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.     

二垩英与资源回收-Ⅰ考虑到二垩英生成的资源与能量回收基础研究

目前在日本,存在大量工业垃圾,包括各种塑料制品,ASR(汽车破碎垃圾),含有毒PCB(多氯联苯)的110变压器和PVC(聚氯乙稀)制品等.而来自城市垃圾焚烧炉的废气含有大量能量.因此,在充分考虑环境、避免二垩英生成的同时,安全回收来自工业垃圾、城市和/或工业垃圾焚烧炉的资源和能量是个非常重要的课题,这也将对抑制CO2排放作出贡献.正确地阐明焚烧过程中二垩英的生成机理及详细研究含少量二垩英的焚烧废气在冷却过程中大量形成二垩英的临界温度是项很重要的工作.解决这个问题可有效实现资源和能量的回收.本报告介绍日本在二垩英排放方面目前采取的对策和存在的问题以及大阪大学为阻止二垩英生成所做的基础研究工作.     

Thraustochytrid as a potential source of carotenoids

Thraustochytrids, marine protists whose dominant genera are Thraustochytrium and Schizochytrium, belong to the kingdom Chromista and are known as an industrial source of DHA. We describe here that thraustochytrid strain KH105, isolated as a DHA producer, also accumulates significant levels of β-carotene and xanthophylls including canthaxanthin and astaxanthin. A4-d cultivation using a medium composed of 10% glucose and less than 0.3% of nitrogen sources in a half-concentration of seawater gave an astaxanthin production up to 6.1 mg/L, and canthaxanthin content reached more than 10 mg/L under conditions where a higher concentration of nitrogen sources (6%) was employed. It might be advantageous in mass production systems for these carotenoids to be extracted readily by simply suspending the cells with organic solvents such as acetone and chloroform. Analyses on the morphological and life history features of the KH105 strain revealed that it belongs to the genus Schizochytrium. This particular species of thraustochytrids is thus considered to be a promising source of xanthophylls as well as DHA for use in the food industry.     

Development of probe-to-probe approach method for an independently controlled dual-probe scanning tunneling microscope

We developed a method of fast probe-to-probe approach for an independently controlled dual-probe scanning tunneling microscope (STM), which is essential to measure the transport property of nanostructures, without scanning electron microscopy (SEM). In the approach method, inchworm motors are used as the coarse positioning devices, which are controlled with a personal computer. The method enables an automatic approach of the probe to the other probe within a short time (typically 30 min). After the approach, a real distance between contact points of each probe tip to a sample can be measured from the overlapped part of the STM images obtained with individual probe. The approach method without SEM is also useful to measure the charge transport in the atmosphere, which will be essential for measurement of the bio molecules.     

Design of type-1 servo systems possessing prescribed stability margins using a generalized Riccati-type equation

A design method for type-1 servo systems having prescribed stability margins at the control input and error channels is presented. The former and latter stability margins affect the properties of sensitivity and robustness and the transient response characteristics, respectively. As a preliminary, a class of state feedback laws for regulators that possess a prescribed stability margin is parametrized by means of a generalized Riccati-type equation. This is applied to designing servo systems, which enables us to specify the stability margins at the above two portions. We can improve the output response of the system by the proposed design procedure and the effect is ascertained by an example. The integrity at the error channel is also investigated.     

Purification and characterization of sea squirt alpha-N-acetylgalactosaminidase

Sea squirt alpha-N-acetylgalactosaminidase was purified to homogeneity. Its molecular weight was estimated to be approximately 160,000 by gel filtration and 40,000 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing condition. The chromatographic and electrophoretic behaviors indicated that the enzyme was composed of four subunits. The optimum pH of the enzyme reaction was about 4.0 at 37 degrees C, while the enzyme was stable in the range of pH 5.0 to 6.0 during 4 h preincubation at 37 degrees C. Although the enzyme (0.1 unit) was stable at 0 degrees C for 30 min in the presence of 7.5 mM metal ions (Al3+, Ba2+, Ca2+, K+, Mn2+, Pb2+, Sr2+, and Zn2+), almost 40% of the enzyme activity was lost in the presence of Cu2+, Hg2+, monoiodoacetic acid, and EDTA. The enzyme hydrolyzed aryl N-acetyl-alpha-D-galactosaminide as well as GalNAcalpha1(-->4GalNAcalpha1-->)n 4GalNAc-p-aminobenzoic acid ethyl ester (ABEE) (n = 1-4), but GalNAcalpha1-->4GalNAc-ABEE only scarcely. Furthermore, an allergenic pentasaccharitol ABEE derivative, GalNAcalpha1-->2Fucalpha1-->3(GalNAcbeta1-->4) GlcNAcbeta1-->2(3-acetoamido-3-deoxy)L-threose-ABEE, the minimum structural unit for the sea squirt allergenicity was hydrolyzed to 95 mol% for 72 h incubation with the enzyme. The enzyme could be utilized as a powerful tool for the structural analyses of the carbohydrate epitopes of the sea squirt allergen molecules.     

Approaches to antiviral chemotherapy for acute respiratory infections

This paper describes a telemedicine system for diabetic patients management, presenting its architecture, the technical solutions adopted and the methodologies on which it is based. The system, designed to provide decision support in a distributed environment, is composed of two modules, a Patient Unit and a Medical Unit, connected by telecommunication services. We outline how the two modules can interact to perform an effective monitoring and a cooperative control of glucose metabolism. In particular, we detail the data analysis tasks performed by the two units and how the results are exploited to assist patients and physicians in revising and adjusting the therapeutic protocol. We will finally describe the current prototypical implementation of the system that uses HTTP as the communication protocol and HTML pages as the graphical user interface.     

Production and properties of phytase and acid phosphatase from a sake koji mold, Aspergillus oryzae

We identified three types of acid phosphatase (ACP-I, ACP-II, and ACP-III) produced by Aspergillus oryzae in a submerged culture using only phytic acid as the phosphorous substrate. The optimum pH for the activities of the three enzymes was in the range of 4.5 to 5.5. Analysis of the substrate specificities of these enzymes revealed that ACP-I and ACP-III were acid phosphatases, and ACP-II was a phytase. These enzymes were produced during different periods of mycelial growth: ACP-II was produced during the early phase of cultivation (around 24 h), and ACP-I was produced between 24 to 72 h. ACP-III was detected after the production of ACP-I and ACP-II had ceased. The release of phosphate from phytic acid was expected to be due to the cooperative hydrolysis of these enzymes.