Alterations in cholesterol sulfate and its biosynthetic enzyme during multistage carcinogenesis in mouse skin

A novel series of nonpeptide angiotensin II antagonists containing the acrylamide group at the 4-position of the imidazole ring was synthesized and their antagonistic activity was examined by functional assay in rabbit aorta. The acrylamide group was selected as a large lipophilic surrogate for the chloro group of EXP3174. A structure-activity relationship study of the acrylamide moiety has shown that substitution at the 4-position with the N-methyl-3,3-dimethylacrylamide group resulted in the optimal compound, 2-butyl-4-[(3,3-dimethylacryloyl)methyl-amino]-1-[[2'-(1H-tetra zol-5- yl)biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylic acid (1), which was superior to EXP3174 in vitro. Since 1 showed only poor activity against angiotensin II-induced pressor response in rats after oral administration, the carboxylic acid function of 1 was converted into prodrug esters (13). Among these, the 1-[(ethoxycarbonyl)oxy]ethyl ester (13a) showed the most potent and longest-lasting activity when given orally to rats. When administered orally to conscious furosemide-treated dogs, 13a showed an approximately 3-fold increased hypotensive activity in comparison with DuP 753. These data suggest that 13a may be an useful agent for the treatment of angiotensin II-dependent diseases, such as hypertension.     

Synchronous generator control using neural network-based nonlinear adaptive regulator

Control equipment of synchronous generators such as automatic voltage regulators, speed governors and power system stabilizers have been developed to maintain stability and to improve damping of power systems. When an operating condition changes greatly, however, such controllers may become less effective because of nonlinearity of the power system. In this paper, a nonlinear adaptive generator control system using neural networks is proposed. The proposed neurocontrol system consists of two neural networks which work as an identifier and a controller, respectively, and generates supplementary control signals to the conventional controllers. An essential feature of the proposed system is that the internal connection weights of both neural networks are adjusted adaptively so as to generate appropriate control signals for transient stability and damping enhancement in response to changes of the operating conditions and the network configuration. To investigate the control performance of the proposed neurocontrol system, digital time simulations are carried out for a one-machine infinite bus model system. As a result, it is clarified that the proposed adaptive neurocontrol system effectively improves the system damping and shows adaptability against the wide changes of the operating conditions.     

Thermal degradation characteristics of oil‐filled cable joint with extremely degraded tan δ oil

Much of oil‐filled (OF) cable has been used for a long time as 66‐ to 500‐kV extrahigh‐voltage cable. Sometimes we can see extremely degraded tan δ oil (several tens of percent of tan δ, for example) in joint boxes, etc. The values of tan δ calculated by a simple combination model of paper/oil show that the oil‐impregnated paper with such a high tan δ oil likewise has an extremely high tan δ, which must result in thermal breakdown. However, such an event has not taken place up to the present in actually operated transmission lines. This fact suggests that some mechanism for the suppression of tan δ has acted in the paper insulation impregnated with degraded tan δ oil. Therefore, we investigated in detail the tan δ characteristics of paper impregnated with extremely high tan δ oil. In addition, based on the investigation results, we developed a method for simulation of heat generation by dielectric loss in an OF cable joint (which has degraded tan δ oil). © 2011 Wiley Periodicals, Inc. Electr Eng Jpn, 178(1): 1–10, 2012; Published online in Wiley Online Library ( wileyonlinelibrary.com ). DOI 10.1002/eej.21184     

Capability of Utilizing CYP3A5 Polymorphisms to Predict Therapeutic Dosage of Tacrolimus at Early Stage Post-Renal Transplantation

While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78–1.17) vs. 0.59 (0.45–0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.     

Engineering surface and development of a new DNA micro array chip

This paper proposes a new concept of the ‘engineering surface’, which extends the conventional idea of a functional surface by combining it with micro/nano manufacturing technology. Characteristic features and possibilities of the engineering surface are discussed in detail. This paper reviews studies on micro/nano fabrication technologies for advanced materials and evaluation technology for surface function. New fabrication technologies, micro machining and nano forming, are introduced, which will be basic manufacturing processes of the engineering surface. Also, a new surface evaluation technique is introduced for the surface energy of the nano fabricated surface. Design of a new DNA micro array chip is introduced as an example of applications of the engineering surface. Controllability of surface property by nano fabrication is studied.     

Electrical and electroluminescent properties of poly(p-phenylene vinylene) LB films based LEDs using aluminum metal as the electrode

The electrical properties of poly(p-phenylene vinylene) (PPV) Langmuir-Blodgett (LB) films were investigated, wherein transparent indium-tin oxide (ITO) and aluminum (Al) were used as the electrodes. Their I–V characteristics depended strongly on the thickness of PPV LB film, and the electric conductivity of the PPV LB film was in the range of 10⁻²–10⁻¹⁵ (S/cm). Their C–V characteristics showed that the capacitance was reversibly proportional to the thickness of PPV LB film and was kept constant when the applied voltage changed from −1.0 V to +1.0 V. These results indicated that PPV LB film was an insulator in this range of applied voltage without doping. Under forward bias, yellow-green light emission was observed in PPV LB film based light emitting diodes (LEDs), the highest light emission reached more than 100 cd/m² in the case that PPV LB film was deposited for 80 layers, i.e. a ITO/PPV(80L)/Al device.     

Determination of the glass transition temperature of polymer/layered silicate nanocomposites from positron annihilation lifetime measurements

The glass transitions of acrylonitrile-butadiene rubber (NBR)/organoclay nanocomposites with various silicate contents were investigated using positron annihilation lifetime spectroscopy (PALS). The nanocomposites were prepared through melt intercalation of NBR with various concentrations of organoclay (OC30B) modified with the organic modifier, methyl tallow bis(2-hydroxyethyl) quaternary ammonium (MT2EtOH), i.e., Cloisite^® 30B. X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HR-TEM) measurements of the NBR/OC30B nanocomposites showed that the NBR chains were intercalated between the silicate layers, thereby increasing the gallery heights of the organosilicates. The glass transition temperature of NBR was determined using differential scanning calorimetry (DSC). However, it seemed to be very difficult to clearly resolve the very small differences in T_gs caused from various loading of nanosized silicate in NBR/OC30B nanocomposites. Hence, we performed positron annihilation lifetime spectroscopy (PALS) on NBR/OC30B nanocomposites containing various amounts of OC30B (1-10 wt%). Significant changes in the temperature dependencies of free volume parameters (i.e., lifetimes and intensities) were observed at the transition temperature, T_g,PALS, and the T_g,PALS values were found to increase with increasing organoclay content in the samples. These observations are consistent with PALS having a higher sensitivity in the detection of very small changes in free volume properties. The present findings thus highlight the usefulness of PALS for studying phase transition phenomena in polymeric materials with nanoscale structural variations.     

Zirconia Coating on Stainless Steel Sheets from Organozirconium Compounds

The stability and the coating characteristics of a variety of organozirconium compounds have been investigated to coat ZrO₂ films on stainless steets for the improvement of heat resistance against oxidation. Zirconium tetraoctylate and zirconium tetrakis(acetylacetonate) were found to be more stable than zirconium alkoxides in an ambient atmosphere. The ZrO₂ films from zirconium alkoxides became white and discontinuous when the thickness of the films exceeded about 200 Å (20 nm). On the other hand, transparent ZrO₂ films were obtained from zirconium tetraoctylate and zirconium tetrakis(acetylacetonate). The IR spectra of the films showed that the heat treatment at 400°C for 5 min produced organic-free ZrO₂ films. The heat resistance of stainless steel sheets against oxidation was improved by the ZrO₂ coating, depending on the film thickness.     

Novel flexible network polymers consisting of oligomeric primary polymer chains originated in the mechanistic discussion of multiallyl crosslinking polymerization

Summary It is well known that allyl monomers polymerize only with difficulty and yield polymers having low molecular weights, i.e., oligomers. Inevitably, free-radical multiallyl crosslinking polymerization provides network polymers consisting of oligomeric primary polymer chains, i.e., having abundant dangling chains. This led to the development of novel flexible network polymers such as amphiphilic network polymers (I) consisting of short primary polymer chains and long crosslink units with opposite polarities, simultaneous interpenetrating networks (II) consisting of both polyurethane (PU) and polymethacrylate (PM) networks with oligomeric primary polymer chains, and network polymers (III) consisting of centipede-type primary polymer chains. Thus, the solution copolymerizations of benzyl methacrylate with tricosaethylene glycol dimethacrylate in the presence of lauryl mercaptan yielded I consisting of nonpolar, short primary polymer chains and polar, long crosslink units. The opposite type of I was prepared by the copolymerization of 2-hydroxyethyl methacrylate, a polar monomer having a hydroxyl group, with heneicosapropylene glycol dimethacrylate, a nonpolar monomer having a poly(oxypropylene) unit. The equimolar polyaddition crosslinking reaction of poly(methyl methacrylate-co-2-methacryloyloxyethyl isocyanate) with tri(oxytetramethylene) glycol, leading to PU networks, and the free-radical crosslinking copolymerization of methyl methacrylate with tri(oxytetramethylene) dimethacrylate in the presence of CBr₄, leading to PM networks, were progressed simultaneously, providing II formed via the topological crosslink between PU and PM network structures. The post-copolymerizations of oligomeric allyl methacrylate/alkyl methacrylate precopolymers, having different amounts of pendant allyl groups and different molecular weights, with allyl benzoate/vinyl benzoate monomer mixtures were conducted to give III.