Peptide and protein mimetics inhibiting amyloid beta-peptide aggregation

Protein misfolding is related to some fatal diseases including Alzheimer's disease (AD). Amyloid beta-peptide (Abeta) generated from amyloid precursor protein can aggregate into amyloid fibrils, which are known to be a major component of Abeta deposits (senile plaques). The fibril formation of Abeta is typical of a nucleation-dependent process through self-recognition. Moreover, during fibrillization, several metastable intermediates such as soluble oligomers, including Abeta-derived diffusible ligands (ADDLs) and Abeta*56, are produced, which are thought to be the most toxic species to neuronal cells. Therefore, construction of molecules that decrease the Abeta aggregates, including soluble oligomers, protofibrils, and amyloid fibrils, might further our understanding of the mechanism(s) behind fibril formation and enable targeted drug discovery against AD. To this aim, various peptides and peptide derivatives have been constructed using the "Abeta binding element" based on the structural models of Abeta amyloid fibrils and the mechanisms of self-assembly. The central hydrophobic amino acid sequence, LVFF, of Abeta is a key sequence to self-assemble into amyloid fibrils. By combination of this core sequence with a hydrophobic or hydrophilic moiety, such as cholic acid or aminoethoxy ethoxy acetic acid units, respectively, good inhibitors of Abeta aggregation can be designed and synthesized. A peptide, LF, consisting of the sequence Ac-KQKLLLFLEE-NH 2, was designed based on the core sequence of Abeta but with a simplified amino acid sequence. The LF peptide can form amyloid-like fibrils that efficiently coassemble with mature Abeta1-42 fibrils. The LF peptide was also observed to immediately transform the soluble oligomers of Abeta1-42, which are thought to pose toxicity in AD, into amyloid-like fibrils. On the other hand, two Abeta-like beta-strands with a parallel orientation were embedded in green fluorescent protein (GFP), comprised of a beta-barrel structure, to make pseudo-Abeta beta-sheets on its surface. The GFP variant P13H binds to Abeta1-42 and inhibits Abeta1-42 oligomerization effectively in a substoichiometric condition. Thus, molecules capable of binding to Abeta can be designed based on structural similarities with the Abeta molecule. The peptide and protein mimetics based on the structural features of Abeta might lead to the development of drug candidates against AD.     

Starting method of a superconducting generator in a combined‐cycle power plant

In the combined‐cycle power plant generators are started by using the igniting arrangement up to the ignition rotational speed of the gas turbine. On the other hand, in the case of using the superconducting generator, it is difficult to apply the igniting arrangement used to generate electricity on the combined cycle for the structure as is. We examined the induction motor starting method for the superconducting generator by using the 70‐MW‐class quick‐response excitation superconducting model generator and the VVVF power supply. From the examination, we confirmed the ability to raise the rotational speed from 6 to 360 rpm. Moreover, it was found to be able to start 200‐MW‐class superconducting generators by the induction motor starting method with the analysis. © 2007 Wiley Periodicals, Inc. Electr Eng Jpn, 160(2): 30– 38, 2007; Published online in Wiley InterScience ( www.interscience. wiley.com ). DOI 10.1002/eej.20283     

A Nifedipine Coground Mixture with Sodium Deoxycholate. II. Dissolution Characteristics and Stability

Nifedipine is a poorly water soluble drug that demonstrates low bioavailability. In a previous study, a coground mixture of nifedipine with sodium deoxycholate (DCNa), a bile salt, immediately produced colloidal particles when dispersed in water. In this study, the effect of the weight fraction of DCNa, grinding time, dissolution media, and storage conditions on colloidal particle formation in solution was investigated. The coground mixture was prepared with a vibration rod mill, and its solid state was characterized using powder X-ray diffraction. A laser diffraction particle size analyzer was used to determine the particle size distribution curve in water. The size of particles formed in solution decreased with an increase in the weight fraction of DCNa and grinding time. A nifedipine-DCNa (1 : 2 w/w) mixture coground for 30 min was used in the experiments. Colloidal particle formation from the coground mixture was also observed in dissolution media of water and a pH 6.8 buffer solution at 37°C. Most precipitates passed through a filter with a pore size of 0.8 μm, but the particle size distribution in water was different from that in the pH 6.8 buffer solution. DCNa exhibited not only micellar solubilization for drug crystals, but also a retarding effect on drug crystal growth in a supersaturated solution. The latter effect could serve to form colloidal particles in solution. When stored under 75% relative humidity at 40°C for 1 month, the amorphous coground mixture crystallized, and the particle size in water markedly increased. Therefore, the weight fraction of DCNa, grinding time, dissolution media, and humidity during storage influence the dissolution characteristics of nifedipine from a coground mixture.     

Epitaxial growth of titanium oxide thin films on MgO(100) single-crystal substrates by reactive deposition methods

We synthesized titanium oxide thin films on MgO(100) single-crystal substrates by two reactive deposition methods and compared the structures of the thin films formed by these methods. In one method (pulsed-molecular-beam deposition method), molecular oxygen is supplied to the substrates by using a pulsed-molecular-oxygen beam source and deposition of one unit layer of titanium and subsequent supply of molecular oxygen are repeatedly performed. In the other method (radical beam deposition method), atomic oxygen is irradiated to the substrates by using an atomic oxygen beam generated by the radical beam source and irradiation of the atomic oxygen and deposition of titanium are simultaneously performed. In the case of the pulsed-molecular-beam deposition method, the crystal structure was changed by increasing the number of oxygen pulses supplied from the beam source. We found that the crystal structure of titanium oxide depended on the composition ratio of O:Ti in the film. The maximum ratio of O:Ti attainable by this method was 1.85, and at this ratio, (100)-oriented pseudorutile was formed. In the case of the radical beam deposition method, (100)-oriented anatase was formed below the titanium deposition rate of 0.10 nm/s and pseudorutile (TiO_2−δ) was formed above 0.15 nm/s. The pseudorutile structure synthesized on this experiment was very stable in air. We concluded that the crystal structure of the pseudorutile is a new crystal structure of titanium oxide.     

Purification, characterization, and steady-state kinetics of a meta-cleavage compound hydrolase from Pseudomonas fluorescens IPO1

2-Hydroxy-6-oxo-7-methylocta-2,4-dienoate (6-isopropyl-HODA) hydrolase (CumD), an enzyme of the cumene biodegradation pathway encoded by the cumD gene of Pseudomonas fluorescens IP01, was purified to homogeneity from an overexpressing Escherichia coli strain. SDS-polyacrylamide gel electrophoresis and gel filtration demonstrated that it is a dimeric enzyme with a subunit molecular mass of 32 kDa. The pH optima for activity and stability were 8.0 and 7.0-9.0, respectively. The enzyme exhibited a biphasic Arrhenius plot of catalysis with two characteristic energies of activation with a break point at 20 degrees C. The enzyme has a K(m) of 7.3 microM and a k(cat) of 21 s(-1) for 6-isopropyl-HODA (150 mM phosphate, pH 7.5, 25 degrees C), and its substrate specificity covers larger C6 substituents compared with another monoalkylbenzene hydrolase, TodR Unlike TodF, CumD could slightly hydrolyze 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate (6-phenyl-HODA). A mutant enzyme as to a putative active site residue, S103A, had 10(5)-fold lower activity than that of the wild-type enzyme.     

Preparation of Sm-Ru bimetallic alloy films on Ru(0001) surface by vapour-deposition and annealing

Sm-Ru intermetallic surface alloy films were prepared by vacuum deposition and annealing of rare earth Sm on single crystal Ru(0001) surface. The Ru 3 d and Sm 3 d core level spectra clearly show the formation of surface alloy layers. XPS measurements on surface alloy film revealed an induced peak in the Ru 3 d region at lower binding energy by 1 eV compared to the bulk Ru (elemental) suggesting an electronic effect of alloying and Sm-Ru bond formation. The Sm 3 d _5/2 photoemission peak of Sm film consists of strong features characteristic of Sm(II) with electron configuration 4 f ⁶ (5 d 6 s ) ² and Sm(III) with electron configuration 4 f ⁵ (5 d 6 s ) ³ .It is observed that the Sm(II) feature decreases in intensity upon alloy formation with surface Ru atoms. Oxidation of these films with carbon monoxide indicates alloy breakdown due to the oxidation of Sm atoms selectively. Alloy oxidation also shows a clear shift of Sm 3 d _5/2 feature.     

Preparation of 6FDA-based polyimide composite membrane by CVDP process

Preparation of polyimide composite membranes by a chemical vapor deposition and polymerization process (CVDP) was studied for the development of pervaporation or gas separation membranes. Hexafluoroisopropylidene-2,2-bis [phethalic acid anhydride] (6F-dianhydride) (6FDA) and 4,4′-diaminodiphenyl ether (ODA) were used as monomers and were simultaneously deposited on an asymmetric polyimide membrane in vacuum of 10⁻⁶ Torr. The deposited layer of the monomers was converted to polyimide by heating at 250°C at 3 h in an ordinary vacuum oven, and its separation performance for water-ethanol and CO₂−N₂ systems was characterized.     

软件需求定量分析及其映射的模糊层次分析法

在用数量化理论3类(quantification theory of type 3,简称QT3)定量地分析软件需求的基础上,以质量功能展开(quality function deployment,简称QFD)中的质量屋(house of quality,简称HOQ)系列矩阵为纲领,基于由模糊技术改进后的模糊层次分析法(fuzzy analytic hierarchy process,简称FAHP),提出了一种软件需求定量分析及其向设计实现过程模糊映射的方法.将该方法具体应用于CD-R/RW光盘刻录机软件的开发过程,其有效性得到了验证.