Multiple target screening method for robust and accurate in silico ligand screening

We developed a new in silico multiple target screening (MTS) method, based on a multi-receptor versus multi-ligand docking affinity matrixes, and examined its robustness against changes in the scoring system. According to this method, compounds in a database are docked to multiple proteins. The compounds among these proteins that are likely bind to the target protein are selected as the members of the candidate-hit compound group. Then, the compounds in the group are sorted into descending order using the docking score: the first (n-th) compound is expected to be the most (n-th) probable hit compound. This method was applied to the analysis of a set of 142 receptors and 142 compounds using a receptor-ligand docking program, Sievgene [Y. Fukunishi, Y. Mikami, H. Nakamura, Similarities among receptor pockets and among compounds: analysis and application to in silico ligand screening, J. Mol. Graphics Modelling, 24 (2005) 34-45], and the results demonstrated that this method achieves a high hit ratio compared to uniform sampling. We prepared two new scores: the DeltaG score, designed to reproduce the protein-ligand binding free energy, and the hit-optimized score, designed to maximize the hit ratio of in silico screening. Using the Sievgene docking score, DeltaG score and hit-optimized score, the MTS method is more robust than the multiple active-site correction scoring method [G.P.A. Vigers, J.P. Rizzi, Multiple active site corrections for docking and virtual screening, J. Med. Chem., 47 (2004) 80-89].     

Experimental evaluation of teleoperation system with force-free control and visual servo control by human operator perception

This research considers the teleoperation of an articulated robot arm by means of force-free control and visual servo control (VSC) over communication channels using the Internet technology. A semi-autonomous type teleoperation system contains a human supervisory control and VSC schemes and switches one scheme to another for accomplishing the required task accurately. The main investigation is carried out to find how it effectively improves the accuracy and the effectiveness of the teleoperation after provision of a visual feedback channel to the system. The system accuracy, effectiveness, repeatability and handleability based on the human operator’s skills and operator’s cognitive aspects are evaluated using experimental results and statistical data analysis. Effectiveness of the statistical analysis is assured by increasing the number of experiment data and assuming environmental factors, and implicit variables maintain to be unchanged. Correlation coefficients are calculated to find out how controlled input parameters are related to the successful output given by the system.     

通过功率MOSFET的顶面温度估算结点温度

通常,MOSFET数据手册中提供的结点温度数据只限于结到引脚和结到环境之间的热阻。虽然可根据定制条件使用一些工具来实现更精确的热仿真,但有时只需要时间来运行仿真就可以了。     

Trends of internet auctions and agent-mediated Web commerce

Electronic Commerce (EC) is a promising field for applying agent and Artificial Intelligence technologies. In this article, we give an overview of the trends of Internet auctions and agent-mediated Web commerce. We describe the theoretical backgrounds of auction protocols and introduce several Internet auction sites. Furthermore, we describe various activities aimed toward utilizing agent technologies in EC and the trends in standardization efforts on agent technologies. Makoto Yokoo, Ph.D.: He received the B.E. and M.E. degrees in electrical engineering, in 1984 and 1986, respectively, from the University of Tokyo, Japan, and the Ph.D. degree in information and communication engineering in 1995 from the University of Tokyo, Japan. He is currently a distinguished technical member in NTT Communication Science Laboratories, Kyoto, Japan. He was a visiting research scientist at the Department of Electrical Engineering and Computer Science, the University of Michigan, Ann Arbor, from 1990 to 1991. His current research interests include multi-agent systems, search, and constraint satisfaction. Satoru Fujita, D.Eng.: He received his B.E. and M.E. degrees in electronic engineering from the University of Tokyo in 1984 and 1986, respectively. He also received his D.Eng. from the University of Tokyo in 1989 for his research on context comprehension in natural language understanding. He joined NEC Corporation in 1989, and is now a principal researcher of Internet Systems Research Laboratories of NEC. He is engaged in research on mobile agents, distributed systems and Web services.     

A machine discovery from amino acid sequences by decision trees over regular patterns

This paper describes a machine learning system that discovered a “negative motif”, in transmembrane domain identification from amino acid sequences, and reports its experiments on protein data using PIR database. We introduce a decision tree whose nodes are labeled with regular patterns. As a hypothesis, the system produces such a decision tree for a small number of randomly chosen positive and negative examples from PIR. Experiments show that our system finds reasonable hypotheses very successfully. As a theoretical foundation, we show that the class of languages defined by decesion trees of depth at mostd overk-variable regular patterns is polynomial-time learnable in the sense of probably approximately correct (PAC) learning for any fixedd, k≥0.     

Diabetes mellitus-associated glycogen storage hepatomegaly: report of a case and review of the Japanese literature

A huge hepatomegaly was seen in a 30-yr-old female diabetic who was treated with high dose of insulin for her uncontrollable food ingestion. The liver function at the peak of the hepatic enlargement showed a moderate increase of transaminases, alkaline phosphatase, and gamma-glutamyl transpeptidase. The histology of the enlarged liver revealed PAS-positive granules in enlarged hepatocytes, indicating the presence of massive glycogen storage. On admission, she was maintained under a calorie-restricted diet and received approximately 15 to 20 units per day of insulin supplement. At one month after admission, a marked shrinkage of her enlarged liver and restoration of normal liver function were observed concomitantly with the return of fair control of her blood sugar levels. One year later, she had an episode of diabetic ketoacidosis which subsequently was treated with a continuous low-dose infusion of insulin; however, she showed neither hepatomegaly nor liver dysfunction during this episode. There have been 20 cases reported of Japanese diabetics with marked hepatomegaly, in whom the vigorous treatment of diabetic ketoacidosis with insulin seemed to be a trigger of the enlarged liver. This has occurred mostly in patients with insulin-dependent diabetes mellitus. We present a case of non-insulin-dependent diabetes mellitus with glycogen storage hepatomegaly, presumably due to excessive insulin supplements. This suggests that glycogen storage hepatomegaly in diabetics may not be only due to an acute restoration from diabetic ketoacidosis, but may also be due to an overinsulinization in an attempt to maintain a euglycemic condition in spite of excess food intake.     

Preferential supporting of potassium carbonate around the peripheral region of activated carbon fibre

Abstracts are not published in this journal This revised version was published online in November 2006 with corrections to the Cover Date.     

Friction and adhesion properties of fluorocarbon polymer thin films prepared by magnetron sputtering

Fluorocarbon polymer thin films were deposited onto a SUS302 substrate with a poly(tetrafluoroethylene) (PTFE) target by three different types of r.f. magnetron sputtering systems with strong, weak and unbalanced magnetic fields. Friction and adhesion properties of these polymer thin films were evaluated.Friction coefficient of polymer thin films prepared with strong magnetic field, unbalanced magnetron and without magnetron (r.f. sputtering) was almost the same level, however, that prepared with the weak magnetic field was slightly lower than those of other thin films. Wear durability of polymer thin film increased with increase of the magnetic field.Adhesion strength between these thin films and SUS302 substrate and shear stress were measured by SAICAS. Both of the adhesion strength and shear stress of polymer thin films prepared with r.f. sputtering (without magnetron) were slightly higher than those prepared by magnetron sputtering systems.     

Effect of pre-deformation on the precipitation process and magnetic properties of Fe–Cu model alloys

The effect of pre-deformation on the precipitation process and magnetic properties of Fe–Cu model alloys was investigated. These specimens simulate irradiation embrittlement of nuclear reactor pressure vessel (RPV) steels. Fe–1 wt%Cu alloys with and without pre-deformation in solid-state solution were thermally aged at 773 K for various times and the evolution of hardness, conductivity, and microstructure were investigated. Pre-deformation enhanced Cu precipitation and caused precipitation at dislocations. The coercive force tended to decrease for the pre-deformed specimen and the underlying mechanism is discussed. The results obtained are related to the magnetic characteristics of irradiated RPV steels.     

Construction of a subnanosecond time-resolved, high-resolution ultraviolet resonance Raman measurement system and its application to reveal the dynamic structures of proteins

A subnanosecond time-resolved ultraviolet (UV) resonance Raman system has been developed to study protein structural dynamics. The system is based on a 1 kHz Nd:YLF-pumped Ti:Sapphire regenerative amplifier with harmonic generation that can deliver visible (412, 440, 458, and 488 nm) and UV (206, 220, 229, and 244 nm) pulses. A subnanosecond (0.2 ns) tunable near-infrared pulse from a custom-made Ti:Sapphire oscillator is used to seed the regenerative amplifier. A narrow linewidth of the subnanosecond pulse offers the advantage of high resolution of UV resonance Raman spectra, which is critical to obtain site-specific information on protein structures. By combination with a 1 m single spectrograph equipped with a 3600 grooves/mm holographic grating and a custom-made prism prefilter, the present system achieves excellent spectral (<10 cm(-1)) and frequency (approximately 1 cm(-1)) resolutions with a relatively high temporal resolution (<0.5 ns). We also report the application of this system to two heme proteins, hemoglobin A and CooA, with the 440 nm pump and 220 nm probe wavelengths. For hemoglobin A, a structural change during the transition to the earliest intermediate upon CO photodissociation is successfully observed, specifically, nanosecond cleavage of the A-E interhelical hydrogen bonds within each subunit at Trpalpha14 and Trpbeta15 residues. For CooA, on the other hand, rapid structural distortion (<0.5 ns) by CO photodissociation and nanosecond structural relaxation following CO geminate recombination are observed through the Raman bands of Phe and Trp residues located near the heme. These results demonstrate the high potential of this instrument to detect local protein motions subsequent to photoreactions in their active sites.