Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

探地雷达在莲花电站二坝坝顶路面裂缝探测中的应用

介绍探地雷达探测方法,探讨使用高频探地雷达探测粘土心墙堆石坝坝顶混凝土路面裂缝,达到快速、无损查明坝顶混凝土裂缝的性质与成因的目的.     

The Zinc-Sensing Receptor GPR39 in Physiology and as a Pharmacological Target

The G-protein coupled receptor GPR39 is abundantly expressed in various tissues and can be activated by changes in extracellular Zn²⁺ in physiological concentrations. Previously, genetically modified rodent models have been able to shed some light on the physiological functions of GPR39, and more recently the utilization of novel synthetic agonists has led to the unraveling of several new functions in the variety of tissues GPR39 is expressed. Indeed, GPR39 seems to be involved in many important metabolic and endocrine functions, but also to play a part in inflammation, cardiovascular diseases, saliva secretion, bone formation, male fertility, addictive and depression disorders and cancer. These new discoveries offer opportunities for the development of novel therapeutic approaches against many diseases where efficient therapeutics are still lacking. This review focuses on Zn²⁺ as an endogenous ligand as well as on the novel synthetic agonists of GPR39, placing special emphasis on the recently discovered physiological functions and discusses their pharmacological potential.     

The Role of LGR4 (GPR48) in Normal and Cancer Processes

Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4) is a receptor that belongs to the superfamily of G protein-coupled receptors that can be activated by R-spondins (RSPOs), Norrin, circLGR4, and the ligand of the receptor activator of nuclear factor kappa-B (RANKL) ligands to regulate signaling pathways in normal and pathological processes. LGR4 is widely expressed in different tissues where it has multiple functions such as tissue development and maintenance. LGR4 mainly acts through the Wnt/β-catenin pathway to regulate proliferation, survival, and differentiation. In cancer, LGR4 participates in tumor progression, invasion, and metastasis. Furthermore, recent evidence reveals that LGR4 is essential for the regulation of the cancer stem cell population by controlling self-renewal and regulating stem cell properties. This review summarizes the function of LGR4 and its ligands in normal and malignant processes.     

深圳市抛石填海区物探方法研究

在深圳某抛石填海区,由于存在较厚的淤泥层,而且在淤泥层中大量的分布着大小不均的石块,在物探作业的时候,往往难以探测到淤泥下面的基岩面,本文基于以上情况,通过对几种常规的物探方法的对比,从理论到实践,从中找到了最优的勘探方法,为以后从事此类工程的物探工作者提供一些借鉴。     

前视探地雷达三维合成孔径成像及多视处理

提出了一种变波速条件下前视探地雷达三维合成孔径成像及多视处理方法。该方法利用非平稳卷积滤波处理在频率域重构目标图像频谱,经傅里叶反变换后实现前视探地雷达三维合成孔径成像;利用估计的目标入射角实现折射校正及前视探地雷达多视处理。对实测数据进行处理,结果证明了该方法的有效性。     

基于复合协方差函数的多任务模仿学习算法的研究与实现

针对多任务下机器人模仿学习控制策略的获取问题,构建复合协方差函数,采用高斯过程回归方法对示教机器人的示教行为样本点建立高斯过程回归模型,并对其中的超参数进行优化,从而得出模仿学习控制策略,模仿机器人应用控制策略完成模仿任务。以Braitenberg车为仿真实验研究对象,对其趋光、避障多任务的模仿学习进行研究。仿真实验研究结果表明：与基于单一协方差函数的模仿学习算法相比,基于复合协方差函数的模仿学习算法不仅能够实现单任务环境下的机器人模仿学习,而且能够实现多任务环境下的机器人模仿学习,且精度更高。任务环境改变实验研究结果表明该方法有很好的适应性。     

埋地非金属管道雷达探测成像定位方法研究

非金属管道在地下管网建设中得到广泛应用。 探地雷达法作为地下公共设施主要检测方法之一,常被用于地下非金属 管线探测中。 由于探测过程中存在非金属管道回波信号微弱、地下结构复杂、波速难以精确估算等问题,使雷达探测成像及定 位成为难题。 针对上述问题,研究了适用于埋地非金属管道的波速估算和回波信号处理方法,提出了空间频域插值成像和二值 化定位算法;通过数值仿真验证了所述成像定位方法的可行性,并进行了 0. 400、0. 600 和 1. 100 m 埋深的非金属管道现场测 试。 实验结果表明,所提方法能够有效消除双曲线效应,探测区域的成像定位误差分别为 0. 006、0. 006 和 0. 012 m,满足埋地非 金属管道定位需求。 研究成果可为埋地非金属管道成像及定位提供技术支持,有益于提高探地雷达对地下非金属管线的探测 精度。     

基于无线通信实现方式的PLC网络研究

针对PLC控制系统在工业领域中的应用需求,分析了PLC-DCS控制网络结构,对比总结了三类PLC网络的无线通讯实现方式;通过对不同类型实现PLC无线网络的硬件拓扑结构和组网要点的分析,总结了各种方式的应用特点,并比对了它们的适用场合及局限性,以便针对不同PLC的无线通讯模式,进行具体方案的设计。