Estimation of impurity profiles of drugs and related materials: part 19: theme with variations. Identification of impurities in 3-oxosteroids

Due to the varied reactions leading to the 3-oxo group in steroids and the reactivity of its environment, a large number of impurities related to this group are formed during the reaction steps and the degradation studies. In this paper the experiences from the authors laboratory with the 3-oxo-related impurities in 19-nor-4-ene-3-oxosteroids (norgestrel, norethisterone, nandrolone, its esters and Nestorone) as well as corticosteroids (prednisolone, mazipredone, etc) are presented. The impurities include saturated 3-ones, 1-ene-3-ones, 5(10)-ene-3-ones, 3-deoxo and 3-ethinyl-3,5-diene derivatives, 6-ene, 8(14)-ene, 6,8(14)-diene, 6-hydroxy (alpha and beta), 10beta-hydroxy and 6-one derivatives in 4-ene-3-oxosteroids and 8(9)-ene, 9(11)-ene, 11alpha-hydroxy, 11-oxo and 4-ene-3-one derivatives in 11beta-hydroxy-1,4-diene-3-oxosteroids. The chromatographic, spectroscopic and hyphenated techniques used in this study include TLC, GC, HPLC with diode array UV detector, GC-MS, LC-MS and NMR methods.     

The effect of laryngeal mask cuff pressure on postoperative sore throat incidence

OBJECTIVE: To determine whether a significant association occurs between the presence of various periodontal diseases and recoverable infectious HIV-I in the saliva of injecting drug users. DESIGN: Five hundred and fifty-one injecting drug users were recruited from various programs associated with the Beth Israel Medical Center. Examiners were 'blinded' to the subject's HIV-I serostatus. A socio-economic and risk factors' survey was conducted and a complete oral examination, including periodontal disease indices was performed. Whole saliva and blood were collected for virus culture. MAIN OUTCOME MEASUREMENTS: Recovery of infectious HIV-I in saliva related to presence of periodontal diseases. RESULTS: Those HIV-I seropositive subjects with periodontal diseases did not differ from those HIV-I seropositive subjects without periodontal disease in mean age and immune status. Less than 1% of the HIV-I seropositive subjects had cultivable HIV-I in their saliva while it was present in 78% of PBMCs and 35% of the sera. There was no significant association between infectious HIV-I in saliva, serum, or PBMCs and any of the various periodontal diseases. CONCLUSIONS: The presence of periodontal disease in HIV-I seropositive injecting drug users does not appear to be a potential risk factor for infectious HIV-I in saliva, probably due to the various anti-viral components of saliva.     

Two-laboratory collaborative study on identification of mycobacteria: molecular versus phenotypic methods

Previous studies have indicated that the conventional tests used for the identification of mycobacteria may (i) frequently result in erroneous identification and (ii) underestimate the diversity within the genus Mycobacterium. To address this issue in a more systematic fashion, a study comparing phenotypic and molecular methods for the identification of mycobacteria was initiated. Focus was given to isolates which were difficult to identify to species level and which yielded inconclusive results by conventional tests performed under day-to-day routine laboratory conditions. Traditional methods included growth rate, colonial morphology, pigmentation, biochemical profiles, and gas-liquid chromatography of short-chain fatty acids. Molecular identification was done by PCR-mediated partial sequence analysis of the gene encoding the 16S rRNA. A total of 34 isolates was included in this study; 13 of the isolates corresponded to established species, and 21 isolates corresponded to previously uncharacterized taxa. For five isolates, phenotypic and molecular analyses gave identical results. For five isolates, minor discrepancies were present; four isolates remained unidentified after biochemical testing. For 20 isolates, major discrepancies between traditional and molecular typing methods were observed. Retrospective analysis of the data revealed that the discrepant results were without exception due to erroneous biochemical test results or interpretations. In particular, phenotypic identification schemes were compromised with regard to the recognition of previously undescribed taxa. We conclude that molecular typing by 16S rRNA sequence determination is not only more rapid (12 to 36 h versus 4 to 8 weeks) but also more accurate than traditional typing.     

Fast and one-step folding of closely and distantly related homologous proteins of a four-helix bundle family

Bovine acyl-coenzyme A binding protein is a four-helix bundle protein belonging to a group of homologous eukaryote proteins that binds medium and long-chain acyl-coenzyme A esters with a very high affinity. The three-dimensional structure of both the free and the ligated protein together with the folding kinetics have been described in detail for the bovine protein and with four new sequences reported here, a total of 16 closely related sequences ranging from yeasts and plants to human are known. The kinetics of folding and unfolding in different concentrations of guanidine hydrochloride together with equilibrium unfolding have been measured for bovine, rat and yeast acyl-coenzyme A binding protein. The bovine and rat sequences are closely related whereas the yeast is more distantly related to these. In addition to the three natural variants, kinetics of a bovine mutant protein, Tyr31 --> Asn, have been studied. Both the folding and unfolding rates in water of the yeast protein are 15 times faster than those of bovine. The folding rates in water of the two mammalian forms, rat and bovine, are similar, though still significantly different. A faster unfolding rate both for rat and the bovine mutant protein results from a lower stability of the native states of these. These hydrophobic regions, mini cores, have been identified in the three-dimensional structure of the bovine protein and found to be formed primarily by residues that have been conserved throughout the entire eukaryote evolution from yeasts to both plants and mammals as seen in the sample of 16 sequences. The conserved residues are found to stabilize helix-helix interactions and serve specific functional purposes for ligand binding. The fast one-step folding mechanism of ACBP has been shown to be a feature that seems to be maintained throughout evolution despite numerous differences in sequence and even dramatic differences in folding kinetics and protein stability. The protein study raises the question to what extent does the conserved hydrophobic residues provide a scaffold for an efficient one-step folding mechanism.     

浅析环境艺术设计创作中的文化构思

文化的意识形态特征,使环境艺术设计过程中的文化构思成为整体设计方案的灵魂。通过充分的文化构思准备,明确的构思立意以及具体深入的构思表现,具体而合理的呈现出文化构思的思维脉络,有利于突出环境艺术设计创作的精神性和创新性,并保证设计与实施的顺利进行。     

基于CSS技术的安防定位系统的设计

随着科学技术和人们生活水平的提高,人们对已有的定位系统提出新的要求。针对目前中低档汽车的安防系统功能不完善,不能满足用户的需求,介绍了一种采用CSS定位技术实现适时了解车辆的具体位置及运行情况的系统。用户如发现车辆有异常情况,可以及时通过手机短信请求控制中心对车辆进行远程控制。紧急情况下控制中心可协助报警。经测试,系统定位准确,采集数据可靠,可适用于更多的场合,具有实用价值。     

采用时间差分算法的九路围棋机器博弈系统

围棋机器博弈是机器博弈中重要的分支之一,其庞大的博弈空间给机器博弈研究者带来了巨大挑战.目前围棋机器博弈多采用静态估值搜索与蒙特卡洛树搜索,故将时间差分算法引入至九路围棋机器博弈系统中,提出基于时间差分算法的围棋机器博弈系统模型,该博弈系统具有一定的自学习能力,能在不断的对弈中逐步提高博弈能力.通过与采用α-β搜索算法的博弈系统进行实际对弈,证明了该方法的可行性.     

网络对抗训练混合虚拟化平台设计研究

讨论了虚拟化技术实现原理及其在网络对抗教学中的应用上,分析了各类虚拟化技术的优缺点和构建网络对抗训练环境存在的问题。提出了一种混合虚拟化平台设计,该平台利用Libvirt虚拟化的应用程序编程接口（API）调用两种虚拟化技术同时运行在同一物理主机上。并详细叙述了混合虚拟化平台的实现过程和方法,并在多个虚拟机内同时运行测试基准,分析其可扩展性。多种虚拟化技术在同一物理机上的混合,实现了复杂实验环境的创建,对构建大规模的网络实验平台具有一定的参考价值。