Thieno[2,3-d]pyrimidine-3-acetic acids. A new class of nonpeptide endothelin receptor antagonists

On the basis of structural information for the cyclic hexapeptide endothelin (ET) receptor antagonist, TAK-044, a series of thieno[2,3-d]pyrimidine-2,4-dione derivatives bearing a carboxyl group and aromatic rings that were important for receptor binding were designed, synthesized, and evaluated for ET receptor binding affinities and inhibitory activities against ET-induced vasoconstriction. Optimization of each substituent in the thieno[2,3-d]pyrimidine ring led to the discovery of a novel and potent nonpeptide ET receptor antagonist, 6-(4-methoxymethoxyphenyl)-5-methylsulfonylaminomethyl-1-(2- methylthiobenzyl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]p yrimidine-3- acetic acid (32 g), which binded to human ETA and ETB receptor subtypes with affinities (IC50) of 7.6 and 100 nM, respectively. Compound 32 g effectively antagonized ET-induced vasoconstriction and the inhibitory effect mediated by the ETB receptor was more potent than that of bosentan, while the inhibitory effect mediated by the ETA receptor was slightly less potent than that of bosentan.     

Radiation-induced polymerization of ethylene in pilot plant. III. Heavy-phase recycling process

Radiation-induced polymerization of ethylene using aqueous tert-butyl alcohol as medium was carried out in a large-scale pilot plant with a 50-liter central source-type reactor at a pressure of 105 to 395 kg/cm², temperature of 30° to 80°C, mean dose rate of 4.5 × 10⁴ to 1.9 × 10⁵ rads/hr, ethylene feed rate of 5.5 to 23.5 kg/hr, and medium feed rate of 21 to 102 l./hr. The space–time yield and molecular weight of the polymer were in the range of 4.7 to 16.8 g/l.-hr and 1.3 × 10⁴ to 8.9 × 10⁴, respectively. The space–time yield and molecular weight increased with mean residence time at 30°C, whereas at 80°C they became almost independent of the time. The space–time yield increased with pressure and dose rate, slightly decreased with temperature, and was maximum at ethylene molar fraction of 0.5. The polymer molecular weight increased with pressure and ethylene molar fraction, and decreased with dose rate and temperature. The total amount of deposited polymer on the reactor wall, source case wall, and scraping blades was usually less than 1 kg, which was negligibly small for the analysis of polymerization. Continuous discharge of the polymer slurry and production of fine-powder polyethylene were successfully carried out. In the central source-type reactor, a dose rate of 1.9 × 10⁵ rads/hr was obtained with a ⁶⁰Co source of ca. 12 kCi.     

Stable and super‐low friction of amorphous carbon nitride coatings in nitrogen gas by using two‐step ball‐on‐disk friction test

Effect of running‐in process on friction behaviour of carbon nitride (CNx) coating in N₂ gas stream was investigated with a newly introduced two‐step ball‐on‐disk friction test, where the rubbed Si₃N₄ ball in the pre‐sliding (step 1) was replaced by a new CNx‐coated Si₃N₄ ball in the subsequent sliding stage under N₂ gas (step 2). The two‐step friction test is clarified to be a simple but effective technique for obtaining contact material combination of self‐mated CNx coatings and for achieving stable and low frictions of CNx coatings. Friction coefficients of CNx/CNx in N₂ gas stream decrease greatly from 0.07 without pre‐sliding to less than 0.025 in two‐step friction tests. The minimum friction coefficient of 0.004 was obtained by introducing 500 cycles of pre‐sliding in ambient air. These stable and low frictions are attributed to the generation of self‐mated CNx coatings and the formation of a lubricious layer on the disk surface. Copyright © 2014 John Wiley & Sons, Ltd.     

Endothelial cells actively synthesize and secrete adrenomedullin

This study demonstrates active production of adrenomedullin (AM) in cultured vascular endothelial cells (ECs). To identify the origin of plasma AM and its functional relationship to vascular smooth muscle cells (VSMCs), we checked production of AM in a series of tissues and cell lines and found immunoreactive (ir-) AM in culture media of rat, porcine, human and bovine ECs. Ir-AM was accumulated linearly for up to 48 hours in the culture medium of rat ECs, and the secretion rate of AM was almost comparable to that of endothelin-1. By gel filtration and reverse phase high performance liquid chromatography, ir-AM in the culture medium was shown to have chromatographic behavior indistinguishable from that of synthetic rat AM. By RNA blot analysis of rat tissue, the most highly positive band was detected in cultured ECs, at an intensity 20 to 40 fold higher than that in adrenal gland. Based on these data as well as the presence of AM specific receptor on VSMCs, AM secreted from ECs is deduced to act directly on VSMCs, regulating vascular tone.     

Radiation-induced polymerization of ethylene in a pilot plant. I. Bulk process

Radiation-induced bulk polymerization of ethylene was carried out with use of a pilot plant with a 10 liter reactor at pressures of 225–400 kg/cm², temperatures of 30–95°C, ethylene feed rates of 5–28 kg/hr, and dose rate of 3.8 × 10⁵ rad/hr. Characteristics of the process are mild polymerization conditions and capability of producing medium density polyethylene in powder form. The spacetime yield and molecular weight of polymer were in the range of 3.5 to 13.1 g/liter hr and 2.2 × 10⁴ to 14 × 10⁴, respectively. The space-time yield increased with mean residence time and 2.4 powders of pressure, and decreased with temperature. Molecular weight changed similarly with the reaction conditions. These results were consistent with those of the bench plant experiment and the scale effect was small. Polymer deposit to the reactor wall limited a period of continuous operation of the plant. The amount of deposited polymer was increased with the square of reaction time. The rate of polymer deposit was proportional to polymer concentration and to the cube of pressure. The polymer deposit cannot be solved in the bulk process.     

Hydroxyapatite chromatographic procedures for phospholipids: Endotoxin purification methods

We studied the one-step purification of endotoxin by hydroxyapatite chromatography using total lipids extracted from Escherichia coli by the Bligh and Dyer method. High endotoxic activity was detected in a fraction eluted from 0.5 mg total lipids using an isopropanol gradient under salt-free buffer conditions. The fraction contained at least 7,000 endotoxin units and was completely free from other phospholipids. Notably, the running time of the chromatographic separation was approximately 4 h, whereas purification by the conventional hot phenol–water procedure requires ≥60 h. The procedure developed here is a simple, scalable, and rapid method for the purification of endotoxin.     

Thick films for multilayer substrates

Abstract

Low temperature fired ceramics based on alumina/glass added oxide ceramics have been developed and are being used by several companies as substrates for high density assembled modular packaging.^1–3 The features of low temperature fireable substrates are the cofireability with highly conductive metals such as Ag, Ag-Pd, or Cu, and the cofireability with other passive component materials for L, C, R and relatively low dielectric constant elements. But most of these substrates have the disadvantage that their thermal expansion coefficient is not perfectly compatible with Si or GaAs. This paper reports the results of a newly developed cordierite/glass based substrate employing Cu as the surface and internal conductors and having the freedom of tuning the thermal expansion coefficient by changing the composition. The ceramic composition with adjustable thermal expansion coefficient value of 3 to 7 ppm/°C can be manufactured and easily matched with the thermal expansion coefficient of Si or GaAs without a big change of electrical performance.     

HDPE膜预辐照接枝VBTAC制备阴离子交换膜

在氮气保护下,利用预辐照接枝技术在高密度聚乙烯(HDPE)膜上接枝苯乙烯三甲基氯化铵(VBTAC)单体,以甲基丙烯酸二甲氨基乙酯(DMAEMA)单体作为接枝辅助单体来提高VBTAC的接枝率,制备出阴离子交换膜,解决了在HDPE上难以直接接枝聚合VBTAC的问题.本文研究了接枝条件及接枝液的组分对接枝的影响,并用X射线显微分析方法研究了VBTAC的接枝进程和接枝分布.