Open-Source Browser-Based Tools for Structure-Based Computer-Aided Drug Discovery

We here outline the importance of open-source, accessible tools for computer-aided drug discovery (CADD). We begin with a discussion of drug discovery in general to provide context for a subsequent discussion of structure-based CADD applied to small-molecule ligand discovery. Next, we identify usability challenges common to many open-source CADD tools. To address these challenges, we propose a browser-based approach to CADD tool deployment in which CADD calculations run in modern web browsers on users’ local computers. The browser app approach eliminates the need for user-initiated download and installation, ensures broad operating system compatibility, enables easy updates, and provides a user-friendly graphical user interface. Unlike server apps—which run calculations “in the cloud” rather than on users’ local computers—browser apps do not require users to upload proprietary information to a third-party (remote) server. They also eliminate the need for the difficult-to-maintain computer infrastructure required to run user-initiated calculations remotely. We conclude by describing some CADD browser apps developed in our lab, which illustrate the utility of this approach. Aside from introducing readers to these specific tools, we are hopeful that this review highlights the need for additional browser-compatible, user-friendly CADD software.     

基于微流控技术的细胞水平高通量药物筛选系统的研究进展

药物筛选是新药研发的关键步骤,创新药物的发现需要采用适当的药物作用靶点对大量化合物样品进行筛选.高通量筛选系统能够实现数千个反应同时测试和分析,大大提高了药物筛选的实验规模和效率.其中基于细胞水平的高通量药物筛选系统因为更加接近人体生理条件,成为主要的筛选模式.而目前发展成熟的高通量细胞筛选系统主要基于多孔板,存在细胞...     

近江牡蛎受精细胞学研究

用醋酸──地衣红染色的方法对近江牡蛎人工授精的卵子减数分裂和受精过程进行了详细的细胞学观察．精子入卵前，卵子处于第一次减数分裂的前期（胚泡期），精子入卵后，胚泡消失，然后进行两次减数分裂，在海水温度为２８．８℃的情况下，授精后３３ｍｉｎ和４５ｍｉｎ，绝大部分受精卵已排出第一极体和第二极体，雄原核可在第一极体排出后及第二极体排出前任何时期内形成，雌雄原核以联合的方式将两组染色体合并，授精后１ｈ，大部分卵子完成第一次卵裂．在２５℃和２６℃授精的情况下，观察到了较多的多精入卵的现象．卵子发育的非同步性现象非常明显．     

7-Aminoalkoxy-Quinazolines from Epigenetic Focused Libraries Are Potent and Selective Inhibitors of DNA Methyltransferase 1

Inhibitors of epigenetic writers such as DNA methyltransferases (DNMTs) are attractive compounds for epigenetic drug and probe discovery. To advance epigenetic probes and drug discovery, chemical companies are developing focused libraries for epigenetic targets. Based on a knowledge-based approach, herein we report the identification of two quinazoline-based derivatives identified in focused libraries with sub-micromolar inhibition of DNMT1 (30 and 81 nM), more potent than S-adenosylhomocysteine. Also, both compounds had a low micromolar affinity of DNMT3A and did not inhibit DNMT3B. The enzymatic inhibitory activity of DNMT1 and DNMT3A was rationalized with molecular modeling. The quinazolines reported in this work are known to have low cell toxicity and be potent inhibitors of the epigenetic target G9a. Therefore, the quinazoline-based compounds presented are attractive not only as novel potent inhibitors of DNMTs but also as dual and selective epigenetic agents targeting two families of epigenetic writers.     

第十讲数字信号处理与数字信号处理器(DSP)

文章简要介绍了“数字信号处理”与“数字信号处理器（DSP）”的发展历史．在数字信号处理的应用中，实时实现是非常重要的，而DSP在实时处理中，扮演了一个重要的角色．文章中还介绍了DSP在实际应用中的一些关键技术，例如DSP的种类和选型，DSP的开发工具，实时软件的开发过程等．最后，还介绍了一些DSP的应用实例，如语音编码器，视频电话和视频会议系统，用于雷达和声纳的DSP并行处理系统     

Role of Intracellular Iron in Switching Apoptosis to Ferroptosis to Target Therapy-Resistant Cancer Stem Cells

Iron is a crucial element required for the proper functioning of the body. For instance, hemoglobin is the vital component in the blood that delivers oxygen to various parts of the body. The heme protein present in hemoglobin comprises iron in the form of a ferrous state which regulates oxygen delivery. Excess iron in the body is stored as ferritin and would be utilized under iron-deficient conditions. Surprisingly, cancer cells as well as cancer stem cells have elevated ferritin levels suggesting that iron plays a vital role in protecting these cells. However, apart from the cytoprotective role iron also has the potential to induce cell death via ferroptosis which is a non-apoptotic cell death dependent on iron reserves. Apoptosis a caspase-dependent cell death mechanism is effective on cancer cells however little is known about its impact on cancer stem cell death. This paper focuses on the molecular characteristics of apoptosis and ferroptosis and the importance of switching to ferroptosis to target cancer stem cells death thereby preventing cancer relapse. To the best of our knowledge, this is the first review to demonstrate the importance of intracellular iron in regulating the switching of tumor cells and therapy resistant CSCs from apoptosis to ferroptosis.     

发展经济学的演变、行为转向及其当代意义

发展经济学是经济学的一个重要分支,往往会受到不同经济学流派的影响。通过考察发展经济学的演变过程,可以揭示新古典发展经济学、政府主导发展经济学、新制度发展经济学和不完全信息发展经济学之间的异同点。由于现有新古典传统下的经济发展理论都没有涉及信息处理不完美或心理维度问题,因此有必要重点探讨行为经济学对发展经济学的心理或行为的作用机制。因心理账户、默认规则和认知偏差等非理性行为系统性偏离经济人模型,从而对当代经济发展会产生重大的影响。综合研究表明,行为失灵与市场失灵、交易成本和信息不对称等经济理论形成的互补认识,摆脱了自由市场和政府主导的简单两分法,更全面认识到政府在经济和社会发展中的助推作用,为有效市场与有为政府“两只手”有机结合奠定新的微观基础,也进一步丰富了发展经济学的理论研究视野,为新时代推动经济高质量发展提供新的政策启示。     

基于证据推理的电化学综合实验探究

盐桥的作用众所周知,如果“将铜锌双液原电池的盐桥换成铜片后,电路中还有电流吗?两液中的铜片到底发生了什么反应?”,基于这些问题,开发了一系列实验,利用观察到的各种证据,如:生成的沉淀、溶液颜色的变化、电极质量的改变、溶液pH和电流计指针偏转方向等,引导学生对各个电极变化的反应进行假设,并设计新颖实验逐步探究证实,依据宏...