Microtubule Destabilizing Sulfonamides as an Alternative to Taxane-Based Chemotherapy

Pan-Gyn cancers entail 1 in 5 cancer cases worldwide, breast cancer being the most commonly diagnosed and responsible for most cancer deaths in women. The high incidence and mortality of these malignancies, together with the handicaps of taxanes—first-line treatments—turn the development of alternative therapeutics into an urgency. Taxanes exhibit low water solubility that require formulations that involve side effects. These drugs are often associated with dose-limiting toxicities and with the appearance of multi-drug resistance (MDR). Here, we propose targeting tubulin with compounds directed to the colchicine site, as their smaller size offer pharmacokinetic advantages and make them less prone to MDR efflux. We have prepared 52 new Microtubule Destabilizing Sulfonamides (MDS) that mostly avoid MDR-mediated resistance and with improved aqueous solubility. The most potent compounds, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methylaminobenzenesulfonamide 38, N-methyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 42, and N-benzyl-N-(3,4,5-trimethoxyphenyl-4-methoxy-3-aminobenzenesulfonamide 45 show nanomolar antiproliferative potencies against ovarian, breast, and cervix carcinoma cells, similar or even better than paclitaxel. Compounds behave as tubulin-binding agents, causing an evident disruption of the microtubule network, in vitro Tubulin Polymerization Inhibition (TPI), and mitotic catastrophe followed by apoptosis. Our results suggest that these novel MDS may be promising alternatives to taxane-based chemotherapy in chemoresistant Pan-Gyn cancers.     

基于Sql Server BI平台和决策树技术的CET-4成绩分析

文章首先对Sql Server 2008商业智能平台及决策树技术相关理论作了介绍,然后对挖掘数据源数据进行了一系列预处理。利用Sql Server 2008商业智能平台下的决策树技术并采用数据挖掘扩展语言即DMX语言创建了CET-4成绩分析决策树模型。分类矩阵和挖掘提升图分别对该模型的评估结果表明了模型具有较高的可靠性和分类准确度,同时模型对应的一些规则可作为英语教学管理和改革的重要参考依据。     

基于MVC模式的Web0A系统的设计与实现

为了方便企业的管理和提高协同办公效率,越来越多的企业采用了WebOA系统。针对传统设计模式开发的WebOA系统存在维护成本高、难以扩展等缺陷,文中提出一种基于MVC设计模式的系统开发方案。首先详细介绍了MVC模式的设计思想和ZendFramework的工作流程及原理,然后阐述了系统设计与实现的整个过程。该设计方案充分利用了MVC的结构和特点并已成功应用于某办公自动化系统的开发。实践表明,基于MVC模式开发的OA系统运行稳定,具有较好的灵活性和高效性,并且大大减少了系统的开发周期,达到了预期的效果。     

一种新型校园在线管理系统研究与开发

随着全球化进程的加快和网络技术的高速发展,高校多校区办学成为一种趋势,传统的信息管理系统已难以满足校园信息资源充分利用和高效管理的要求。针对此现状．研究B／S体系架构,使用Visual Studio2008、ASP．NET3．5、SQL Server2005等技术设计开发一种新型校园在线管理系统。系统主要包括用户登录及注销模块、大学管理员模块、校区管理员模块、教师模块、学生模块、权限管理模块等。     

煤矿瓦斯监控系统关键数据加密算法的研究与实现

为了防止煤矿瓦斯监控系统中关键数据被篡改,保证数据安全,提出一种在SQL Server 2008数据库中利用对称加密算法对重要字段进行加密,并使用密钥和解密函数还原数据的方法。字段被对称加密后,任何对该字段数据的更改操作都需要得知密钥,并使用解密函数才能实现,从而有效地防止了对关键数据的非法操作,保护了敏感数据。实际应用证实了关键数据加密算法的有效性。     

基于PLC的船舶机舱监测报警系统的改进方案

针对原机舱监测报警系统的老化以及无法表示监测点的具体数值的问题,利用西门子PLC S7-200作为数据的采集和发送单元,利用西门子触摸屏MP377搭载组态软件WinCC flexible 2010,对数据进行实时的监测与报警,同时PLC将机舱监测报警系统所有测点的实时数据发送到轮机长室,实现对机舱主机及付机的各项参数的实时监测。改进的监测系统已经投入使用,事实证明该系统安全可靠。     

Thermotropic liquid crystalline polymer (Rodrun LC5000)/polypropylene in situ composite films: rheology, morphology, molecular orientation and tensile properties

In situ composite films were prepared by a two-step method. First, polypropylene and thermotropic liquid crystalline polymer (TLCP), Rodrun LC5000 (80 mol% p-hydroxy benzoic acid (HBA)/20 mol% polyethylene terephthalate (PET)), were melt blended in a twin-screw extruder and then fabricated by extrusion through a mini-extruder as cast film. Rheological behavior of the blends, morphology of the extruded strands and films, and tensile properties of the in situ composite films were investigated. Rheological behavior of the blends at 295 °C studied using a plate-and-plate rheometer revealed a substantial reduction of the complex viscosity with increasing TLCP content, and all specimens exhibited shear thinning behavior. Over the angular frequency range of 0.6-200 rad/s, the viscosity ratio (dispersed phase to matrix phase) was found to be very low, in the range of 0.03-0.07. Morphologies of the fracture surfaces of the blend extrudates and the film surfaces etched in permanganic solution were investigated by scanning electron microscope (SEM). The TLCP droplets in the extruded strands were seen with a progressive deformation into fibrillar structure when TLCP content was increased up to 30 wt%. In the extruded films, TLCP fibrils with increasing aspect ratio (length to width) were observed with increasing TLCP concentration. Orientation functions of each component were determined by X-ray diffraction using a novel separation technique. It was observed that the Young's modulus in machine direction of the extruded film was greatly improved with increasing TLCP loading, due to the increase in fiber aspect ratio and also molecular orientation.     

基于乘坐舒适、节能的电梯变频调速系统设计及实现

电梯作为高层建筑中大量使用的机电一体化设备,为了改善乘坐的舒适度、节能,电梯的控制系统中广泛使用交流变压变频调速,作为变压变频控制装置,变频器以其成熟的技术和可靠性被应用于电梯控制系统中,与其他类型交流调速系统相比具有运行效率高、节能效果显著,电梯运行乘坐舒适等优点。本文以日本富士电梯专用变频器5000G11UD为控制器,组成电梯变频调速系统,从理论上分析了实现电梯乘坐舒适、节能的控制关键点,并给出了实际操作方法,具体应用取得了较好的效果。     

基于B/S的资料信息管理系统的设计和实现

该文介绍了基于B/S资料信息管理系统的设计和开发,重点阐述了资料信息管理系统的开发设计的难点和要点,同时提供了部分数据库表信息和代码。     

基于RISC-V浮点指令集FPU的研究与设计

针对目前浮点运算软件实现速度慢,不能满足嵌入式处理器实时性要求以及运算种类有限等问题,提出了一种基于RISC-V指令集的浮点处理器,能够执行加法、减法、乘法、除法、平方根、乘累加以及比较运算,完全符合IEEE 754-2008标准。在VCS仿真环境下对浮点处理器进行了功能验证,各模块均能满足正确性要求。将浮点处理器与一款开源处理器核蜂鸟E203集成,使用SMIC 0.18工艺库完成了逻辑综合,并在FPGA上对设计进行了测试。结果表明,该浮点处理器的逻辑门数仅为24 200,吞吐量为150 MFLOPS,与已公开文献的设计方案相比,硬件面积分别减少7%、1.5%。综合运行频率可达100 MHz。