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.     

梦露大厦,密西沙加,加拿大

<正>现代主义有一句有名的宣言:建筑是居住的机器。但是我们必须发问,在机器及其所代表的社会基础发生了如此剧变的今天,我们应该怎样理解建筑?如果建筑正在远离工业,那么她更应该表达什么内容?与北美其他迅速发展的近郊城市一样,加拿大多伦多地区的密西沙加市也一直在努力寻找着自己的性格和定位。我们认为这是一个机会,她没有必     

Identification and Characterization of D‐Succinylase,and a Proposed Enzymatic Method for D‐Amino Acid Synthesis

Chiral amino acids are important intermediates for the pharmaceutical industry. We have developed a novel one‐pot enzymatic method for D ‐amino acid synthesis by the dynamic kinetic resolution of N‐succinyl‐dl ‐amino acids using D ‐succinylase (DSA) and N‐succinylamino acid racemase (NSAR, EC 4.2.1.113). The DSA from Cupriavidus sp. P4‐10‐C, which hydrolyzes N‐succinyl‐D ‐amino acids enantioselectively to their corresponding D ‐amino acids, was identified for the first time by screening soil microorganisms. Subsequently, the DSA gene was cloned and overexpressed in Escherichia coli. DSA was shown to comprise two subunits with molecular masses of 26 kDa and 60 kDa. Additionally, the NSAR gene from Geobacillus stearothermphilus NCA1503, which racemizes N‐succinylamino acids, was also cloned and overexpressed in E. coli. The highly purified DSA and NSAR prepared from each recombinant E. coli were characterized and used for D ‐amino acid synthesis. A one‐pot enzymatic method converted 100 mM N‐succinyl‐dl ‐phenylalanine to D ‐phenylalanine in 91.1% conversion with 86.7% ee. This novel enzymatic method may be useful for the industrial production of many D ‐amino acids.

     

A Coupled MPM-FDM Analysis Method for Multi-Phase Elasto-Plastic Soils

The Material Point Method (MPM), as proposed by Sulsky et al. (1994), has been developed to simulate large deformations and failure evolution involving different material phases in a single computational domain. A continuum body is divided into a finite number of subregions represented by Lagrangian material points, while the governing equations are formulated and solved with the Eulerian grid. Since this grid can be chosen arbitrarily, mesh tangling does not appear in the MPM. To design a simple but robust spatial discretization procedure, the MPM is coupled with the finite difference method (FDM) in the present study for simulating fully and partially saturated elasto-plastic soil responses based on the simplified three-phase method. Governing equations for the soil skeleton and the pore fluid are discretized by the MPM and FDM, respectively. Soil-water coupled analyses for fully saturated soils and seepage-deformation coupled analyses for unsaturated soils are performed, and the potential of the proposed method is demonstrated via numerical examples.     

Highly unsaturated fatty acid might act as an antioxidant in emulsion system oxidized by azo compound

Now it is recognized that DHA is oxidatively stable fatty acid compared with linoleic acid (LA) in emulsified system, although DHA is oxidatively unstable in a bulk system. In fact, an emulsified mixture of DHA and LA behaves as in a bulk system, namely the oxidative stability of DHA becomes lower than that of LA. Therefore, in this study, tridocosahexaenoate (DDD) and glycerol trilinoleate (LLL) were separately emulsified using TritonX-100 as an emulsifier and DDD emulsion was mixed with the oxidizing LLL emulsion using a water-soluble radical initiator, 2,2'-azobis(2-aminopropane) dihydrochloride. As a result, DHA suppressed the oxidation of LA, while DHA was not significantly oxidized. This suppression ability was examined using glycerol trieicosapentaenoate, glycerol trilinolenate, or glycerol trioleate instead of DDD and it was found that this activity was increased with the increasing number of double bonds in the structure. Furthermore, the same type of experiment was carried out using a lipid-soluble radical initiator, 2,2'-azobisisobutyronitrile and the similar result was obtained. These results indicated that a highly polyunsaturated fatty acid might act as an antioxidant in an emulsion system oxidized by an azo compound.     

Metal‐Free Growth of Nanographene on Silicon Oxides for Transparent Conducting Applications

Conventional methods to prepare large‐area graphene for transparent conducting electrodes involve the wet etching of the metal catalyst and the transfer of the graphene film, which can degrade the film through the creation of wrinkles, cracks, or tears. The resulting films may also be obscured by residual metal impurities and polymer contaminants. Here, it is shown that direct growth of large‐area flat nanographene films on silica can be achieved at low temperature (400 °C) by chemical vapor deposition without the use of metal catalysts. Raman spectroscopy and TEM confirm the formation of a hexagonal atomic network of sp²‐bonded carbon with a domain size of about 3–5 nm. Further spectroscopic analysis reveals the formation of SiC between the nanographene and SiO₂, indicating that SiC acts as a catalyst. The optical transmittance of the graphene films is comparable with transferred CVD graphene grown on Cu foils. Despite the fact that the electrical conductivity is an order of magnitude lower than CVD graphene grown on metals, the sheet resistance remains 1–2 orders of magnitude better than well‐reduced graphene oxides.     

Simultaneous Perturbation Stochastic Approximation with Norm‐Limited Update Vector

This paper addresses the convergence of simultaneous perturbation stochastic approximation (SPSA) with a norm‐limited update vector. We first illustrate an unstable solution of the standard SPSA algorithm which motivates the consideration of a modified version, where the norm of the update vector is limited to a certain value. Next, a result on the almost‐sure convergence is presented by reducing the modified algorithm into the standard SPSA algorithm and restricting the probability distribution for the perturbation to a Bernoulli distribution. Finally, we apply the modified algorithm to a system identification problem to demonstrate its performance.     

Reinforcement of polypropylene by cellulose microfibers modified with polydopamine and octadecylamine

Cellulose microfibers (CMFs) having surfaces modified with polydopamine (PDPA) and octadecylamine (ODA) were prepared, and their reinforcing abilities for polypropylene (PP) were investigated. The PDPA coating was made via self-polymerization of dopamine (P-CMF), and subsequent alkylation was conducted by the reaction with ODA (OP-CMF). The modified CMFs exhibited improved dispersibility in the PP matrix due to the reduced hydrophilicity. The OP-CMF/PP composite prepared by batch mixing had a higher tensile modulus compared to that for the pure PP and composites with unmodified CMFs. However, excess alkylation lowered the tensile modulus, and the presence of an optimal degree of alkylation was demonstrated. The CMF/PP-IM composites fabricated by injection molding exhibited improved tensile properties compared to those prepared by batch mixing. Both the tensile modulus and yield stress were increased by increasing the CMF content and improved by the surface modification of the CMFs.     

Development of gap sensing system for narrow gap laser welding

Narrow gap welding with an oscillation laser beam is one of the effective processes for thick plate welding. To put this welding process into practical manufacturing, a groove-sensing system using image processing for narrow gap welding with an oscillation laser beam is used. This developed system uses still images of the weld zone taken by a coaxial CMOS camera. It can recognize the position of the groove wall by analysing the brightness distribution in the still image. It can then control the oscillation width and the laser-irradiated area by calculating the groove width and the groove centre position. Some narrow gap welding experiments were performed to evaluate the performance of the developed system. The results revealed that the developed system is effective for narrow gap welding with an oscillation laser beam. Using this system, the narrow gap groove can be welded even if the groove width has changed during the welding process.     

Effects of casting solvents on characteristics of organic EL devices containing poly(l-glutamate) as hole-transport material

The characteristics of EL devices containing α-helical poly(l-glutamate) and having a carbazole side chain (PCELG) were found to strongly depend on the casting solvents. Among EL devices fabricated using chlorine-containing casting solvents such as 1,2-dichloroethane (DCE), 1,1,2,2-tetrachloroethane (TCE), chloroform (CHCl₃), and monochlorobenzene (?-Cl), the EL device fabricated using the DCE solvent exhibited the maximum luminance (65.8 cd/m²). The difference between the threshold voltages of the devices ranged up to 6.0 V, despite their fabrication by using solutions with the same composition ratio. The maximal efficiency of the devices fabricated using the DCE solvent was found to be 20 times greater than that of the devices fabricated using TCE solvents. A comparison of the current densities and voltages among devices fabricated using different casting solvents at their maximal efficiencies showed that the maximal efficiencies tended to significantly increase in the order TCE < CHCl₃ < DCE solvents at similar voltages (～15 V), despite a lowering of the current density. The current density was considered to be directly related to the number of carriers injected into the device. The above-mentioned observations suggested that the maximal efficiency in these devices was not the hole and electron injection efficiencies, but the values of some parameters subsequent to carrier injection, such as the recombination rate, amount of excitons generated, and the diffusion length.