药物免修饰的药靶鉴定蛋白质组方法研究进展

药物靶蛋白的筛选是现代药物研发过程必不可少的步骤。传统的药物靶点筛选通常使用假设驱动的生物学实验进行药物靶点的逐个验证，近年来高通量、高分辨质谱技术的进步以及液相色谱-质谱联用技术的发展，促进了蛋白质组学技术在药物靶蛋白筛选领域的广泛应用。化学蛋白质组学技术在药物-蛋白相互作用研究领域已取得巨大突破，因其需要在药物小分子结构上进行化学衍生等问题，最近新兴的药物免修饰的靶蛋白筛选技术引起广泛关注。本文综述了近15年来药物免修饰（非化学修饰）的药物靶蛋白筛选方法的研究进展，包括细胞热位移分析（CETSA）、热蛋白质组分析（TPP）、蛋白质氧化速率稳定性分析（SPROX）、基于有机溶剂沉淀蛋白稳定性方法（SIP）、药物亲和相应靶点稳定性分析（DARTS）、脉冲酶解法（PP）、限制性酶解法（LiP）等，并比较了这些方法的优势、局限性以及应用场景。     

Method for Characterization of Solvents for Physical Absorption Processes

A method for solvent screening and searching for additives in the field of physical absorption processes is presented. A model based on the concept of virtual components and on the concept of a simplified abstract flow sheet is created. An estimation procedure for thermodynamically consistent property sets for the virtual component is developed. The model is implemented into MATLAB®. Its application is demonstrated in two studies including a study for a solvent additive. Potential candidates can be characterized and ranges for properties of the solvent or additive are found by means of the model. Conclusions obtained from the model support the screening process by a reduction of the number of further investigated components.     

3D QSAR Studies,Pharmacophore Modeling and Virtual Screening on a Series of Steroidal Aromatase Inhibitors

Aromatase inhibitors are the most important targets in treatment of estrogen-dependent cancers. In order to search for potent steroidal aromatase inhibitors (SAIs) with lower side effects and overcome cellular resistance, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of SAIs to build 3D QSAR models. The reliable and predictive CoMFA and CoMSIA models were obtained with statistical results (CoMFA: q² = 0.636, r²_ncv = 0.988, r²_pred = 0.658; CoMSIA: q² = 0.843, r²_ncv = 0.989, r²_pred = 0.601). This 3D QSAR approach provides significant insights that can be used to develop novel and potent SAIs. In addition, Genetic algorithm with linear assignment of hypermolecular alignment of database (GALAHAD) was used to derive 3D pharmacophore models. The selected pharmacophore model contains two acceptor atoms and four hydrophobic centers, which was used as a 3D query for virtual screening against NCI2000 database. Six hit compounds were obtained and their biological activities were further predicted by the CoMFA and CoMSIA models, which are expected to design potent and novel SAIs.     

Three-level designs: Evaluation and comparison for screening purposes

Since their introduction by Box and Hunter, resolution criteria have been widely used when comparing regular fractional factorials designs. In this article, we investigate how a generalized resolution criterion can be used to assess some recently developed three-level screening designs, such as definitive screening designs (DSDs) and screening designs from weighing matrices. The aim of this paper is to capture the projection properties of those three-level screening designs, complementing the work of Deng and Tang, who used generalized resolution and minimum aberration criteria for ranking different two-level designs, particularly Plackett-Burman and other nonregular factorial designs. An advantage of generalized resolution, extended here to work on three-level designs, is that it offers a useful criterion for ranking three-level screening designs, whereas the Deng and Tang resolution is used mainly for the assessment of two-level designs. In addition, we applied a projection estimation capacity (PEC) criterion to select three-level screening designs with desirable properties. Practical examples and the best projections of the designs are presented in tables.     

Scheme design considering network topology and multi-attribute decision-making for under frequency load shedding

Power system emergency control is one key defense strategy in contingencies for protecting the system from cascading blackout. Under Frequency Load Shedding (UFLS) is one such strategy to ensure system stability by shedding load to retrieve balance between power supply and demand. Novel UFLS scheme design and a scheme optimization approach are proposed in this paper to find the optimal load-shedding schemes for different network partition resulted from contingencies. To obtain all possible UFLS schemes for a certain area, a candidate scheme set design algorithm based on value assigning of scheme parameters is proposed and then a relatively complete candidate scheme set is constructed. Considering network splitting caused by protection, several subsystems may exist from the reconstruction of independent network areas. The concept of homological area is defined and a graph-based method is used to analyse system topology change. Then, a multi-attribute decision-making (MADM) algorithm is introduced for order preference by similarity to an ideal solution (TOPSIS) for global optimizing candidate schemes. Optimal schemes for an area in both isolated area and homological area cases can be derived from all feasible UFLS schemes by MADM method. Simulation results demonstrate that the UFLS schemes can effectively restore system frequency in different network topologies.     

变频节能技术在山煤国际澄蓉选煤厂的应用

随着国家对环保、节能降耗要求的提高,以重介工艺为主的选煤厂大力响应国家的环保政策,实现节能降耗。山煤国际能源澄蓉选煤厂对合格介质泵304(450 kW)、精磁泵328(200 kW)、中矸泵(90 kW)、浮选入料泵402(185 kW)、循环水泵604(200 kW)等大功率电机(占全厂总容量33.3%)采用美国圣诺变频器进行调控,仅电能一项每年就为公司节省了近200万元。采用变频器来控制大功率的泵类设备,还可以降低电机的噪音污染、减少管路阀门的机械磨损、延长泵的使用寿命,节省了人力和物力。     

煤炭装卸系统增设筛分设备的改造方法

在简单介绍煤炭专业化连续输送系统和煤炭筛分设备知识的基础上,结合天津港煤码头公司卸车系统筛分设备改造的相关内容,阐述了在传统煤炭连续输送系统中进行煤炭筛分设备改造的方法。     

Increasing X-ray image interpretation competency of cargo security screeners

X-ray screening of containers and unit load devices in the area of cargo shipping is becoming an essential and common feature at ports and airports all over the world. The detection of prohibited items in X-ray images is a challenging task for screening officers as they need to know which items are prohibited and what they look like in X-ray images. The main aim of this study was to investigate whether X-ray image interpretation competency of cargo security screeners can be increased by computer-based training. More specifically, effects of training were investigated by conducting tests before training started and after approximately three months of training. Moreover, it was examined whether viewing X-ray images in pseudo color would lead to a better detection performance compared to when X-ray images are shown in greyscale. Recurrent computer-based training resulted in large performance increases after three months. No significant difference in detection performance could be found for tests when using X-ray images in greyscale vs. pseudo color.     

Development of efficient docking strategies and structure-activity relationship study of the c-Met type II inhibitors

c-Met is a transmembrane receptor tyrosine kinase and an important therapeutic target for anticancer drugs. In the present study, we systematically investigated the influence of a range of parameters on the correlation between experimental and calculated binding free energies of type II c-Met inhibitors. We especially focused on evaluating the impact of different force fields, binding energy calculation methods, docking protocols, conformation sampling strategies, and conformations of the binding site captured in several crystallographic structures. Our results suggest that the force fields, the protein flexibility, and the selected conformation of the binding site substantially influence the correlation coefficient, while the sampling strategies and ensemble docking only mildly affect the prediction accuracy. Structure-activity relationship study suggests that the structural determinants to the high binding affinity of the type II inhibitors originate from its overall linear shape, hydrophobicity, and two conserved hydrogen bonds. Results from this study will form the basis for establishing an efficient computational docking approach for c-Met type II inhibitors design.