Development of sustained-release tablets containing sodium valproate: in vitro and in vivo correlation

We have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting C_max was only 20% higher than the fasting C_max. An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug.     

High Precision,Electrochemical Detection of Reversible Binding of Recombinant Proteins on Wide Bandgap GaN Electrodes Functionalized with Biomembrane Models

We report a novel hybrid charge sensor realized by the deposition of phospholipid monolayers on highly doped n‐GaN electrodes. To detect the binding of recombinant proteins with histidine‐tags, lipid vesicles containing chelator lipids were deposited on GaN electrodes pre‐coated with octadecyltrimethoxysilane monolayers. Owing to its optical transparency, GaN allows the confirmation of the fluidity of supported membranes by fluorescence recovery after photo‐bleaching (FRAP). The electrolyte‐(organic) insulator‐semiconductor (EIS) setup enables one to transduce variations in the surface charge density ΔQ into a change in the interface capacitance ΔC _p and, thus, the flat‐band potential ΔU _FB. The obtained results demonstrate that the membrane‐based charge sensor can reach a high sensitivity to detect reversible changes in the surface charge density on the membranes by the formation of chelator complexes, docking of eGFP with histidine tags, and cancellation by EDTA. The achievable resolution of ΔQ ≥ 0.1 μC/cm² is better than that obtained for membrane‐functionalized p‐GaAs, 0.9 μC/cm², and for ITO coated with a polymer supported lipid monolayer, 2.2 μC/cm². Moreover, we examined the potential application of optically active InGaN/GaN quantum dot structures, for the detection of changes in the surface potential from the photoluminescence signals measured at room temperature.     

Bending fatigue strength of case-carburized helical gears with large helix angles up to 40 degrees

Case-carburizing of helical gears with large helix angles may form too large hardened layers near the tooth width end on the acute angle side (ACUTE-END), and adversely affect the bending fatigue strength. We investigated the bending fatigue strength of casecarburized helical gears with large helix angles up to approximately 40° through a bending fatigue test, hardness test, and residual stress measurement. We found that the case-carburizing formed large hardened layers near ACUTE-END, reduced the compressive residual stress near ACUTE-END, and restricted the improvement of the bending fatigue strength in a meshing state where tooth root stress became large near ACUTE-END. Based on the obtained bending fatigue limits, we revealed that ISO 6336-3:2006 overestimated the rate of increase of the permissible circumferential loads for helix angles exceeding approximately 30°, and ISO/DIS 6336-3:2018 underestimated this rate for helix angles near 30°.

     

Evaluation of photo-induced cellular damage using photoautotrophic cultures of puk-bung hairy roots as a sensing tool

In photoautotrophic cultures of pak-bung hairy roots, strong light irradiation (22 W/m²) increased the content of reactive oxygen species (ROS) in the cells, resulting in chlorophyll (Chl) degradation and DNA injury. The Chl degradation rate, R_D, can be used as a parameter to measure the cellular damage caused by photo-induced stress. The presence of the antioxidants ascorbic acid, chlorogenic acid or catechin reduced the R_D, while lowering the content of ROS and moderating the DNA injury.     

Supramolecular Ligands for Histone Tails by Employing a Multivalent Display of Trisulfonated Calix[4]arenes

Post‐translational modification of histone tails plays critical roles in gene regulation. Thus, molecules recognizing histone tails and controlling their epigenetic modification are desirable as biochemical tools to elucidate regulatory mechanisms. There are, however, only a few synthetic ligands that bind to histone tails with substantial affinity. We report CA2 and CA3, which exhibited sub‐micromolar affinity to histone tails (especially tails with a trimethylated lysine). Multivalent display of trisulfonated calix[4]arene was important for strong binding. CA2 was applicable not only to synthetic tail peptides but also to endogenous histone proteins, and was successfully used to pull‐down endogenous histones from nuclear extract. These findings indicate the utility of these supramolecular ligands as biochemical tools for studying chromatin regulator protein and as a targeting motif in ligand‐directed catalysis to control epigenetic modifications.     

A hydrogen production method using latent heat of liquefied natural gas

In recent years, fuel cell electrical vehicles have offered promise of improving the urban environment. In particular, hydrogen‐fueled FCEVs have been considered for urban use because of their excellent characteristics such as short start‐up time, high responsiveness, and zero emissions. On the other hand, as far as hydrogen production is concerned, large amounts of CO₂ are exhausted into the atmosphere by the process of LNG reforming. In our research, we studied the utilization of LNG latent heat for hydrogen gas production as well as the liquefied hydrogen process. CO₂ capture in the liquid or solid state from hydrogen gas production by LNG was also studied. The results of our research show that the latent heat of LNG is very effective in cooling hydrogen gas for the conventional hydrogen liquefaction process. However, the latent heat LNG is not available for the LNG reforming process. If we want to use LNG latent heat for this process, we must develop a new hydrogen gas production process. In this new method, both hydrogen and CO₂ are cooled directly by LNG, and CO₂ is removed from the reforming gas. In order to make this method practical, we must develop a new type of heat exchanger to prevent solid CO₂ from interfering with performance. © 2004 Wiley Periodicals, Inc. Electr Eng Jpn, 147(4): 32–42, 2004; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.10299     

Bending fatigue strength of case-carburized helical gears (In the case of large helix angles)

Case-carburizing enlarges the depth of the hardened layer at the tooth width end on the acute angle side of helical gears. For the helical gears with large helix angles (Exceeding 25°), this hardened layer may lower their bending fatigue strength. Therefore, we investigated the influence of this hardened layer on their bending fatigue strength through the bending fatigue tests. Our results suggest that this hardened layer might reduce the case-carburizing’s effect to enhance their bending fatigue strength. Thus, using only the maximum tooth root stress would be inadequate for evaluating their bending fatigue strength, and it would be necessary to consider the relationship between the hardened layer and the tooth root stress distribution (Especially, the stress applied at the tooth width end on the acute angle side) from the beginning of meshing to the end.     

Binding of small mono- and oligomeric integrin ligands to membrane-embedded integrins monitored by surface plasmon-enhanced fluorescence spectroscopy

We recently developed a binding assay format by incorporating native transmembrane receptors into artificial phospholipid bilayers on biosensor devices for surface plasmon resonance spectroscopy. By extending the method to surface plasmon-enhanced fluorescence spectroscopy (SPFS), sensitive recording of the association of even very small ligands is enabled. Herewith, we monitored binding of synthetic mono- and oligomeric RGD-based peptides and peptidomimetics to integrins alphavbeta3 and alphavbeta5, after having confirmed correct orientation and functionality of membrane-embedded integrins. We evaluated integrin binding of RGD multimers linked together via aminohexanoic acid (Ahx) spacers and showed that the dimer revealed higher binding activity than the tetramer, followed by the RGD monomers. The peptidomimetic was also found to be highly active with a slightly higher selectivity toward alphavbeta3. The different compounds were also evaluated in in vitro cell adhesion tests for their capacity to interfere with alphavbeta3-mediated cell attachment to vitronectin. We hereby demonstrated that the different RGD monomers were similarly effective; the RGD dimer and tetramer showed comparable IC50 values, which were, however, significantly higher than those of the monomers. Best cell detachment from vitronectin was achieved by the peptidomimetic. The novel SPFS-binding assay platform proves to be a suitable, reliable, and sensitive method to monitor the binding capacity of small ligands to native transmembrane receptors, here demonstrated for integrins.     

Recent Development in Synthetic Strategies for Oseltamivir Phosphate

Recent developments in synthetic strategies toward an important anti-influenza drug, oseltamivir phosphate, are discussed. The importance of the drug further increased after the influenza A (H1N1) pandemic in 2009 and the emergence of the highly virulent avian influenza H5N1, which might eventually acquire the ability to spread between humans. Currently, the drug is produced in an industrial process of 11 chemical steps starting from (–)-shikimic acid, whose availability is limited due to the massive demand of the drug. Thus, many chemists have been working to develop alternative synthetic processes to produce this important drug starting from readily available materials using environmentally benign, operationally safe, and cost-effective methods. Synthetic efforts made by each group of chemists are described in this review article. The development of novel synthetic methodologies and novel reactions has had a great impact on the efficient syntheses of functional molecules, such as drugs like oseltamivir phosphate.     

Infection of the Sunagoke moss panels with fungal pathogens hampers sustainable greening in urban environments

Drought and heat tolerance of the Sunagoke moss (Racomitrium japonicum) and the low thermal conductivity of the dry moss tissue offer novel greening and insulation possibilities of roofs and walls to mitigate the heat island phenomenon in urban environments. However, damage may appear in the moss panels under humid conditions in Japan. In this study we characterized fungi associated with the damaged areas of the Sunagoke moss panels. Fungi were identified by morphology and internal transcribed spacer (ITS) sequence analysis and tested for pathogenicity on R. japonicum (Grimmiaceae) and an unrelated moss species (Physcomitrella patens; Funariaceae) under controlled conditions. Alternaria alternata, Fusarium avenaceum and Fusarium oxysporum caused severe necrosis and death, whereas Cladosporium oxysporum and Epicoccum nigrum caused milder discoloration or chlorosis in both moss species. The fungi pathogenic on moss were closely related to fungal pathogens described from cultivated vascular plants. Ammonium increased severity of fungal diseases in moss. This study demonstrated that fungi can cause economically significant diseases in cultivated moss and hamper commercial use of the moss panels unless appropriate control methods are developed. Use of a single moss clone to cover large surfaces and the air pollutants such as ammonium may increase the risk for fungal disease problems.