Het(aryl)isatin to het(aryl)aminoindoline scaffold hopping: A route to selective inhibitors of matrix metalloproteinases

Matrix metalloproteinases (MMPs) are a large family of zinc-dependent endoproteases known to exert multiple regulatory roles in tumor progression. A variety of chemical classes have been explored for targeting individual MMP isoforms. In the present study, we further developed our isatin based scaffold BB0223107 capable of binding to and inactivating MMP-2 in a zinc-independent manner (Agamennone et al., 2016). Forty four new compounds were synthesized based on the modified BB0223107. All compounds were tested in enzyme inhibition assays against MMP-2, ?8 and ?13. SAR studies demonstrated that 5-het(aryl)-3-aminoindolin-2-ones (37–39) were active toward MMP-2 and MMP-13. The most potent compounds 33 and 37 displayed an IC₅₀ of 3 µM against MMP-13 and showed a negligible activity toward MMP-8; almost all new compounds were inactive toward MMP-8. Replacement of the isatin ring with a biaryl system (compound 33) did not decrease the potency against MMP-13 but reduced the selectivity. Structure-based computational studies were carried out to rationalize the inhibitory activity data. The analysis of binding geometries confirmed that all fragments occupied the S1′ site in the three enzymes while no ligand was able to bind the catalytic zinc ion. To the best of our knowledge, this is the first example of 3-aminoindolin-2-one-based MMP inhibitors that, based on the computer modeling study, do not coordinate the zinc ion. Thus, the het(aryl)-3-aminoindolin-2-one derivatives emerge as a drug-like and promising chemotype that, along with the hetaryl variations, represents an alternative and thrifty tool for chemical space exploration aimed at MMP inhibitor design.     

Concurrent multiresponse non-linear screening: Robust profiling of webpage performance

Profiling engineered data with robust mining methods continues attracting attention in knowledge engineering systems. The purpose of this article is to propose a simple technique that deals with non-linear multi-factorial multi-characteristic screening suitable for knowledge discovery studies. The method is designed to proactively seek and quantify significant information content in engineered mini-datasets. This is achieved by deploying replicated fractional-factorial sampling schemes. Compiled multi-response data are converted to a single master-response effectuated by a series of distribution-free transformations and multi-compressed data fusions. The resulting amalgamated master response is deciphered by non-linear multi-factorial stealth stochastics intended for saturated schemes. The stealth properties of our method target processing datasets which might be overwhelmed by a lack of knowledge about the nature of reference distributions at play. Stealth features are triggered to overcome restrictions regarding the data normality conformance, the effect sparsity assumption and the inherent collapse of the ‘unexplainable error’ connotation in saturated arrays. The technique is showcased by profiling four ordinary controlling factors that influence webpage content performance by collecting data from a commercial browser monitoring service on a large scale web host. The examined effects are: (1) the number of Cascading Style Sheets files, (2) the number of JavaScript files, (3) the number of Image files, and (4) the Domain Name System Aliasing. The webpage performance level was screened against three popular characteristics: (1) the time to first visual, (2) the total loading time, and (3) the customer satisfaction. Our robust multi-response data mining technique is elucidated for a ten-replicate run study dictated by an L₉(3⁴) orthogonal array scheme where any uncontrolled noise embedded contribution has not been necessarily excluded.     

基于老厂房改造的景观规划设计

随着城市化高速发展，老厂房再利用的问题日益急迫.上海是中国近代工业起源地,也是率先着手对彰显城市文脉的工业遗产进行调查和保护的历史文化名城.本文以上海典型案例入手，分析了具有代表性的老厂房改造的项目特点，并在此基础上，对常州大成三厂这一民国时期的纺织业遗留地块进行改造设计手法进行介绍，从设计理念、设计内容和节点设计3个方面，体现了文化传承和生态技术相融合理念.     

Molecular design of ambipolar redox-active molecules II: closed-shell systems

This mini-review highlights key structural features that should be taken into account when creating ambipolar redox-active closed-shell metal-free molecules. This type of compound is strongly required for the fabrication of all-organic ‘poleless’ batteries and semiconductors. The suggested strategies aimed at stabilization of both oxidized (cationic) and reduced (anionic) redox-states are based on the comprehensive analysis of the most successful structures taken from the recent publications.     

基于Android系统的斗地主游戏的设计与实现

随着智能手机的迅猛发展,Wi Fi的全民时代到来,手机网络游戏越来越得到人们的青睐.首先设计了基于Android系统的斗地主纸牌游戏的功能模块、类以及数据库,实现了客户端注册、登录、游戏房间选择、多人斗地主以及服务器端接收多个用户连接请求且管理用户信息功能,然后对该游戏中的关键技术进行了详细描述,最后展示了游戏的运行界面.测试效果表明,软件界面友好、操作便捷,能够满足手机用户对斗地主游戏的基本需求.     

重卡驱动桥壳疲劳稳健性与轻量化设计

驱动桥壳轻量化设计对于提高承载能力、降低生产成本具有重要的意义.本文在驱动桥壳有限元分析和疲劳分析计算的基础上建立驱动桥壳多目标优化模型，对重型卡车驱动桥壳进行参数化设计，建立正交试验表，利用田口方法和综合评价方法对驱动桥壳的疲劳性能稳健性和质量进行优化设计.优化结果表明，此方法可以应用于驱动桥壳的多目标优化，优化后驱动桥壳的疲劳稳健性能得到提高，减轻了质量，因此节约了桥壳材料，降低了生产和运营成本，提高了设计水平.     

图书管理系统的设计与应用

结合图书馆信息化发展趋势,对图书管理系统的功能特点进行了总结,并详细介绍了图书管理系统的设计与应用.     

铸造工艺仿真设计前处理及过程处理应用技术

以应用ProCAST和MAGMAsoft 2款软件为例，针对铸造工艺仿真设计前处理和过程处理每个环节的主要内容与使用方法进行了较为详细地归纳、分析和总结。提出了处理过程的技术路线，并系统地介绍了每项应用内容的操作平台与使用步骤，从而为高效地应用铸造工艺仿真设计提供理论和技术支持。     

Response surface methodology toward the optimization of high-energy carotenoid extraction from Aristeus antennatus shrimp

High-energy assisted extraction techniques, like ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE), are widely applied over the last years for the recovery of bioactive compounds such as carotenoids, antioxidants and phenols from foods, animals and herbal natural sources. Especially for the case of xanthophylls, the main carotenoid group of crustaceans, they can be extracted in a rapid and quantitative way with the use of UAE and MAE.