Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase inhibitors: 2-oxetanones with a meta-substituent on the benzene ring in the side chain

Isosteric side chain analogs of 3a were synthesized and tested for inhibitory activities towards 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and upon cholesterol production in Hep G2 cells and in mouse liver. It became clear that the lipophilic substituent on the aromatic ring and the terminal hydrophilic group in the side chain were important in the enhancement of activity. 4-[2-(3-n-Hexyloxyphenyl)ethyl]-3-hydroxy-methyl-2-oxetanone (5a) showed equivalent inhibitory activity in vivo to that of 1233A.     

The dominant negative effect of a kinase-defective insulin receptor on insulin-like growth factor-I-stimulated signaling in Rat-1 fibroblasts

To study the interaction between insulin receptor (IR) and insulin-like growth factor-I (IGF-I) receptor (IGF-IR) tyrosine kinases, we examined IGF-I action in Rat-1 cells expressing a naturally occurring tyrosine kinase-deficient mutant IR (Asp 1048 IR). IGF-I normally stimulated receptor autophosphorylation, IRS-I phosphorylation, and glycogen synthesis in cells expressing Asp 1048 IR. However, the Asp 1048 IR inhibited IGF-I-stimulated thymidine uptake by 45% to 52% and amino acid uptake (aminoisobutyric acid [AIB]) by 58% in Asp 1048 IR cells. Furthermore, IGF-I-stimulated tyrosine kinase activity toward synthetic polymers, Shc phosphorylation, and mitogen-activated protein (MAP) kinase activity was inhibited. The inhibition of mitogenesis and AIB uptake was restored with the amelioration of the impaired tyrosine kinase activity and Shc phosphorylation by the introduction of abundant wild-type IGF-IR in Asp 1048 IR cells. These results suggest that the Asp 1048 IR causes a dominant negative effect on IGF-IR in transmitting signals to Shc and MAP kinase activation, which leads to decreased IGF-I-stimulated DNA synthesis, and that the kinase-defective insulin receptor does not affect IGF-I-stimulated IRS-I phosphorylation, which leads to the normal IGF-I-stimulated glycogen synthesis.     

Amphotericin B-induced resistance to Pseudomonas aeruginosa infection in mice

We evaluated the effects of amphotericin B (AmB) against Pseudomonas aeruginosa (P. aeruginosa) infection in mice. Pretreatment with 2 mg/kg of AmB 24 hours before infection significantly increased the survival rates of mice intraperitoneally infected with either P. aeruginosa or Escherichia coli. To evaluate the mechanism of this AmB-induced resistance to infection, we conducted a number of experiments. Peritoneal macrophages exposed in vitro to AmB showed superior bactericidal activity compared to that of control macrophages. Interleukin-1 production by peritoneal macrophages from mice pretreated with 2 mg/kg of AmB was significantly higher than that in control mice. Serum tumor necrosis factor level after intravenous injection of P. aeruginosa was also higher in mice pretreated with 2 mg/kg of AmB than in control mice. These data indicate that AmB induces resistance to P. aeruginosa in mice. Furthermore AmB-induced activation of peritoneal macrophages and their production of interleukin-1 and tumor necrosis factor appeared to play important roles in this phenomenon.     

Interactivity in broadcasting and its application to ISDB services

Given that broadcasting is generally characterized by real-time one-way transmission, it is an essential task for this medium to provide interactivity developed in the fields of telecommunications and computers when introducing multimedia into a broadcasting system. This paper discusses how to use and implement interactivity in broadcasting services. It further discusses what functions are required for introducing interactivity into broadcasting. The practicality of interactive services in one-way broadcasting transmission is clarified. A simulation system of ISDB services to evaluate viewers' human interface was developed. The results of experiments using the simulation system are also discussed. It is shown that user-friendly ISDB services can be achieved     

Measurement method for dispersion states of filler particles in particulate composite materials by macroscopic permittivity

A new model for estimating macroscopic permittivity was proposed to predict filler particles' dispersion states in a particulate composite material. In the model, the estimation targets are randomly packed composite materials. The composite materials were represented as a cluster of unit cells. A proposed layer structure model connected the unit cells. The macroscopic permittivity was estimated by calculating the synthetic capacity of the cluster. The proposed model was validated by comparisons between estimated and measured macroscopic permittivity of several particulate composite materials. It was also identified that the proposed model could estimate the permittivity more accurately than an existing theoretical equation's one due to considering the effects for the dispersion states of filler particles. Furthermore, it was indicated that the proposed model could also estimate the dispersion states of filler particles by the measured permittivity. The applicability of the method was confirmed by comparisons between estimated and experimental dispersion states of filler particles.     

Ad-Molecule Orientation and Thermo- and Photo-Induced Surface-Aligned Desorption

Two-directional N₂ desorption was found in N₂O decomposition on Pd(110) at 100–160 K. It collimated ±43° off the surface normal in the (001) plane. A hot-atom-assisted model is proposed for N₂ desorption. Inclined O₂ desorption was simulated by hot atoms emitted from aligned oxygen molecules on stepped Pt(112) at 308 nm irradiation.     

High- Purity inp grown by hydride vpe technique with impurity gettering by indium source and oxygen

Purification methods for vapor-grown InP layers have been investigated for the hydride (In/HCl/PH₃/H₂) process. The carrier concentration of non-doped InP layers was found to be decreased with a commensurate increase in mobility by increasing the indium source temperature and by introducing a small amount (a few ppm) of oxygen into the growth region. At 910 δC of In source temperature with 1.2 ppm oxygen, a 77 K mobility as high as 40,000 cm²/v.sec (3,480 cm²/v.sec at 300K) with a carrier concentration as low as 5x10¹⁴cm^?3 (8×10¹⁴cm^?3 at 300K) was obtained. Photoluminescence efficiency was also found to be improved by the above-mentioned two methods. Mass spectroscopy analysis of used In metal showed a few ppm impurity contamination, such as Sn, Fe and Cu, which were hardly detected in raw 6’9-purity In metal before the growth experiment. These results indicate that the In source has a gettering effect for impurities in input gases, mainly HC1 from a cylinder, and the effect was enhanced by increasing the In source temperature. The oxygen may play a role in the conversion to non-volatile oxides of residual impurities and hence a reduction in the impurity incorporation.     

Wet electrolytic oxidation of organic pollutants in wastewater treatment

Wet electrolytic oxidation of organics in the presence of electrolytes and externally added oxygen gas was investigated for wastewater treatment. The experimental apparatus was a 300 ml electrolytic batch autoclave operated mainly at 250 C and 7 MPa. The results showed that the presence of halide ions such as chlorides and bromides strongly catalyses the conversion of pollutant organic compounds to innocuous compounds such as CO₂ and water. The addition of external oxygen gas in wet electrolytic oxidation of acetic acid strongly suppressed the cathodic evolution of hydrogen gas and demonstrated a TOC removal profile with an apparent current efficiency higher than 100% for high concentration acetic acid solutions.     

Induced technological change and the timing of public R&D investment in the Japanese electricity sector considering a two-factor learning curve

The UNFCCC has stated that energy policies and measures to address climate change should be cost-effective to ensure global benefits at the lowest possible cost. To mitigate the bulk of carbon emission from the electricity sector, a large market penetration of renewable energy technologies with as low cost as possible is a key research topic. The energy-related R&D policy in Japan aims to achieve a green economy. In our study, based on this context, we demonstrated how to optimize the timing of public R&D investment within the framework of a bottom-up partial equilibrium model. The developed optimization model represents the Japanese electricity sector and minimizes the total system cost subject to an accumulated carbon emission constraint. Our main research focus is the role of R&D activity, especially in the innovation stage of renewable technologies. We employ a two-factor learning curve and quantify the impact of the learning effect on the dynamic diffusion of major renewable technologies. The study shows a dynamic technology transition in the Japanese electricity sector and the optimized R&D investment schedule for each renewable technology. With the first-best energy policy, an R&D budget of more than 2000 million USD would be allocated to PV in 2050, which corresponds to 45% of the energy-related Japanese R&D budget in 2050. Because some have criticized the uncertainty problems with dynamic simulations and learning models, supplemental sensitivity analyses are included.