Although mitogen-activated protein kinase kinase (MEK) is a key signaling molecule and a negative regulator of insulin action, it is still uncertain whether MEK can be a therapeutic target for amelioration of insulin resistance (IR) in type 2 diabetes (T2D) in vivo. To clarify whether MEK inhibition improves T2D, we examined the effect of continuous MEK inhibition with two structurally different MEK inhibitors, RO5126766 and RO4987655, in mouse models of T2D. RO5126766 and RO4987655 were administered via dietary admixture. Both compounds decreased blood glucose and improved glucose tolerance in doses sufficient to sustain inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation downstream of MEK in insulin-responsive tissues in db/db mice. A hyperinsulinemic-euglycemic clamp test showed increased glucose infusion rate (GIR) in db/db mice treated with these compounds, and about 60% of the increase was attributed to the inhibition of endogenous glucose production, suggesting that the liver is responsible for the improvement of IR. By means of adenovirus-mediated Mek1 shRNA expression, we confirmed that blood glucose levels are reduced by suppression of MEK1 expression in the liver of db/db mice. Taken together, these results suggested that the MEK signaling pathway could be a novel therapeutic target for novel antidiabetic agents.

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Cross-laminated timber (CLT) has gained popularity worldwide in recent years, and its use in buildings and civil engineering structures has attracted attention in Japan. In this study, the life-cycle greenhouse gas (GHG) balance and costs associated with CLT floor slabs were evaluated with respect to small-scale bridge repair as the first instance of the use of CLT in civil engineering projects in Japan. Additionally, waterproofing treatment was applied to CLT slabs, and the potential GHG and cost reduction of CLT in comparison with reinforced concrete (RC) slabs were examined. GHG emissions were the smallest for non-waterproofed CLT slabs and the greatest for RC slabs. When replacing RC slabs with CLT slabs without waterproofing, fossil-derived GHG emissions can be reduced by 73 kg-CO2eq/m2 per slab, and fossil/wood-derived GHG emissions can be reduced by 67 kg-CO2eq/m2; however, the use of disposed CLT as fuel is essential. Moreover, a reduction in GHG emissions can be expected if RC slabs are replaced with CLT slabs that are waterproofed only once every 20 years. Further, the cost associated with RC slabs is 20% of that attributable to CLT slabs. Hence, measures need to be taken to reduce the cost of CLT and waterproofing materials.

We present a detailed angle-resolved photoemission study on the layered transition-metal dichalcogenide 1T-TaS1.2Se0.8 in the commensurate charge-density-wave (CDW) phase. A drastic reduction in the spectral weight along the high symmetry line GammaM, particularly around the point M, is observed when s-polarized light was used. This implies that the initial state must be symmetric with respect to a mirror plane perpendicular to the line GammaK, which is consistent with conventional band calculations in the absence of the CDW. We conclude that there is only a limited amount of modification of the electronic structure of 1T-TaS1.2Se0.8 in the commensurate CDW phase due to the CDW-related potential.

In this study, we focused on optimizing a part of the furnace and operating conditions of the fiber yielding system from fused coal ash to expand ash utilization for building materials; promotion of ash use is desirable because slag inhibits the elution of toxic heavy metals, such as Hg, Pb and As, to undetectable levels, making the fibers safe to use. In particular, the fiber materials from coal ash slag are expected to be used as thermal insulators and acoustic materials. We designed a coal ash fusing furnace which is suitable for the fiber manufacturing and recovery process. To manufacture fiber materials which are both safe and homogeneous, the slag viscosity had to be stabilized to approximately 1 Pa•s at the slag-tapping hole of the furnace. However, the slag temperature at 1 Pa•s was too high to measure. Thus, we estimated the slag temperature at 1 Pa•s using Riboud's and Urbain's expressions. To control the slag viscosity and temperature, CaCO 3 addition to coal ash was effective. When the basicity (CaO/SiO 2 (wt%/wt%)) of the coal ash sample was 0.98, the fused slag temperature at 1 Pa•s was estimated as 1563 ο C. Then, we verified that to yield 1 Pa•s fusing slag from 120 kg/h coal ash, the necessary fuel quantity of the coal ash fusing furnace was 40 kg/h coal and 4 m 3 N/h LPG.