Development of Selective TGR5 Ligands Based on the 5,6,7,8-Tetrahydro-5,5,8,8-tetramethylnaphthalene Skeleton

TGR5, a G-protein-coupled receptor (GPCR), plays an important role in several physiological functions. TGR5 activation through bile acids induces an increase in energy expenditure. Therefore, synthetic TGR5 ligands could be useful for the treatment of obesity or dyslipidemia. In this study, we designed and synthesized a set of TGR5 ligands with a 5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene (TMN) skeleton, and evaluated their TGR5 agonistic activity. We also investigated the selectivity of the synthesized compounds for TGR5 relative to the farnesoid X receptor (FXR) and retinoic acid receptor (RAR). Our results show that compound 4 b [N-(2-chlorophenyl)-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenecarboxamide] exhibited potent TGR5 agonist activity with an IC₅₀ value of 8.4 nM without significant cytotoxicity. In addition, compound 4 b showed only slight agonistic activity toward FXR and RAR at 1 μM treatment. These data indicate that compound 4 b is a selective TGR5 agonist, and could be a promising therapeutic agent for dyslipidemia.     

One-year monthly monitoring of Torque teno virus (TTV) in wastewater treatment plants in Japan

Torque teno virus (TTV) is a novel hepatitis virus which is considered to be transmitted by the fecal-oral route. Wastewater samples were collected monthly from eight wastewater treatment plants in Japan for 1 year, from July 2003 to June 2004, and tested for the presence of TTV by TaqMan PCR. TTV was detected in 97% (93/96) of influent samples, implying that TTV is epidemic in Japan. TTV was also isolated in 18% (17/96) of secondary effluent samples before chlorination and in 24% (23/95) of final effluent samples after chlorination. There was no significant difference between the concentration of total coliform in TTV-positive final effluents and that in TTV-negative final effluents, which indicates that total coliform cannot be used as an indicator of TTV. No TTV was detected in 24 effluents for reuse from two wastewater treatment plants using sand filtration and ozonation.     

Excess Solute Carbon and Retained Tetragonality in Tempered Fe-0.6C-1Mn Martensite and the Effect of Silicon Addition

The tetragonality and carbon distribution in tempered Fe-0.6C-1Mn martensite were investigated by X-ray diffraction and atom probe tomography to elucidate strain relaxation in the tetragonal lattice during tempering and its relationship with the solubility of excess carbon in martensite. Even though tetragonality (c/a) decreased with an increase in the tempering temperature, it persisted at low levels up to 400 °C. Si addition suppressed the decrease in tetragonality at 400 °C by inhibiting recovery in the dislocated matrix. Such persistence implies that dislocation migration is crucial for the complete release of tetragonal lattice strain at such a temperature, in addition to the decrease in the amount of solute carbon in martensite. A low level of tetragonality was observed for martensite containing carbon in the solid solution below the critical value of ~ 0.2 mass pct, at which a bcc structure was predicted. The amount of solute carbon after tempering was linearly correlated with tetragonality in the solute carbon content range of 0.07 to 0.6 mass pct, and the correlation coefficient was similar to those for as-quenched auto-tempered martensite and bainitic ferrite; these results indicate that the amount of excess carbon is simply determined by the amount of tetragonal lattice distortions remaining after carbide precipitation and recovery.

     

Effects of low- or medium-pressure ultraviolet lamp irradiation on Microcystis aeruginosa and Anabaena variabilis

A pure culture of Microcystis aeruginosa or Anabaena variabilis, the representatives of water blooming algae, was exposed to low-pressure (LP) or medium-pressure (MP) UV lamps. Irradiated pure culture suspension was subsequently incubated for 7d under white light fluorescent lamps. During incubation, profiles of the number of cells, DNA damage and photosynthetic activity were determined. When UV fluence was 600mJ/cm(2), M. aeruginosa cell numbers decreased throughout the 7-d incubation period, to produce 1.5log reduction (LP) or 1.2log reduction (MP) compared with control. The amount of DNA damage was 2.02x10(-4) ESS/base (LP) and 3.42x10(-4) ESS/base (MP) just after UV irradiation, which became 0.05x10(-4) ESS/base and 0.23x10(-4) ESS/base, respectively, after 3d incubation. However, cell number kept decreasing, even after DNA repair. Photosynthetic activity decreased by 1.5log within 1d (LP) or 3d (MP). Thus, reduction in photosynthetic activity could contribute to the reduction in M. aeruginosa cell numbers. A. variabilis cell numbers reduced by 2.3log (LP) or 2.2log (MP) during the 7-d incubation period; however, after DNA damage repair, cell number began to increase. The amount of DNA damage was 6.07x10(-4) ESS/base (LP) and 4.48x10(-4) ESS/base (MP) just after UV irradiation, which became 0.23x10(-4) ESS/base and 0.40x10(-4) ESS/base, respectively, after 3d incubation. No reduction was observed in photosynthetic activity/cell. Therefore, DNA damage is the main contributor of the reduction in cell number of A. variabilis.     

Evaluation of standing‐sitting support system with passive rotational seat mechanism in standing motion

Since a decrease in muscle mass of elderly people, the physical burden of them in standing‐sitting motion of a seat are increasing than young people. For this problem, several standing‐sitting support systems have been developed, and evaluations of these systems focusing on a reduction of physical load have been discussed. However, these evaluations are of support systems with an active actuators or of support systems when they use a handrail and a standing aid. Thus, an evaluation of a support system with only passive actuators has not been reported. In this paper, in standing motion with using a standing‐sitting support system with passive rotational seat mechanism which our group proposes, we objectively evaluate an effectiveness of the passive rotational seat mechanism by statistical analysis.     

Three-dimensional rainbow schlieren measurements in underexpanded sonic jets from axisymmetric convergent nozzles

The rainbow schlieren deflectometry has been combined with the computed tomography to obtain three-dimensional density fields of shock containing free jets and we call the method the schlieren CT. Experiments on the schlieren CT have been performed at a nozzle pressure ratio of 4.0 by using an axisymmetric convergent nozzle with an inner diameter of 10 mm at the exit where the nozzle was operated at an underexpanded condition. Multidirectional rainbow schlieren pictures of an underexpanded sonic jet can be acquired by rotating the nozzle about its longitudinal axis in equal angular intervals and the three-dimensional density fields are reconstructed by the schlieren CT. The validity of the schlieren CT is verified by a comparison with the density fields reconstructed by the Abel inversion method. As a result, it is found that excellent quantitative agreement is reached between the three-dimensional jet density fields reconstructed from both methods.     

Hydrogen incorporation in tungsten deposits growing by deuterium plasma sputtering

Tungsten deposits were produced by sputtering method using hydrogen isotope RF plasma, and the density and the incorporated components in the deposits were investigated. The density changed in the range from 14.2 g/cm³ to 6.1 g/cm³, and hydrogen isotope retention changed in the range from 0.25 to 0.05 as (H + D)/W by the difference of deposition conditions. Both the density and hydrogen isotope retention tended to decrease with an increase of pressure. Even though a deuterium gas was used for producing tungsten deposits, not only deuterium but also hydrogen, oxygen and water vapor were incorporated in the deposits. It is considered that the incorporation of these components originated in water vapor unintentionally existing in the vacuum chamber.     

Micromechanical effective elastic moduli of continuous fiber-reinforced composites with near-field fiber interactions

A higher-order micromechanical framework is presented to predict the overall elastic deformation behavior of continuous fiber-reinforced composites with high-volume fractions and random-fiber distributions. By taking advantage of the probabilistic pair-wise near-field interaction solution, the interacting eigenstrain is analytically derived. Subsequently, by making use of the Eshelby equivalence principle, the perturbed strain within a continuous circular fiber is accounted for. Further, based on the general micromechanical field equations, effective elastic moduli of continuous fiber-reinforced composites are constructed. An advantage of the present framework is that the higher-order effective elastic moduli of composites can be analytically predicted with relative simplicity, requiring only material properties of the matrix and fibers, the fiber?Cvolume fraction and the microstructural parameter ??. Moreover, no Monte Carlo simulation is needed for the proposed methodology. A series of comparisons between the analytical predictions and the available experimental data for isotropic and anisotropic fiber reinforced composites illustrate the predictive capability of the proposed framework.     

Multiferroics with Spiral Spin Orders

Cross correlation between magnetism and electricity in a solid can host magnetoelectric effects, such as magnetic (electric) induction of polarization (magnetization). A key to attain the gigantic magnetoelectric response is to find the efficient magnetism–electricity coupling mechanisms. Among those, recently the emergence of spontaneous (ferroelectric) polarization in the insulating helimagnet or spiral‐spin structure was unraveled, as mediated by the spin‐exchange and spin–orbit interactions. The sign of the polarization depends on the helicity (spin rotation sense), while the polarization direction itself depends on further details of the mechanism and the underlying lattice symmetry. Here, we describe some prototypical examples of the spiral‐spin multiferroics, which enable some unconventional magnetoelectric control such as the magnetic‐field‐induced change of the polarization direction and magnitude as well as the electric‐field‐induced change of the spin helicity and magnetic domain.