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. 相似文献
Abstract: An efficient knowledge-acquisition support method is required for improvement and maintenance of the knowledge base in durability evaluation of an RC bridge deck. Such a method is proposed in this paper to automatically acquire fuzzy production rules. This method makes joint use of genetic algorithms and a neural network. Using a neural network as a subsystem, the evaluation function of genetic algorithms can be provided with the weights of the neural network. Introducing a neural network into genetic algorithms, it is possible to acquire new knowledge so that the method is useful when it is difficult to acquire knowledge in the field. 相似文献
Combinations of PCR-based amplification platform using 5′ thiolated and biotinylated specific primers, S1 nuclease-PCR products treatment, ferrocene-streptavidin (Fc-Stv)-magnetic binding for DNA accumulation, and screen printed gold electrode for the DNA allocation, were applied to Hoechst 33258-induced DNA aggregation and signals induction system for direct signals detection and DNA quantification in food samples. Thiolated and biotinylated at each 5′ terminus enabled DNA purification through S1 nuclease treatment for primers and non-specific DNA elimination and enabled DNA trapping with a ferrocene-streptavidin-magnetic system. This facilitated the accumulation of target DNAs at higher concentration, resulting in enhanced signals. After allocation of DNA on the surface of gold electrode via thiol binding, intensity of DNA signals through these treatments could be measured directly after being induced by Hoechst 33258. Wider amplitude changes in anodic current peaks between negative and positive samples (increasing from 3.70 to 10.10 μA) compared with those applied with no treatment combinations (decreasing from 3.92 to 1.23 μA) were observed. This enhancement of the signals allowed a greater efficiency of DNA quantification. When this combination was used for GMOs content estimation in reference samples, results revealed an improved accuracy from 66% to 96%. The combined biosensor system, although more costly than the standard Hoechst 33258/carbon electrode system, provided an alternative choice for DNA quantification, offering labor-free immobilization of probe onto electrode surface, easy test administration, and efficient semi-quantitative test without expensive instruments. 相似文献
The sintering behavior of α-alumina powders doped with magnesia (500 or 1500 ppm) and yttria (0, 500, or 1500 ppm) was investigated using constant-heating-rate dilato-metric experiments. The apparent activation energies for the intermediate stage of sintering were 740, 800, and 870 kJ/mol for 0, 500, and 1500 ppm yttria doping levels, respectively; these were independent of magnesia doping. Yttria-doped powder compacts exhibited systematic anomalous second peaks in the densification rate curves at certain grain sizes which were determined only by yttria doping levels. Before the anomalous peak, with lower yttrium contents at grain boundaries, yttrium in an atomic state delays densification and raises the apparent activation energy. Beyond the peak, with higher yttrium contents at grain boundaries, yttria-rich precipitation delays the densification. Within the peak, yttrium segregation near the saturation level enhances densification. 相似文献
In order to obtain information on the lattice location of B atoms in graphite, channelling experiments have been performed at room temperature with a proton beam of an energy of 0.65-0.77 MeV for the 〈0 0 0 1〉 axial channel in highly oriented pyrolytic graphite (HOPG) crystals doped with 0.32 at.% B. The B atoms are detected by measuring α-particles which are emitted as a result of a nuclear reaction 11B(p,α)αα. It is clearly demonstrated that most of B atoms are shadowed behind the 〈0 0 0 1〉 C atomic rows. Taking account of the already reported experimental results on a change of lattice parameters by B-doping, it is concluded that most of B atoms are located at substitutional sites. It is also observed that B-doping introduces lattice strain on the c-plane. In addition, the presence of a small portion of interstitial B atoms is suggested. 相似文献
To cope with the high rate of increase of power demand in the main industrialized districts in Japan, 550-kV transmission systems covering the districts have been reinforced, with most of the main power plants connected directly to these systems. Through 550-/300-kV substations, the majority of power to the districts is supplied by 300-kV systems. To limit the excess short-circuit capacity in the 300-kV systems, they tend to be reconstructed as so-called radial networks. In radial networks with high short-circuit capacity and relatively small number of transmission lines connected to the substation busbars, the rate of rise of TRV can be far higher than standard value. This paper analyzes the transient recovery voltages (TRV) in such extra-high-voltage radial networks in Japan, together with the relevant stresses to circuit-breakers during fault clearings. Future system conditions have also been introduced. As the typical rate of rise of the TRV values, more than twice that of today's standard ones are probable. 相似文献