A novel LC–MS/MS method for the determination of ziritaxestat in rat plasma and its pharmacokinetic study

Ziritaxestat is a first-in-class autotoxin inhibitor. The purpose of this study was to develop a liquid chromatography/electrospray ionization tandem mass spectrometric (LC–MS/MS) method for the determination of ziritaxestat in rat plasma. The plasma sample was deproteinated using acetonitrile and then separated on an Acquity BEH C₁₈ column with water containing 0.1% formic acid and acetonitrile as mobile phase, which was delivered at 0.4 ml/min. Ziritaxestat and the internal standard (crizotinib) were quantitatively monitored with precursor-to-product transitions of m/z 589.3 > 262.2 and m/z 450.1 > 260.2, respectively. The total running time was 2.5 min. The method showed excellent linearity over the concentration range 0.5–2000 ng/ml, with correlation coefficient >0.9987. The extraction recovery was >82.09% and the matrix effect was not significant. Inter- and intra-day precisions (RSD) were <11.20% and accuracies were in the range of −8.50–7.45%. Ziritaxestat was demonstrated to be stable in rat plasma under the tested conditions. The validated LC–MS/MS method was successfully applied to study the pharmacokinetic profiles of ziritaxestat in rat plasma after intravenous and oral administration. Pharmacokinetic results demonstrated that ziritaxestat displayed a short half-life (~3 h) and low bioavailability (20.52%).     

The antidepressant effect of 4-hydroxybenzyl alcohol 2-naphthoate through monoaminergic,GABAergic system and BDNF signaling pathway

Abstract

Gastrodigenin, also known as 4-hydroxybenzyl alcohol (HBA), is one of the main components of Gastrodia elata, which is a perfect lead compound of natural products. In order to get new active compounds, we modified the structure of HBA through esterification with carboxylic acid, and got a series of derivatives in which 4-hydroxybenzyl alcohol 2-naphthoate (NHBA) showed stronger antidepressant activity than HBA. In this paper, we firstly evaluated the antidepressant activity of NHBA by tail suspension test (TST) and forced swimming test (FST). Then, we carried out the biochemical assay and western blot to determine its mechanism. The results displayed that NHBA could increase the content of serotonin, dopamine, norepinephrine, γ-aminobutyric acid, brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) in mice brain. It suggested that NHBA exhibited an antidepressant-like effect through monoaminergic system, GABAergic system and BDNF/TrkB signaling pathways.     

基于DIS数字信息化系统对透光物质透光性能的研究

采用DIS数字信息化系统,对不同浓度的蓝墨水溶液在激光光源照射下的透射平均照度及照度分布图像进行实验研究,得到了平均照度值随溶液浓度变化的规律。对不同颜色塑料膜片对白炽灯光源透过照度值及照度分布图像进行实验研究得到及其相关之规律。     

Decay rate for viscoelastic wave equation of variable coefficients with delay and dynamic boundary conditions

In this paper, we consider a viscoelastic wave equation of variable coefficients in the presence of past history with nonlinear damping and delay in the internal feedback and dynamic boundary conditions. Under suitable assumptions, we establish an explicit and general decay rate result without imposing restrictive assumption on the behavior of the relaxation function at infinity by Riemannian geometry method and Lyapunov functional method.     

基于CVSD编码的无线语音系统方案的设计

简要介绍了连续可变斜率增量(CVSD)调制的原理。与目前应用较为广泛的其它语音编码方式相比较,CVSD拥有更优的数字特性。着重介绍了由CML公司研制开发的基于CVSD的语音编码芯片———CMX649的特点及相关的应用方式。CMX649能够成功地应用在广泛的语音编码系统中,尤其适合无线语音系统应用。在此基础上,给出了一种实用性很强的低成本、低功耗无线语音系统的设计与应用方案。该方案可提供清晰可靠的语音传输,可广泛应用于农村地区,具有广阔的市场空间。     

IDS告警融合与关联模型的研究

入侵检测是保障网络安全的重要手段,针对现有入侵检测系统中告警数量多、协调性差等问题,论文提出了一种具有告警融合与关联功能的告警处理系统模型,该模型冗余告警量少、整体检测能力强,并能进行攻击企图的预测,能有效提高入侵检测的效率,有助于进一步增强网络的健壮性。     

Frequency Insertion Strategy for Channel Assignment Problem

This paper presents a new heuristic method for quickly finding a good feasible solution to the channel assignment problem (CAP). Like many other greedy-type heuristics for CAP, the proposed method also assigns a frequency to a call, one at a time. Hence, the method requires computational time that increases only linear to the number of calls. However, what distinguishes the method from others is that it starts with a narrow enough frequency band so as to provoke violations of constraints that we need to comply with in order to avoid radio interference. Each violation is then resolved by inserting frequencies at the most appropriate positions so that the band of frequencies expands minimally. An extensive computational experiment using a set of randomly generated problems as well as the Philadelphia benchmark instances shows that the proposed method perform statistically better than existing methods of its kind and even yields optimum solutions to most of Philadelphia benchmark instances among which two cases are reported for the first time ever, in this paper. Won-Young Shin was born in Busan, Korea in 1978. He received B.S. in industrial engineering from Pohang University of Science and Technology (POSTECH) in 2001 and M.S in operation research and applied statistics from POSTECH in 2003. Since 2003 he has been a researcher of Agency for Defense Development (ADD) in Korea. He is interested in optimization of communication system and applied statistics. Soo Y. Chang is an associate professor in the Department of Industrial Engineering at Pohang University of Science and Technology (POSTECH), Pohang, Korea. He teaches linear programming, discrete optimization, network flows and operations research courses. His research interests include mathematical programming and scheduling. He has published in several journals including Discrete Applied Mathematics, Computers and Mathematics with Application, IIE Transactions, International Journal of Production Research, and so on. He is a member of Korean IIE, and ORMSS. Jaewook Lee is an assistant professor in the Department of Industrial Engineering at Pohang University of Science and Technology (POSTECH), Pohang, Korea. He received the B.S. degree in mathematics with honors from Seoul National University, and the Ph.D. degree from Cornell University in applied mathematics in 1993 and 1999, respectively. He is currently an assistant professor in the department of industrial engineering at the Pohang University of Science and Technology (POSTECH). His research interests include nonlinear systems, neural networks, nonlinear optimization, and their applications to data mining and financial engineering. Chi-Hyuck Jun was born in Seoul, Korea in 1954. He received B.S. in mineral and petroleum engineering from Seoul National University in 1977, M.S. in industrial engineering from Korea Advanced Institute of Science and Technology in 1979 and Ph.D. in operations research from University of California, Berkeley, in 1986. Since 1987 he has been with the department of industrial engineering, Pohang University of Science and Technology (POSTECH) and he is now a professor and the department head. He is interested in performance analysis of communication and production systems. He has published in several journals including IIE Transactions, IEEE Transactions, Queueing Systems and Chemometrics and Intelligent Laboratory Systems. He is a member of IEEE, INFORMS and ASQ.     

运动会新闻发布系统的设计与实现

针对运动会比赛期间随时需要方便、快捷、高效地更新大量新闻的需求 ,研制和开发一套运动会新闻发布系统。利用微软最新推出的asp .net动态网页开发工具 ,采用web分布式三层设计模型设计实现了一套操作简单、功能完善、具有通用性的运动会新闻发布系统     

简化形式的系统EMC预测分析技术概述

本文探讨了系统级简化形式的电磁兼容性预测分析方法，该方法对于只有几对发-收干扰对的系统EMI的预测分析简洁有效，它避免了大系统间繁复的建模与大量的数据采集及其计算工作，从而对于只考虑其结果的系统间的EMC预测分析提高了效率。     

指纹考勤管理软件的研究与实现

针对企、事业单位原有的考勤系统，如打卡钟、磁卡、IC卡等考勤方式存在代打卡、卡丢失等不足和缺陷的实际，结合指纹识别技术，建立一套考勤、薪资、人事管理于一体的软件系统。给出了系统的体系结构和功能实现，能使企业考勤管理更加简便快捷、客观公正。并提出了进一步的发展方向和展望。