t(11;21)(p14;q22) RUNX1/KIAA1549L

Review on t(11;21)(p14;q22) RUNX1/KIAA1549L, with data on clinics and the genes implicated

Economic effects analysis of public investment in road improvement works in Hokkaido. Simulation analysis based on a macro-econometric model of Hokkaido

The objective of this study is to clarify how public investment in road improvement projects over a given analytical period of time has affected Hokkaido`s economic structure on the whole in relation to the industrial economy, prefectural income, household consumption, and commodity prices, through a simulation analysis based on a macro-econometric model. More specifically, our goal is to model both the direct effects achieved through the use of improved roads including the reduction of time-distance coefficients, the reduction of transportation costs and market expansion, and the indirect effects such as enhancement of lifestyles and convenience and influence on other public projects including living area improvement and promotion of regional areas, and to identify these effects quantitatively. Taking data availability into consideration, this study covers a 21-year analysis period covering the years 1976 through 1996. In constructing a quantitative model, the effect flow to be modeled was examined from two perspectives: 1) an effect flow showing the effects of road improvement works on production efficiency and market efficiency; and 2) an effect flow showing the effects of road improvement works on living standards considering convenience and lifestyle improvement. Then we attempted building a model that could indicate the occurrence of these effects in both Flow and Stock contexts. As a result of the simulation analysis, it was clarified that application of road improvement works would bring about pronounced positive economic benefits in tertiary industries, particularly in the transportation-service and wholesale/retail sectors, and greatly expand the prefectural net product on the whole. It was also revealed that these expansion effects would stimulate an increase in the prefectural income and in private final consumption expenditure. Furthermore, a simulation analysis on the economic effects that the expansion of the express-highway network would have on Hokkaido`s entire economy revealed that there would be a large effect particularly on investment and production within the transportation/communication industry and also on the commercial output of the wholesale/retail industry.

Control of immunity and allergy by steroid hormones

Steroid hormones, especially glucocorticoids, androgens, and estrogens, have profound influence on immunity. Recent studies using cell-type specific steroid hormone receptor-deficient mice have revealed the precise roles of some of these hormones in the immune system. Glucocorticoids are known to have strong anti-inflammatory and immunosuppressive effects and pleiotropic effects on innate and adaptive immune responses. They suppress the production of inflammatory cytokines by macrophages and DCs and the production of IFN-γ by NK cells, thus inhibiting innate immunity. By contrast, glucocorticoids enhance the immune response by inducing the expression of IL-7R and CXCR4 in T cells and the accumulation of T cells in lymphoid organs in accordance with the diurnal change of the glucocorticoid concentration. Thus, glucocorticoids suppress innate immunity but enhance adaptive immunity. Androgens suppress the homeostasis and activation of ILC2s and the differentiation of Th2 and Th17 cells and enhance the suppressive function of Tregs, thereby alleviating allergic airway inflammation. Thus, these steroid hormones have pleiotropic functions in the immune system. Further investigations are awaited on the regulation of immunity and allergy by estrogens using cell-specific steroid hormone receptor-deficient mice

Generation of monkey iPS cell-derived cartilage lacking MHC class I molecules on the cell surface

Multiple immune reactions when transplanting cartilage into monkeys. 京都大学プレスリリース. 2021-07-07.Due to the poor capacity for articular cartilage to regenerate, its damage tends to result in progressively degenerating conditions such as osteoarthritis. To repair the damage, the transplantation of allogeneic human induced pluripotent stem cell (iPSC)-derived cartilage is being considered. However, although allogeneic cartilage transplantation is effective, immunological reactions can occur. One hypothetical solution is to delete the expression of MHC class I molecules in order to reduce the immunological reactions. For this purpose, we deleted the β2 microglobulin (B2M) gene in a cynomolgus monkey (crab-eating monkey (Macaca fascicularis)) iPS cells (cyiPSCs) to obtain B2M⁻/⁻ cyiPSCs using the CRISPR/Cas9 system. Western blot analysis confirmed B2M⁻/⁻ cyiPSCs lacked B2M protein, which is necessary for MHC class I molecules to be transported to and expressed on the cell surface by forming multimers with B2M. Flow cytometry analysis revealed no B2M⁻/⁻ cyiPSCs expressed MHC class I molecules on their surface. The transplantation of B2M⁻/⁻ cyiPSCs in immunodeficient mice resulted in teratoma that contained cartilage, indicating that the lack of MHC class I molecules on the cell surface affects neither the pluripotency nor the chondrogenic differentiation capacity of cyiPSCs. By modifying the chondrogenic differentiation protocol for human iPSCs, we succeeded at differentiating B2M⁺/⁺ and B2M⁻/⁻ cyiPSCs toward chondrocytes followed by cartilage formation in vitro, as indicated by histological analysis showing that B2M⁺/⁺ and B2M⁻/⁻ cyiPSC-derived cartilage were positively stained with safranin O and expressed type II collagen. Flow cytometry analysis confirmed that MHC class I molecules were not expressed on the cell surface of B2M⁻/⁻ chondrocytes isolated from B2M⁻/⁻ cyiPSC-derived cartilage. An in vitro mixed lymphocyte reaction assay showed that neither B2M⁺/⁺ nor B2M⁻/⁻ cyiPSC-derived cartilage cells stimulated the proliferation of allogeneic peripheral blood mononuclear cells. On the other hand, osteochondral defects in monkey knee joints that received allogeneic transplantations of cyiPSC-derived cartilage showed an accumulation of leukocytes with more natural killer (NK) cells around B2M⁻/⁻ cyiPSC-derived cartilage than B2M⁺/⁺ cartilage, suggesting complex mechanisms in the immune reaction of allogeneic cartilage transplanted in osteochondral defects in vivo

Formation experiments of CO2 hydrate chimney in a pressure cell

Experimental investigations were conducted to understand the formation process of CO_2 hydrate the chimney structure by using a gas bubble emission technique in water within a pressure cell. The detailed process was video-recorded and analyzed to study the initiation and growth behavior of hydrate chimney while the cell pressure was increased and gas supply rate decreased gradually with time. In the initial stage of chimney growth, a hydrate crystal started to form in a cup shape at the gas nozzle and ascended together with gas bubbles due to mechanical weakness of the hydrate/nozzle contact. Growth of hydrate chimney occurred with supercooling of 3K(overpressure of 0.60MPa) or more, and continued until the top end was closed completely by hydrate

経済学の哲学的基礎づけの試み : パース的プラグマティズムの応用を通じて

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 柴田 徳太郎, 東京大学教授 小野塚 知二, 東京大学教授 佐口 和郎, 東京大学講師 野原 慎司, 東京女子大学教授 乗立 雄輝University of Tokyo(東京大学

Deep Learning for Echocardiography

Objectives: The aim of this study was to evaluate whether a deep convolutional neural network (DCNN) could detect regional wall motion abnormalities (RWMAs) and differentiate groups of coronary infarction territories from conventional 2-dimensional echocardiographic images compared with cardiologist/sonographer or resident readers. Background: An effective intervention for reduction of misreading of RWMAs is needed. We hypothesized that a DCNN trained with echocardiographic images may provide improved detection of RWMAs in the clinical setting. Methods: A total of 300 patients with history of myocardial infarction were enrolled. In this cohort, 100 each had infarctions of the left anterior descending branch (LAD), left circumflex branch (LCX), and right coronary artery (RCA). The age-matched 100 control patients with normal wall motion were selected from our database. Each case contained cardiac ultrasound images from short axis views at end-diastolic, mid-systolic and end-systolic phases. After 100 steps of training, diagnostic accuracies were calculated on the test set. We independently trained 10 versions of the same model, and performed ensemble predictions with them. Results: For detection of the presence of wall motion abnormality, the area under the receiver-operating characteristic curve (AUC) by deep learning algorithm was similar to that by cardiologist/sonographer readers (0.99 vs. 0.98, p =0.15), and significantly higher than the AUC by resident readers (0.99 vs. 0.90, p =0.002). For detection of territories of wall motion abnormality, the AUC by the deep learning algorithm was similar to the AUC by cardiologist/sonographer readers (0.97 vs. 0.95, p =0.61) and significantly higher than the AUC by resident readers (0.97 vs. 0.83, p =0.003). In a validation group from an independent site (n=40), the AUC by the DL algorithm was 0.90. Conclusions: Our results support the possibility of DCNN use for automated diagnosis of RWMAs in the field of echocardiography

Generation of Monkey Induced Pluripotent Stem Cell-Derived Cartilage Lacking Major Histocompatibility Complex Class I Molecules on the Cell Surface

Due to the poor capacity for articular cartilage to regenerate, its damage tends to result in progressively degenerating conditions such as osteoarthritis. To repair the damage, the transplantation of allogeneic human induced pluripotent stem cell (iPSC)-derived cartilage is being considered. However, although allogeneic cartilage transplantation is effective, immunological reactions can occur. One hypothetical solution is to delete the expression of major histocompatibility complex (MHC) class I molecules to reduce the immunological reactions. For this purpose, we deleted the β2 microglobulin (B2M) gene in a cynomolgus monkey (crab-eating monkey [Macaca fascicularis]) iPS cells (cyiPSCs) to obtain B2M−/− cyiPSCs using the CRISPR/Cas9 system. Western blot analysis confirmed B2M−/− cyiPSCs lacked B2M protein, which is necessary for MHC class I molecules to be transported to and expressed on the cell surface by forming multimers with B2M. Flow cytometry analysis revealed no B2M−/− cyiPSCs expressed MHC class I molecules on their surface. The transplantation of B2M−/− cyiPSCs in immunodeficient mice resulted in teratoma that contained cartilage, indicating that the lack of MHC class I molecules on the cell surface affects neither the pluripotency nor the chondrogenic differentiation capacity of cyiPSCs. By modifying the chondrogenic differentiation protocol for human iPSCs, we succeeded at differentiating B2M+/+ and B2M−/− cyiPSCs toward chondrocytes followed by cartilage formation in vitro, as indicated by histological analysis showing that B2M+/+ and B2M−/− cyiPSC-derived cartilage were positively stained with safranin O and expressed type II collagen. Flow cytometry analysis confirmed that MHC class I molecules were not expressed on the cell surface of B2M−/− chondrocytes isolated from B2M−/− cyiPSC-derived cartilage. An in vitro mixed lymphocyte reaction assay showed that neither B2M+/+ nor B2M−/− cyiPSC-derived cartilage cells stimulated the proliferation of allogeneic peripheral blood mononuclear cells. On the contrary, osteochondral defects in monkey knee joints that received allogeneic transplantations of cyiPSC-derived cartilage showed an accumulation of leukocytes with more natural killer cells around B2M−/− cyiPSC-derived cartilage than B2M+/+ cartilage, suggesting complex mechanisms in the immune reaction of allogeneic cartilage transplanted in osteochondral defects in vivo.Okutani Y., Abe K., Yamashita A., et al. Generation of Monkey Induced Pluripotent Stem Cell-Derived Cartilage Lacking Major Histocompatibility Complex Class I Molecules on the Cell Surface. Tissue Engineering - Part A 28, 94 (2022); https://doi.org/10.1089/ten.tea.2021.0053

Vacuum phenomenon of sacroiliac joint

Study Design: A radiologic study of sacropelvic morphology and vacuum phenomenon of sacroiliac joint in subjects unrelated to low back pain. Purpose: The aim of this study is to describe the relationship between sacropelvic morphology and vacuum phenomenon of the sacroiliac joint. Overview of Literature: Lumbopelvic alignment and sacropelvic morphology are associated with the pathomechanisms of various spinal disorders. The vacuum phenomena of the sacroiliac joint (SJVP) are often observed in clinical practice, but the relationships between these phenomena and sacropelvic morphology have not been investigated. This study examined the prevalence of SJVP in computed tomography (CT) images and the relationship between sacropelvic morphology and SJVP. Methods: We analyzed multiplanar CT images of 93 subjects (59 men, 34 women). Pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and lumbar lordosis (LL) were measured using the three-dimensional reconstruction method. The prevalence of SJVP in multiplanar CT images were reviewed. Roland-Morris Disability Questionnaire (RDQ) scores and the modified Japanese Orthopedic Association (JOA) score, which focuses on subjective symptoms and restriction of activities of daily living, were also obtained from all the subjects. Results: Thirty-six of the 93 subjects had SJVP (39%), with marked female predominance (91% women, 8.5% men). Men with SJVP had significantly lower PI than men without SJVP (35.1° vs. 46.3°, p<0.05). There was no correlation between SJVP and the modified JOA or RDQ scores. Conclusions: These data suggest that differences in sacropelvic morphology can influence the biomechanical environment and contribute to SJVP in men. Presence of SJVP did not affect JOA or RDQ scores