高效液相色谱(HPLC)中泵的单向阀要承受反复的机械强度压力,故容易发生故障.由于外部漏液会导致泵压明显下降,所以这种情况很容易诊断,然而遗憾的是,泵内部连接的漏液却是比较复杂的,因为此时不会有一个明显的压力下降,所以HPLC软件程序中的诊断算法也无法识别.本文讨论了一个测试发现单向阀隐藏故障并清除故障的方法.
在比较蛋白质组学中,分级过程经常被用于去除高丰度蛋白质,从而提高低丰度蛋白质的浓度至检出限以上.作者为了证实在二维凝胶电泳分离流程中增加额外的分级过程将会减小对金头鲷宰前应激响应时间依赖检测中所引入的噪声和批次间的偏差,采用多维标度对结果数据进行了多参数分析.结果表明生物响应比分级引入的误差高出几个数量级,而批次间误差不小于不同IEF/SDS-PAGE运行所引入的偏差.
The efficacy and subsequent success of a pharmaceutical is strongly dependent on its shelf life and its stability under targeted solution conditions. A typical manifestation of formulation instability is an increase in particle size, due to aggregation of the analyte or carrier. As the particle size increases, efficacy is diminished, primarily due to the decrease in the active surface area. Because of the correlation between efficacy and size, particle sizing is quickly becoming a routine step in the development of more stable and effective formulations. Dynamic light scattering (DLS), also known as photon correlation spectroscopy (PCS) and quasi-elastic light scattering (QELS), provides many advantages as a particle size analysis method. DLS is a noninvasive technique that measures a large population of particles in a very short time period, with no manipulation of the surrounding medium. Modern DLS instruments, notably the Zetasizer Nano system (Malvern Instruments, Southborough,
during normal metabolism and in higher fluxes under pathological conditions. The oxidative modification of proteins by ROS is implicated in the etiology and/or progression or manifestations of a number of physiological disorders and diseases such as aging, muscular dystrophy, amyotrophic lateral sclerosis, A l z h e i m e r’s disease, Parkinson’s disease, cataractogenesis, respiratory distress syndrome, progeria, and Werner’s syndrome. The oxidation of proteins causes the modification of several amino acids, protein aggregation, and protein fragmentation. The induction of protein carbonyl is the most general indicator and a widely applied marker of protein oxidation, arising from primary oxidative insult to several amino acids (arginine, lysine, proline, or threonine residues), in addition to sugars and lipids. A specific oxidative amino acid modification involves the abstraction of the phenolic hydrogen atom from tyrosine residues. The resulting tyrosyl radical is relatively long-lived and can combine with another tyrosyl radical to generate a stable, covalent, carbon–carbon bond resulting in the formation of 1,3dityrosine (F i g u re 1), a highly fluorescent molecule that is resistant to acid hydrolysis and protease activi t y. Dityrosine is a specific product of protein oxidation and is formed by various oxidation systems, including hypochlorous acid (HOCl), during oxidant exposure of both purified proteins in vitro and intact cells. Dityrosine formation leads to the cross-linking of proteins intraor intermolecularly.
One of the company’s major research targets is to deliver more than 15 candidate drugs annually by 2003. To reach this target, the company needs to constantly find ways to improve the speed and accuracy of its preclinical research processes. An example of this is the company’s current work in one of its Cancer Research Groups at Alderley Park (Cheshire, UK). The Cancer Research Group is working on a range of cancers, including breast, colorectal, lung and prostate, and it is studying how small molecules can regulate the proteins involved in apoptosis (programmed cell death). Studying molecular functions of the protein involved in the mechanisms of apoptosis could lead to insights into how to design molecules that eliminate these types of tumour cells through apoptosis induction. Broadly, there are two mechanisms by which cells die due to apoptosis; one is generated by signals arising within the cell and the other mechanism is triggered by death activator proteins that bind to receptors at the cell surface. The group has been looking at ways to improve the accuracy and speed of Western blot and clonogenicity assay endpoints to measure the effectiveness of small molecules and antisense oligonucleotide as potential lead compounds.
