Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

功能性小麦品种的概念、类别和发展前景（网络首发、推荐阅读）

结合全球倡导的营养导向型农业和功能性食品的内容，首次提出“功能性小麦品种”的概念，将其定义为“含有对人体健康有益的活性成分，可调节人体有益代谢，能给人体健康带来某种益处或满足特定人群的特殊需求，同时可以作为日常食物的口感正常、无毒副作用的小麦品种类型”；结合疫情警示和我国进入后工业时代后，人们需求必将由“吃得饱”、“吃得好”向“吃得健康”转变，因而提出继高产品种、优质品种之后培育“功能性小麦品种”的育种目标。根据多年关于小麦淀粉、蛋白、酯类和其他成分的功能研究结果，介绍新育成的“麦黄酮”、“高色素”、“高抗性淀粉”、“富锌”、“低醇溶蛋白”和“低植酸”等功能性小麦新品种（系）的营养特性和农艺产量状况；根据“健康中国2030”规划等国家战略，进行“功能性品种培育是解决我国功能性食品‘卡脖子’的关键基础，一种功能性品种可以形成一类功能性食品，多种功能性品种可以形成我国功能性面制品产业，推动我国整个食品工业的发展”的前景展望；根据功能性品种及其食品的稳定性和可靠性是产品和市场的“生命线”，从对消费者负责的高度，提出关于“功能性农作物品种审定导向和组建功能性成分检测机构；编制有关功能性品种和食品的国家或行业标准，设立功能性食品和功能性农作物品种的商业标志，保证我国功能性农作物品种及其食品健康发展”等方面的具体建议。     

Low/intermediate temperature pyrolyzed polysiloxane derived ceramics with increased carbon for electrical applications

This study focuses on the chemistry, thermal stability, and electrical conductivity of low/intermediate pyrolysis temperature (700?900 °C) polysiloxane derived ceramics. These ceramics were modified with additional carbon derived from divinylbenzene (DVB) added to the precursor. Their electrical properties were investigated for potential uses in micro-electrical mechanical systems (MEMS) and anodes for lithium batteries. The microstructure and chemical composition was investigated by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), Raman spectroscopy, and x-ray photoelectron spectroscopy (XPS); thermogravimetric analysis (TGA) provided insight into the thermal stability; and electrochemical impedance spectroscopy (EIS) into the electrical properties of the material. The increase of pyrolysis temperature and carbon content lead to an enhancement of the electrical conductivity, higher than previously reported values for intermediate pyrolysis temperature SiOC polymer derived ceramics. A limit of the amount of DVB that can be added to PHMS to produce a hybrid precursor has also been obtained.     

基于ADAMS和MATLAB的双足机器人运动轨迹规划和控制的联合仿真

相比ADAMS仿真的不稳定性,利用ADAMS和MATLAB联合仿真对双足机器人运动轨迹规划和控制设计的可靠性及高效性进行了研究。首先绘制双足机器人三维参数模型进行逆运动学分析,验证其合理性后导入ADAMS中添加约束,进行动力学仿真。基于此,在MATLAB中使用多项式插值法完成模型的步态规划。最后利用Simulink试验台建立控制系统的框图,由ADAMS输入关节角之后控制台输出关节的驱动力矩,完成双足机器人ADAMS和MATLAB的联合仿真。仿真结果显示,联合仿真相较于ADAMS仿真的波动性所获得的数据更加稳定,此法高效可行,可作为下一步设计双足机器人的控制系统电机选型的重要理论依据。     

Vertex-Edge Degree Based Indices of Honey Comb Derived Network

Chemical graph theory is a branch of mathematics which combines graph theory and chemistry. Chemical reaction network theory is a territory of applied mathematics that endeavors to display the conduct of genuine compound frameworks. It pulled the research community due to its applications in theoretical and organic chemistry since 1960. Additionally, it also increases the interest the mathematicians due to the interesting mathematical structures and problems are involved. The structure of an interconnection network can be represented by a graph. In the network, vertices represent the processor nodes and edges represent the links between the processor nodes. Graph invariants play a vital feature in graph theory and distinguish the structural properties of graphs and networks. In this paper, we determined the newly introduced topological indices namely, first -degree Zagreb index, first -degree Zagreb index, second -degree Zagreb index, -degree Randic index, -degree atom-bond connectivity index, -degree geometric-arithmetic index, -degree harmonic index and -degree sum-connectivity index for honey comb derived network. In the analysis of the quantitative structure property relationships (QSPRs) and the quantitative structureactivity relationships (QSARs), graph invariants are important tools to approximate and predicate the properties of the biological and chemical compounds. Also, we give the numerical and graphical representation of our outcomes.     

电信运营商云网规划数字化研究和实现

基于电信运营商数字化转型，系统性地提出了数据驱动的云网发展规划体系，以及六大关键数字化能力构建，设计和实现了一种云网规划数字化平台，该平台可用于实现目标网络精细规划、边缘计算精准预测等场景，并探讨了数字孪生在规划领域的应用前景，对运营商推进云网融合战略、推进高质量发展具有指导和参考意义。     

Granulocytes and Cells of Granulocyte Origin—The Relevant Players in Colorectal Cancer

Colorectal cancer (CRC) is one of the most common malignancy and cause of cancer death worldwide, and it still remains a therapeutic challenge for western medicine. There is strong evidence that, in addition to genetic predispositions, environmental factors have also a substantial impact in CRC development. The risk of CRC is attributed, among others to dietary habits, alcohol consumption, whereas physical activity, food containing dietary fiber, dairy products, and calcium supplements have a protective effect. Despite progress in the available therapies, surgery remains a basic treatment option for CRC. Implementation of additional methods of treatment such as chemo- and/or targeted immunotherapy, improved survival rates, however, the results are still far from satisfactory. One of the reasons may be the lack of deeper understanding of the interactions between the tumor and different types of cells, including tumor infiltrating granulocytes. While the role of neutrophils is quite well explored in many cancers, role of eosinophils and basophils is often underestimated. As part of this review, we focused on the function of different granulocyte subsets in CRC, emphasizing the beneficial role of eosinophils and basophils, as well as dichotomic mode of neutrophils action. In addition, we addressed the current knowledge on cells of granulocyte origin, specifically granulocytic myeloid derived suppressor cells (Gr-MDSCs) and their role in development and progression of CRC.     

A mathematical model for open pit mine production scheduling with Grade Engineering® and stockpiling

This paper presents the development and implementation of an innovative mixed integer programming based mathematical model for an open pit mining operation with Grade Engineering framework. Grade Engineering comprises a range of coarse-separation based pre-processing techniques that separate the desirable (i.e. high-grade) and undesirable (i.e. low-grade or uneconomic) materials and ensure the delivery of only selected quantity of high quality (or high-grade) material to energy, water, and cost-intensive processing plant. The model maximizes the net present value under a range of operational and processing constraints. Given that the proposed model is computationally complex, the authors employ a data pre-processing procedure and then evaluate the performance of the model at several practical instances using computation time, optimality gap, and the net present value as valid measures. In addition, a comparison of the proposed and traditional (without Grade Engineering) models reflects that the proposed model outperforms the traditional formulation.     

Dynamic shovel allocation approach to short-term production planning in open-pit mines

The complexity and uncertainties associated with mining operations often lead to deviations from short-term plans. A proactive approach will predict such deviations and help minimise opportunity losses, providing economic and operational gains. This paper presents an optimisation tool as a dynamic shovel allocation decision-maker for mining operation simulation models. The objectives of the optimisation tool are to provide shovel allocations to mining faces in order to maximise production, meet desired head grade and tonnage at the crushers, and minimise shovel movements. This paper presents the development and implementation of the optimisation tool with an iron ore mine case study.     

A lightweight autonomous MAV for indoor search and rescue

Micro Aerial Vehicles (MAVs) have great potentials to be applied for indoor search and rescue missions. In this paper, we propose a modular lightweight design of an autonomous MAV with integrated hardware and software. The MAV is equipped with the 2D laser scanner, camera, mission computer and flight controller, running all the computation onboard in real time. The onboard perception system includes a laser‐based SLAM module and a custom‐designed visual detection module. A dual Kalman filter design provides robust state estimation by multiple sensor fusion. Specifically, the fusion module provides robust altitude measurement in the circumstance of surface changing. In addition, indoor‐outdoor transition is explicitly handled by the fusion module. In order to efficiently navigate through obstacles and adapt to multiple tasks, a task tree‐based mission planning method is seamlessly integrated with path planning and control modules. The MAV is capable of searching and rescuing victims from unknown indoor environments effectively. It was validated by our award‐winning performance at the 2017 International Micro Air Vehicle Competition (IMAV 2017), held in Toulouse, France. The performance video is available on https://youtu.be/8H19ppS_VXM .