The Pharmacokinetics in Mice and Cell Uptake of Thymus Immunosuppressive Pentapeptide Using LC-MS/MS Analysis

Thymus immunosuppressive pentapeptide (TIPP) is a novel anti-inflammatory peptide with high efficacy and low toxicity. This study aims to establish a selective LC-MS/MS method for analyzing the analyte TIPP in biological samples, laying the foundation for further PK and PD studies of TIPP. Protein precipitation was conducted in acetonitrile supplemented with 2% formic acid and 25 mg/mL dithiothreitol as a stabilizer, which was followed by backwashing the organic phase using dichloromethane. The chromatographic separation of TIPP was achieved on a C18 column with a gradient elution method. During positive electrospray ionization, TIPP was analyzed via multiple-reaction monitoring. The linear relationships between the concentration of TIPP and peak area in murine plasma cell lysates, supernatants, and the final cell rinse PBS were established within the ranges of 20–5000 ng/mL, 1–200 ng/mL, 10–200 μg/mL, and 0.1–20 ng/mL, respectively (r² > 0.99). Validated according to U.S. FDA guidelines, the proposed method was proved to be acceptable. Such a method had been successfully applied to investigate the pharmacokinetics of TIPP in mice via subcutaneous injection. The plasma half-life in mice was 5.987 ± 1.824 min, suggesting that TIPP is swiftly eliminated in vivo. The amount of TIPP uptake by RBL-2H3 cells was determined using this method, which was also visually verified by confocal. Furthermore, the effective intracellular concentration of TIPP was deduced by comparing the intracellular concentration of TIPP and degrees of inflammation, enlightening further investigation on the intracellular target and mechanism of TIPP.     

基于均匀先验分布武器射程评定的Bayes方法

应用Bayes统计方法进行武器射程的评定,可以有效减少试验的样本量,节省试验弹药,Bayes方法的关键是确定先验分布,均匀分布是比较容易确定的一种先验分布,该文给出了基于均匀先验分布武器射程评定的Bayes方法,对改进射程的评定方法,减少试验用弹量,具有重要作用.     

中国银行间拆借利率扩散模型的极大拟似然估计

本文用极大拟似然估计法估计了中国银行间市场七天拆借利率扩散模型的参数。并用自助法对众多不同的模型进行了广义拟似然比检验。结论表明:中国货币市场利率具有均值回复效应:利率敏感系数γ值为1.421265,对利率水平具有较高敏感性。     

The DI-SPME Method for Determination of Selected Narcotics and Their Metabolites,and Application to Bone Marrow and Whole Blood Analysis

The present investigation utilised the quick and easy SPME/LC-MS method to determine selected narcotic substances and their metabolites in whole blood. The study included qualitative analysis and validation of the method. Analytes were determined in the linearity range of 25–300 ng/mL. The precision during and between days (in general CV < 13.41%), and the LOD which results in between 0.36 and 11.08 ng/mL, and the LOQ between 1.20 and 36.90 ng/mL were investigated. The validation results obtained, as well as the results of subsequent in-laboratory tests, confirmed the applicability of the method in the analysis of blood samples. An attempt to apply the method to the analysis of bone marrow samples has yielded promising results; however, more detailed studies are needed in this area.     

基于改进GMM与帧差法的运动棉杂率分析算法研究

针对清梳棉流程中产出棉含杂高、质量差的问题,结合改进高斯混合模型(Gaussian mixed model,GMM)与帧差法,提出一种局部运动棉杂率控制优化方法。首先针对清棉机除杂原理及棉杂特性进行分析;其次通过提取视频关键帧并改进GMM与帧差法对图像序列“与”运算实现目标的精确提取,进而通过设计GMM分类器获得棉杂率并进行分析;最后与传统的检测算法作对比验证。实验表明,改进后的算法在有效性以及实用性方面优于传统算法。同时,通过引入闭环控制能满足工业高精度、实时性的需求。     

Theoretical Investigating Mechanisms of Drug-Resistance Generated by Mutation-Induced Changes in Influenza Viruses

Influenza A (A/H\begin{document}$ x $\end{document}N\begin{document}$ y $\end{document}) is a significant public health concern due to its high infectiousness and mortality. Neuraminidase, which interacts with sialic acid (SIA) in host cells, has become an essential target since its highly conserved catalytic center structure, while resistance mutations have already generated. Here, a detailed investigation of the drug resistance mechanism caused by mutations was performed for subtype N9 (A/H7N9). Molecular dynamics simulation and alanine-scanning-interaction-entropy method (ASIE) were used to explore the critical differences between N9 and Zanamivir (ZMR) before and after R294K mutation. The results showed that the mutation caused the hydrogen bond between Arg294 and ZMR to break, then the hydrogen bonding network was disrupted, leading to weakened binding ability and resistance. While in wild type (A/H7N9\begin{document}$ ^{ \rm{WT}} $\end{document}), this hydrogen bond was initially stable. Meanwhile, N9 derived from A/H11N9 was obtained as an R292K mutation. Then the relative binding free energy of N9 with five inhibitors (SIA, DAN, ZMR, G28, and G39) was predicted, basically consistent with experimental values, indicating that the calculated results were reliable by ASIE. In addition, Arg292 and Tyr406 were hot spots in the A/H11N9\begin{document}$ ^{ \rm{WT}} $\end{document}-drugs. However, Lys292 was not observed as a favorable contributing residue in A/H11N9\begin{document}$ ^{ \rm{R292K}} $\end{document}, which may promote resistance. In comparison, Tyr406 remained the hotspot feature when SIA, ZMR, and G28 binding to A/H11N9\begin{document}$ ^{ \rm{R292K}} $\end{document}. Combining the two groups, we speculate that the resistance was mainly caused by the disruption of the hydrogen bonding network and the transformation of hotspots. This study could guide novel drug delivery of drug-resistant mutations in the treatment of A/H\begin{document}$ x $\end{document}N9.     

一类由一维概率密度函数构造多维概率密度函数的方法

将文献[1]给出的由一维连续型随机变量的概率密度函数构造二维连续型随机变量的概率密度函数的方法,推广为由一维连续型随机变量的概率密度函数构造三维连续型随机变量的概率密度函数的情况,并作出了证明和举例说明.说明利用本文的方法构造多维概率密度函数,其方法简单易行.     

用方阵乘幂求和法求线性方程组的数值解

介绍了一种新型的,不同于传统的雅克比或高斯塞德尔迭代法的,求解线性方程组的方阵乘幂求和法,并引入了方阵意义上求积分的龙贝格法.该算法成立须以方阵A为实阵,非奇异且主对角元素占优.该法较雅克比或高斯塞德尔迭代的计算量小,特别有助于求解大型线性方程组的问题.     

基于谐波结构的钢琴基频估计方法

精确估计钢琴声音的基频,可以帮助调音师进行调律.由于钢琴声音的谐波结构存在基频丢失、谐波丢失以及不谐和性等特殊性,常用基频估计方法精度低甚至出现严重错误.本文基于谐波频率的不谐和性特征,应用最小二乘法估计声音的基频和不谐和系数.仿真实验表明,该方法切实可行,检测精度显著提高,满足钢琴定音调律的要求.     

基于嵌入式的智能流速仪研制

流速仪为水工筑建设计提供准确的江河的流速值,随着应用需求的增加,原有的8位单片机控制系统不能完全满足现代水文测量的需要。本文研制了一种旋桨式传感器的智能流速仪,以AT91SAM9261为微处理器,采用CPLD芯片为流速数据采集接口,配以TFT-LCD显示屏,移植uClinux实时操作系统,具有测周、计数、双向测速等多种测量方式,可实现16个通道同步独立检测。系统测量方式灵活,测量时间短,测量精度高,稳定可靠等特点,广泛用于水文检验部门和科研设计院等单位。