Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

A Multiscale-Porous Anion Exchange Membrane for Convenient and Scalable Electrokinetic Concentration of Cationic Species

A device able to electrokinetically concentrate cationic samples has many potential medical and industrial applications, but until now has remained undeveloped due to the lack of a commercial anion-permselective material leading to a prohibitively complex fabrication procedure. Herein, a novel multiscale-porous anion exchange membrane (MP-AEM) that enables the convenient and scalable electrokinetic concentration of cationic species is proposed. A mechanically enhanced multiscale-porous structure with a solid framework is realized by adopting polyester resin as an additive to overcome the intrinsic limitations of the AEM material. The scalable MP-AEM-embedded electrokinetic concentrator is devised based on the peculiar properties of the MP-AEM that for allow both ion and fluid transport. With the MP-AEM, the concentrator is fabricated in a highly streamlined manner consisting only of a simple insertion and assembly. The concentration performance of the MP-AEM-embedded electrokinetic concentrator is demonstrated with a positively charged fluorescent dye and a fluorescein-labeled protein, and the results show enrichment factors of 250 and 500, respectively. The MP-AEM makes cationic electrokinetic concentration more accessible and scalable, thereby enabling further progress in a wide range of fields.     

“人工智能+”背景下的数据安全与隐私保护探析

随着大数据和云计算的技术的深入应用，人工智能时代的机器学习和深度学习更需要日益增长的数据，因此数据安全与隐私保护变得更加迫切。本文介绍人工智能的定义以及特征，探究数据安全和隐私保护现状，分析数据安全和隐私保护面临的诸多问题，并提出在人工智能时代对数据安全和隐私保护的措施。     

基于DSP的多元数据同步采集与存储系统的设计与实现

从硬件和软件两个角度出发,介绍基于DSP的多元数据同步采集与存储系统的组成、工作模式以及功能的测试。系统主要由上位机和数字采集与存储单元组成,其中数字采集与存储单元的硬件部分包括电源模块,值班电路模块,数据采集模块,数据存储模块,时钟同步模块。系统采用DSP作为中央处理芯片,利用经过同步后的秒脉冲作为触发信号,实现同步数据采集。以CF卡作为存储介质,实现数据自容式存储。软件部分实现自检、同步、数据采集存储功能。经过测试,系统工作稳定,功能正常,同步精度在100ns以内。     

Identification of digital technologies and digitalisation trends in the mining industry

Digitalisation in mining refers to the use of computerised or digital devices or systems and digitised data that are to reduce costs, improve business productivity, and transform mining practices. However, it remains increasingly difficult for mining companies to decide which digital technologies are most relevant to their needs and individual mines. This paper provides an overview of digital technologies currently relevant to mining companies as presented and discussed by mining journals, the media and insight reports of leading consultancy agencies. Relevant technologies were systematically identified using text-mining techniques, and network analyses established the relations between significant technologies. Results demonstrated that currently 107 different digital technologies are pursued in the mining sector. Also, an analysis of the actual implementation of digital technologies in 158 active surface and underground mines reveals a limited uptake of digital technologies in general and that the uptake increases with the run-of-mine production. Large-scale mining operations appear to select and apply digital technologies suitable to their needs, whereas operations with lower production rates do not implement the currently available digital technologies to the same extent. These minor producers may require other digital transformation solutions tailored to their capabilities and needs and applicable to their scale of operations.     

基于云概率密度分布估计的大坝监测数据分析

大坝运行监测易受自然环境和监测条件影响，存在时间和空间上的变异性，监测数据具有不确定性。以云理论的随机性和不确定性分析方法为基础，并与空间数据辐射思想相结合，建立了云滴概率密度分布估计模型，然后导出云概率密度分布函数，依据样本监测数据推求母体空间数据的分布特征，并设计了基于逆向云算法云变换的计算程序。分析陆浑水库1979~1999年测压管监测数据和位移变形数据的云概率密度分布特征和云数字特征，得出了20 a来大坝的数据分布特征和运行状态。监测数据分析结果表明，云概率密度分布估计不仅能有效合理地分析大坝的运行状态，而且能够依据云数字特征来判断监测状态和监测环境的异常变化。      

Physics‐based spectral sharpening through filter‐chart calibration

The spectral overlap of color‐sampling filters increases errors when using a diagonal matrix transform, for color correction and reduces color distinction. Spectral sharpening is a transformation of colors that was introduced to reduce color‐constancy errors when the colors are collected through spectrally overlapping filters. The earlier color‐constancy methods improved color precision when the illuminant color is changed, but they overlooked the color distinction. In this article, we introduce a new spectral sharpening technique that has a good compromise of color precision and distinction, based on real physical constraints. The spectral overlap is measured through observing a gray reference chart with a set of real and spectrally disjoint filters selected by the user. The new sharpening method enables to sharpen colors obtained by a sensor without knowing the camera response functions. Experiments with real images showed that the colors sharpened by the new method have good levels of color precision and distinction as well. The color‐constancy performance is compared with the data‐based sharpening method in terms of both precision and distinction. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 564–576, 2015     

基于聚类的数据加权优化在犯罪预测中的应用

近年来，我国传统暴力犯罪与成年人犯罪呈下降态势，但是，犯罪案由层出不穷。为有效提升公安实践工作中犯罪预测能力，打击各类违法犯罪事件,本文针对犯罪数据，提出一种新型犯罪预测模型。利用密度聚类分析方法将犯罪数据分类，然后进行数据降维提取关键属性生成特征数据，继而对特征数据进行加权优化并采用机器学习的方式对特征数据进行学习，从而预测犯罪案由。实验结果表明，与传统方法相比，本文方法具有更好的预测效果，为公安实践工作中类似案件的侦破和预防，提供新的路径支撑。