Chemistry,Properties, and in Vitro and in Vivo Applications of 2′‐O‐Methoxyethyl‐4′‐thioRNA,a Novel Hybrid Type of Chemically Modified RNA

We report the synthesis, properties, and in vitro and in vivo applications of 2′‐O‐methoxyethyl‐4′‐thioRNA (MOE‐SRNA), a novel type of hybrid chemically modified RNA. In its hybridization with complementary RNA, MOE‐SRNA showed a moderate improvement of T_m value (+3.4 °C relative to an RNA:RNA duplex). However, the results of a comprehensive comparison of the nuclease stability of MOE‐SRNA relative to 2′‐O‐methoxyethylRNA (MOERNA), 2′‐O‐methyl‐4′‐thioRNA (Me‐SRNA), 2′‐O‐methylRNA (MeRNA), 4′‐thioRNA (SRNA), and natural RNA revealed that MOE‐SRNA had the highest stability (t_1/2>48 h in human plasma). Because of the favorable properties of MOE‐SRNA, we evaluated its in vitro and in vivo potencies as an anti‐microRNA oligonucleotide against miR‐21. Although the in vitro potency of MOE‐SRNA was moderate, its in vivo potency was significant for the suppression of tumor growth (similar to that of MOERNA).     

Dispersion Behavior of Barium Titanate Nanoparticles Prepared by Using Various Polycarboxylic Dispersants

The effects of the polycarboxylic dispersant structures on the crystallinity and sedimentation behavior of prepared BaTiO₃ nanoparticles were analyzed using four types of dispersants—ethylenediaminetetraacetic acid dipotassium salt (EDTA), trans -aconitic acid (TAA), ammonium acrylate–methyl acrylate co-polymer (PAA50), and sodium polyacrylate (PAA100). In the case of EDTA and TAA, the adsorbed ratio of the dispersants on BaTiO₃ nanoparticles was relatively low, and only slight improvement of sedimentation behavior was observed. On the other hand, in the case of PAA50 and PAA100, the adsorbed ratio was high, and the sedimentation behavior was gratefully improved. Next, in order to analyze the relationships among the additive amount of polycarboxylic dispersants, crystallinity, and sedimentation behavior, various amounts of PAA100 or PAA50 were treated in the synthesis solution. The sedimentation behavior of BaTiO₃ nanoparticles improved with increasing amounts of PAA100 and PAA50 while their crystal phase became amorphous. Adding PAA50 at a molar ratio of COO⁻/Ba²⁺=0.266 resulted in BaTiO₃ nanoparticles with the best dispersion stability in an aqueous media.     

Phylogenetic diversity of microbial communities associated with the crude-oil, large-insoluble-particle and formation-water components of the reservoir fluid from a non-flooded high-temperature petroleum reservoir

The diversity of microbial communities associated with non-water-flooded high-temperature reservoir of the Niibori oilfield was characterized. Analysis of saturated hydrocarbons revealed that n-alkanes in crude oil from the reservoir were selectively depleted, suggesting that crude oil might be mildly biodegraded in the reservoir. To examine if any specific microorganism(s) preferentially attached to the crude oil or the other components (large insoluble particles and formation water) of the reservoir fluid, 16S rRNA gene clone libraries were constructed from each component of the reservoir fluid. The clones in the archaeal libraries (414 clones in total) represented 16 phylotypes, many of which were closely related to methanogens. The bacterial libraries (700 clones in total) were composed of 49 phylotypes belonging to one of 16 phylum-level groupings, with Firmicutes containing the greatest diversity of the phylotypes. In the crude-oil- and large-insoluble-particle-associated communities, a Methanosaeta-related phylotype dominated the archaeal sequences, whereas hydrogenotrophic methanogens occupied a major portion of sequences in the library of the formation-water-associated community. The crude-oil associated bacterial community showed the largest diversity, containing 35 phylotypes, 16 of which were not detected in the other bacterial communities. Thus, although the populations associated with the reservoir-fluid components largely shared common phylogenetic context, a specific fraction of microbial species preferentially attached to the crude oil and insoluble particles.     

Prospective Validation of High-Shear Wet Granulation Process by Wet Granule Sieving Method. II. Utility of Wet Granule Sieving Method

The general utility of a method for determination of high-shear wet granulation end point by monitoring the wet granule particle size distribution was evaluated. Wet granulation was conducted in a 25-liter high-shear mixer using four model drugs with different solubilities and particle sizes (ethenzamide, unmilled and milled acetaminophen, and antipyrine). For each drug formulation, its wet granule particle size fraction and target range for granulation end point determination were selected based on the tablet characteristics that are known to be influenced by the wet granulation process. Granules manufactured under different conditions (i.e., different main and chopper blade speeds and binder supplying rate) but manufactured to the same granulation end point determined by the selected fraction and range showed very similar granule characteristics and subsequently very similar tabler characteristics. From the fact that there was a good correlation between the wet and dry-sized granule particle size distributions even if the drying method was changed from fluid-bed drying to vacuum drying, the general application of the end point determining method was verified. Further, the method was shown to be sensitive to the critical granulation parameters for granulation progression and to be very capable of determining the granulation extent. Thus, it was suggested that the method is applicable to various drugs and formulations for determination of wet granulation end point.     

Molecular design of hybrid tumor necrosis factor-alpha III: polyethylene glycol-modified tumor necrosis factor-alpha has markedly enhanced antitumor potency due to longer plasma half-life and higher tumor accumulation

We have reported that chemical modification of tumor necrosis factor-alpha (TNF-alpha) with polyethylene glycol (PEG) markedly increases its antitumor potency without any adverse side effects. MPEG-TNF-alpha, especially, in which 56% of the lysine amino groups of TNF-alpha are coupled with PEG, exhibits 100-fold more antitumor activity in vivo than native TNF-alpha in the Meth-A murine sarcoma model. In this study, we investigated the pharmacokinetics of PEG-modified TNF-alpha with various molecular sizes to clarify the mechanisms of the enhanced antitumor potency of MPEG-TNF-alpha. The plasma half-lives of modified TNF-alpha increased with increasing molecular size. The decreased plasma clearance of modified TNF-alpha was partially caused by the shielding effect of the proteolytic sites in TNF-alpha by the attached PEG and the decreased transport from blood to various tissues. Almost all native TNF-alpha was uniformly distributed to the kidney and reticuloendothelial system within 1 hr of an intravenous administration, and rapidly disappeared from these tissues at 3 hr. However, very little native TNF-alpha was transported into the tumor. The absolute distributed amount and distribution profile of modified TNF-alpha to tissues other than the tumor were the same as those of native TNF-alpha, whereas the plasma levels of the modified TNF-alpha were higher than plasma levels of the native TNF-alpha. The tumor distribution of modified TNF-alpha was markedly enhanced compared with native TNF-alpha and gradually increased over time. About 9-fold more MPEG-TNF-alpha was distributed to the tumor than native TNF-alpha. Thus, we found that the marked increase in the antitumor potency of PEG-modified TNF-alpha resulted from the enhanced blood residency and tumor accumulation. The antitumor effect of MPEG-TNF-alpha against sarcoma-180 other than Meth-A fibrosarcoma was also about 100 times greater than that of native TNF-alpha when systemically administered. The optimal PEGylation of TNF-alpha facilitated its antitumor potency and MPEG-TNF-alpha may be useful systemic antitumor therapeutic drug.     

Running-wheel avoidance learning in rats (Rattus norvegicus): Effects of contingencies and comparisons of different strains.

In Experiment 1, we showed that active- and passive-avoidance responding in a running wheel was learned because of the avoidance contingency. In Experiment 2, strain differences among four commercially bred rats were assessed in an active-avoidance paradigm. Wistar, Donryu, and Fischer rats learned faster than Sprague-Dawleys. In Experiment 3, learning in a multiple active/passive avoidance schedule was examined, and both components of this task were learned. This multiple schedule was used to investigate strain differences in selectively bred rats in Experiments 4 and 5. Tsukuba low-emotional (TLE) rats responded more than Tsukuba high-emotional (THE) rats in both components. However, discrimination of passive components was better in THE than in TLE rats. Syracuse high-avoidance rats were superior in the active component, whereas Syracuse low-avoidance rats showed superior performance in the passive component. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chemical association in symbiosis sterol donors in planthoppers

The role of intracellular symbionts contributing to their host has been investigated in the planthoppers,Nilaparvata lugens Stal andLaodelphax striatellus Fallen. We have found that the isolated yeastlike symbionts, identified as a member of the genusCandida, from the host's egg produce ergosterol when cultured. A comparative study of sterols in the cultured symbionts, the host insects, aposymbiotic host insects, and dietary plants demonstrated that ergosterol produced in the symbiotes is provided to the host insects and possibly transformed in the host insects into cholesterol via 24-methylenecholesterol. The conversion of injected 24-methylenecholesterol-d₃ into cholesterol has been shown in the brown planthopper (N. lugens).     

Enhancement of electrochemical ion/electron-transfer reaction at solid|liquid interface by polymer coating on solid surface

Controlling the ion/electron-transfer reaction at the electrode|electrolyte (solid/liquid) interface is a necessary and vitally important point for improving the operation of various electrochemical devices. In this paper, we propose a polymer coating technique which enhances the Li⁺ ion-transfer reaction at the LiCoO₂|electrolyte interface, and confirm the effects of the polymer coating by cyclic voltammetry (CV) and AC impedance techniques. The results from the experiments indicated that the application of an F-introduced polymer on the LiCoO₂ (LCO) surface decreased the activation barrier for Li⁺ ion transfer. Besides the electrochemical studies, the present computational results indicated that the Li⁺ exchange process between two states, which are both solved with ethylene carbonate (EC) and coordinated with an F-introduced polymer, might occur due to the close energy levels of Li⁺ stability. Accordingly, we inferred that the transition state of this exchange process promotes the observed decrease in activation energy for the interfacial Li⁺-transfer reaction.     

Implementation and performance evaluation of a communication-avoiding GMRES method for stencil-based code on GPU cluster

The Journal of Supercomputing - In this study, a communication-avoiding generalized minimum residual method (CA-GMRES) is implemented on a hybrid CPU–GPU cluster, targeted for the performance...     

Simultaneous Quantification of Plant Glyceroglycolipids Including Sulfoquinovosyldiacylglycerol by HPLC–ELSD with Binary Gradient Elution

Membrane lipids of photosynthetic organisms consist of glycerophospholipids and glyceroglycolipids. We investigated a method for the simultaneous quantitative analysis of neutral and acidic lipids using HPLC–ELSD, and quantified monogalactosyldiacylglycerol (MGDG), digalactosyldiacylglycerol (DGDG) and sulfoquinovosyldiacylglycerol (SQDG). Ten complex lipid classes were separated with a binary gradient system consisting of chloroform and methanol–acetone–water–acetic acid (30:60:9:1, v/v/v/v) with 0.3% triethylamine (pH 4), and were eluted within 16 min. The contents of SQDG in ten edible plants ranged from 3 to 101 mg/100 g, and were positively correlated to the neutral glyceroglycolipids contents.