Novel hepatitis C virus protease inhibitors: thiazolidine derivatives

This study evaluated the inhibitory effects of thiazolidine derivatives on hepatitis C virus (HCV) protease and other human serine proteases. The inhibition efficacy was tested with a reversed-phase high-performance liquid chromatography (HPLC) assay system using a NS3-NS4A fusion protein as the HCV protease and a synthetic peptide substrate that mimics the NS5A-5B junction. Nine thiazolidine derivatives showed more than 50% inhibition at 50 microg/ml. The most potent derivative was RD4-6250, with 50% inhibition at a concentration of 2.3 microg/ml; this concentration was lower than those of other protease inhibitors reported previously. The most selective derivative was RD4-6205, with 50% inhibition at a concentration of 6.4 microg/ml, a lower concentration than those on other serine proteases (chymotrypsin, trypsin, plasmin, and elastase). These results suggest that the RD4-6205 skeleton is an important structure for inhibitory activity on the HCV protease NS3-NS4A.     

Optical and electronic properties of cobalt-doped zinc oxide films prepared by the sputtering method

In-doped ZnO, Co-doped ZnO and Li-doped NiO are successively deposited on quartz by the sputtering method. A current versus voltage curve of the three-layer device, in which the Indoped ZnO and Li-doped NiO are used as electrodes, reveals that the In-doped ZnO is an ohmic electrode and the Li-doped NiO is a blocking electrode with respect to electron injection. In photocurrent spectra of the three-layer device, there are two distinct peaks around 410 and 640 nm. The former is ascribed to the photoionization caused by the electric-dipole transition from the ground states,⁴A₂(F), to the conduction band, and the latter to the thermal emission from electronic excited states of Co²⁺,⁴T₁(P).     

Neutronic and thermodynamic feasibility of UF6-NpF6 fueled transmutation reactor

Transmutation of neptunium, which is contained in radioactive wastes discharged from nuclear reactors, was investigated as a substitutional method for geologic disposal. We proposed a transmutation reactor fueled with a mixture of gaseous ²³³UF₆ and ²³⁷NpF₆. Neutronic and thermodynamic analysis of the reactor revealed the feasibility of the concept. The reactor has two principal advantages: (1) use of the fuel gas enables on-line reprocessing, (2) ²³⁷Np can be transmuted by a high neutron flux. Our calculation indicated that the transmutation rate of ²³⁷Np was 335 g/year/MW_th, which is much larger than the annual yield of ²³²Np in PWR (6.19 g/year/MW_th).     

Lipid-Lowering Effect of Eriocitrin, the Main Flavonoid in Lemon Fruit, in Rats on a High-Fat and High-Cholesterol Diet

ABSTRACT:  Eriocitrin (eriodictyol 7- O -β-rutinoside) is the main flavonoid in lemon fruit. In this study, eriocitrin was investigated for its lowering effect on serum and hepatic lipids in high-fat and high-cholesterol fed rats. Rats in the control group ( N = 6) were fed a 20% lard and 1% cholesterol diet for 21 d, and rats in the 0.35% eriocitrin group ( N = 6) and 0.70% eriocitrin group ( N = 6) were fed a diet supplemented with eriocitrin 0.35% and 0.70%, respectively. The content of hepatic total cholesterol and triglyceride in the eriocitrin group was no different from that of the control group. The total cholesterol, VLDL+LDL, triglyceride, and phospholipid in the serum of the 0.35% eriocitrin group showed significantly lower concentrations than the control group ( P < 0.05), although there was no difference in the HDL concentrations among the groups. The lowering effect of eriocitrin for serum total cholesterol was thought to be caused by a decrease in VLDL+LDL. The 0.35% eriocitrin group was shown to have a significant increase in excretion of fecal bile acid ( P < 0.05) and a tendency for enhanced hepatic m-RNA levels of LDL receptor in comparison with the control group.     

Some experimental findings in compression-after-impact (CAI) tests of CF/PEEK (APC-2) and conventional CF/epoxy flat plates

Compression-after-impact (CAI) tests have been conducted for quasi-isotropic thick plates with 48 plies by using the NASA method and on plates with 32 plies by using the SACMA method. Specimens are made of CF/PEEK (APC-2) and conventional CF/epoxy for the NASA plates and CF/epoxy for the SACMA plates. In the NASA CAI tests, the sequence of delamination buckling and its propagation is clearly revealed through various experimental techniques. One major technique is moiré topography, and the other is thermo-mechanical stress analysis with a high-accuracy infrared sensor. The arrest of delamination propagation just before catastrophic failure due to high fracture toughness is clearly captured by the moiré camera. This behavior provides good CAI values of CF/PEEK. The initial buckling properties of the delaminated region by the impact are then extensively discussed. Numerical predictions of initial buckling stress have been obtained by modelled geometry of the delaminated region simplified from its precise structure clarified by ultrasonic C-scanning. They agree fairly well with the experimental results. The in-plane stress distribution in the delaminated region before initial buckling is measured by an infrared stress graphic system. This compared favorably with finite element predictions. Two types of symmetric buckling modes with respect to the central plate surface, twin and single peak ones, are experimentally captured.     

A new voltage control equipment using fuzzy inference

Power system control equipment needs higher sensitivity and operational reliability. Advanced voltage control equipment is needed for reducing the frequency of tap changes and improving the characteristics (the relationship between the actual voltage and reference voltage) of the voltage to meet today's power system requirements. However, these objectives are in a trade-off relationship. Studies of voltage control derived from a knowledge base suitable for electric power systems can satisfy these objectives using fuzzy inference. Compared with corresponding conventional equipment, the new equipment improved the deviation of 30 min average voltage of 30 percent. This paper describes the design concept of new voltage control equipment using fuzzy inference. In addition, field test results are described along with rules of fuzzy inference, membership functions, and the deviation of 30 min average voltage through detailed simulation.     

Simulation with an improved plasma model utilized to design a new structure of microwave plasma discharge for chemical vapor deposition of diamond crystals

A new structure of microwave plasma for chemical vapor deposition of diamond crystal is proposed. The structure is designed numerically, for which an improved model given in our previous work [H. Yamada et al., J. Appl. Phys. 101 (2007), art. no. 063302.] is utilized. The experimental observations and numerical predictions agree well with each other. It is demonstrated experimentally that the proposed structure can achieve a growth rate larger than 50 μm/h over an area 1 in. in diameter.     

Gene expression in brain during cuprizone-induced demyelination and remyelination

When C57BL/6J mice, 8 weeks of age, received 0.2% Cuprizone in their diet, extensive demyelination in corpus callosum was detectable after 3 weeks, and there was massive demyelination by 4 weeks. As expected, the accumulation of phagocytically active microglia/macrophages correlated closely with demyelination. When Cuprizone was removed from the diet, remyelination was soon initiated; after 6 weeks of recovery, myelin levels were near-normal and phagocytic cells were no longer prominent. Steady-state levels of mRNA for myelin-associated glycoprotein, myelin basic protein, and ceramide galactosyltransferase were already profoundly depressed after 1 week of Cuprizone exposure and were only 10-20% of control values after 2 weeks. Unexpectedly, upregulation of mRNA for these myelin genes did not correlate with initiation of remyelination but rather with accumulation of microglia/macrophages. After 6 weeks of exposure to Cuprizone, mRNA levels were at control levels or higher-in the face of massive demyelination. This suggests that in addition to effecting myelin removal, microglia/macrophages may simultaneously push surviving oligodendroglia or their progenitors toward myelination.