Dilated cardiomyopathy (DCM) is a myocardial disorder that is characterized by dilation and dysfunction of the left ventricle (LV). Accumulating evidence has implicated aberrant Ca(2+) signaling and oxidative stress in the progression of DCM, but the molecular details are unknown. In the present study, we report that inhibition of the transient receptor potential canonical 3 (TRPC3) channels partially prevents LV dilation and dysfunction in muscle LIM protein-deficient (MLP (-/-)) mice, a murine model of DCM. The expression level of TRPC3 and the activity of Ca(2+)/calmodulin-dependent kinase II (CaMKII) were increased in MLP (-/-) mouse hearts. Acitivity of Rac1, a small GTP-binding protein that participates in NADPH oxidase (Nox) activation, and the production of reactive oxygen species (ROS) were also increased in MLP (-/-) mouse hearts. Treatment with pyrazole-3, a TRPC3 selective inhibitor, strongly suppressed the increased activities of CaMKII and Rac1, as well as ROS production. In contrast, activation of TRPC3 by 1-oleoyl-2-acetyl-sn-glycerol (OAG), or by mechanical stretch, induced ROS production in rat neonatal cardiomyocytes. These results suggest that up-regulation of TRPC3 is responsible for the increase in CaMKII activity and the Nox-mediated ROS production in MLP (-/-) mouse cardiomyocytes, and that inhibition of TRPC3 is an effective therapeutic strategy to prevent the progression of DCM.

The process of high-pressure sliding (HPS) is a method of severe plastic deformation developed recently for grain refinement of metallic materials under high pressure. The sample for HPS is used with a form of sheet or rod. In this study, an HPS facility with capacities of 500 tonnes for vertical pressing and of 500 and 300 tonnes for horizontal forward and backward pressings, respectively, was newly built and applied for grain refinement of a Mg alloy as AZ61, Al alloys such as Al-Mg-Sc, A2024 and A7075 alloys, a Ti alloy as ASTM-F1295, and a Ni-based superalloy as Inconel 718. Sheet samples with dimensions of 10 to 30 mm width, 100 mm length, and 1 mm thickness were processed at room temperature and ultrafine grains with sizes of~200 to 300 nm were successfully produced in the alloys. Tensile testing at elevated temperatures confirmed the advent of superplasticity with total elongations of more than 400 pct in all the alloys. It is demonstrated that the HPS can make all the alloys superplastic through processing at room temperature with a form of rectangular sheets.

The relationship between the electrochemical behavior and the arrangement of lithium/vacancies has been investigated with electrochemical Li removal in Li(x)M(y)Mn(2-y)O4 (x < or = 1.0, 0.0 < or = y < or = 0.3, M = Co, Cr). It was shown that the electrochemical removal proceeds via two voltage regions: (1) approximately 3.9 V at x > or = approximately 0.5 and (2) approximately 4.2 V at x < or = approximately 0.5. To understand the stepwise behavior, entropy measurement of reaction, DeltaS(obs), was performed by using the electrochemical methods. The changes of the sign in deltaS(obs) from negative to positive at the composition x approximately 0.50 in Li(x)M(y)Mn(2-y)O4 indicated that the ordered arrangement of Li/vacancies was formed with electrochemical Li removal. Moreover, such an ordering was suppressed by the substitution of Co3+ and Cr3+ for Mn3+. To clarify the nature and origin of Li/vacancy ordering, the Monte Carlo simulation was performed in view of Coulombic interaction. The simulation reproduced the formation of a new phase arising from Li/vacancy ordering at x = 0.50 in Li(x)Mn2O4. In addition, the ordered arrangement of Li/vacancy at x = 0.5 was perturbed by the trivalent M3+ replacement in spinel structure due to the local clustering of Li+ around M3+. Consequently, the electrochemical behavior in spinel LiMn2O4 was deeply related to the Coulombic interactions, proved by the fact that experimentally observed changes in entropy agreed well with Monte Carlo simulation based on the Coulombic interaction.

We report the results of a new experimental setup to measure the mechanical loss of coating layers on a thin sapphire disk at cryogenic temperatures. Some of the authors previously reported that there was no temperature dependence of the mechanical loss from a multilayer tantala/silica coating on a sapphire disk, both before and after heat treatment, although some reports indicate that Ta2O5 and SiO2 layers annealed at 600• C have loss peaks near 20 K. Since KAGRA, the Japanese gravitational wave detector, currently under construction, will be operated at 20 K and have coated sapphire mirrors, it is very important to clarify the mechanical loss behavior of tantala/silica coatings around this temperature. We carefully investigated a tantala/silica-coated sapphire disk with the new setup, annealed the disk, then investigated the annealed disk.

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