Application of Sensitivity Analysis to Discover Potential Molecular Drug Targets

Mathematical modeling of signaling pathways and regulatory networks has been supporting experimental research for some time now. Sensitivity analysis, aimed at finding model parameters whose changes yield significantly altered cellular responses, is an important part of modeling work. However, sensitivity methods are often directly transplanted from analysis of technical systems, and thus, they may not serve the purposes of analysis of biological systems. This paper presents a novel sensitivity analysis method that is particularly suited to the task of searching for potential molecular drug targets in signaling pathways. Using two sample models of pathways, p53/Mdm2 regulatory module and IFN-β-induced JAK/STAT signaling pathway, we show that the method leads to biologically relevant conclusions, identifying processes suitable for targeted pharmacological inhibition, represented by the reduction of kinetic parameter values. That, in turn, facilitates subsequent search for active drug components.     

强流管辐射剂量率点灵敏度计数值误差范围确定

主要介绍了盖革-米勒计数管(GM计数管)中一种强流管的工作原理,强流管辐射剂量率点灵敏度计数率误差范围确定,以及误差范围如何计算,为以后的强流管产品生产和源室主管提供一些参考.     

基于数据预测的手机总全向灵敏度(TIS)的快速测试

手机总全向灵敏度（TIS）是OTA测试的重要指标之一。而基于CTIA的步进测试法,测试非常耗时。本文在深入研究基站发射功率和误码率关系的基础上,得出具有一定通用性的拟合函数,进而提出了一种基于数据预测的TIS测试方法。通过编写相应自动测试软件,实现快速测试。该法将大大提高测试效率,有很高的应用和推广价值。     

HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs

HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity.     

矿井火区典型可燃气体对甲烷化学动力学的影响分析

为研究多元混合气体对CH₄爆炸过程的影响,选取矿井火区典型可燃气体CH₄、C₂H₆、C₂H₄、CO、H₂,利用CHEMKIN软件模拟分析了不同组分C₂H₆/C₂H₄/CO/H₂瓦斯混合气体爆炸反应过程。研究结果表明：随着混合气体组分中各可燃气体体积分数的增大,CH₄的爆炸压力和温度不断增高,CH₄体积分数和O₂体积分数迅速下降,点火延迟时间明显缩短;在爆炸产生的有毒有害气体中,CO的体积分数最高;H^*、OH^*自由基的体积分数持续增大,O^*自由基呈现先增大后减小的趋势。敏感性分析发现促进自由基生成的反应步主要是R38(H+O₂$ \\rightleftharpoons $O+OH)和R119(HO₂+CH₃$ \\rightleftharpoons $OH+CH₃O),抑制其生成的主要反应步为R98(OH+CH₄$ \\rightleftharpoons $CH₃+H₂O)和R53(H+CH₄$ \\rightleftharpoons $CH₃+H₂)。     

EFAST Method for Global Sensitivity Analysisof Remote Sensing Model’s Parameters

Sensitivity analysis for parameters of remote sensing physical models is a prerequisite for inversion.The EFAST(Extended Fourier Amplitude Sensitivity Test)as a global sensitivity analysis method,can analyze not only a single parameter’s sensitivity but also the coupling effects among parameters.It is usually applied to analyse parameters’ sensitivity of the high-dimensional nonlinear models.In this paper,the SAIL model is taken as an example,the EFAST method and the field measured data of winter wheat in Shunyi district in 2001 were applied to analyze the model parameters’ sensitivity throughout the growing season and in different growth stages respectively.The results are compared with those of the USM (Uncertainty and Sensitivity Matrix) method.The results show that either the EFAST or the USM method for parameters’ sensitivity analysis of the SAIL model is feasible;but the EFAST method,which takes into account of the coupling effects among all the parameters and the analysis result is global,compared to the USM method,is more objective and comprehensive.     

Error evaluation on experimental stress–strain curve obtained from tube bulging test

To get precise material data for advanced numerical modelling of tube hydroforming process, the tube bulging test is recommended. Stresses and strains in the tube cannot be evaluated easily and several approaches have been proposed. A review is proposed and points out their advantages and drawbacks.     

HTPB推进剂危险性实验研究

依据联合国危险品分级方法,探讨了热刺激、机械刺激和冲击波刺激对低燃速HTPB推进剂、高燃速HTPB推进剂和四组元HTPB推进剂危险性的影响。结果表明,3种HTPB推进剂的热安定性良好,但对火焰热刺激均十分敏感,具有爆燃性;高燃速HTPB推进剂对机械刺激也极其敏感,摩擦感度(p)为96%,撞击感度特性(H50)为37.2 cm。在无约束条件下,3种HTPB推进剂裸药柱对雷管爆轰作用不敏感,而在钢管的强约束条件下,四组元HTPB推进剂对爆轰冲击波作用敏感,隔板值大于18mm。     

Correction and evaluation of the effect due to parasitic motion on primary accelerometer calibration

Primary accelerometer calibration is carried out under the assumption that a vibration exciter gives a rectilinear motion to an accelerometer to be calibrated. However practical vibration given by the vibration exciter includes parasitic motion such as transverse, rocking, and bending motion. Such parasitic motion would give two serious effects on primary calibration results, transverse motion effect and vibration distribution effect. Transverse motion effect is caused by an inner product of the vectors of both transverse motion and transverse sensitivity. On the other hand, the vibration distribution effect is caused by relative motion between a sensing point of accelerometer and a spot sensed by the interferometer. As these effects have close interaction between parasitic motion and measuring instruments, it would be very difficult to evaluate them by measuring independently each component.     

SVC位置和容量的灵敏度和概率分析

可控并补装置位置和容量的合理选择,有助于提高电网运行安全性和经济性。确定运行方式下节点电压对并联电纳的灵敏度指标,反映了有效并补位置,但非必要补偿位置。文中提出采用灵敏度和概率潮流算法,综合确定实际需要并补位置。根据随机故障后并联电纳的概率分布,确定固定和可控补偿容量比例。研究结果表明:根据并补电纳的区间概率分布,可确定可控并补容量及其满足电压控制目标的概率;补偿容量不仅受电网故障方式,也与并补装置电压设定值有关。