A new series of antiallergic agents. I. Synthesis and activity of 11-(2-aminoethyl)thio-6,11-dihydrodibenz[b,e]oxepin derivatives.

A new series of 11-substituted 6,11-dihydrodibenz[b,e]oxepin derivatives was synthesized and evaluated for antiallergic activity. Convenient methods for the preparation of sulfides from alcohols were developed. Structure-activity relationships are described. Compound 7, 11-[2-(dimethylamin)ethyl]thio-6,11-dihydrodibenz[b,e] oxepin-2-carboxylic acid hydrochloride, was the most potent in the rat passive cutaneous anaphylaxis test (ED50 = 0.92 mg/kg p.o.). It had a potent inhibitory effect on anaphylactic bronchoconstriction in guinea pigs (ED50 = 0.029 mg/kg p.o.) and H1 receptor antagonistic effect (Ki = 14 nM) with few central nervous system side effects. Additionally, an antagonistic effect against prostaglandin D2-induced contraction of isolated guinea pig trachea (pA2 = 5.73) was an attractive mechanism of action of the new antiallergic agent. Compound 7 was selected for further evaluation as KW-4994.     

Sensitive determination of cystathionine and assays for cystathionine beta- and gamma-lyase, as well as cystathionine beta-synthase, using high-performance liquid chromatography.

Cystathionine was cleaved into 2-ketobutyric acid, cysteine and ammonia by cystathionase. 2-Ketobutyric acid was converted into 3-ethyl-2-hydroxy-6,7-dimethoxyquinoxaline (EHDQ) by reaction with 1,2-diamino-4,5-dimethoxybenzene. When EHDQ was measured in a mobile phase of pH 2.1 using high-performance liquid chromatography with ultraviolet detection, 250 pmol of L-cystathionine in 250 microliters of the reaction mixture could be determined. Because EHDQ has a strong fluorescence in a mobile phase of pH 6.5 at 447 nm, on excitation at 365 nm, as little as 2.5 pmol of cystathionine in 250 microliters of the reaction mixture could be determined by high-performance liquid chromatography with fluorimetric detection. Cystathionase activity was assayed on the basis of the same principle by determining cystathionine in as little as 63 ng of rat liver by fluorimetric detection. Cystathionine beta-synthase activity was measured by the same method by determining cystathionine formed in only 113 ng of wet weight of rat liver. Using these methods, both cystathionine beta- and gamma-lyase activities in Saccharomyces cerevisiae were determined, because quinoxaline derivatives from pyruvate and 2-ketobutyrate could be measured simultaneously by high-performance liquid chromatography.     

On the convergence of finite element solutions to the interface problem for the Stokes system

The Stokes system with a discontinuous coefficient (Stokes interface problem) and its finite element approximations are considered. We firstly show a general error estimate. To derive explicit convergence rates, we introduce some appropriate assumptions on the regularity of exact solutions and on a geometric condition for the triangulation. We mainly deal with the MINI element approximation and then consider P1-iso-P2/P1 element approximation. Results are expected to give an instructive remark in numerical analysis for two-phase flow problems.     

Instrumental Requirements for Non-Invasive Blood Glucose Measurement Using NIR Spectroscopy

The magnitude of spectral change in blood glucose measurements with diffuse reflectance spectroscopy is investigated. Spectral change is estimated by simulation of light propagation in skin tissue and measurements of absorbance spectra of aqueous glucose solution. Required sensitivity of spectrophotometers for monitoring change in the blood glucose concentration as small as 10 mg/dL has been obtained using the estimated change in the absorbance spectrum and mean pathlength of light in tissue.     

Photorefractive effect in the relaxor ferroelectric material 0.91Pb(Zn1/3Nb2/3)O3-0.09PbTiO3

The photorefractive effect in a nominally undoped 0.91Pb(Zn1/3Nb2/3)O3-0.09PbTiO3 single crystal is measured. We report what is, to our knowledge, the first observation of the photorefractive effect in Pb-based relaxor ferroelectric crystals. The crystal is grown by the flux solution method. Then it is cut into a 2 mm x 4 mm x 8 mm piece and electrically poled along the [111] direction. The coupling constant of the two-wave mixing is 17 cm(-1), and the normalized time constant under 1-W/cm(2) illumination is 12 s at a wave-length of 476 nm. The effective trap density is calculated as 5 x 10(16) cm(-3) from the Debye screening length under the assumption of Kukhtarev's band-transport model. The dominant carrier is identified to be holes from the direction of two-wave mixing energy transfer.     

Nonlinear effects of electrolyte diodes and transistors in a polymer gel medium

The polarization curve of an acid-base interface in a hydrogel medium has a diode characteristic. Two of each such electrolyte diodes can be combined to give an electrolyte transistor. When a salt is added to the alkaline or to the acidic part of a reverse biased electrolyte diode, the current response is highly nonlinear. If the salt is added to the acidic side, even bistability can be observed. This bistability can generate complex oscillations in a base-acid-base electrolyte transistor. These nonlinear effects are studied experimentally and theoretically. While the nonlinear salt effect can be explained with the Nernst-Planck equations, to understand the bistable behavior further investigations are necessary. (c) 1999 American Institute of Physics.     

Local chemical state change in Co–O resistance random access memory

Kelvin probe force microscopy (KFM) and conductive atomic force microscopy (C‐AFM) together with micro X‐ray photoelectron spectroscopy (XPS) were performed for the stacking structure comprising of the transition metal oxide Co–O and metal electrode, which exhibits large reproducible resistance switching. The application of the external voltage by the C‐AFM cantilever decreases the resistance of Co–O, which well accords with the non‐polar forming process observed in the Pt/Co–O/Pt trilayer, known as the candidate of resistance random access memory (ReRAM). Furthermore, the KFM and micro XPS experimentally revealed that the local reductive reaction of Co–O possibly nucleates the defect related energy levels which dominates the current conduction in the low resistance state. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Beta-replacement reaction of serine-O-carbonate derivatives with thiols catalyzed by a pyridoxal model having an ionophore side-chain

Serine-O-carbonate derivatives, including peptides having a serine-O-carbonate residue at the N-terminal position, are catalytically transformed into S-substituted cysteine derivatives employing the pyridoxal model having an ionophore function in the presence of Li+; this is the first artificial model mimicking cystathionine Beta-synthase.