Desulfurization of phosphorothioate oligonucleotides via the sulfur‐by‐oxygen replacement induced by the hydroxyl radical during negative electrospray ionization mass spectrometry

While the occurrence of desulfurization of phosphorothioate oligonucleotides in solution is well established, this study represents the first attempt to investigate the basis of the unexpected desulfurization via the net sulfur‐by‐oxygen (S‐O) replacement during negative electrospray ionization (ESI). The current work, facilitated by quantitative mass deconvolution, demonstrates that considerable desulfurization can take place even under common negative ESI operating conditions. The extent of desulfurization is dependent on the molar phosphorothioate oligonucleotide‐to‐hydroxyl radical ratio, which is consistent with the corona discharge‐induced origin of the hydroxyl radical leading to the S‐O replacement. This hypothesis is supported by the fact that an increase of the high‐performance liquid chromatography (HPLC) flow rate and the on‐column concentration of a phosphorothioate oligonucleotide, as well as a decrease of the electrospray voltage reduce the degree of desulfurization. Comparative LC‐tandem mass spectrometry (MS/MS) sequencing of a phosphorothioate oligonucleotide and its corresponding desulfurization product revealed evidence that the S‐O replacement occurs at multiple phosphorothioate internucleotide linkage sites. In practice, the most convenient and effective strategy for minimizing this P = O artifact is to increase the LC flow rate and the on‐column concentration of phosphorothioate oligonucleotides. Another approach to mitigate possible detrimental effects of the undesired desulfurization is to operate the ESI source at a very low electrospray voltage to diminish the corona discharge; however this will significantly compromise sensitivity when analyzing the low‐level P = O impurities in phosphorothioate oligonucleotides. Copyright © 2012 John Wiley & Sons, Ltd.     

Optimal maintenance strategy for non‐renewing replacement–repair warranty

In this paper, we study the maintenance policy following the expiration of the non‐renewing replacement–repair warranty (NRRW). For such purposes, we first define the non‐renewing free replacement–repair warranty and the non‐renewing pro rata replacement–repair warranty. Then the maintenance model following the expiration of the NRRW is discussed from the user's point of view. As the criterion to determine the optimal maintenance strategy, we formulate the expected cost rate per unit time from the user's perspective. All system maintenance costs incurred after the warranty is expired are paid by the user. Given the cost structures during the life cycle of the system, we determine the optimal maintenance period following the expiration of the NRRW. Finally, a few numerical examples are given for illustrative purposes. Copyright © 2012 John Wiley & Sons, Ltd.     

氦气置换过程中未知杂质分析

用美国GOW—MAC公司的气相色谱仪和Agilent公司的气相色谱仪对某卫星气体贮箱在氦气置换化验过程中发现的未知杂质进行试验分析,经分析未知杂质的来源可能是所用气体贮箱处理时的残留物。试验发现,氧化剂贮箱氦气和燃烧剂贮箱氦气经3次氦气置换后未知杂质的色谱峰消失。提出了消除未知杂质的的建议。     

3D-shaping of biodegradable photopolymers for hard tissue replacement

Continuously increasing life expectancy results in a rising number of bone diseases and fractures. Replacements from natural sources are not only limited in their availability, they also have some serious disadvantages such as possible immunological reactions or transmission of diseases. New synthetic biodegradable materials based on photopolymers could be an alternative solution. In these investigations an acrylate-based monomer formulation has been developed, consisting of a biodegradable basis monomer which is derived from gelatin, different reactive diluents, an appropriate photoinitiator and filler materials. For the three-dimensional shaping process stereolithography is the method of choice because of its capability to produce cellular structures with high resolutions.     

体外预应力加固的技术研究

通过ANSYS有限元模型, 以体外预应力筋为研究对象, 对体外预应力加固的关键技术进行了研究, 得出体外预应力的作用位置, 尽可能拟合原结构的受力状况, 保证加固工程的安全性; 体外预应力的补强力筋, 应采用等效面积的置换原则, 使施工的过程趋于合理; 体外力筋的连接装置, 应该``适、薄、强'; 在加固工程中, 体外预应力筋纵向交错布筋的设置, 能提升结构的整体延性.     

燃气管网置换过程动态仿真计算与研究

燃气置换过程难以监测,供气压力、置换时间等参数计算大都依赖人员经验,容易产生资源浪费和安全隐患。本文建立燃气管网置换过程动态仿真模型,在采用一维拓扑网络算法的基础上,对管网中的阻力系数进行精确求解。文章首先建立水平直管结构,结合Fluent仿真对算法进行验证,并对燃气置换过程的规律进行分析和总结。最后将模型应用于实际燃气管网置换工程中,与实测数据进行对比,结果表明所提出的模型精度可以满足工程需求,能为燃气管网置换方案的制定提供重要指导依据。

     

基于截断δ-冲击模型的不完全维修更换策略

本文在截断δ-冲击模型的基础上,考虑了因系统劣化而导致的冲击失效门限值与维修时间的变化,扩充失效状态,从而提出一种新的截断δ-冲击模型。以最小费用为目标,稳态可用度为约束条件,建立N型更换策略的不完全维修更换策略模型,并给出三种常用冲击到达间隔分布的期望寿命。最后通过算例验证模型的有效性,并对参数进行灵敏度分析。     

Synthesis of Conformationally Constrained d-Glu-meso-DAP Analogs as Innate Immune Agonists

The dipeptide d-Glu-meso-DAP (iE-DAP) is the minimal structural fragment capable of activating the innate immune receptor nucleotide-binding oligomerization domain protein (NOD1). The meso-diaminopimelic acid (meso-DAP) moiety is known to be very stringent in terms of the allowed structural modifications which still retain the NOD1 activity. The aim of our study was to further explore the chemical space around the meso-DAP portion and provide a deeper understanding of the structural features required for NOD1 agonism. In order to achieve the rigidization of the terminal amine functionality of meso-DAP, isoxazoline and pyridine heterocycles were introduced into its side-chain. Further, we incorporated the obtained meso-DAP mimetics into the structure of iE-DAP. Collectively, nine innovative iE-DAP derivatives additionally equipped with lauroyl or didodecyl moieties at the α-amino group of d-Glu have been prepared and examined for their NOD1 activating capacity. Overall, the results obtained indicate that constraining the terminal amino group of meso-DAP abrogates the compounds’ ability to activate NOD1, since only compound 6b retained noteworthy NOD1 agonistic activity, and underpin the stringent nature of this amino acid with regard to the allowed structural modifications.     

Marginal cost analysis of single-item maintenance policies with several decision variables

The marginal cost approach for the analysis of repair/replacementmodels was introduced by Berg in 1980 and has since been appliedto many maintenance policies of various complexity. All modelshitherto analysed in the literature by the marginal cost approachhave one single decision variable only, this being, typically,the age of the current item at the time of ordering or replacement.This paper is concerned with the extension of the marginal costtechnique to maintenance policies with several decision variables.After addressing the general framework appropriate for the multi-parametercase, we exemplify the workings of the technique by analysinga two-variable maintenance model involving replacement and minimalrepair. We demonstrate that the marginal cost approach is anattractive and intuitively appealing technique also for modelswith several decision variables. Just as in the single-parametersituation, the approach is amenable to economic interpretation,a welcome feature for users of maintenance models with a primeinterest in its economic (rather than its mathematical) aspects.As an added bonus of the marginal cost approach, in our example,some otherwise necessary tools from the theory of stochasticprocesses are dispensable.     

一个可供选择的敏感问题调查技术

为了估计一个人群总体中具有敏感属性个体的未知比例，本文提出了一种简便易行的随机化回答技术．提出的方法不需要对样本个体直接询问敏感问题．每个响应者要求根据抽自两个卡片包的两张卡片的颜色和响应者是否具有敏感属性作出一个序对的回答．通过设计参数的适当选择，说明提出的方案比已有的一些随机化策略具有更高的效率．另外，这一策略对个体隐私具有很好的保护性且容易实施．