•18MeV W6+ irradiation to pure W and W–3%Re was conducted at 500 and 800°C.•Voids were observed in all of specimen without W–3%Re irradiated to 0.2 dpa.•Irradiation hardening was saturated in pure W ...after 1 dpa irradiation.•After 5 dpa irradiation, irradiation hardening of W–3%Re was smaller than pure W.
The irradiation hardening and microstructures of pure W and W–3%Re for up to 5.0 dpa by self-ion irradiation were investigated in this work. The ion irradiation was conducted using 18 MeV W6+ at 500 and 800°C. A focused ion beam followed by electro-polishing was used to make thin foil specimens for transmission electron microscope observations. Dislocation loops were observed in all the irradiated samples. Voids were observed in all of the specimens except the W–3%Re irradiated to 0.2 dpa. The hardness was measured by using nanoindentation. The irradiation hardening was saturated at 1.0 dpa for pure W. In the case of W–3%Re, the irradiation hardening showed a peak at 1.0 dpa. The correlation between the microstructure and hardening was investigated.
The invariant mass spectra of e+e- pairs produced in 12 GeV proton-induced nuclear reactions are measured at the KEK Proton Synchrotron. On the low-mass side of the meson peak, a significant ...enhancement over the known hadronic sources has been observed. The mass spectra, including the excess, are well reproduced by a model that takes into account the density dependence of the vector meson mass modification, as theoretically predicted.
Engineered T-cell therapy using a CD19-specific chimeric antigen receptor (CD19-CAR) is a promising strategy for the treatment of advanced B-cell malignancies. Gene transfer of CARs to T-cells has ...widely relied on retroviral vectors, but transposon-based gene transfer has recently emerged as a suitable nonviral method to mediate stable transgene expression. The advantages of transposon vectors compared with viral vectors include their simplicity and cost-effectiveness. We used the Tol2 transposon system to stably transfer CD19-CAR into human T-cells. Normal human peripheral blood lymphocytes were co-nucleofected with the Tol2 transposon donor plasmid carrying CD19-CAR and the transposase expression plasmid and were selectively propagated on NIH3T3 cells expressing human CD19. Expanded CD3(+) T-cells with stable and high-level transgene expression (~95%) produced interferon-γ upon stimulation with CD19 and specifically lysed Raji cells, a CD19(+) human B-cell lymphoma cell line. Adoptive transfer of these T-cells suppressed tumor progression in Raji tumor-bearing Rag2(-/-)γc(-/-) immunodeficient mice compared with control mice. These results demonstrate that the Tol2 transposon system could be used to express CD19-CAR in genetically engineered T-cells for the treatment of refractory B-cell malignancies.
Aluminium alloy have high strength and easily recycle due to its low melting point. Therefore, aluminium is widely used in the manufacturing of cars and electronic devices. In recent years, the most ...common way for bonding aluminium alloy is brazing and friction stir welding. However, brazing requires positional accuracy and results in the formation of voids by the flax residue. Moreover, aluminium is an excellent heat radiating and electricity conducting material; therefore, it is difficult to bond together using other bonding methods. Because of these limitations, liquid phase diffusion bonding is considered to the suitable method for bonding aluminium at low temperature and low bonding pressure. In this study, the effect of metal formate coating processing of zinc surface on the bond strength of the liquid phase diffusion bonded interface of A1070 has been investigated by SEM observation of the interfacial microstructures and fractured surfaces after tensile test. Liquid phase diffusion bonding was carried out under a nitrogen gas atmosphere at a bonding temperature of 673 K and 713 K and a bonding load of 6 MPa (bonding time: 15 min). As a result of the metal formate coating processing, a joint having the ultimate tensile strength of the base aluminium was provided. It is hypothesized that this is because metallic zinc is generated as a result of thermal decomposition of formate in the bonded interface at lower bonding temperatures.
Summary
Our previous work revealed that the recipients with the highest pre‐existing numbers of CD8+ effector T cells (TE) hyperparathyroidism (HPT)E recipients occupied approximately 30% of adult ...transplant recipients performed in our hospital. HPTE recipients demonstrated very poor clinical outcome compared with the remaining 70% of recipients with the lowest pre‐existing TE (LPTE recipient). This study aimed to clarify the best combined immunosuppressive regimen related to function of cytotoxic T lymphocytes (CTLs) for HPTE recipients. Eighty‐one HPTE recipients were classified into three types, according to the immunosuppressive regimens: type 1, tacrolimus (Tac)/glucocorticoid (GC); type 2, Tac/mycophenolate mofetil (MMF)/GC; and type 3, Tac/MMF. Frequencies of severe infection, rejection and hospital death were the highest in types 1 and 2, whereas the lowest occurred in type 3. The survival rate in type 3 was the highest (100%) during follow‐up until post‐operative day 2000. Regarding the immunological mechanism, in type 1 TE perforin and interferon (IFN)‐γ were generated through the self‐renewal of CD8+ central memory T cells (TCM), but decreased in the early post‐transplant period due to marked down‐regulation of interleukin (IL)‐12 receptor beta‐1 of TCM. In type 2, the self‐renewal TCM did not develop, and the effector function could not be increased. In type 3, in contrast, the effectors and cytotoxicity were correlated inversely with IL‐12Rβ1+ TCM levels, and increased at the highest level around the pre‐transplant levels of IL‐12Rβ1+ TCM. However, the immunological advantage of Tac/MMF therapy was inhibited strongly by additive steroid administration.
Transplantation of cells overexpressing a target protein represents a viable gene therapeutic approach for treating hemophilia. Here, we focused on the use of autologous mesenchymal stem cells (MSCs) ...expressing coagulation factor for the treatment of coagulation factor VIII (FVIII) deficiency in mice.
Analysis of luciferase gene constructs driven by different promoters revealed that the plasminogen activator inhibitor-1 (PAI-1) gene promoter coupled with the cytomegalovirus promoter enhancer region was one of the most effective promoters for producing the target protein. MSCs transduced with the simian immunodeficiency virus (SIV) vector containing the FVIII gene driven by the PAI-1 promoter expressed FVIII for several months, and this expression was maintained after multiple mesenchymal lineage differentiation. Although intravenous injection of cell supernatant derived from MSCs transduced with an SIV vector containing the FVIII gene driven by the PAI-1 promoter significantly increased plasma FVIII levels, subcutaneous implantation of the MSCs resulted in a transient and weak increase in plasma FVIII levels in FVIII-deficient mice. Interestingly, intra-articular injection of the transduced MSCs significantly ameliorated the hemarthrosis and hemophilic arthropathy induced by knee joint needle puncture in FVIII-deficient mice. The therapeutic effects of a single intra-articular injection of transduced MSCs to inhibit joint bleeding persisted for at least 8 weeks after administration.
MSCs provide a promising autologous cell source for the production of coagulation factor. Intra-articular injection of MSCs expressing coagulation factor may offer an attractive treatment approach for hemophilic arthropathy.
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