Effect of additional magnesium on mechanical and high-cycle fatigue properties of 6061–T6 alloy

The effect of additional solute magnesium (Mg) on mechanical and high-cycle-fatigue properties of 6061-T6 aluminum alloy is investigated in detail. By adding 0.5% and 0.8% Mg to the 6061-T6 alloy with a normal stoichiometric Mg2Si composition (base alloy), the alloy exhibits eminent strain-aging characteristics demonstrated by the emergence of serrated flow, the negative strain-rate-sensitivity and relatively weakened temperature dependency of flow stress. The Mg-added new alloy also shows higher work-hardening rate than the base alloy particularly at initial flow regime and at lower strain rate. The S-N curve of the new alloy shows a clear fatigue limit which is absent in the base alloy. The fatigue limit of the new alloy is shown to be controlled by the threshold against small crack growth. Moreover, the new alloy clearly exhibits a coaxing phenomenon (time-dependent strengthening) which is absent in the base alloy. The coaxing effect is attributed to the existence of a small quasi-non-propagating crack whose growth resistance gradually increases during stress amplitude step-ups.This study was financially supported in part by the Kansai University Grant-in-Aid for progress ofresearch in graduate course (2012) and also by the Kansai University Expenditures for Support ofTraining Young Scholars (2013)

Observation of second harmonic electron cyclotron resonance heating and current-drive transition during non-inductive plasma start-up experiment in QUEST

Noninductive plasma current start-up using 2nd harmonic electron cyclotron resonance heating (ECRH) with oblique radio frequency (RF) injection is demonstrated in a Q-shu University experiment with steady-state spherical tokamak. A strong transition was observed in the heating and plasma current ramp-up. The initial bulk electron heating regime exhibits Tebulk ∼ 140 eV and no hard x-ray (HXR) emission with a low Ip of ∼15 kA; it abruptly transitions to a regime that exhibits a low Tebulk of ∼10 eV and a strong HXR emission with a high Ip of ∼50 kA. This behavior is distinctly different from that observed in previous fundamental ECRH experiments. The mechanism of the heating and current drive transition are investigated considering wave power absorption and plasma power balance. The results indicate that the transition is caused by the favorable heating of tail electrons where the RF power absorption at the 2nd harmonic increases nearly linearly with Tetail, while the power transfer from the tail electrons to the bulk electrons decreases with 1/Tetail0.5. This causes a rapid transition to a state with high Tetail while reducing Tebulk towards colder ion temperature. The understanding of the transition mechanism helps to consider plasma current start-up using 2nd harmonic ECRH for tokamak reactors such as JT-60 SA and ITER

Involvement of Na+/Ca2+ exchanger in migration and contraction of rat cultured tendon fibroblasts

In response to injury and inflammation of tendons, tendon fibroblasts are activated, migrate to the wound, and eventually induce contraction of the extracellular matrices to repair the tissue. Under such conditions, Ca2+ signalling is involved in motility and contractility of tendon fibroblasts. Using cultured tendon fibroblasts isolated from rat Achilles tendons, we investigated functional expression of Na+/Ca2+ exchangers (NCX). The fluorometric study showed that the intracellular Ca2+ concentration ([Ca2+]i) was increased by reducing extracellular Na+ concentration ([Na+]o) in tendon fibroblasts. Selective NCX inhibitors, KB-R7943 and SEA0400, both attenuated [Na+]o-dependent [Ca2+]i elevation and the resting [Ca2+]i in tendon fibroblasts. RT-PCR, Western blots and sequence analyses revealed that NCX1.3 and NCX1.7 were expressed in cultured tendon fibroblasts. NCX2 mRNA was undetected. NCX3 expression was negligibly low. Immunofluorescence microscopy indicated that NCX1 protein localized in the plasma membrane especially at the microspikes of tendon fibroblasts. In the wound-healing scratch assay, the cells migrated toward the space created by a scratch and almost completely filled the space within 48 h. This phenomenon was significantly suppressed by KB-R7943 and SEA0400. Furthermore, the NCX inhibitors abrogated the tendon fibroblast-mediated collagen-matrix contractions. Two types of siRNAs for NCX1 also suppressed the migration and contraction of tendon fibroblasts. We conclude that NCX is expressed and mediates Ca2+ influx in cultured tendon fibroblasts. Since the pharmacological inhibitors and siRNA for NCX1 suppressed motility and contractility of tendon fibroblasts, NCX may play an important role in the function of tendon fibroblasts in the wound healing

Therapeutic options for CTLA-4 insufficiency.

BACKGROUND Heterozygous germline mutations in cytotoxic T lymphocyte-associated antigen-4 (CTLA4) impair the immunomodulatory function of regulatory T cells. Affected individuals are prone to life-threatening autoimmune and lymphoproliferative complications. A number of therapeutic options are currently being used with variable effectiveness. OBJECTIVE Our aim was to characterize the responsiveness of patients with CTLA-4 insufficiency to specific therapies and provide recommendations for the diagnostic workup and therapy at an organ-specific level. METHODS Clinical features, laboratory findings, and response to treatment were reviewed retrospectively in an international cohort of 173 carriers of CTLA4 mutation. Patients were followed between 2014 and 2020 for a total of 2624 months from diagnosis. Clinical manifestations were grouped on the basis of organ-specific involvement. Medication use and response were recorded and evaluated. RESULTS Among the 173 CTLA4 mutation carriers, 123 (71%) had been treated for immune complications. Abatacept, rituximab, sirolimus, and corticosteroids ameliorated disease severity, especially in cases of cytopenias and lymphocytic organ infiltration of the gut, lungs, and central nervous system. Immunoglobulin replacement was effective in prevention of infection. Only 4 of 16 patients (25%) with cytopenia who underwent splenectomy had a sustained clinical response. Cure was achieved with stem cell transplantation in 13 of 18 patients (72%). As a result of the aforementioned methods, organ-specific treatment pathways were developed. CONCLUSION Systemic immunosuppressants and abatacept may provide partial control but require ongoing administration. Allogeneic hematopoietic stem cell transplantation offers a possible cure for patients with CTLA-4 insufficiency