博士学位論文 学位の種類:博士(工学) (課程) 学位授与年月日:平成17年9月30日doctoral thesi

車載向けソフト仕様書記述方式の研究と有効性実証

This article presents a summary of joint research with Calsonic Kansei Corporation on the topic of specification methodology of in-vehicle software. Industrial embedded software, including in-vehicle software in particular, has a large variety of implementations under a single specification according to regional regulations, product grades, customer options and more. This research is to formalize each variation as a component which can be applied to a specification independently with each other. Using a modeling framework, MATLAB/Simulink, and a software engineering technique called “aspect oriented software”, we proved the ability of our approach on a practical in-vehicle software, “Auto Light System” provided by Calsonic Kansei Corporation.textapplication/pdfdepartmental bulletin pape

Evidence for Muon Neutrino Oscillation in an Accelerator-Based Experiment

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Isomers of RA

<p>Isomers of RA</p

Leukemogenic Effects of PML-RARá and Mechanisms of ATRA/Arsenic Trioxide in the Treatment of APL

<div><p>(A) In the absence of RA, RARα/RXR heterodimers recruit the transcription corepressor (CoR), which mediates transcriptional silencing by mechanisms that include direct inhibition of the basal transcription machinery and recruitment of chromatin-modifying enzymes. Chromatin modification includes histone deacetylation, which leads to a compact chromatin structure that impairs the access of transcriptional activators. In the presence of physiological concentrations (10⁻⁹–10⁻⁸ M) of RA, the transcription corepressor is released and the coactivator is recruited to the RARα/RXR heterodimer, resulting in histone acetylation (AC) and overcoming of the transcription blockage.</p> <p>(B) PML-RARα fusion protein binds to RARα target genes either on its own or with RXR and then recruits corepressors, leading to transcriptional repression and myeloid differentiation inhibition. PML-RARα oncoprotein sequesters the normal RXR and PML, inhibits the PML/P53 apoptotic pathway, and delocalizes PML and other proteins from the nuclear body. PML-RARα also may affect interferon (IFN) and other signal pathways. Abnormalities in protein tyrosine kinases (e.g., FLT3, c-fms) may collaborate with PML-RARα to cause APL.</p> <p>(C) In the presence of pharmacological doses of ATRA or arsenic trioxide, the PML-RARα fusion is degraded in ways that are dependent on caspases and proteasomes. The degradation of PML-RARα may lead to derepression of transcription suppression and restoration of PML nuclear body structure. The blockade of other signaling pathways is also released, and the anti-apoptotic effect of PML-RARα is lost. ATRA also induces cyclic AMP (cAMP), which reverses the silencing of RXR, induces the expression of RA-induced genes and cyclooxygenase 1 (Cox 1), inhibits angiogenesis, and downregulates tissue factor. Subsequently, ATRA induces terminal cell differentiation, while arsenic trioxide induces partial differentiation and/or apoptosis of APL cells. The effects of ATRA and arsenic trioxide are indicated with red and blue arrows, respectively. AF2, the ligand-dependent transcriptional activation domain contained within the C-terminal E domain of RARα; D522, aspartate at residue 522; K160, lysine at residue 160; K490, lysine at residue 490; RARE, retinoic acid response element; SUG-1, a component of proteasome 19S complex that can bind with the activated AF2 domain of RARα.</p></div

The Three Features of APL

<p>The three features of APL are (A) accumulation of abnormal promyelocytes, (B) fibrinogenopenia and disseminated intravascular coagulation, and (C) the chromosomal translocation t(15;17)(q22;q21), the resultant fusion transcripts, and variants.</p

GSTT1 Deletion Is Related to Polycyclic Aromatic Hydrocarbons-Induced DNA Damage and Lymphoma Progression

<div><p>The interrelationship between genetic susceptibility and carcinogenic exposure is important in cancer development. Polymorphisms in detoxification enzymes of the glutathione-S-transferases (GST) family are associated with an increased incidence of lymphoma. Here we investigated the molecular connection of the genetic polymorphism of <i>GSTT1</i> to the response of lymphocytes to polycyclic aromatic hydrocarbons (PAH). In neoplastic situation, <i>GSTT1</i> deletions were more frequently observed in lymphoma patients (54.9%) than in normal controls (42.0%, P = 0.009), resulting in an increased risk for lymphoma in individuals with <i>GSTT1</i>-null genotype (Odds ratio = 1.698, 95% confidence interval = 1.145–2.518). <i>GSTT1</i> gene and protein expression were accordingly decreased in <i>GSTT1</i>-deleting patients, consistent with activated profile of cell cycle regulation genes. Mimicking environmental exposure using long-term repeat culture with low-dose PAH metabolite Hydroquinone, malignant B- and T-lymphocytes presented increased DNA damage, pCHK1/MYC expression and cell proliferation, which were counteracted by ectopic expression of <i>GSTT1</i>. Moreover, <i>GSTT1</i> expression retarded xenograft tumor formation of Hydroquinone-treated lymphoma cells in nude mice. In non-neoplastic situation, when zebrafish was exposed to PAH Benzo(a)pyrene, molecular silencing of <i>gstt1</i> enhanced the proliferation of normal lymphocytes and upregulated <i>myca</i> expression. Collectively, these findings suggested that <i>GSTT1</i> deletion is related to genetic predisposition to lymphoma, particularly interacting with environmental pollutants containing PAH.</p></div

Additional file 1: of MiR155 sensitized B-lymphoma cells to anti-PD-L1 antibody via PD-1/PD-L1-mediated lymphoma cell interaction with CD8+T cells

Figure S1. Anti-PD-L1 antibody exhibited in vivo activity on GV369-CON B-cell lymphoma. A and B: CD8+T cell percentage was enhanced, as well as CD8+T cell apoptosis and Fas expression were inhibited in GV369-CON group treated with anti-PD-L1 antibody. C and D: Expression of p-AKT and p-ERK on CD8+T cells was significantly upregulated in GV369-CON group treated with anti-PD-L1 antibody. (JPG 724 kb

<i>GSTT1</i> expression protects lymphoma cells from PAH-induced DNA damage.

<p>A: <i>GSTT1</i> gene expression assessed by semi-quantitative PCR in Namalwa and Jurkat cells transfected with <i>GSTT1</i> (GSTT1) and the negative control vector (FU). B: Images represent results from three independent experiments. GSTT1 protein expression detected by immunohistochemistry assay. C: DNA damage measured by alkaline and modified comet assay in Namalwa and Jurkat cells treated with Hydroquinone (Upper panels). Mean tail moments were calculated in the same cells (Lower panels). Data represents Mean ± SE from at least 50 cells in each group. D: Immunofluorescence assay of γH2AX and 53BP1 in Hydroquinone-treated lymphoma cells. *<i>P</i><0.05 comparing with the FU cells.</p

Additional file 1 of Dynamic change of soluble interleukin-2 receptor distinguished molecular heterogeneity and microenvironment alterations in diffuse large B-cell lymphoma

Additional file 1: Supplementary Methods. Figure S1. Dynamic change of sIL-2R in DLBCL. Figure S2. Univariate and multivariate risk models in DLBCL according to sIL-2R dynamic change. Figure S3. Survival analysis in DLBCL according to sIL-2R dynamic change in patients risked by R-IPI. Figure S4. Genetic and lymphoma microenvironment features of sIL-2R subtypes. Table S1. Clinical and pathological characteristics of DLBCL patients. Table S2. Multivariate analysis and C-index for progression-free survival (PFS) and overall survival (OS) in DLBCL. Table S3. Pathway alterations in RES subtype. Table S4. Pathway alterations in RET subtype