Enhanced Charge Transport in a Conjugated Polymer Blended with an Insulating Polymer

Herein, the hole transport in a quinoxaline–thiophene based conjugated polymer (PTQ1) mixed with an insulating polystyrene (PS) was studied by macroscopic and local current density−voltage characteristics measurements. As a result, we found that the hole conductivity in PTQ1 : PS blends increases as the weight ratio of PTQ1 is reduced down to 20 wt%. This is mainly ascribed to increases in mobility because the charge carrier density would be constant in the insulating PS matrix. With decreasing PTQ1 weight ratio in the blends, the absorption bandwidth of PTQ1 and additional emission due to excimer decreased, suggesting that interchain interactions are suppressed. By measuring the temperature‐dependent conductivity, we also found that the activation energy for the hole conductivity is smaller in PTQ1 : PS blends than in PTQ1 neat films. These findings suggest that trap sites decrease because of the suppressed interaction between PTQ1 chains in blend films. We also measured conductive atomic force microscope images of the blend films to clarify the local conductive property. For PTQ1 neat films, a low conductive image was observed over the entire film. For PTQ1 : PS blends, on the other hand, many highly conductive spots were locally found. We thus conclude that the dilution of PTQ1 chains in the PS matrix leads to a lower formation of trap sites, resulting in more conductive transport in PTQ1 : PS blends than in PTQ1 neat films

後天性肺胞蛋白症発症におけるT細胞内T-bet過剰発現の役割解明

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 中内 啓光, 東京大学教授 渡邉 俊樹, 東京大学教授 東條 有伸, 東京大学教授 北村 俊雄, 東京大学准教授 高橋 聡University of Tokyo(東京大学

Perceptions of Self of Persons

Not much is known about the self-perceptions of persons using prosthetic devices. The purpose of the literature review was to explore the self-perceptions of persons living with visible artificial devices from published articles between 2010 and 2017. Using key words to search for published literature in the PubMed, CINAHL, IEEE Proceedings, and Scopus indices showed 680 articles. Braun and Clarke's six phases of qualitative thematic analysis were used on 25 articles meeting the inclusion criteria, revealing 29 data extracts (themes) as data summaries. Three key thematic categories were revealed : Body image and ownership, integration of prosthetic device into the self-body, and suspended enjoyment or delight, reflecting the longings for completeness affecting persons' use of prosthetic devices. Consistent with self-perceptions understood through social biases and customs, completeness is achieved through the happy paradox of a person made whole through artificial devices. This experience informs nursing practice in helping people find meaning in their life. Further research into self-perceptions with prosthetic devices is essential, particularly those reflecting the cultural influences of artificial devices on quality of life

Magnetic diagnostics using the third-harmonic magnetic response for a molecule-based magnet networked by a single chiral ligand

We investigated complex magnetic domain formation on a chiral molecule-based magnet, [Cr(CN)6][Mn(R)-pnH(H2O)](H2O) (termed as R-GN), whose two-dimensional molecular network was constructed with the help of a single-handed chiral ligand ((R)-pn). There, the first- and third-harmonic magnetic responses (M1ω and M3ω) against the ac magnetic field were observed, and magnetic hysteresis in ac field of a few Oe was discussed in terms of Rayleigh loop. The diagnostics of this magnetic hysteresis clarified the complex process of magnetic domain formation against a change in temperature. For R-GN, it was reported that a giant M3ω (termed #4 in this paper) appeared just above the so-called “magnetic ordering temperature (TC)." In the present study, three M3ω responses (#1-3) were newly observed on the lower-temperature side of #4, and the ac field dependencies for all of #1-#4 were investigated. #1 also accompanied the giant M3ω, which suggests that a significant degree of magnetic fluctuation surviving below TC. This glassy behavior below TC is an attractive new phenomenon in molecule-based magnets with a single-handed chiral ligand. #2 and #3 exhibited magnetic ordering and the formation of a small magnetic domain, respectively. The M3ω responses of #1-3 were suppressed with increasing the amplitude of ac field, and the corresponding magnetic hysteresis was a normal Rayleigh loop accompanying the out-of-phase of the M1ω response. The M3ω response of #4 without the out-of-phase of M1ω was, however, enhanced with increasing the amplitude of ac field, and #4 represented a large magnetic hysteresis in the paramagnetic region, intrinsically different from those of #1-#3

Optimization of the proliferation and persistency of CAR T cells derived from human induced pluripotent stem cells

CARシグナルを補完する遺伝子改変により *iCAR-T細胞の固形がん治療効果が改善される. 京都大学プレスリリース. 2022-12-13.Genetic modifications boosting CAR signaling improve the therapeutic efficacy of iPSC-derived CAR-T cells against solid tumors. 京都大学プレスリリース. 2022-12-13.The effectiveness of chimaeric antigen receptor (CAR) T-cell immunotherapies against solid tumours relies on the accumulation, proliferation and persistency of T cells at the tumour site. Here we show that the proliferation of CD8αβ cytotoxic CAR T cells in solid tumours can be enhanced by deriving and expanding them from a single human induced-pluripotent-stem-cell clone bearing a CAR selected for efficient differentiation. We also show that the proliferation and persistency of the effector cells in the tumours can be further enhanced by genetically knocking out diacylglycerol kinase, which inhibits antigen-receptor signalling, and by transducing the cells with genes encoding for membrane-bound interleukin-15 (IL-15) and its receptor subunit IL-15Rα. In multiple tumour-bearing animal models, the engineered hiPSC-derived CAR T cells led to therapeutic outcomes similar to those of primary CD8 T cells bearing the same CAR. The optimization of effector CAR T cells derived from pluripotent stem cells may aid the development of long-lasting antigen-specific T-cell immunotherapies for the treatment of solid tumours

A clinically applicable and scalable method to regenerate T-cells from iPSCs for off-the-shelf T-cell immunotherapy

動物由来の成分を含まないより安全な製法でiPS細胞から大量の再生T細胞を培養する方法の開発 --T細胞を使ったがん免疫療法での利用も--. 京都大学プレスリリース. 2021-01-18.Clinical successes demonstrated by chimeric antigen receptor T-cell immunotherapy have facilitated further development of T-cell immunotherapy against wide variety of diseases. One approach is the development of “off-the-shelf” T-cell sources. Technologies to generate T-cells from pluripotent stem cells (PSCs) may offer platforms to produce “off-the-shelf” and synthetic allogeneic T-cells. However, low differentiation efficiency and poor scalability of current methods may compromise their utilities. Here we show improved differentiation efficiency of T-cells from induced PSCs (iPSCs) derived from an antigen-specific cytotoxic T-cell clone, or from T-cell receptor (TCR)-transduced iPSCs, as starting materials. We additionally describe feeder-free differentiation culture systems that span from iPSC maintenance to T-cell proliferation phases, enabling large-scale regenerated T-cell production. Moreover, simultaneous addition of SDF1α and a p38 inhibitor during T-cell differentiation enhances T-cell commitment. The regenerated T-cells show TCR-dependent functions in vitro and are capable of in vivo anti-tumor activity. This system provides a platform to generate a large number of regenerated T-cells for clinical application and investigate human T-cell differentiation and biology

Extracellular laminin regulates hematopoietic potential of pluripotent stem cells through integrin β1-ILK-β-catenin-JUN axis

血液細胞へ効率よく変化させる弱い接着を明らかに --血液細胞の産生効率を向上--. 京都大学プレスリリース. 2021-03-31.Stuck stem cells are no good at making blood. 京都大学プレスリリース. 2021-03-31.Recombinant matrices have enabled feeder cell-free maintenance cultures of human pluripotent stem cells (hPSCs), with laminin 511-E8 fragment (LM511-E8) being widely used. However, we herein report that hPSCs maintained on LM511-E8 resist differentiating to multipotent hematopoietic progenitor cells (HPCs), unlike hPSCs maintained on LM421-E8 or LM121-E8. The latter two LM-E8s bound weakly to hPSCs compared with LM511-E8 and activated the canonical Wnt/β-catenin signaling pathway. Moreover, the extracellular LM-E8-dependent preferential hematopoiesis was associated with a higher expression of integrin β1 (ITGB1) and downstream integrin-linked protein kinase (ILK), β-catenin and phosphorylated JUN. Accordingly, the lower coating concentration of LM511-E8 or addition of a Wnt/β-catenin signaling activator, CHIR99021, facilitated higher HPC yield. In contrast, the inhibition of ILK, Wnt or JNK by inhibitors or mRNA knockdown suppressed the HPC yield. These findings suggest that extracellular laminin scaffolds modulate the hematopoietic differentiation potential of hPSCs by activating the ITGB1-ILK-β-catenin-JUN axis at the undifferentiated stage. Finally, the combination of low-concentrated LM511-E8 and a revised hPSC-sac method, which adds bFGF, SB431542 and heparin to the conventional method, enabled a higher yield of HPCs and higher rate for definitive hematopoiesis, suggesting a useful protocol for obtaining differentiated hematopoietic cells from hPSCs in general