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 new algorithm for packet routing problems using chaotic neurodynamics and its surrogate analysis

We propose a new algorithm for routing packets which effectively avoids packet congestion in computer networks. The algorithm involves chaotic neurodynamics. To realize effective packet routing, we first composed a basic method by a neural network, which routes packets with shortest path information between two nodes in the computer network. When the computer network has an irregular topology, the basic routing method does not work well, because most of packets cannot be transmitted to their destinations due to packet congestion in the computer network. To avoid such an undesirable problem, we employed chaotic neurodynamics to extend the basic method. Numerical experiments show that our proposed method exhibits good performance for scale-free networks. We also analyze why the proposed routing method is effective, comparing the proposed method with several stochastic methods. We introduced the method of surrogate data, a statistical hypothesis testing which is often used in the field of nonlinear time-series analysis. Analysis of the proposed method by the method of surrogate data reveals that the chaotic neurodynamics is most effective to decentralize the packet congestion in the computer network.     

Nanoindentation as a strength probe—a study on the hardness dependence of indent size for fine-grained and coarse-grained ferritic steel

A nanoindentation hardness testing system, including an atomic-force microscope (AFM)-based nanoindentation tester and a calibration method using electrolytically polished single-crystal metals as references, was proposed. This was applied to a study of the mechanical properties of fine-grained ferritic steel (grain size of 1.2 μm) and coarse-grained ferritic steel (30 μm). An empirical function giving the macroscopic hardness for all four reference metals from the nanoindentation force curves was established. The converted Vickers hardness (HV*) of the coarse-grained steel is almost independent of the indent size. The fine-grained steel shows only HV* 130 with an indent of only 100 nm, compared with a macroscopic hardness of HV 210. The difference, HV 80, is considered to reflect the amount of grain-boundary strengthening. The critical indent size for the hardness transition seems to be around 1 μm, comparable to the grain size of the specimen. This result supports the explanation of grainboundary strengthening. It is also consistent with Pickering’s work on low-carbon steel, as the estimated locking parameter (k of 2.6×10⁵ N/m^3/2) in the Hall-Petch relationship is in good agreement with his value of 2.4×10⁵ N/m^3/2.     

Temperature Estimation and Al Content Prediction Focusing on Microstructural Change in a Thermal Barrier Coating

A superalloy with a thermal barrier coating (TBC) simulating a gas turbine blade is exposed to a high-temperature environment to develop a method for predicting the local temperature and Al content in a bond coat (BC). The Al content decreases with an increase in the test time due to the Al transport induced by the oxidation of the BC and the interdiffusion between the BC and the substrate. This brings about Al-decreased layer (ADL) at the boundary between the BC and the top coat. The thickness of the ADL increases in proportion to the square root of the test time, and the temperature dependence of the growth rate shows an Arrhenius-type behavior. Based on this relation, the local temperature of an in-service blade can be estimated by measuring the ADL thickness when the operation time is known. The Al content decreases in proportion to the ADL thickness. The prediction method of the Al content based on the relation is also presented.     

Oxidative Dehydrogenation of Propane with CO2 Over Cr/H[B]MFI Catalysts

Abstract  

Cr/silicalite-1 and Cr/H[B]MFI catalysts were prepared by the impregnation method, and Cr/H[B]MFI were further treated by steaming. The catalysts were employed for the oxidative dehydrogenation of propane to propylene with CO₂ as the oxidant. Cr/H[B]MFI showed significantly higher catalytic activity than Cr/silicalite-1, and steamed Cr/H[B]MFI was superior in the reaction stability to Cr/H[B]MFI. The nature of the supported chromium species have been characterized by a number of physicochemical techniques, such as Raman, UV–vis and NMR. It is concluded that the steaming led to the auto-reduction of some Cr⁶⁺ to Cr³⁺, and resultant Cr³⁺ species might be located near the boron center in the borosilicate framework to counterbalance the negative charge of the framework. The transformation of Cr⁶⁺ species to Cr³⁺ species, facilitated by the steaming process and the presence of boron in the catalyst, is responsible for the enhanced stability of oxidative dehydrogenation of propane to propylene with carbon dioxide as the oxidant.     

Development of multianode photomultiplier tube

We have developed a multianode photomultiplier tube (MAPMT) which has a sensitive cathode diameter of 36 mm and an anode with 88 segments. The position sensitivity of the tube was studied by using light from a LED and scintillation light from a scintillation-fiber bundle. We observed particle tracks for the first time by using a single photomultiplier tube.     

Osteoinduction by Functionally Graded Apatites of Bovine Origin Loaded with Bone Morphogenetic Protein-2

Bioresorbable and functionally graded apatites (fg-HAp) ceramics, which are characterized by gradations in crystallinity and the grain size of hydroxyapatite (HAp:Ca₁₀(PO₄)₆(OH)₂), were designed using bovine bone by the calcination and partial dissolution–precipitation method. The fg-HAp ceramics had macropores of 100–600 μm originated from spongy bone, and micropores of 10–160 nm. Fg-HAp ceramics loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2/fg-HAp) were implanted into the subcutaneous tissue of rats. Eight weeks after the implantation, the surface and bulk degradations of the fg-HAp-containing body fluid occured, and small pieces of fg-HAp were incorporated into the induced bone and fatty marrow, suggesting that osteoinduction occurred in conjunction with bone remodeling. The rhBMP-2/fg-HAp ceramics developed could become a resorbable biomimetic material with fast bioresorption and osteoinduction characteristics.     

Modified thermoelectric figure of merit estimated from enhanced mobility of [100] oriented beta-FeSi<Subscript>2</Subscript> thin film

The modification of thermoelectric figure of merit was estimated from enhanced mobility of [100] oriented beta-FeSi₂ film. beta-FeSi₂ on Si(001) substrate was prepared by molecular beam epitaxy method using an Fe source. The crystallographic orientation of beta-FeSi₂ film on Si(001) substrate was characterized by using X-ray diffraction. Using scanning electron microscopy, surface morphology and film thickness of samples were observed and estimated, respectively. The mobility of beta-FeS₂ film on Si(001) substrate were also characterized by Hall measurement at room temperature. A part of the enhancement of figure of merit was evaluated as the functions of mobility and crystallographic orientation of samples.     

Purification and characterization of an extracellular alpha-neoagarooligosaccharide hydrolase from Bacillus sp. MK03

An agarolytic bacterium was isolated from soil in Gifu prefecture, Japan, and identified as Bacillus sp. strain MK03. The strain secreted neoagarooligosaccharide hydroluse into the culture medium. The enzyme was purified 49.7-fold from the culture fluid by ammonium sulfate precipitation and anion-exchange and gel-filtration column chromatographic methods. The purified enzyme appeared as a single band on polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS)-PAGE. Estimations of the molecular mass by gel filtration and SDS-PAGE gave values of 320 kDa and 42 kDa, respectively, indicating that the enzyme is octametric. The enzyme cleaved the alpha-1,3 linkage in neoagarobiose to produce 3,6-anhydro-L-galactose and D-galactose. It also selectively cleaved the alpha-1,3 linkage at the nonreducing end in neoagarotetraose or neoagarohexaose to give 3,6-anhydro-L-galactose and agarotriose or agaropentaose. The optimum temperature and pH for the enzyme were 30 degrees C and 6.1, respectively. The N-terminal amino acid sequence showed no homology to sequences of other known neoagarooligosaccharide hydrolases and agarases.