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.     

基于双洞效应的黄土公路隧道地层变形规律离心模型试验

鉴于目前黄土公路隧道修筑面临的一些特有问题,为了更全面地了解双洞效应影响下黄土公路隧道地层变形规律,运用离心模型试验设备,系统开展了4组基于先加载后开洞思路的模型试验,研究了双洞不同净距对黄土公路隧道地层变形的影响.试验结果表明:随着双洞净距的增大,双洞间的相互影响程度减弱,靠近拱顶处的地层变形曲线由单峰值的V形逐步变为双峰值的W形;存在压力拱效应且压力拱的形成高度随双洞净距的增大而增大;先行洞室各层沉降范围及沉降值均略大于后行洞室,且随双洞净距的增大,先行洞室对后行洞室的影响程度逐渐减弱;选用0.5D间距形式,易在隧道间形成应力与变形强影响区,需对中间土体进行加固,选用D及以上间距形式,隧道间可以形成自稳的宽底承载土柱体,故小净距黄土公路隧道双洞间合理净距可选取为D.     

An SVD-based image watermarking in wavelet domain using SVR and PSO

The paper presents a novel blind watermarking scheme for image copyright protection, which is developed in the discrete wavelet transform (DWT) and is based on the singular value decomposition (SVD) and the support vector regression (SVR). Its embedding algorithm hides a watermark bit in the low–low (LL) subband of a target non-overlap block of the host image by modifying a coefficient of U component on SVD version of the block. A blind watermark-extraction is designed using a trained SVR to estimate original coefficients. Subsequently, the watermark bit can be computed using the watermarked coefficient and its corresponding estimate coefficient. Additionally, the particle swarm optimization (PSO) is further utilized to optimize the proposed scheme. Experimental results show the proposed scheme possesses significant improvements in both transparency and robustness, and is superior to existing methods under consideration here.     

Extracting performance rules of suppliers in the manufacturing industry: an empirical study

Performance evaluation of suppliers is increasingly recognized as a critical indicator in supply chain cooperation. Traditional performance evaluation methods have the problems of a simple buy/sell relation and in one’s subjective views between manufacturers and suppliers, and they lack objective automatic evaluation processes in the supply chain considered. Statistical techniques used for evaluation rely on the restrictive assumptions of linear separability, multivariate normality, and independence of the predictive variables. Unfortunately, many of the common models of performance evaluation of suppliers violate these assumptions. The study proposes an integrated model by combining K-means clustering, feature selection, and the decision tree method into a single evaluation model to assess the performance of suppliers and simultaneously tackles the above-mentioned shortcomings. The integrated model is illustrated with an empirical case study of a manufacturer for an original design manufacturer (ODM) to demonstrate the model performance. The experimental results indicate that the proposed method outperforms listed methods in terms of accuracy, and three redundant attributes can be eliminated from the empirical case. Furthermore, the extracted rules by the decision tree C4.5 algorithm form an automatic knowledge system for supplier performance evaluation.     

A scalable multi-attribute hybrid overlay for range queries on the cloud

Cloud computing has become a promising paradigm as next generation computing model, by providing computation, software, data access, and storage services that do not need to know the location of physical resources interconnected across the globe providing such services. In such an environment, important issues as information sharing and resource/service discovery arise. In order to overcome critical limitations in centralized approaches for information sharing and resource/service discovery, this paper proposes a framework of a scalable multi-attribute hybrid overlay featured with decentralized information sharing, flexible resource/service discovery, fault tolerance and load balancing. Additionally, the proposed hybrid overlay integrates a structured P2P system with an unstructured one to support complex queries. Mechanisms such as load balancing and fault tolerance implemented in our proposed system to improve the overall system performance are also discussed. Experimental results show that the performance of the proposed approach is feasible and stable, as the proposed hybrid overlay improves system performance by reducing the number of routing hops and balancing the load by migrating requests.     

Negative emotional and cognitive responses to being unfriended on Facebook: An exploratory study

We consider Facebook unfriending as a form of relationship termination with negative emotional and cognitive consequences. Specifically, ruminative and negative emotional responses are examined via an online survey of adult Facebook users who were unfriended. These responses were positively related to each other and to Facebook intensity. Rumination was positively predicted by using Facebook to connect with existing contacts and was more likely when the unfriender was a close partner. Participants also responded with greater rumination and negative emotion when they knew who unfriended them, when they thought they were unfriended for Facebook-related reasons, and when participants initiated the Facebook friend request. The contribution of these exploratory findings to our growing understanding of negative relational behaviors on Facebook are discussed.     

Recovery of online service: Perceived justice and transaction frequency

Recovery of online service is an issue in need of study. The current study empirically examines (1) the relationships among perceived justice, satisfaction with recovery of online service and repurchase intention of online service/failure encounters; and (2) the moderating effects of transaction frequency on these relationships. The current study collects 187 self-administered questionnaires to gather customers’ perceptions of actual online service/failure encounters. Research findings demonstrate that distributive justice, interactional justice and procedural justice can positively lead to satisfaction with recovery of online service and repurchase intention toward online service. These results further show that customers with low transaction frequency tend to focus more on interactional justice to establish their satisfaction with recovery of online service. On the other hand, customers with high transaction frequency focus more on procedural justice.     

A method for transformation of engineering bill of materials to maintenance bill of materials

In order to solve the transformation problem of Bill of Materials (BOM) from engineering BOM to maintenance BOM for Maintenance, Repair and Overhaul (MRO) systems, a formal transformation model of BOM view is proposed. In this model, the intermediate component, inherited component, virtual component are defined in the specific maintenance management domain, and the transformation process from engineering BOM to maintenance BOM is discussed through feature recognition methods and rules. The proposed transformation model has been developed and deployed in an MRO system for a steel manufacturing enterprise.     

An assessment of student preferences for PowerPoint presentation structure in undergraduate courses

Studies have demonstrated that students prefer PowerPoint and respond favorably to classes when it is used. Few studies have addressed the physical structure of PowerPoint. In this study, students enrolled in several psychology classes on two campuses completed a 36 item questionnaire regarding their preferences for the use of PowerPoint in the classroom. Students preferred the use of key phrase outlines, pictures and graphs, slides to be built line by line, sounds from popular media or that support the pictures or graphics on the slide, color backgrounds, and to have the lights dimmed. It is recommended that professors pay attention to the physical aspects of PowerPoint slides and handouts to further enhance students’ educational experience.     

自适应AP聚类算法研究

偏向参数和阻尼因子是影响AP聚类算法聚类效果的两个重要参数,但他们均取固定值。随着数据量的改变,原有参数取值不能使算法聚类结果达到最优。鉴此,本文提出自适应AP聚类算法,当数据量发生改变时,自动调整并获取最优的偏向参数和阻尼因子,最终得到最优聚类结果。与原来算法相比,改进后的算法能自动消除震荡,还可获取最优聚类结果,提高聚类结果的准确性和算法快速性。通过人造数据集和Iris数据集实验,证明了自适应AP聚类算法的有效性。