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.     

A case of cardiac sarcoidosis with remarkable atrophy of the left ventricular septum on two-dimensional echocardiography

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology which mainly affects the lungs, skin, the lymphoreticular system, and the heart. We report a case of cardiac sarcoidosis in which a remarkably thin ventricular septum was demonstrated on two-dimensional echocardiography.     

Performance Improvement of Current Source Inverter-Fed Induction Motor Drives

A high performance variable speed drive system using current source inverter fed induction motor is described. The principle of the drive control is based on the field-orientation method, where the stator current is used as the vector quantity. To improve the system response and to operate smoothly at low speed, a current pulsewidth modulation (PWM) control is provided by means of a feedback loop. This system operates stably and shows a high dynamic performance in a wide range, from zero to rated speed. Dual current source inverter is applied to this drive system which results in a remarkably low copper loss of the motor, even in PWM operation.     

Experimental study of the flow in helical circular pipes: Torsion effect on the flow velocity and turbulence

An objective of the present paper is to experimentally clarify the torsion effect on the flow in helical circular pipes. We have made six helical circular pipes having different pitches and common non-dimensional curvature δ of about 0.1. The torsion parameter β0, which is defined by β0 = τ/（2δ）1/2 with non-dimensional torsion r, are taken to be 0.02, 0.45, 0.69, 1.01, 1.38 and 1.89 covering from small to very large pitch. The velocity distributions and the turbulence of the flow are measured using an X-type hot-wire anemometer in the range of the Reynolds number from 200 to 20000. The results obtained are summarized as follows： The mean secondary flow pattern in a cross section of the pipe changes from an ordinary twin-vortex type as is seen in a curved pipe without torsion （toroidal pipe） to a single vortex type after one of the twin-vortex gradually disappears as β0 increases. The circulation direction of the single vortex is the same as the direction of torsion of the pipe. The mean velocity distribution of the axial flow is similar to that of the toroidal pipe at small β0, but changes its shape as β0 increases, and attains the shape similar to that in a straight circular pipe when ,β0 = 1.89. It is also found that the critical Reynolds number, at which the flow shows a marginal behavior to turbulence, decreases as ,β0 increases for small ,β0, and then increases after taking a minimum at ,β0 ≈ 1.4 as ,β0 increases. The minimum of the critical Reynolds number experimentally obtained is about 400 at ,β0 ≈ 1.4.     

Fermi surface of NbO

Studies of the dHvA effect have been made on NbO single crystals grown by a zone melting techniques and 13 separate frequency branches ranging from 5.2×10⁶ G to 1.2×10⁸G have been observed. To understand the origin of the dHvA frequencies, we have made a self-consistent band structure calculation. Most experimental frequencies are found to be assigned to the extremal orbits on the calculated Fermi surfaces. There is good qualitative agreement between experiment and calculation, but some quantitative discrepancies still exist. We also report some physical properties, i.e., electrical resistivity, superconducting transition temperature, and electronic specific heat, of this high-quality NbO crystal.     

Biosynthesis of p-anisaldehyde by the white-rot basidiomycete Pleurotus ostreatus

The white-rot basidiomycete Pleurotus ostreatus produced sweet flavor compounds on a liquid medium. The major and minor compounds identified by GC-MS analysis were p-anisaldehyde (4-methoxybenzaldehyde) and 3-chloro-p-anisaldehyde (3-chloro-4-methoxybenzaldehyde), respectively. p-Anisaldehyde was only produced under static culture conditions. Differences in the type and quantity of flavor compounds produced among wild strains of P. ostreatus were observed. Aryl alcohol oxidase and manganese peroxidase activities increased parallel to the production of p-anisaldehyde. These results indicated that the biosynthesis of p-anisaldehyde is concerned in generating H2O2-activated peroxidase in the lignin-degradation system. Addition of L-tyrosine to the culture led to higher production of p-anisaldehyde. The flavor extract, which contains p-anisaldehyde, exhibited antimicrobial activity against Bacillus subtilis, Pseudomonas aeruginosa, Aspergillus niger and Fusarium oxysporum.     

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.     

Effects of halothane and sevoflurane on the electroretinogram of dogs

OBJECTIVE: To study the effects of halothane and sevoflurane on the electroretinogram of dogs. ANIMALS: 6 clinically normal Beagles. PROCEDURE: Beagles were paralyzed by continuous IV administration of muscle relaxant and were artificially ventilated with a gas mixture of nitrous oxide and oxygen during experiments. Corneal electroretinograms were recorded, using full-field stimuli under several recording conditions before and during 1% halothane or 2% sevoflurane inhalation. RESULTS: The amplitude of the scotopic threshold response (STR) and b-wave was significantly decreased by halothane or sevoflurane inhalation, but the degree of decrease in the STR was much greater. In contrast, the amplitudes of oscillatory potentials were increased. The peak latencies of the 3 components tended to be prolonged by inhalation of the anesthetic. There seemed to be no difference between the effects of halothane and sevoflurane. CONCLUSIONS: Halothane and sevoflurane strongly depressed the STR in Beagles while moderately depressing the b-wave and increasing oscillatory potential amplitudes. Thus, neither is an appropriate anesthetic for use in recording of the STR in dogs.     

Low-Thermal-Expansion Properties of Sodium- and Lithium-Substituted Cubic Cesium Leucite Compounds

Cubic cesium leucite-based compounds, namely cesium leucites, cesium sodium leucites, and cesium lithium leucites, were synthesized using a multistep solid-state reaction method. The thermal expansion properties, in the temperature range of 298-1273 K, for the synthesized cubic cesium leucite-based compounds were examined using high-temperature powder X-ray diffractometry data. The thermal expansions of the cubic cesium leucite-based compounds were found to vary with the chemical composition. For instance, the thermal expansions of Cs_0.7Na_0.2Al_0.9Si_2.1O₆ and Cs_0.7Li_0.2Al_0.9Si_2.1O₆ were 0.14% at 1273 K and 0.081% at 1073 K, values lower than those of Cs_0.9Al_0.9Si_2.1O₆, which were 0.16% at 1073 K and 0.2% at 1273 K. The results showed that the thermal expansions of the cubic cesium leucite-based compounds changed with ionic substitution at the Cs⁺ sites because of ionic size differences between Cs⁺ and the Na⁺ or Li⁺ substitutional ions.