Recognition and Excision Properties of 8‐Halogenated‐7‐Deaza‐2′‐Deoxyguanosine as 8‐Oxo‐2′‐Deoxyguanosine Analogues and Fpg and hOGG1 Inhibitors

Cellular DNA continuously suffers various types of damage, and unrepaired damage increases disease progression risk. 8‐Oxo‐2′‐deoxyguanine (8‐oxo‐dG) is excised by repair enzymes, and their analogues are of interest as inhibitors and as bioprobes for study of these enzymes. We have developed 8‐halogenated‐7‐deaza‐2′‐deoxyguanosine derivatives that resemble 8‐oxo‐dG in that they adopt the syn conformation. In this study, we investigated their effects on Fpg (formamidopyrimidine DNA glycosylase) and hOGG1 (human 8‐oxoguanine DNA N‐glycosylase 1). Relative to 8‐oxo‐dG, Cl‐ and Br‐deaza‐dG were good substrates for Fpg, whereas they were less efficient substrates for hOGG1. Kinetics and binding experiments indicated that, although hOGG1 effectively binds Cl‐ and Br‐deaza‐dG analogues with low K_m values, their lower k_cat values result in low glycosylase activities. The benefits of the high binding affinities and low reactivities of 8‐oxo‐dG analogues with hOGG1 have been successfully applied to the competitive inhibition of the excision of 8‐oxoguanine from duplex DNA by hOGG1.     

Pollution of montane soil with Cu, Zn, As, Sb, Pb, and nitrate in Kanto, Japan

Soil cores and rainwater were sampled under canopies of Cryptomeria japonica in four montane areas along an atmospheric depositional gradient in Kanto, Japan. Soil cores (30 cm in depth) were divided into 2-cm or 4-cm segments for analysis. Vertical distributions of elemental enrichment ratios in soils were calculated as follows: (X/Al)_i/(X/Al)_BG (where the numerator and denominator are concentration ratios of element-X and Al in the i- and bottom segments of soil cores, respectively). The upper 14-cm soil layer showed higher levels of Cu, Zn, As, Sb, and Pb than the lower (14-30 cm) soil layer. In the four areas, the average enrichment ratios in the upper 6-cm soil layer were as follows: Pb (4.93) ≥ Sb (4.06) ≥ As (3.04) > Zn (1.71) ≥ Cu (1.56). Exogenous elements (kg/ha) accumulated in the upper 14-cm soil layer were as follows: Zn (26.0) > Pb (12.4) > Cu (4.48) ≥ As (3.43) ≥ Sb (0.49). These rank orders were consistent with those of elements in anthropogenic aerosols and polluted (roadside) air, respectively, indicating that air pollutants probably caused enrichment of these elements in the soil surface layer. Approximately half of the total concentrations of As, Sb, and Pb in the upper 14-cm soil layer were derived from exogenous (anthropogenic) sources. Sb showed the highest enrichment factor in anthropogenic aerosols, and shows similar deposition behavior to NO₃⁻, which is a typical acidic air pollutant. There was a strong correlation between Sb and NO₃⁻ concentrations in rainfall (e.g., in the throughfall under C. japonica: [NO₃⁻] = 21.1 [dissolved Sb], r = 0.938, p < 0.0001, n = 182). Using this correlation, total (cumulative) inputs of NO₃⁻ were estimated from the accumulated amounts of exogenous Sb in soils, i.e., 16.7 t/ha at Mt. Kinsyo (most polluted), 8.6 t/ha at Mt. Tsukuba (moderately polluted), and 5.8 t/ha at the Taga mountain system (least polluted). There are no visible ecological effects of these accumulated elements in the Kanto region at present. However, the concentrations of some elements are within a harmful range, according to the Ecological Soil Screening Levels determined by the U.S. Environmental Protection Agency.     

Numerical computation on the control of aerial flow by the magnetizing force in gravitational and nongravitational fields

Two-dimensional numerical computations were carried out in order to examine the effect of magnetizing force for the air in a cylindrical container with thermal and magnetic field gradients. In a gravitational field, the air was driven by both gravitational and magnetizing forces, and flow pattern and the heat transfer rate greatly depended on the axial position of the coil. Moreover, when the magnetizing and gravitational forces cancel out each other, convection became almost quiescent. On the other hand, the aerial flow was induced by the magnetizing force even in a nongravitational field, and the air behaved like an electrically conducting fluid.     

Role of transverse temperature gradients in the generation of lamellar eutectic solidification patterns

In directional solidification, a sample is pulled in an externally imposed temperature gradient. When the pulling direction and the temperature gradient are not perfectly aligned, a transverse temperature gradient is generated in the sample. We investigate the dynamics of lamellar eutectic patterns, both by experimental observations and by numerical simulations, and find that it is dramatically affected by a transverse gradient. Whereas, in its absence, the labyrinth patterns that are formed in the initial stage of solidification persist over the entire duration of the experiments, a transverse temperature gradient induces a drift of the pattern which rapidly generates a regular array of lamellae. The drift speed is found to be consistently larger than expected from the normal growth hypothesis, both in simulations and experiments.     

Effect of surface roughness and surface modification of indium tin oxide electrode on its potential response to tryptophan

The effect of surface modification of indium tin oxide (ITO) electrode on its potential response to tryptophan was investigated for ITO substrates with different surface roughness. It was found that a small difference in surface roughness, between ∼1 and ∼2 nm of R_a evaluated by atomic force microscopy, affects the rest potential of ITO electrode in the electrolyte. A slight difference in In:Sn ratio at the near surface of the ITO substrates, measured by angle-resolved X-ray photoelectron spectrometry and Auger electron spectroscopy is remarkable, and considered to relate with surface roughness. Interestingly, successive modification of the ITO surface with aminopropylsilane and disuccinimidyl suberate, of which essentiality to the potential response to indole compounds we previously reported, improved the stability of the rest potential and enabled the electrodes to respond to tryptophan in case of specimens with R_a values ranging between ∼2 and ∼3 nm but not for those with R_a of ∼1 nm. It was suggested that there are optimum values of effective work function of ITO for specific potential response to tryptophan, which can be obtained by the successive modification of ITO surface.     

Improved efficiency of Al0.36Ga0.64As solar cells with a ppnn structure

Improvement of efficiency of Al_0.36Ga_0.64As solar cells is advanced in two aspects of minority-carrier lifetime: reduction of majority-carrier concentration in the emitter and base layers, and reduction of deep levels in the back-surface-field (BSF) layer. A pp⁻n⁻n structure is proposed to optimize the use of the effect of reduced majority-carrier concentration, and its effectiveness verified in a preparatory experiment on Al_0.3Ga_0.7As solar cells. A very poor photoluminescence (PL) decay time (below 0.3 ns) of a BSF layer heavily doped with Si becomes 14-fold longer when Se is applied to the dopant instead of Si, resulting in an improvement of the external quantum efficiency near the absorption edge. These two aspects of this study lead to the realization of 16.6% efficiency under 1-sun, AM 1.5 global conditions with an Al_0.36Ga_0.64As solar cell.     

Fullerene Production in Tons and More: From Science to Industry

In the last decade, application of fullerenes has been proposed actively in a wide range of areas, and recent developments suggest that many of those applications are to be practical technologies. However, there has been no large-scale production enterprise for commercial usage of fullerenes. High production cost and limited availability of fullerenes have been the main obstacle in the development of the Fullerene Market. Improved flame-based technology leads to the most feasible process for mass production of fullerenes, since it is a continuous process and uses inexpensive hydrocarbons as its starting materials. In May 2003, we started fullerene production in tons and more to supply fullerenes with reasonable price as practical materials for industries.     

Tubulin Photoaffinity Labeling with Biotin‐Tagged Derivatives of Potent Diketopiperazine Antimicrotubule Agents

NPI‐2358 ( 1 ) is a potent antimicrotubule agent that was developed from a natural diketopiperazine, phenylahistin, which is currently in Phase I clinical trials as an anticancer drug. To understand the precise recognition mechanism of tubulin by this agent, we focused on its potent derivative, KPU‐244 ( 2 ), which has been modified with a photoreactive benzophenone structure, and biotin‐tagged KPU‐244 derivatives ( 3 and 4 ), which were designed and synthesized for tubulin photoaffinity labeling. Introduction of the biotin structure at the p′‐position of the benzophenone ring in 2 exhibited reduced, but significant biological activities with tubulin binding, tubulin depolymerization and cytotoxicity in comparison to the parent KPU‐244. Therefore, tubulin photoaffinity labeling studies of biotin‐derivatives 3 and 4 were performed by using Western blotting analysis after photoirradiation with 365 nm UV light. The results indicated that tubulin was covalently labeled by these biotin‐tagged photoprobes. The labeling of compound 4 was competitively inhibited by the addition of diketopiperazine 1 or colchicine, and weakly inhibited by the addition of vinblastine. The results suggest that photoaffinity probe 4 specifically recognizes tubulin at the same binding site as anticancer drug candidate 1 , and this leads to the disruption of microtubules. Probe 4 serves well as a useful chemical probe for potent antimicrotubule diketopiperazines, much like phenylahistin, and it also competes for the colchicine‐binding site.