156 research outputs found

    Metaverse Perspectives from Japan: A Participatory Speculative Design Case Study

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    Currently, the development of the metaverse lies in the hands of industry. Citizens have little influence on this process. Instead, to do justice to the pluralism of (digital) societies, we should strive for an open discourse including many different perspectives on the metaverse and its core technologies such as AI. We utilize a participatory speculative design (PSD) approach to explore Japanese citizens' perspectives on future metaverse societies, as well as social and ethical implications. Our contributions are twofold. Firstly, we demonstrate the effectiveness of PSD in engaging citizens in critical discourse on emerging technologies like the metaverse, offering our workshop framework as a methodological contribution. Secondly, we identify key themes from participants' perspectives, providing insights for culturally sensitive design and development of virtual environments. Our analysis shows that participants imagine the metaverse to have the potential to solve a variety of societal issues; for example, breaking down barriers of physical environments for communication, social interaction, crisis preparation, and political participation, or tackling identity-related issues. Regarding future metaverse societies, participants' imaginations raise critical questions about human-AI relations, technical solutionism, politics and technology, globalization and local cultures, and immersive technologies. We discuss implications and contribute to expanding conversations on metaverse developments

    Verification of Japanese language classes that foster logical thinking skills

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    In this study, based on the hypothesis that it is effective to develop logical thinking ability in the Japanese language department, we will examine the reading comprehension and instruction of "strategy" at low, middle and high levels. By conducting lessons based on these hypotheses, the types of logical thinking and the characteristics of developmental stages were clarified. One is logical thinking as a process of interpreting the logic contained in the content of the story. The other is the logic of linguistic expression, or logical thinking as a process of interpreting the narrator or author of a story

    Flavonoids Enhance Lipofection Efficiency and Ameliorate Cytotoxicity in Colon26 and HepG2 Cells via Oxidative Stress Regulation

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    The generation of reactive oxygen species (ROS) can affect cationic liposome-mediated transfection. In this study, we focused on a specific class of antioxidants, flavonoids, to investigate the transfection efficiency using cationic liposome/plasmid DNA complexes (lipoplexes) in 2D and 3D cultures of Colon26 and HepG2 cells, respectively. All tested flavonoids enhanced the transfection efficiency in 2D Colon26 and HepG2 cells. Among the tested flavonoids, 25 µM quercetin showed the highest promotion effect of 8.4- and 7.6-folds in 2D Colon26 and HepG2 cells, respectively. Transfection was also performed in 3D cultures of Colon26 and HepG2 cells using lipoplexes with quercetin. Quercetin (12.5 µM) showed the highest transfection efficiency at all transfection timings in 3D Colon26 and HepG2 cells with increased cell viability. Flow cytometry revealed that quercetin treatment reduced the population of gene expression-negative cells with high ROS levels and increased the number of gene expression-positive cells with low ROS levels in HepG2 cells. Information from this study can be valuable to develop strategies to promote transfection efficiency and attenuate cytotoxicity using lipoplexes

    HBO1-MLL interaction promotes AF4/ENL/P-TEFb-mediated leukemogenesis

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    白血病を引き起こすタンパク質間相互作用の発見. 京都大学プレスリリース. 2021-08-31.Leukemic oncoproteins cause uncontrolled self-renewal of hematopoietic progenitors by aberrant gene activation, eventually causing leukemia. However, the molecular mechanism underlying aberrant gene activation remains elusive. Here, we showed that leukemic MLL fusion proteins associate with the HBO1 histone acetyltransferase (HAT) complex through their trithorax homology domain 2 (THD2) in various human cell lines. MLL proteins associated with the HBO1 complex through multiple contacts mediated mainly by the ING4/5 and PHF16 subunits in a chromatin-bound context where histone H3 lysine 4 tri-methylation marks were present. Of the many MLL fusions, MLL-ELL particularly depended on the THD2-mediated association with the HBO1 complex for leukemic transformation. The C-terminal portion of ELL provided a binding platform for multiple factors including AF4, EAF1, and p53. MLL-ELL activated gene expression in murine hematopoietic progenitors by loading an AF4/ENL/P-TEFb (AEP) complex onto the target promoters wherein the HBO1 complex promoted the association with AEP complex over EAF1 and p53. Moreover, the NUP98-HBO1 fusion protein exerted its oncogenic properties via interaction with MLL but not its intrinsic HAT activity. Thus, the interaction between the HBO1 complex and MLL is an important nexus in leukemic transformation, which may serve as a therapeutic target for drug development

    Balancing risk-return decisions by manipulating the mesofrontal circuits in primates

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    リスクと報酬の意思決定バランスを光で調節 --精神神経疾患などの病態解明に期待--. 京都大学プレスリリース. 2024-01-05.Lighting the Circuits to Risky Decision-Making. 京都大学プレスリリース. 2024-01-05.Decision-making is always coupled with some level of risk, with more pathological forms of risk-taking decisions manifesting as gambling disorders. In macaque monkeys trained in a high risk–high return (HH) versus low risk–low return (LL) choice task, we found that the reversible pharmacological inactivation of ventral Brodmann area 6 (area 6V) impaired the risk dependency of decision-making. Selective optogenetic activation of the mesofrontal pathway from the ventral tegmental area (VTA) to the ventral aspect of 6V resulted in stronger preference for HH, whereas activation of the pathway from the VTA to the dorsal aspect of 6V led to LL preference. Finally, computational decoding captured the modulations of behavioral preference. Our results suggest that VTA inputs to area 6V determine the decision balance between HH and LL

    Influence of chronic hepatic failure on disposition kinetics of valproate excretion through a phase II reaction in rats treated with carbon tetrachloride

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    The influence of chronic hepatic failure on the disposition kinetics of valproate (VPA) excretion via a phase II reaction was examined in rats treated with carbon tetrachloride (1.0 mg/kg, s.c., 3 times a week) for 2 or 3 months. There was no significant difference in the plasma concentration-time courses of VPA among the control and two treated groups up to 120 min after i.v. administration of VPA (75 mg/kg), but subsequently the plasma concentrations of the treated groups declined significantly below the control levels. Expression of Mrp2 mRNA in the liver of the treated groups was significantly lower than in the control group; conversely that in the kidney was significantly higher. The enzyme activity of UGTs in the liver of the treated groups decreased significantly, but UGT1A8 mRNA expression in the duodenum was increased about 3-fold. Cumulative excretion of VPA glucuronide (VPA-G) in bile of the treated groups was reduced significantly, while that in urine was markedly increased. In conclusion, the area under the VPA plasma concentration-time curve was decreased significantly in rats with chronic hepatic failure owing to increased excretion of VPA-G via the kidney as a result of induction of Mrp2, and inhibition of enterohepatic circulation of VPA-G. Copyright © 2007 John Wiley & Sons, Ltd

    Verification of Japanese language classes that foster logical thinking skills

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    In this study, based on the hypothesis that it is effective to develop logical thinking ability in the Japanese language department, we will examine the reading comprehension and instruction of "strategy" at low, middle and high levels. By conducting lessons based on these hypotheses, the types of logical thinking and the characteristics of developmental stages were clarified. One is logical thinking as a process of interpreting the logic contained in the content of the story. The other is the logic of linguistic expression, or logical thinking as a process of interpreting the narrator or author of a story

    Monitoring method for transgene expression in target tissue by blood sampling

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    In this study, we have developed a novel method to monitor transgene expression in tissues by blood sampling. We administered plasmid DNA (pDNA) encoding non-secretory form of firefly luciferase as a reporter gene and pDNA encoding secretable Gaussia princeps luciferase as a monitor gene simultaneously into mice. Good positive correlations were found between log-transgene expression of the reporter gene and the monitor gene in the treated muscle, between the monitor gene in the treated muscle and plasma, and consequently between the reporter gene in the treated muscle and the monitor gene in plasma after naked pDNA transfer into the muscle of mice. Such positive correlations were also found with gastric serosal surface instillation of naked pDNA, intravenous injection of lipoplex, and hydrodynamics-based injection of naked pDNA. We developed monitoring method of transgene expression in tissues by blood sampling, which was named ‘Therapeutic transgene monitoring (TTM)’, after ‘Therapeutic drug monitoring (TDM)’

    Evaluation of changes in hepatic disposition of phenolsulfonphthalein, indocyanine green and fluorescein isothiocyanate-dextran at low temperatures using a rat liver perfusion system

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    Objectives The aim of this study was to determine the factor changing the hepatic disposition of a drug during hypothermia using a rat liver perfusion system. Methods The livers of male Wistar rats were perfused at 37, 32 or 28°C in the single-pass mode. Venous outflow dilution patterns and biliary excretion rate patterns of phenolsulfonphthalein (PSP), indocyanine green (ICG) and fluorescein isothiocyanate (FITC)-dextran (FD-4, MW 4400) after the injection of a bolus into the perfused rat liver were analysed based on statistical moment theory. Key findings The first-pass extraction ratio (E h) of PSP was significantly decreased at 32 and 28°C compared with 37°C. The biliary recovery of PSP and its conjugate was decreased and the biliary excretion was kept at a high concentration and was prolonged by low perfusion temperatures. ICG was almost extracted by a single-pass through the liver even at 32 and 28°C. The biliary recovery of ICG was significantly decreased at low temperature. Although the distribution volume of FD-4 as a vascular reference was not changed by perfusion temperature, the E h of FD-4 was decreased at 28°C although not markedly. Conclusion The change in hepatic disposition of a drug at low perfusion temperatures differed according to disposition processes under hypothermia
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