一种车用单刀双掷开关的质检仪器研发

介绍了一种车用单刀双掷开关质量检测仪器的研发,包括检测系统的硬件设计、检测原理以及算法软件开发。首先,根据单刀双掷开关的工作原理及质量检测要求,开发了检测手指触觉压力的机械装置,以及控制开关通道切换的继电器控制电路;在此基础上,开发了相应的检测算法,可实现对开关切换状态、电压差以及手指触觉压力进行自动化的数据采集、分析、检测和判断,从而挑选出合格的开关;最后,设计了触屏人机交互界面,可实时显示产品检测的参数。该检测设备在某自动化生产线上经过近一年时间的检测验证,证明系统运行平稳,检测效果良好、误检率低,可以完全取代传统的人工检测方式,提高了开关的检测效率,降低了检测人员的工作量。     

黑腔冷冻靶传热与自然对流的数值模拟研究

惯性约束聚变的设计要求在靶丸内形成均匀光滑的氘氚冰层, 靶丸周围的热环境对冰层的质量特别是低阶粗糙度有很大的影响. 本文对自主研发的黑腔冷冻靶实验装置中的热物理问题展开了数值模拟, 重点考察了黑腔冷冻靶的传热和流体力学特性. 通过参数分析得到了自然对流对靶丸温度均匀性产生影响的临界条件. 比较了黑腔不同布置朝向时的流场和温度分布, 结果显示黑腔水平布置时自然对流更加强烈, 造成的靶丸温度不均匀性也更大. 在此基础上, 讨论了消除自然对流影响的可能性, 结果发现仅当黑腔垂直布置时利用黑腔分区方法能够消除对流效应对靶丸温度不均匀性的影响而黑腔水平布置时不能消除. 研究结论对于实验中冷冻靶结构的设计、改进和实验的开展等具有指导意义.     

Computer-aided design and discovery of protein–protein interaction inhibitors as agents for anti-HIV therapy

Protein–protein interactions (PPI) are involved in most of the essential processes that occur in organisms. In recent years, PPI have become the object of increasing attention in drug discovery, particularly for anti-HIV drugs. Although the use of combinations of existing drugs, termed highly active antiretroviral therapy (HAART), has revolutionized the treatment of HIV/AIDS, problems with these agents, such as the rapid emergence of drug-resistant HIV-1 mutants and serious adverse effects, have highlighted the need for further discovery of new drugs and new targets. Numerous investigations have shown that PPI play a key role in the virus’s life cycle and that blocking or modulating them has a significant therapeutic potential. Here we summarize the recent progress in computer-aided design of PPI inhibitors, mainly focusing on the selection of the drug targets (HIV enzymes and virus entry machinery) and the utilization of peptides and small molecules to prevent a variety of protein–protein interactions (viral–viral or viral–host) that play a vital role in the progression of HIV infection.     

Redesigning the DNA‐Targeted Chromophore in Platinum–Acridine Anticancer Agents: A Structure–Activity Relationship Study

Platinum–acridine hybrid agents show low‐nanomolar potency in chemoresistant non‐small cell lung cancer (NSCLC), but high systemic toxicity in vivo. To reduce the promiscuous genotoxicity of these agents and improve their pharmacological properties, a modular build–click–screen approach was used to evaluate a small library of twenty hybrid agents containing truncated and extended chromophores of varying basicities. Selected derivatives were resynthesized and tested in five NSCLC cell lines representing large cell, squamous cell, and adenocarcinomas. 7‐Aminobenz[c]acridine was identified as a promising scaffold in a hybrid agent ( P1–B1 ) that maintained submicromolar activity in several of the DNA‐repair proficient and p53‐mutant cancer models, while showing improved tolerability in mice by 32‐fold compared to the parent platinum–acridine ( P1–A1 ). The distribution and DNA/RNA adduct levels produced by the acridine‐ and benz[c]acridine‐based analogues in NCI‐H460 cells (confocal microscopy, ICP‐MS), and their ability to bind G‐quadruplex forming DNA sequences (CD spectroscopy, HR‐ESMS) were studied. P1–B1 emerges as a less genotoxic, more tolerable, and potentially more target‐selective hybrid agent than P1–A1 .     

Probing the Anticancer Mechanism of (−)‐Ainsliatrimer A through Diverted Total Synthesis and Bioorthogonal Ligation

Herein, we report an efficient approach for exploring the novel anticancer mechanism of (?)‐ainsliatrimer A, a structurally complex and unique trimeric sesquiterpenoid, through a combined strategy of diverted total synthesis (DTS) and bioorthogonal ligation (TQ ligation), which allowed us to visualize the subcellular localization of this natural product in live cells. Further biochemical studies facilitated by pretarget imaging revealed that PPARγ, a nucleus receptor, was a functional cellular target of ainsliatrimer A. We also confirmed that the anticancer activity of ainsliatrimer A was caused by the activation of PPARγ.     

Inverse screening of Simvastatin kinase targets from glioblastoma druggable kinome

The statin drug Simvastatin is a HMG-CoA reductase inhibitor that has been widely used to lower blood lipid. However, the drug is clinically observed to reposition a significant suppressing potency on glioblastoma (GBM) by unexpectedly targeting diverse kinase pathways involved in GBM tumorigensis. Here, an inverse screening strategy is described to discover potential kinase targets of Simvastatin. Various human protein kinases implicated in GBM are enriched to define a druggable kinome; the binding behavior of Simvastatin to the kinome is profiled systematically via an integrative computational approach, from which most kinases have only low or moderate binding potency to Simvastatin, while only few are identified as promising kinase hits. It is revealed that Simvastatin can potentially interact with certain known targets or key regulators of GBM such as ErbB, c-Src and FGFR signaling pathways, but exhibit low affinity to the well-established GBM target of PI3K/Akt/mTOR pathway. Further assays determine that Simvastatin can inhibit kinase hits EGFR, MET, SRC and HER2 at nanomolar level, which are comparable with those of cognate kinase inhibitors. Structural analyses reveal that the sophisticated T790 M gatekeeper mutation can considerably reduce Simvastatin sensitivity to EGFR by inducing the ligand change between different binding modes.     

In vitro antiproliferative activity of glabridin derivatives and their in silico target identification

Abstract

Novel Mannich base derivatives of glabridin were synthesized and their antiproliferative activity were performed along with our previously reported glabridin-chalcone hybrids molecules (GCHMs) against various human cell lines MDA-MB-231 (breast adenocarcinoma), HEK-293 (embryonic kidney cell line), K562 (leukemia), MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma), HepG2 (hepatocellular carcinoma) and WRL-68 (hepatic carcinoma). The result showed that the glabridin significantly reduced cell proliferation with IC₅₀ ranges from 3.67 to 58.30?µM against all the tested cell lines. The remarkable reduction in antiproliferative activity 2’,4’-dimethoxyglabridin and GCHMs compounds with phenolic OH groups protected by methoxy (OCH₃) groups suggested that the free OH groups are essential factor for the antiproliferative activity of glabridin and its derivatives. The Mannich base derivatives of glabridin showed moderate activity IC₅₀ (2.20–>95.78?µM). Furthermore, in silico target identification analysis revealed that AKT1, DECR1 and NOS1 are the potential targets for glabridin and their derivatives.     

北斗一号卫星信号高灵敏度捕获方法

研究在复杂环境下弱北斗一号卫星信号的捕获方法.利用北斗一号卫星在同一频率上发射两个波束和帧头与卷尾组成已知连续信息序列的特点,可以对两个波束做长时间相干联合捕获.从增加捕获信号功率和减小非相干累加损失两个方面提高捕获灵敏度.仿真和实测结果表明,联合捕获方法可以捕获低于—133 dBm的信号,性能优于单波束串行搜索捕获方法.     

一种直接序列扩频系统的大频偏二次捕获算法

研究多普勒频偏大于码元速率的扩频信号捕获问题和大频偏估计的模糊问题,提出了一种扩频系统的大频偏二次捕获算法,并提出了二次捕获概念.该算法采用时频并行搜索的大频偏估计完成频偏预估计和补偿,将准基带信号的频偏预估解扩值进行预处理后构造相邻频点,并依据该频点对输入信号进行二次捕获消除频偏粗估计的频点模糊,完成大频偏下的正确捕获输出原始数据信息.仿真和实测结果表明,该算法采用时频并行搜索的大频偏预估计、FFT细频偏估计与二次捕获相结合的方法可以有效缩短二次捕获的时间,满足大频偏下载波快速同步要求,提高了低信噪比通信环境下的捕获概率,算法实现简单、灵活,频偏估计精度高.     

一种间断观测下的无人机地面目标跟踪方法

提出了一种基于贝叶斯滤波器和适航地图的跟踪算法(BF-Hmap),解决间断观测下的无人机地面目标跟踪问题.采用基于中心线和梯度图的快速道路提取算法生成目标适航地图,该图描述了地面目标与当前地形相关的运动能力.采用贝叶斯滤波器分两步在线更新目标状态的后验概率分布,即在预测阶段考虑适航地图对目标运动的约束,以及在估计阶段充分利用目标的所有观测信息.仿真结果表明,在间断观测下该算法对地面机动目标有着良好的跟踪效果.