Dichlorophenylacrylonitriles as AhR Ligands That Display Selective Breast Cancer Cytotoxicity in vitro

Knoevenagel condensation of 3,4‐dichloro‐ and 2,6‐dichlorophenylacetonitriles gave a library of dichlorophenylacrylonitriles. Our leads (Z)‐2‐(3,4‐dichlorophenyl)‐3‐(1H‐pyrrol‐2‐yl)acrylonitrile ( 5 ) and (Z)‐2‐(3,4‐dichlorophenyl)‐3‐(4‐nitrophenyl)acrylonitrile ( 6 ) displayed 0.56±0.03 and 0.127±0.04 μm growth inhibition (GI₅₀) and 260‐fold selectivity for the MCF‐7 breast cancer cell line. A 2,6‐dichlorophenyl moiety saw a 10‐fold decrease in potency; additional nitrogen moieties (‐NO₂) enhanced activity (Z)‐2‐(2,6‐dichloro‐3‐nitrophenyl)‐3‐(2‐nitrophenyl)acrylonitrile ( 26 ) and (Z)‐2‐(2,6‐dichloro‐3‐nitrophenyl)‐3‐(3‐nitrophenyl)acrylonitrile ( 27 ), with the corresponding ‐NH₂ analogues (Z)‐2‐(3‐amino‐2,6‐dichlorophenyl)‐3‐(2‐aminophenyl)acrylonitrile ( 29 ) and (Z)‐2‐(3‐amino‐2,6‐dichlorophenyl)‐3‐(3‐aminophenyl)acrylonitrile ( 30 ) being more potent. Despite this, both 29 (2.8±0.03 μm ) and 30 (2.8±0.03 μm ) were found to be 10‐fold less cytotoxic than 6 . A bromine moiety effected a 3‐fold enhancement in solubility with (Z)‐3‐(5‐bromo‐1H‐pyrrol‐2‐yl)‐2‐(3,4‐dichlorophenyl)acrylonitrile 18 relative to 5 at 211 μg mL^?1. Modeling‐guided synthesis saw the introduction of 4‐aminophenyl substituents (Z)‐3‐(4‐aminophenyl)‐2‐(3,4‐dichlorophenyl)acrylonitrile ( 35 ) and (Z)‐N‐(4‐(2‐cyano‐2‐(3,4‐dichlorophenyl)vinyl)phenyl)acetamide ( 38 ), with respective GI₅₀ values of 0.030±0.014 and 0.034±0.01 μm . Other analogues such as 35 and 36 were found to have sub‐micromolar potency against our panel of cancer cell lines (HT29, colon; U87 and SJ‐G2, glioblastoma; A2780, ovarian; H460, lung; A431, skin; Du145, prostate; BE2‐C, neuroblastoma; MIA, pancreas; and SMA, murine glioblastoma), except compound 38 against the U87 cell line. A more extensive evaluation of 38 ((Z)‐N‐(4‐(2‐cyano‐2‐(3,4‐dichlorophenyl)vinyl)phenyl)acetamide) in a panel of drug‐resistant breast carcinoma cell lines showed 10–206 nm potency against MDAMB468, T47D, ZR‐75‐1, SKBR3, and BT474. Molecular Operating Environment docking scores showed a good correlation between predicted binding efficiencies and observed MCF‐7 cytotoxicity. This supports the use of this model in the development of breast‐cancer‐specific drugs.     

脉冲宽度对偏转电场法内表面等离子体浸没离子注入的影响

近年来 ,采用等离子体浸没离子注入 (PIII)对零部件内表面进行改性处理引起了各国研究工作者的广泛关注 .研究表明 ,提出的偏转电场法是进行内表面注入处理的有效方法 ,可以极大提高内表面注入的注入剂量和注入能量 .研究了采用偏转电场法注入时注入电压脉冲宽度对注入效果的影响 .结果表明 ,长注入脉宽可以提高内表面注入能量 ,但对注入剂量影响不大 ;脉冲宽度对注入峰值深度和注入剂量的分布有很大影响 ,长注入脉宽使注入峰值深度和注入剂量的最大值向筒内部移动 ;采用适当的不同宽度脉冲进行注入 ,可以改善注入均匀性 .     

谈VRML在教学中的使用

虚拟现实技术是近年兴起的一门综合性信息技术,在教育领域内具有广泛的前景,同时也对传统教学产生了很大的冲击。本文介绍了一些虚拟现实技术的基本知识及一些基本理论,通过这些来提示广大教师,用先进的思想和行动来改善教学环境和教学方法。     

A New Robust Adaptive Control of Uncertain Nonlinear Systems and Pendulum Application

A new robust adaptive control of uncertain nonlinear systems is proposed in this paper. The proposed method combines sliding mode control with the immersion and invariance (I&I) adaptive scheme, and it has more available degrees of freedom than using the backstepping scheme. Via the proposed method, a class of nonlinear systems with mismatched parametric perturbations can be rendered asymptotically stable and the performance of the system can also be improved. Finally, the proposed method is applied to a simple pendulum with motor dynamics, and simulation results show the effectiveness and performance of the proposed method.     

The stress and workload of virtual reality training: the effects of presence,immersion and flow

The present investigation evaluated the effects of virtual reality (VR) training on the performance, perceived workload and stress response to a live training exercise in a sample of Soldiers. We also examined the relationship between the perceptions of that same VR as measured by engagement, immersion, presence, flow, perceived utility and ease of use with the performance, workload and stress reported on the live training task. To a degree, these latter relationships were moderated by task performance, as measured by binary (Go/No-Go) ratings. Participants who reported positive VR experiences also tended to experience lower stress and lower workload when performing the live version of the task. Thus, VR training regimens may be efficacious for mitigating the stress and workload associated with criterion tasks, thereby reducing the ultimate likelihood of real-world performance failure.

Practitioner Summary: VR provides opportunities for training in artificial worlds comprised of highly realistic features. Our virtual room clearing scenario facilitated the integration of Training and Readiness objectives and satisfied training doctrine obligations in a compelling engaging experience for both novice and experienced trainees.     

聚焦爬虫常见算法分析

聚焦爬虫搜集与特定主题相关的页面,为搜索引擎构建页面集。传统的聚焦爬虫采用向量空间模型和局部搜索算法,精确率和召回率都比较低。文章分析了聚焦爬虫存在的问题及其相应的解决方法。最后对未来的研究方向进行了展望。     

支持向量机在化学主题爬虫中的应用

爬虫是搜索引擎的重要组成部分,它沿着网页中的超链接自动爬行,搜集各种资源。为了提高对特定主题资源的采集效率,文本分类技术被用来指导爬虫的爬行。本文把基于支持向量机的文本自动分类技术应用到化学主题爬虫中,通过SVM 分类器对爬行的网页进行打分,用于指导它爬行化学相关网页。通过与基于广度优先算法的非主题爬虫和基于关键词匹配算法的主题爬虫的比较,表明基于SVM分类器的主题爬虫能有效地提高针对化学Web资源的采集效率。     

氨浸 - 碳化法制活性氧化锌

对以菱锌矿为原料,用硫化碱为除杂剂,二氧化碳为沉锌剂的活性氧化锌制备方法进行了研究,重点考察了除杂和碳化沉锌过程的工艺条件,实验得出,除杂时硫化碱加入量为理论量的120％较好;碳化沉锌终点定在pH值为8时较为适宜;碳化时采用较低的温度,较高的二氧化碳浓度和较高的空塔气速（0．04－0．05m/s)为宜。     

Imaging damage evolution in a small particle metal matrix composite

It is difficult to study effectively microstructural damage in metal matrix composites (MMCs) due to artefacts arising from traditional metallographic sample preparation techniques. The sectioning and imaging capabilities of the focused ion beam (FIB) microscope provide an excellent method for studying damage accumulation in MMCs.
The capabilities of the FIB system have been used to carry out a study of damage evolution in a powder-processed/hot-extruded Al2080/SiC_p MMC. Microvoid damage is found to be preserved accurately during FIB sectioning, allowing measurements of the fraction of decohered particles and the void area fraction. These microscopic damage measurements are correlated with the macroscopic damage parameter, D , as determined by density measurements.
Using transmission electron microscopy, the evolution of dislocation structures at the SiC–matrix interfaces has been examined. A previously unreported decohesion mechanism has been observed.     

用EGS4分析9MeV行波直线加速器屏蔽系统

采用了国际上广泛使用的ＭｏｎｔｅＣａｒｌｏ模拟计算程序ＥＧＳ４对海关集装箱检测系统用加速器屏蔽系统进行了辐射模拟分析，与实际测试数据进行分析、比较，解释了特殊剂量分布的原因，提出了系统改进的参考方案。