Liquid chromatographic analysis of oxcarbazepine and its metabolites in plasma and saliva after a novel microextraction by packed sorbent procedure

A rapid and reliable analytical method suitable for the simultaneous determination of the antiepileptic drug, oxcarbazepine and its metabolites in human plasma and saliva by means of liquid chromatography with diode array detection (DAD) has been developed. Oxcarbazepine and its metabolites (10,11-dihydro-10-hydroxycarbamazepine, trans-10,11-dihydro-10,11-dihydroxycarbamazepine and 3-hydroxycarbamazepine) were baseline separated within 6.5 min on a reversed-phase C18 column with a phosphate buffer-acetonitrile-triethylamine mixture as the mobile phase. The DAD detector was set at 240 nm. A sample preparation method for biological samples using a microextraction by packed sorbent technique has been implemented, employing a C18 sorbent inserted into a microvolume syringe and using only a small volume (25 μL) of plasma or saliva. The extraction yield values were satisfactory for all analytes (>86.5%) as well as the precision data, which were always in the low percentage of relative standard deviation values (<4.6%). The method was successfully applied to both plasma and saliva samples drawn from psychiatric and neurological patients undergoing treatment with oxcarbazepine (Tolep^®) tablets.     

High temporal resolution monitoring of enzyme reaction and inhibition using optically gated vacancy capillary electrophoresis and immobilized enzyme

A novel method for monitoring of enzyme reaction and inhibition with high temporal resolution was developed by using optically gated vacancy capillary electrophoresis (OGVCE) with laser-induced fluorescence (LIF) detection and immobilized enzyme. Trypsin cleavage reaction and inhibition were investigated by the presented OGVCE-LIF assay, using carboxyfluorescein (FAM) end-labeled Angiotensin as the substrate and commercially available immobilized trypsin. The substrate and the product were continuously loaded into the capillary by the electroosmotic flow while the immobilized enzyme remained in the sample vial. Substrate consumption and product formation were monitored simultaneously at 5 s interval during the whole reaction time. The enzymatic reaction rates obtained from the substrate and the product were highly consistent. The enzyme activity and the Michaelis constants of trypsin cleavage reaction, as well as the inhibition constant (for reversible competitive inhibitor) and the inhibition fraction (for irreversible inhibitor), were obtained. It was showed that the reported OGVCE-LIF method can perform fast, accurate, sensitive and reproducible CE enzyme assay with high temporal resolution, thus has great potential in application of the enzyme-substrate systems with fast reaction rate and the fluorescent substrate and products.     

A simulation-based multivariate Bayesian control chart for real time condition-based maintenance of complex systems

When complex systems are monitored, multi-observations from several sensors or sources may be available. These observations can be fused through Bayesian theory to give a posterior probabilistic estimate of the underlying state which is often not directly observable. This forms the basis of a Bayesian control chart where the estimated posterior probability of the state can be compared with a preset threshold level to assess whether a full inspection is needed or not. Maintenance can then be carried out if indicated as necessary by the inspection. This paper considers the design of such multivariate Bayesian control chart where both the transition between states and the relationship between observed information and the state are not Markovian. Since analytical or numerical solutions are difficult for the case considered in this paper, Monte Carlo simulation is used to obtain the optimal control chart parameters, which are the monitoring interval and the upper control limit. A two-stage failure process characterised by the delay time concept is used to describe the underlying state transition process and Bayesian theory is used to compute the posterior probability of the underlying state, which is embedded in the simulation algorithm. Extensive examples are shown to demonstrate the modelling idea.     

横向监督中基于社会偏好匹配的员工组合问题研究

考虑横向监督中基于社会偏好的三种员工组合方式:同质组合、异质组合与双高组合。运用委托代理理论,研究基于社会偏好匹配的员工组合问题。模型分别给出了不存在横向监督、存在横向监督且员工是同质组合、存在横向监督且员工是异质组合与存在横向监督且员工是双高组合四种情形下的均衡结果。根据均衡结果做进一步分析,得出结论:①存在横向监督时员工的努力程度与企业收益总是高于不存在横向监督的情形,但不同的员工组合方式对其努力程度的激励效果是相同的;②异质组合能够通过节约薪酬成本而间接地提高企业总收益,双高组合能够通过获得较多的员工投入而直接增加企业总收益,并且异质组合与双高组合总是优于同质组合;③员工的社会偏好与风险成本是决定企业最佳员工组合方式选择的关键因素:当员工的风险成本很小而社会偏好差距较大时企业应选择异质组合;而当员工的风险成本很大或者风险成本小并且员工社会偏好差距也较小时企业应选择双高组合;因此,根据员工的个性特征选择适宜的组合方式是实现横向监督激励效应最大化的关键。     

Single‐Point Intrinsic Viscosity and Density Measurements for In‐Line MIMO Control Purposes of a Lumped‐Distributed Polymeric System

Simulation and experimental studies are carried out for peroxide‐initiated styrene solution polymerization in a lumped‐distributed reactor. Weight‐average molecular weight (intrinsic viscosity measurements) and conversion (density data) are the output signals, while the manipulated variables are jacket reactor temperature and feed modifier (tert‐dodecylmercaptan) concentration. A simple in‐line viscometrical method makes the in‐line control of weight‐average molecular weight in solution polymerization feasible, using independent conversion measurements from an in‐line densitometer. Successful closed‐loop servo and regulatory control results are obtained.

     

Study of the fragmentation of arginine isobutyl ester applied to arginine quantification in Aedes aegypti mosquito excreta

It has been demonstrated that argininolysis and uricolysis are involved in the synthesis and excretion of urea in Aedes aegypti female mosquitoes. To further investigate the metabolic regulation of urea in female mosquitoes, it is desirable to have a rapid and efficient method to monitor arginine (Arg) concentration in mosquito excreta. Thus, a procedure currently used for the identification of Arg in urea cycle disorders in newborn babies was adapted to analyze Arg in A. aegypti excreta. The fragmentation patterns of the isobutyl esters of Arg and ¹⁵N₂‐Arg (labeled at the guanidino group) were explored by electrospray ionization (ESI)‐tandem mass spectrometry and fragmentation pathways not described before were characterized. In addition, Arg, ¹⁸O₂‐Arg, ¹⁵N₂‐Arg and ¹⁵N₂‐¹⁸O₂‐Arg were also analyzed to elucidate some of the minor fragments in greater detail. Mosquito excreta from individual females were collected before and at different times after feeding a blood meal, mixed with ¹⁵N₂‐Arg, an internal standard, and then derivatized as isobutyl esters. Based on the fragmentation mechanisms of Arg standards, studied by MS² and MS³, Arg in the mosquito excreta was successfully analyzed by ESI‐multiple reaction monitoring in a triple‐quadrupole mass spectrometer. Arg excretion was monitored over a 120 h window before and after feeding female mosquitoes with a blood meal, with the maximum level of Arg excretion observed at 36–48 h post blood feeding. This method provides an efficient and rapid tool to quantify Arg in individual blood‐fed mosquitoes, and can be applied to other organisms, whose small size severally limits the use of conventional biochemical analysis. Copyright © 2012 John Wiley & Sons, Ltd.     

Detection of buffalo mozzarella adulteration by an ultra‐high performance liquid chromatography tandem mass spectrometry methodology

Over the past years, LC–MS‐based approaches have gained a growing interest in food analysis by using different platforms and methodologies. In particular, enhanced selectivity and sensitivity of multiple reaction monitoring (MRM) scan function offer powerful capabilities in detecting and quantifying specific analytes within complex mixtures such as food matrices. The MRM approach, traditionally applied in biomedical research, is particularly suitable for the detection of food adulteration and for the verification of authenticity to assure food safety and quality, both recognized as top priorities by the European Union Commission. Increasingly stringent legislation ensure products safety along every step ‘from farm to fork’, especially for traditional foods designed with the Protected Designation of Origin certification. Therefore, there is a growing demand of new methodologies for defining food authenticity in order to preserve their unique traits against frauds. In this work, an ultra performance liquid chromatopgraphy‐electrospray ionization‐tandem mass spectrometry (MS/MS) methodology based on MRM has been developed for the sensitive and selective detection of buffalo mozzarella adulteration. The targeted quantitative analysis was performed by monitoring specific transitions of the phosphorylated β‐casein f33‐48 peptide, identified as a novel species‐specific proteotypic marker. The high sensitivity of MRM‐based MS and the wide dynamic range of triple quadrupole spectrometers have proved to be a valuable tool for the analysis of food matrices such as dairy products, thus offering new opportunities for monitoring food quality and adulterations. Copyright © 2012 John Wiley & Sons, Ltd.     

Evaluation of protein quantification using standard peptides containing single conservative amino acid replacements

Structural analogs are evaluated as peptide internal standards for protein quantification with liquid chromatography‐multiple reaction monitoring mass spectrometry (LC‐MRM); specifically, single conservative amino acid replacements (SCAR) are performed to create tagged standards that differ by the addition or subtraction of a single methylene group in one amino acid side chain. Because the performance of stable isotope‐labeled standards (SIS) has been shown to be superior to structural analogs, differences in both development and quantitative performance between assays based on SIS and SCAR peptides are explored. To establish an assay using the structural analogs, analysis of endogenous, SCAR and SIS peptides was performed to examine their ion signal, fragmentation patterns and response in LC‐MRM. Performance of SCAR and SIS peptides was compared for quantification of epidermal growth factor receptor from lung cancer cell lysates and immunoglobulin M in the serum of multiple myeloma patients. Copyright © 2012 John Wiley & Sons, Ltd.     

基于异步延迟采样的光通信性能监测方法

基于异步延迟采样和人工神经网络统计学习提出了一种光通信性能监测方法。通过对高速光信号进行异步延迟采样,获得信号二维幅度直方图,然后提取其中特征参数并对人工神经网络进行训练,最后以人工神经网络的预测输出实现对光信号损伤的监测。构建10 Gb/s非归零码开关键控,40 Gb/s光学双二进制码和归零码差分移相键控光通信仿真系统,并对光信噪比、色散和偏振模色散损伤进行监测。仿真结果表明,所提方法对被监测光信号的速率、码型调制格式透明,可同时准确监测多种并存的传输损伤,损伤参数监测误差小于5%。该方法具有电域处理带宽要求低、采样机制简单的特点,适用于分布式在线光性能监测。     

In vitro evaluation of the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves

The objective of this study was to assess in vitro the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curves formed from dynamic contrast-enhanced ultrasound image loops. An indicator-dilution experiment was developed with an in vitro flow phantom setup used with SonoVue contrast agent (Bracco SpA, Milan, Italy). Imaging was performed with a Philips iU22 scanner and two transducers (L9-3 linear and C5-1 curvilinear). The following ultrasound scanner settings were investigated, along with contrast bolus volume: contrast-specific nonlinear pulse sequence, gain, mechanical index, focal zone depth, acoustic pulse center frequency and bandwidth. Four parameters (rise time, mean transit time, peak intensity, and area under the curve) were derived from time-intensity curves which were obtained after pixel by pixel linearization of log-compressed data (also referred to as video data) included in a region of interest. Rise time was found to be the parameter least impacted by changes to ultrasound scanner settings and contrast bolus volume; the associated coefficient of variation varied between 0.7% and 6.9% while it varied between 0.8% and 19%, 12% and 71%, and 9.2% and 66%, for mean transit time, peak intensity, and area under the curve, respectively. The present study assessed the impact of ultrasound scanner settings and contrast bolus volume on time-intensity curve analysis. One should be aware of these issues to standardize their technique in each specific organ of interest and to achieve accurate, sensitive, and reproducible data using dynamic contrast-enhanced ultrasound. One way to mitigate the impact of ultrasound scanner settings in longitudinal, multi-center quantitative dynamic contrast-enhanced ultrasound studies may be to prohibit any adjustments to those settings throughout a given study. Further clinical studies are warranted to confirm the reproducibility and diagnostic or prognostic value of time-intensity curve parameters measurements in a particular clinical scenario of interest, for example that of cancer patients undergoing vascular targeting therapies.