A Time-Series Phrase Correlation Computing System With Acoustic Signal Processing For Music Media Creation

This paper presents a system that analyzes the time-series impression change in the acoustic signal by a unit of music phrase. The aim is to support the music creation using a computer (computer music) by bringing out composers' potentially existing knowledge and skills. Our goal is to realize the cross-genre/cross-cultural music creation. Our system realizes the automatic extraction of musical features from acoustic signals by dividing and decomposing them into “phrases†and “three musical elements†(rhythm, melody, and harmony), which are meaningful for human recognition. By calculating the correlation between the target “target music piece†and the “typical phrase†in each musical genre, composers are able to grasp the time-series impression change of music media by the unit of music phrase. The system leads to a new creative and efficient environment for cross-genre/cross-cultural music creation based on the potentially existing knowledge on the music phrase and structure

メタボリック シンドローム カンレン カンシッカン モデル ドウブツ ノ カイハツ ト オウヨウ : ヒト ビョウタイ カイセキ エノ シッカン ビョウリガクテキ アプローチ

Metabolic syndrome （MS） is a worldwide healthcare issue and a dominant risk factor for the development of incurable diseases that affect the entire body. The hepatic manifestations of MS include nonalcoholic fatty liver disease （NAFLD） and its progressive variant nonalcoholic steatohepatitis （NASH）. NASH is known to extend into liver cirrhosis and hepatocellular carcinoma （HCC）. To determine the pathogenesis and effective treatment, an excellent animal model of NASH/HCC is required. We recently succeeded to develop two MS associated NASH mice model （TSOD mice and DIAR-MSG mice）. Their clinical course and pathological characters were quite similar to those of human MS-NASH patients. Interestingly, most of them developed HCC in aged, which pathological and functional characters were identical to those of human HCC. In addition, we established a novel mouse model of HCC based on type １ diabetes （DIAR-nSTZ mice） and reported its histopathological features. To compare these mice models from various aspects, we can highlight specific and useful characters of MS associated liver diseases including hepatocarcinogenesis

Pathological Features of New Animal Models for Primary Biliary Cirrhosis

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by immune mediated biliary damage and frequent appearance of autoantibodies against mitochondrial enzymes. There is almost no useful animal model that is globally recognized and routinely used, however, several unique animal models manifested the characteristic clinical and pathological features of human PBC within the last 5 years. Herein, we compare the pathological features of previously reported and newly introduced novel animal models of PBC. Knowledge and understanding of the strengths and the limitations of each animal model have led to the development of promising therapies and novel tools to characterize these clinical conditions. Moreover, suitability of the model for the intended purpose should be confirmed by further research and analysis

Utility of Ethylene-Diamine-Tetraacetic Acid Buffer Solution With Boric Acid for Immunostaining of Specimens Stored for an Extended Period

Antigen modification and denaturation are recognized causes of false negatives in immunostaining. Specimens that have been stored for an extended period at room temperature show decreased immunoreactivity and may mislead the diagnosis. Studies of the molecular targeting of drugs often involve immunostaining of previous samples and, in some situations, only unstained specimens can be used. The present study aimed to develop an effective staining method to recover antigen activation in unstained specimens stored for an extended period by using ethylene-diamine-tetraacetic acid (EDTA) buffer solution with boric acid. We compared several commonly used antigen retrieval solutions and found that Tris-borate-EDTA (TBE) buffer solution with a pH ≥8.3 provided sufficient antigen retrieval. However, pH values higher than 8.3 (9.0, 10.0, and 11.0) frequently caused severe tissue damage. Thus, TBE with pH 8.3 was the most suitable antigen retrieval solution for recovering the antigenicity of specimens stored for an extended period. This procedure may allow useful immunohistochemical information, even from sections that have been stored for an extended period

Revisiting Aire and tissue-restricted antigens at single-cell resolution

The thymus is a highly specialized organ that plays an indispensable role in the establishment of self-tolerance, a process characterized by the “education” of developing T-cells. To provide competent T-cells tolerant to self-antigens, medullary thymic epithelial cells (mTECs) orchestrate negative selection by ectopically expressing a wide range of genes, including various tissue-restricted antigens (TRAs). Notably, recent advancements in the high-throughput single-cell analysis have revealed remarkable heterogeneity in mTECs, giving us important clues for dissecting the mechanisms underlying TRA expression. We overview how recent single-cell studies have furthered our understanding of mTECs, with a focus on the role of Aire in inducing mTEC heterogeneity to encompass TRAs

PHENOTYPIC ANALYSIS OF MICE DEFICIENT FOR Ly6C1/Ly6C2

Ly6C comprises two homologous components of Ly6C1 and Ly6C2, and the expression of either of the Ly6C molecules defines unique functional subsets of monocytes. Ly6C is also expressed by other immune cell types, including Aire-expressing medullary thymic epithelial cells. Because the role of Ly6C expression in determining the functional subsets remains unclear, we generated mice deficient for both Ly6C1 and Ly6C2 with CRISPR-Cas9–mediated deletion. Mice deficient for Ly6C1/Ly6C2 showed no major alterations in the subsets and function of monocyte and other immune cells, including the cells involved in the dextran sulfate sodium salt–induced colitis model. By generating the mice deficient for Ly6C1 alone, we have also investigated the expression pattern of Ly6C1 and Ly6C2 in immune cells. Except for medullary thymic epithelial cells and CD4 single-positive T cells, immune cells predominantly expressed Ly6C2. Thus, despite the importance as a marker with a unique differential expression pattern, the Ly6C molecules have no major impact on determining the functional subsets and maintaining immune homeostasis

Amelioration of diabetes in NOD by additive Aire

Tissue-specific autoimmune diseases are assumed to arise through malfunction of two checkpoints for immune tolerance: defective elimination of autoreactive T cells in the thymus and activation of these T cells by corresponding autoantigens in the periphery. However, evidence for this model and the outcome of such alterations in each or both of the tolerance mechanisms have not been sufficiently investigated. We studied these issues by expressing human AIRE (huAIRE) as a modifier of tolerance function in NOD mice wherein the defects of thymic and peripheral tolerance together cause type I diabetes (T1D). Additive huAIRE expression in the thymic stroma had no major impact on the production of diabetogenic T cells in the thymus. In contrast, huAIRE expression in peripheral antigen-presenting cells (APCs) rendered the mice resistant to T1D, while maintaining other tissue-specific autoimmune responses and antibody production against an exogenous protein antigen, because of the loss of Xcr1+ dendritic cells, an essential component for activating diabetogenic T cells in the periphery. These results contrast with our recent demonstration that huAIRE expression in both the thymic stroma and peripheral APCs resulted in the paradoxical development of muscle-specific autoimmunity. Our results reveal that tissue-specific autoimmunity is differentially controlled by a combination of thymic function and peripheral tolerance, which can be manipulated by expression of huAIRE/Aire in each or both of the tolerance mechanisms

Immunohistochemical detection of procalcitonin in fibrolamellar hepatocellular carcinoma

A 25-year-old woman with fever and epigastric pain was referred to our hospital. Blood examination showed significant liver dysfunction, markedly high C-reactive protein (CRP 19.1 mg/dL) and procalcitonin (48.3 ng/mL) levels. Dynamic computed tomography showed a tumor approximately 120 mm in size in the right lobe of the liver, but with no abscess formation. The patient was hospitalized and started on antibiotics; her CRP level improved, but the procalcitonin level did not decrease. Histopathological examination of the liver tumor biopsy revealed fibrolamellar hepatocellular carcinoma (FLC). Positive staining of the FLC with an anti-procalcitonin antibody suggested the production of procalcitonin