PTC124 targets genetic disorders caused by nonsense mutations

Nonsense mutations promote premature translational termination and cause anywhere from 5-70% of the individual cases of most inherited diseases. Studies on nonsense-mediated cystic fibrosis have indicated that boosting specific protein synthesis from <1% to as little as 5% of normal levels may greatly reduce the severity or eliminate the principal manifestations of disease. To address the need for a drug capable of suppressing premature termination, we identified PTC124-a new chemical entity that selectively induces ribosomal readthrough of premature but not normal termination codons. PTC124 activity, optimized using nonsense-containing reporters, promoted dystrophin production in primary muscle cells from humans and mdx mice expressing dystrophin nonsense alleles, and rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure. PTC124 was well tolerated in animals at plasma exposures substantially in excess of those required for nonsense suppression. The selectivity of PTC124 for premature termination codons, its well characterized activity profile, oral bioavailability and pharmacological properties indicate that this drug may have broad clinical potential for the treatment of a large group of genetic disorders with limited or no therapeutic options.     

浑沌：它能有多少规律

40年前A.爱因斯坦给M.玻恩的一封信中写道,“上帝不玩骰子。”爱因斯坦是始终反对量子论的概率解释的,他不倦地探索着与经典力学更为直接的类比,即考虑没有概率不定性的确定过程。如今,40年过去了,没有人会惊讶:甚至在一个经典哈密顿动力系统中也存在着(chas)在物理客体规则运动的领域内,在没有人预期会有的地方冒出     

二甲基甲酰胺中Sm（Ⅲ）电化学性质及其合金膜研究

通过循环伏安法研究二甲基甲酰胺中Sm（Ⅲ）在Pt上的电化学性质,表明Sm（Ⅲ）在Pt上的还原为不可逆反应,同时测得传递系数α=0.0289,扩散系数D0=1.288×10^-5cm^2·S^-1;通过塔菲尔曲线求得交换电流密度i0=1.596×10^-7A/cm^2;对Sm（Ⅲ）在Pt上离子成核机理研究表明,Sm（Ⅲ）在Pt电极上是按三维模式扩散控制下连续成核的;用恒电位法可以制得有金属光泽、附着力好、表面均匀致密的Sm-Ni-Co合金膜,与Ni-Co合金膜相比较结构性能有所提高.     

Nickel solvent extraction from cold purification filter cakes of Angouran mine concentrate using LIX984N

Cold purification filter cakes generated in the hydrometallurgical processing of Angouran mine zinc concentrate commonly contain significant amounts of Zn, Cd, and Ni ions and thus are valuable resources for metal recovery. In this research, a nickel containing solution that was obtained from sulfuric acid leaching of the filter cake following cadmium and zinc removal was subjected to solvent extraction experiments using 10vol% LIX984N diluted in kerosene. Under optimum experimental conditions (pH 5.3, volume ratio of organic/aqueous (O:A) = 2:1, and contact time = 5 min), more than 97.1% of nickel was extracted. Nickel was stripped from the loaded organic by contacting with a 200 g/L sulfuric acid solution, from which 77.7% of nickel was recovered in a single contact at the optimum conditions (pH 1–1.5, O:A = 5:1, and contact time = 15 min).