Discovery and biological activity of 6BrCaQ as an inhibitor of the Hsp90 protein folding machinery

Heat shock protein 90 (Hsp90) is a significant target in the development of rational cancer therapy, due to its role at the crossroads of multiple signaling pathways associated with cell proliferation and viability. Here, a novel series of Hsp90 inhibitors containing a quinolein‐2‐one scaffold was synthesized and evaluated in cell proliferation assays. Results from these structure–activity relationships studies enabled identification of the simplified 3‐aminoquinolein‐2‐one analogue 2 b (6BrCaQ), which manifests micromolar activity against a panel of cancer cell lines. The molecular signature of Hsp90 inhibition was assessed by depletion of standard known Hsp90 client proteins. Finally, processing and activation of caspases 7, 8, and 9, and the subsequent cleavage of PARP by 6BrCaQ, suggest stimulation of apoptosis through both extrinsic and intrinsic pathways.     

RAFT/MADIX polymers for the preparation of polymer/inorganic nanohybrids

Organic–inorganic hybrid nanocomposites are an emerging class of materials that hold significant promise due to their outstanding properties, which usually arise from a combined and/or synergistic effect of the properties of their organic and inorganic components. Despite the numerous functionalization methods described in literature, only a few of them allow precise and easy control of the chemical composition and structure of the organic shell, whereas this point is critical to control some of the nanohybrids properties such as solubility, specific interaction and so forth. In this context, reversible addition-fragmentation chain transfer polymerization/macromolecular design by interchange of xanthates (RAFT/MADIX) technology is a fantastic tool that can be easily performed in mild and “green” conditions, being compatible with a huge variety of functional monomers and providing an excellent control of the organic shell characteristics. This review aims to describe the state of the art of the use of RAFT/MADIX polymers for the preparation of these nanohybrids. After describing the most commonly used synthetic strategies for nanohybrids preparation, the main families of polymers are discussed in view of their chemical composition (homopolymer, copolymer, …) and/or the targeted properties (hydrophilic, hydrophobic, stimuli-responsive). The main advantages of RAFT/MADIX technology are discussed in terms of the numerous applications of those materials.     

MatrixExplorer: a dual-representation system to explore social networks

MatrixExplorer is a network visualization system that uses two representations: node-link diagrams and matrices. Its design comes from a list of requirements formalized after several interviews and a participatory design session conducted with social science researchers. Although matrices are commonly used in social networks analysis, very few systems support the matrix-based representations to visualize and analyze networks. MatrixExplorer provides several novel features to support the exploration of social networks with a matrix-based representation, in addition to the standard interactive filtering and clustering functions. It provides tools to reorder (layout) matrices, to annotate and compare findings across different layouts and find consensus among several clusterings. MatrixExplorer also supports node-link diagram views which are familiar to most users and remain a convenient way to publish or communicate exploration results. Matrix and node-link representations are kept synchronized at all stages of the exploration process     

A study on Dual-Scale data charts

We present the results of a user study that compares different ways of representing Dual-Scale data charts. Dual-Scale charts incorporate two different data resolutions into one chart in order to emphasize data in regions of interest or to enable the comparison of data from distant regions. While some design guidelines exist for these types of charts, there is currently little empirical evidence on which to base their design. We fill this gap by discussing the design space of Dual-Scale cartesian-coordinate charts and by experimentally comparing the performance of different chart types with respect to elementary graphical perception tasks such as comparing lengths and distances. Our study suggests that cut-out charts which include collocated full context and focus are the best alternative, and that superimposed charts in which focus and context overlap on top of each other should be avoided.     

Promoting insight-based evaluation of visualizations: from contest to benchmark repository

Information Visualization (InfoVis) is now an accepted and growing field but questions remain about the best uses for and the maturity of novel visualizations. Usability studies and controlled experiments are helpful but generalization is difficult. We believe that the systematic development of benchmarks will facilitate the comparison of techniques and help identify their strengths under different conditions. We were involved in the organization and management of three information visualization contests for the 2003, 2004 and 2005 IEEE InfoVis Symposia, which requested teams to report on insights gained while exploring data. We give a summary of the state of the art of evaluation in information visualization, describe the three contests, summarize their results, discuss outcomes and lessons learned, and conjecture the future of visualization contests. All materials produced by the contests are archived in the InfoVis Benchmark Repository.     

基于ANSYS的概率有限元分析

受激烈的竞争所驱使,工业制造商们处于一个持续增长的压力当中,即在产品日趋复杂化的今天,他们还需要保持技术和利益的最优化。此外,产品的随机性和不确定性也是一个挑战。因此,需要概率工具来为这些挑战寻找一个平衡。ANSYS公司开发了两个工具,分别是ANSYS概率设计系统和ANSYS Design Xplorer。本文介绍了这些软件的运算法则和方法原理,并特别对软件中提供的变分法提出讨论和解释。变分法是一种非常有效的方法,可以基于单个有限元分析,提供准确、高阶的反应面。本文还讨论了此法的功能和优缺点以及通过并行计算减少程序运行时间的可能性。强调了评估结果准确性和有效性的各种方法、程序对结果进行后处理的多种功能、对多种或可能冲突的目标进行优化的方法和功能。最后,运用各种工程实例说明了软件的应用过程。     

Leaching assessments of hazardous materials in cellular telephones

Protocols for assessing the risks of discarded electronic products (e-waste) vary across jurisdictions, complicating the tasks of manufacturers and regulators. We compared the Federal Toxicity Characteristic Leaching Procedure (TCLP), California's Waste Extraction Test (WET), and the Total Threshold Limit Concentration (TTLC) on 34 phones to evaluate the consistency of hazardous waste classification. Our sample exceeded TCLP criteria only for lead (average 87.4 mg L(-1); range = 38.2-147.0 mg L(-1); regulatory limit = 5.0 mg L(-1), but failed TTLC for five metals: copper (average 203 g kg(-1); range = 186-224 g kg(-1); limit = 2.50 g kg(-1), nickel (9.25 g kg(-1); range = 6.34-11.20 g kg(-1); limit = 2.00 g kg(-1)), lead (10.14 g kg(-1); range = 8.2211.60 g kg(-1); limit = 1.00 g kg-1), antimony (1.02 g kg(-1); range = 0.86-1.29 g kg(-1); limit = 0.50 g kg(-1)), and zinc (11.01 g kg(-1); range = 8.82-12.80 g kg(-1); limit = 5.00 g kg(-1). Thresholds were not exceeded for WET. We detected several organic compounds, but at concentrations below standards. Brominated flame retardants were absent. These results improve existing environmental databases for e-waste and highlight the need to review regulatory testing for hazardous waste.     

Probabilistic finite element analysis using ANSYS

Driven by stiff competition, industrial manufacturers find themselves under growing pressure to optimize apparently conflicting technical and financial goals in an environment of ever increasing product complexity. In addition, this challenge is to be met under the existence of randomness and uncertainty, which the products are subjected to. Consequently, finding the right balance between conflicting goals under the existence of uncertainties requires the use of probabilistic tools. To achieve this, ANSYS Inc. has released two tools, namely the ANSYS Probabilistic Design System and the ANSYS DesignXplorer. This paper describes the problems that can be addressed, the underlying algorithms implemented and methodologies of these methods in both tools. A special topic of the paper is the discussion and explanation of the Variational Technology, which is offered in both tools. Variational Technology is a highly efficient method to provide accurate, high-order response surfaces based on a single finite element analysis. The capabilities, strengths and weaknesses of these methods are discussed. The possibility to reduce the execution time using parallel computing is discussed. Different measures to assess the accuracy and validity of the results obtained with the different probabilistic methods are given special attention. Various capabilities to post-process the probabilistic results are mentioned. The methods and the capabilities to optimize multiple and possibly conflicting goals are highlighted. Finally, the application of the software is illustrated using various industrial example problems.