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.     

Titania NOx sensors for exhaust monitoring

Oxide semiconductors have been examined to develop NO_x sensors for exhaust monitoring. Titania doped with trivalent elements, such as Al³⁺, Sc³⁺, Ga³⁺ or In³⁺, has a good sensitivity and selectivity to NO between 450 and 550 °C, and shows rapid response. A sensor probe for monitoring exhaust NO_x has been fabricated. Many kinds of interference gases, such as C₃H₆, CO and SO₂, have been found to have only a slight influence on the sensor response to NO. The influence of O₂ and H₂O is also negligible, except for the cases of 0% H₂O and fuel-rich conditions. In accordance with these results, the sensor probe operates satisfactority in the exhaust gas of various combustion conditions without interference from the various kinds of gas species in the exhaust gases.     

Breakdown Trade-Off Relation of Mechanical Properties via Micro-alloying in Mg–Mn Alloys

The impact of micro-alloying on tensile behavior at strain rates in various ranges is examined using five types of extruded Mg-0.3 at. pct Mn–0.1 at. pct X ternary alloys, where X is selected as a common element, Al, Li, Sn, Y or Zn. Microstructural observations reveal that the average grain size of these extruded alloys is between 1 and 3 μm, and these micro-alloying elements segregate at grain boundaries. In room temperature tensile and compression tests, these results show that the mechanical properties and deformation behavior are influenced by the micro-alloying element, even as a small addition of 0.1 at. pct. Mg–Mn–Y and Mg–Mn-Zn alloys show higher strength and smaller strain rate sensitivity (m-value) among the present alloys, owing to the rate-controlling mechanism as dislocation slip. On the other hand, the Mg–Mn–Li alloy exhibits the largest elongation to failure in tension and the highest strain rate sensitivity, associated with high contribution of grain boundary sliding to deformation. These differences are due to the grain boundary segregation of the micro-alloying elements. Compared to the common Mg alloys, the present ternary alloys also show a trade-off relationship between strength and ductility, which is similar to that of the well-known Mg alloys; however, these properties of the Mg–Mn system ternary alloys could be controlled via the type of micro-alloying elements with a chemical content of 0.1 at. pct.

     

Effect of the Chiral Center Position of an Optically Active Terminal Group on the Induction of Optical Activity in Polysilanes

Summary Polysilanes with an optically active alkoxy group, i.e., (S)-(+)-2-butoxy, (R)-(-)-2-butoxy, (S)-(-)-2-methyl-1-butoxy, and (S)-(+)-3,7-dimethyl-1-octoxy, at the terminal positions, the chiral carbon centers of which were located at the α, β, and γ positions relative to the oxygen, respectively, were prepared, and the effect of the position of chiral center of the terminal optically active group on the induction of optical activity in polysilanes was investigated. The circular dichroism (CD) spectra of these polymers showed positive Cotton signals around 340 nm at temperatures below -20 °C, but the intensities were small, indicating that the optically active groups at the terminal positions have some ability, albeit small, to induce optical activity to the polysilanes. Further, the optically active (S)-(+)-2-butoxy and (R)-(-)-2-butoxy groups did not control the helical sense direction of the polymers, despite the different chiral stimuli from the 2-butoxy groups introduced to the terminal positions. To control the helical structure of polysilanes by the use of optically active terminal groups, appropriate optically active groups are required.     

Highly Transparent Lu-α-SiAlON

Novel Lu-α-SiAlON ceramics were produced by hot pressing mixtures of Si₃N₄, Lu₂O₃, AlN, and Al₂O₃ at 1950°C for 2 h in a nitrogen atmosphere. The resultant SiAlON was fully dense and possessed a uniform, equiaxed microstructure with a grain size of ∼1 μm, which resulted in a high hardness of >19 GPa. In addition to high hardness, the sample showed very high optical transparency in the visible light region, with >70% transmission at higher wavelengths. This high transparency was attributed to the uniform, dense microstructure and lack of residual grain-boundary phase.     

Fracture Energies of Tape-Cast Silicon Nitride with β-Si3N4 Seed Addition

The fracture energies of the tape-cast silicon nitride with and without 3 wt% rod-like β-Si₃N₄ seed addition were investigated by a chevron-notched-beam technique. The material was doped with Lu₂O₃–SiO₂ as sintering additives for giving rigid grain boundaries and good heat resistance. The seeded and tape-cast silicon nitride has anisotropic microstructure, where the fibrous grains grown from seeds were preferentially aligned parallel to the casting direction. When a stress was applied parallel to the fibrous grain alignment direction, the strength measured at 1500°C was 738 MPa, which was almost the same as room temperature strength 739 MPa. The fracture energy of the tape-cast Si₃N₄ without seed addition was 109 and 454 J/m² at room temperature and 1500°C, respectively. On the contrary, the fracture energy of the seeded and tape-cast Si₃N₄ was 301 and 781 J/m² at room temperature and 1500°C, respectively, when a stress was applied parallel to the fibrous gain alignment. The large fracture energies were attributable primarily to the unidirectional alignment fibrous Si₃N₄ grains.     

Physical properties of silk fibers treated with ethylene glycol diglycidyl ether by the pad/batch method

This paper deals with the epoxide treatment of silk fabrics by the pad/batch method. The optimum reaction conditions, i.e., NaOH concentration, and reaction temperature were 2.5 g/L and 30°C, respectively. A weight gain of 8.5% was attained at a reaction time of 6 h. This value slightly increased to 10% after 24 h. The reactivity of tyrosine and basic amino acid residues was dependent on the reaction time and did not significantly differ from the results of epoxide-treated silk fiber by the conventional method in tetrachloroethylene. The moisture regain slightly decreased at 4% weight gain and then increased with the epoxide content, exceeding the value of the untreated control. The crease recovery of the epoxide-treated silk fabrics measured in the wet state was significantly improved, whereas that in the dry state was almost unchanged. The rate of photoyellowing of the epoxide-treated silk fabrics by the pad/batch method was reduced significantly compared with that of the untreated control. Among the mechanical properties, elongation at break and tensile modulus remained unchanged, whereas the tensile strength slightly increased following the epoxide reaction. The thermal properties were evaluated by DSC and TGA and on the basis of the dynamic viscoelastic measurements. The DSC curve of the epoxide-treated sample showed a slight increase of the decomposition temperature of silk fibroin. The rate of weight loss determined by TGA remained unchanged regardless of the chemical modification, whereas the peak of loss modulus became broader and shifted to lower temperature. The X-ray diffractograms showed that the crystalline structure of silk fibers was not affected by the reaction with epoxides. © 1993 John Wiley & Sons, Inc.     

In Situ Synthesis and Microstructures of Tungsten Carbide-Nanoparticle-Reinforced Silicon Nitride-Matrix Composites

A W₂C-nanoparticle-reinforced Si₃N₄-matrix composite was fabricated by sintering porous Si₃N₄ that had been infiltrated with a tungsten solution. During the sintering procedure, nanometer-sized W₂C particles grew in situ from the reaction between the tungsten and carbon sources considered to originate mainly from residual binder. The W₂C particles resided in the grain-boundary junctions of the Si₃N₄, had an average diameter of ∼60 nm, and were polyhedral in shape. Because the residual carbon, which normally would obstruct sintering, reacted with the tungsten to form W₂C particles in the composite, the sinterability of the Si₃N₄ was improved, and a W₂C–Si₃N₄ composite with almost full density was obtained. The flexural strength of the W₂C–Si₃N₄ composite was 1212 MPa, ∼34% higher than that of standard sintered Si₃N₄.     

Monodisperse nanoparticles of poly(ethylene glycol) macromers and N‐isopropyl acrylamide for biomedical applications

Poly(ethylene glycol)‐based nanoparticles have received significant attention in the field of biomedicine. When they are copolymerized with pH‐ or temperature‐sensitive comonomers, their small size allows them to respond very quickly to changes in the environment, including changes in the pH, ionic strength, and temperature. In addition, the high surface‐to‐volume ratio makes them highly functionalized. In this work, nanoparticles composed of temperature‐sensitive poly(N‐isopropylacrylamide), poly(ethylene glycol) 400 dimethacrylate, and poly(ethylene glycol) 1000 methacrylate were prepared by a thermally initiated, free‐radical dispersion polymerization method. The temperature‐responsive behavior of the hydrogel nanoparticles was characterized by the study of their particle size with photon correlation spectroscopy. The size of the nanoparticles varied from 200 to 1100 nm and was a strong function of the temperature of the system, from 5 to 40°C. The thermal, structural, and morphological characteristics were also investigated. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1678–1684, 2003     

Balanced corpus of contemporary written Japanese

The balanced corpus of contemporary written Japanese (BCCWJ) is Japan’s first 100 million words balanced corpus. It consists of three subcorpora (publication subcorpus, library subcorpus, and special-purpose subcorpus) and covers a wide range of text registers including books in general, magazines, newspapers, governmental white papers, best-selling books, an internet bulletin-board, a blog, school textbooks, minutes of the national diet, publicity newsletters of local governments, laws, and poetry verses. A random sampling technique is utilized whenever possible in order to maximize the representativeness of the corpus. The corpus is annotated in terms of dual POS analysis, document structure, and bibliographical information. The BCCWJ is currently accessible in three different ways including Chunagon a web-based interface to the dual POS analysis data. Lastly, results of some pilot evaluation of the corpus with respect to the textual diversity are reported. The analyses include POS distribution, word-class distribution, entropy of orthography, sentence length, and variation of the adjective predicate. High textual diversity is observed in all these analyses.