Screening of Inhibitors Targeting Heat Shock Protein 47 Involved in the Development of Idiopathic Pulmonary Fibrosis

Heat shock protein 47 (HSP47), a collagen-specific molecular chaperone, is causally related to fibrotic diseases, including idiopathic pulmonary fibrosis. The identification of Compounds that interfere with the HSP47-collagen interaction is essential for the development of relevant therapeutics. Herein, we prepared human HSP47 as a soluble fusion protein expressed in E. coli and established an assay system for HSP47 inhibitor screening. We screened a natural and synthetic Compound library established at Nagasaki University. Among 1023 Compounds, 13 exhibited inhibitory activity against human HSP47, of which three inhibited its function in a dose-dependent manner. Epigallocatechin-3-O-gallate, one of these three Compounds, is a typical polyphenol Compound derived from tea leaves. Structurally related Compounds were synthesized and examined for their activity, revealing a hydroxyl group at A-ring position 5 as important for its activity. The present findings provide valuable insight for the development of natural product-derived therapeutics for fibrotic diseases, including idiopathic pulmonary fibrosis.     

Probability of precision micro-machining of insulating Si3N4 ceramics by EDM

Electrical discharge machining (EDM) is used as a precision machining method for the electrically conductive hard materials with a soft electrode material. But recently we succeeded to machine on insulating material by EDM. The technology is named as an assisting electrode method. The EDMed surface is covered with the electrical conductive layer during discharge. The layer holds the electrical conductivity during discharge. For micro-EDM, the wear of tool electrode becomes lager ratio than the normal machining. So the micro-machining is extremely difficult to get the precision sample.

In this paper to obtain a fine and precise ceramics sample, some trials were carried out considering the EDM conditions, tool electrodes material and assisting electrode materials. Insulating Si₃N₄ ceramics were used for workpiece. The machining properties were estimated by the removal rate and tool wear ratio. To confirm the change of micro-machining process, the discharge waveforms were observed. The micro-machining of the Ø0.05 mm hole could be machined with the commercial sinking electrical discharge machine.     

Mechanical strengthening of Si cantilever by chemical KOH etching and its surface analysis by TEM and AFM

Mechanical strengthening of a Si cantilever by applying KOH wet etching was investigated. Two kinds of Si cantilever specimens having the different crystallographic orientations of the sidewall surfaces, i.e., Si{100} and Si{110}, were fabricated from the same SOI wafer by a Bosch process. The typical height and pitch of the scalloping formed on the sidewall were 248 and 917 nm, respectively. A 50 % KOH (40 °C) chemical wet etching was applied to increase the fracture stress of the Si cantilever. The fracture stress in the both of Si{100} and Si{110} cantilevers increased with the advance of the etching. The obtained maximum fracture stress in Si{100} and Si{110} were 4.2 and 3.7 GPa, respectively. Sidewall surface of the cantilever was analyzed to investigate the mechanical strengthening of Si cantilever by wet etching. The etched surface crystalline was analyzed by the transmission electron microscope (TEM), and confirmed that the thickness of the affected flow layer was less than 10 nm from the obtained TEM image. Then the change of the surface roughness by the KOH etching was analyzed by the atomic force microscope. The surface was smoothened with the advance of the KOH etching. The roughness value of Ra in Si{100} and Si{110} decreased to 12.1 and 37.7 nm, respectively.     

Molecular dynamics simulations of diffusion of submonolayer polar liquid lubricant films on solid surfaces

A fundamental understanding of the diffusion phenomena of submonolayer polar liquid films is important for achieving reliable lubrication between moving mechanical parts separated by a nanometer-sized gap. To acquire this understanding, we conducted molecular dynamics (MD) simulations of diffusion phenomena of submonolayer polar perfluoropolyether (PFPE) Zdol films on solid surfaces. To improve the accuracy of these simulations, we developed an all-atom model that includes hydrogen-bond potential and refined atomic charges for Zdol molecules and tested it through MD simulations of spreading of step-shaped submonolayer PFPE films. Our MD simulations reproduced the experimentally observed effects of polar end groups on the diffusion speed and molecular conformation of Zdol. We then conducted MD simulations of self-diffusion of submonolayer Zdol films; these simulations demonstrated that as the thickness of the submonolayer Zdol films decreases, molecular conformation becomes flatter and the self-diffusion coefficient decreases. These changes in molecular conformation partially explain our experimental finding that the spreading of step-shaped submonolayer polar PFPE films slows down with decreasing initial thickness.     

Moisture profiles of wheat noodles containing hydroxypropylated tapioca starch

Wheat noodles were prepared using flour to which hydroxypropylated tapioca starch was added, and the effect of this addition on the moisture distribution within the noodles during cooking was examined using a digital image processing technique. The addition of the modified starch slightly increased the moisture content and narrowed the flat distribution near the noodle surface. The distribution features reflected the changes in the water absorption behaviour caused by the properties of the modified starch and the reduction in the gluten content. Addition of the modified starch lowered Young's modulus and the energy for 99% strain of the noodles in the texture analysis to, at maximum 35% and 65%, and decreased the breakability of the noodles. These changes in the moisture distribution and textural properties have been ascribed to changes in both the state of the starch granules near the surface and the structure of the gluten network.     

Immobilization of alkaline phosphatase on magnetic particles by site-specific and covalent cross-linking catalyzed by microbial transglutaminase

Bacterial alkaline phosphatase (BAP) was site-specifically and covalently immobilized on magnetic particles (MPs) using the enzymatic reaction of microbial transglutaminase (MTG). Immobilization efficiency was affected by the chemical surface treatment of MPs and immobilized BAP exhibited more than 90% of the initial activity after 10 rounds of recycling.     

Validity of sleep log compared with actigraphic sleep-wake state

OBJECTIVE: To evaluate the efficacy and complications of external cephalic version in term (37 or more weeks) gestation. STUDY DESIGN: A case series from February 1990 until December 1994 studied 160 patients with term singleton breech presentation. External cephalic version (ECV) with prophylactic tocolysis was the method used. RESULTS: ECV was successful in 67% of the cases (107/160) overall, in 56% of the nulliparous (57/102) and 86% of the multiparous women (50/58). About 90% of those with successful ECV (96/107) had a vaginal delivery with a vertex presentation of the fetus. Emergency Caesarean section due to fetal distress was not required during or immediately after the procedure. No perinatal mortality or babies with an Apgar score less than 7 at 5 min were observed. CONCLUSIONS: ECV in term pregnancy seems to be useful and it is safe both for the mother and the fetus. It should be performed at term, with close monitoring of the fetus, and in an environment able to provide an emergency Caesarean section.     

Factors affecting the oxidative activity of laccase towards biphenyl derivatives in homogeneous aqueous-organic systems

Catalytic oxidation of biphenyl derivatives was investigated using laccase in a homogeneous aqueous-organic system. A thermostable laccase from Trametes sp. showed the highest catalytic activity for the oxidation of 4-hydroxybiphenyl (4-HB) at a reaction temperature of 60 degrees C when dimethylsulfoxide (DMSO) was employed as a co-solvent. Furthermore, the catalytic performance was successfully enhanced by the incorporation of a laccase mediator system (LMS) into the aqueous-DMSO media. The catalytic performance strongly depended on the type of mediator, and the highest activity was observed with 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as mediator, suggesting the importance of the selection of a suitable mediator. It was verified that this mediator system is applicable to the oxidation of several biphenyl derivatives with hydroxyl groups.     

Design principle of micromechanical probe with an electrostatic actuator for friction force microscopy

It is important to understand friction force in micro/nano mechanical devices both at high sliding speed and with high lateral resolution. Dual-axis friction force microscopes that can provide high lateral resolution and accuracy have been proposed; however, the sliding speed is limited by the probe scan speed. While a micro mechanical probe (MMP) with an electrostatic actuator can overcome this problem, details of probe design have not been established yet. This paper presents the principle of the mechanical design for an MMP with high force sensitivity and sufficient drive force. The dimensions of the double cantilever beam control the spring constants, resonant frequencies, and drive force. The use of an actuated MMP enables accurate friction force microscopy at high sliding speeds, which is required for the design of micro/nano mechanical devices.