Computer-aided design of a factor Xa inhibitor by using MCSS functionality maps and a CAVEAT linker search

We have investigated a new approach to efficiently find a novel inhibitor against a serine protease (i.e. an activated coagulation factor X, FXa) by using de novo design programs and the X-ray crystal structure of the target enzyme. FXa is a coagulant enzyme that generates thrombin (a serine protease) and participates in both intrinsic and extrinsic coagulation pathways. We adopted multiple copy simultaneous search (MCSS) and CAVEAT linker search techniques, which disclosed a novel FXa inhibitor (T01312) consisting of two binding moieties (the benzamidinyl and adamantyl groups) and a linker unit (the carboxybenzylamine group). The inhibitory activity of T01312 against FXa was determined to be a small K(i)-value of 48nM, which is two orders of magnitude smaller than that against thrombin. An X-ray crystal analysis of T01312 complexed with trypsin (an analogue of FXa) and docking studies of T01312 with trypsin and FXa showed that: (i) the benzamidinyl group is a predominant binding moiety in the anionic pocket (S1 site) with an asparatic acid residue; (ii) a hydrophobic pocket (S4 site) is the binding site of the adamantyl group; (iii) the carboxylate group of the linker contributes to the selectivity for FXa against thrombin. Thus, the combination of the knowledge of the X-ray crystal structure of the target molecule with MCSS and CAVEAT linker search techniques proved to be an effective hit-finding method that does not require the screening of huge compound libraries.     

A novel spacer‐free panel structure and glass for FEDs

Abstract— A new design for an FED envelope, composed of box‐shaped front glass, sheet‐like rear glass, and metal members, has been devised. This design structure is effective in reducing tensile stress induced by vacuum at the sealing points. Also, a new glass composition, a new physical tempering method, and a lead‐free hermetic sealing material have been developed. As a result, a novel lightweight spacer‐free panel structure for FEDs has been developed by integrating these new technologies. It will assist in maximizing the essential advantages of FED such as high image quality, high reliability, and low cost.     

Slow Unfolding of Monomeric Proteins from Hyperthermophiles with Reversible Unfolding

Based on the differences in their optimal growth temperatures microorganisms can be classified into psychrophiles, mesophiles, thermophiles, and hyperthermophiles. Proteins from hyperthermophiles generally exhibit greater stability than those from other organisms. In this review, we collect data about the stability and folding of monomeric proteins from hyperthermophilies with reversible unfolding, from the equilibrium and kinetic aspects. The results indicate that slow unfolding is a general strategy by which proteins from hyperthermophiles adapt to higher temperatures. Hydrophobic interaction is one of the factors in the molecular mechanism of the slow unfolding of proteins from hyperthermophiles.     

Wordline voltage generating system for low-power low-voltage flashmemories

A low-power wordline voltage generating system is developed for low-voltage flash memories. The limit for the stand-by current including the operation current for the band-gap reference and the stand-by wordline voltage generator is discussed. The system was implemented on a 1.8-V 32-Mb flash memory fabricated with a 0.25-μm flash memory process and achieved with very low stand-by current of 2 μA typically, and high operating frequency of 25 MHz in read operation at 1.8 V. A low-voltage level shifter with high-speed switching is also proposed     

Organic Analysis of Peridotite Rocks from the Ashadze and Logatchev Hydrothermal Sites

This article presents an experimental analysis of the organic content of two serpentinized peridotite rocks of the terrestrial upper mantle. The samples have been dredged on the floor of the Ashadze and Logatchev hydrothermal sites on the Mid-Atlantic Ridge. In this preliminary analysis, amino acids and long chain n-alkanes are identified. They are most probably of biological/microbial origin. Some peaks remain unidentified.     

High-speed DCFL circuits with very shallow junction GaAs JFETs

High-speed DCFL (direct-coupled FET logic) circuits implemented with advanced GaAs enhancement-mode J-FETs are discussed. A divide-by-four static frequency divider operates at up to 6 GHz with a power consumption of 20 mW/flip-flop. A high channel concentration of more than 1×10¹⁸ cm^-3 together with a very shallow junction depth of less than 30 nm for the p⁺-gate results in a transconductance as high as 340 mS/mm at a gate length of 0.8 μm. Open-tube diffusion of Zn using diethylzinc and arsine makes it possible to control a very shallow p⁺-layer less than 10 nm thick. The propagation delay time, as measured with a ring oscillator, was 22 ps/gate with a power consumption of 0.42 mW/gate     

On a fast reactor cycle scheme that incorporates a thoria-based minor actinide-containing cermet fuel

A fast reactor cycle scheme that incorporates a thoria-based minor actinide-containing cermet fuel is given. The present cermet fuel consists of an oxide solid solution of Th and minor actinides and Mo-inert matrix. It has been proposed as a high-performance device that can enhance minor actinide incineration in a fast reactor cycle. It is used in an independent small sub-cycle, whereby dedicated cycle technologies are adopted. Two-step reprocessing process was proposed for the present cermet fuel; it consists of a pre-removal of Mo-inert matrix and an actinide recovery. A preliminary test for the pre-removal of Mo-inert matrix was carried out using a surrogate cermet fuel. Burnup characteristics of a fast reactor core loaded with the cermet fuel were investigated by using neutronic calculation codes. It was revealed that a heterogeneous composition of Mo-inert matrix in inner and outer cores may lead to an effective transmutation of minor actinides and a flattened power density. It was concluded that the present cermet fuel was potentially promising as a high-performance incineration device of minor actinides for fast reactors.     

A 60-ns 16-Mbit DRAM with a minimized sensing delay caused by bit-line stray capacitance

Discusses three new techniques that were implemented in a CMOS 60-ns 16-Mbit DRAM device. (1) A two-step half-conductive-state technique was used to control the conductivity of latch transistors, thus minimizing the time delay caused by bit-line stray capacitance. (2) The 'split-block row decoder' technique enabled the decoder layout within the 2.9- mu m cell pitch required for 16-Mbit integration density. The three transistors that are required per word line were split into two and one, placed on both sides of each word line, and alternately reversed on each side of the 2-Mbit cell array. (3) Additional dummy cells were added to the vacant spaces resulting from use of a twisted bit-line architecture, which reduces stray capacitance between adjacent bit lines. The overhead space required for all the dummy cells and twisted bit lines was thus held at 2.6 percent of the entire chip area.<>     

Improvement of dry float–sink separation of smaller sized spheres by reducing the fluidized bed height

In this study, the influence of the fluidized bed height on the float–sink of different sized spheres in a gas–solid fluidized bed was investigated. Fluidized beds with heights h = 200, 150, 100 and 50 mm were prepared using a cylindrical column of inner diameter = 290 mm and a mixture of zircon sand and iron powder as the fluidized medium. Float–sink experiments were carried out using density adjusted spheres of diameter D_sp = 40, 30, 20 and 10 mm. It was found that the float–sink performance at D_sp ?20 mm is not affected by the height of the bed, and the sharpness of separation (the density range where spheres neither float nor sink completely) is less than or equal to 200 kg/m³. In the case of D_sp = 10 mm, the sharpness of separation is a larger value (1100 kg/m³ at h = 200 mm), whereas it decreases with decreasing h and is 400 kg/m³ at h = 50 mm. The fluctuation of the surface height of the fluidized bed was visually recorded. The fluctuation is reduced by reducing h. The fluctuation vs. h correlates with the sharpness of separation at D_sp = 10 mm vs. h. These results indicate that the dry float–sink separation of smaller sized spheres is improved as the fluctuation of fluidized bed surface is decreased by reducing the fluidized bed height.