Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

虚实结合的可穿戴产品适合性检验研究

目的 为了更科学地研究和检验可穿戴产品的适合性,提出一种适合性检验方法,能够精确保留现实环境中的产品佩戴关系,并能将现实与虚拟的适合性检验研究相结合,得到合理的适合性检验结果.方法 以虚拟现实眼镜的适合性检验为例,通过高精度的三维测量技术将现实环境中的人、产品以及人—产品佩戴关系转化为三维虚拟信息,并以人—产品佩戴三维模型为参考基准对齐人和产品的虚拟模型,得到保留现实佩戴关系的人—产品佩戴模型组,再应用偏差分析法得出人—机佩戴区域的可视化适合性结果和统计数据,结合主观评价方法进一步分析产品的适合性.结论 虚实结合的产品适合性检验方法可在虚拟环境中高精度地保留现实环境中的人—产品佩戴关系,并能得到可视化的适合性检验结果,为检验和指导产品的适合性提供依据.     

工艺参数对动态流量控制法挤压弯管应力的影响

采用有限元模拟和实验研究了挤压钛合金弯曲管件。通过实验验证了工件的形状和尺寸精度,并通过有限元模拟分析了工艺参数对挤出过程中变形体的平均压应力分布情况和挤出弯管件的曲率半径的影响规律。结果表明:有限元模拟中,弯管件的曲率半径误差为6.03%,弯管直径误差为3.82%;在靠近定径带处,平均压应力呈非均匀分布;在焊合腔内,靠近细分流孔区域的平均压应力小于靠近粗分流孔区域的平均压应力,平均压应力的大小顺序在通过粗、细分流孔前后相反;在模具结构固定不变时,弯管件的曲率半径随挤压速度的减小而增大,不随挤压温度的变化而变化。     

Influence of Se and Te substitutions at Tl-site of Tl(Ba,Sr)CaCu2O7 superconductor on the AC susceptibility and electrical properties

The Sr and Ba bearing Tl-1212 phase, Tl(Ba,Sr)CaCu₂O₇ is an interesting superconductor. The Sr only bearing TlSr₂CaCu₂O₇ is not easily prepared in the superconducting form. The Ba only bearing TlBa₂CaCu₂O₇ on the other hand does not show improvement in the transition temperature with elemental substitution. In this work the influence of multivalent Se (non-metal) and Te (metalloid) substitutions at the Tl-site of Tl_1-xM_x(Ba,Sr)CaCu₂O₇ (M = Se or Te) superconductors for x = 0–0.6 was studied. The samples were prepared via the conventional solid-state reaction method. XRD patterns showed a single Tl-1212 phase for x = 0 and 0.1 Se substituted samples. The critical current density at the peak temperature, T_p of the imaginary (χ”) part of the AC susceptibility (χ = χ’ +χ”), J_c-inter(T_p) for all samples was between 15 and 21 A cm⁻². The highest superconducting transition temperature was shown by the x = 0.3 Se-substituted sample (T_c-onset = 104 K, T_c-zero = 89 K, T_cχ’ = 104 K and T_p = 80 K). Te suppressed the superconductivity of Tl-1212 phase. The order of highest transition temperatures are as follows: Tl_1-xTe_x(Ba,Sr)CaCu₂O₇<Tl(Ba,Sr)CaCu₂O₇<Tl_1-xSe_x(Ba,Sr)CaCu₂O₇. This work showed that Se was better than Te in improving the transition temperature and flux pinning of the Tl-1212 phase. The roles of ionic radius of Se and Te on the superconductivity of Tl(Ba,Sr)CaCu₂O₇ are discussed in this paper.     

基于PBFT区块链技术的电网企业仓储系统

提出了一种基于实用拜占庭容错(PBFT)算法的区块链技术,首先对传统的实用拜占庭容错算法原理进行了阐述,该传统算法包含前期、需求、预准备、准备、确认、答复6个阶段,但传统算法具有实时性差、缺乏惩罚机制、带宽高的缺点。针对出现的这些问题,又对传统算法进行了改进,具体涉及记账节点、共识过程以及视图切换过程。通过测试进一步证明了该改进算法的实用性,并将该算法应用于电网企业中,构建的虚拟仓库实现了联储联备,降低了库存资金的耗费,并且提高了电网企业库存管理的效率。     

自重湿陷性黄土地基预钻孔浸水处理的可靠度设计方法

为解决传统预浸水法存在的浸水时间长、浸水处理范围难以确定等不足,基于土体中水分运移规律,依据可靠度理论、极限状态设计方法及复合 Poisson 过程原理,提出一种消除黄土湿陷性的处理浸水方法——预钻孔浸水法。给出了利用预钻孔浸水法对自重湿陷性黄土地基进行浸水时,水平向及竖直向浸水影响范围的确定模型;在此基础上结合达西定律给出了浸水孔设计参数如孔深、孔间距及浸水孔个数的确定方法。结合铜川某工程,设计进行了现场预钻孔浸水试验,对该方法的合理性进行了验证,并通过现场钻探、现场勘探、室内湿陷性试验等方法对该方法的处理效果进行了评价。该浸水方法具有浸水时间短、浸水影响范围可根据浸水孔布设进行控制等优点,且浸水处理效果良好,完全符合施工要求。     

电力保护装置自动测试系统设计与研究

电力保护装置在出厂前要进行严格的板卡测试,传统板卡测试系统自动化程度较低,功能不够强大,且开发成本高,通用性不好。针对以上不足,设计了一种基于虚拟仪器的板卡测试系统,该系统主要由测试程序和上位机两部分组成,测试程序主要完成对板卡设备的模块化测试,并给出测试结果;上位机通过以太网与测试板卡通信,借助FTP和telnet技术,完成整个测试程序的发送、执行、测试结果的获取等功能。以电力保护装置内的CPU板卡为研究对象,结果表明,该测试系统可对板卡进行高效率自动测试,测试结果可靠,故障信息可追踪,可有效提高电力保护装置调试的通过率,保证企业产品的可靠性。     

基于虚拟元-有限元耦合的隧道内道床干缩裂缝细观研究

为解释道床与盾构隧道管片产生脱空的现象，研究新混凝土在浇筑后由干燥收缩产生的裂缝机理。基于虚拟元推导任意多边形骨料的刚度矩阵格式，利用UEL子程序实现有限元与虚拟元的耦合计算，纯弯梁数值试验结果表明耦合法较有限元法计算效率明显提升，且具有较好的稳定性。在此基础上，建立细观尺度下新老混凝土的干缩数值模型，并通过圆盘干缩模型验证了模型参数。研究骨料和砂浆的应力分布、内部湿度与裂缝发展的对应关系以及新老混凝土表面和界面的应力发展。结果表明：①收缩过程中，骨料主要承受压应力作用，砂浆沿骨料边界的切线方向受骨料约束作用易形成收缩裂缝，在新混凝土表面首先出现大量微小裂缝，随后界面两端发生剥离; ②受表面下骨料的约束作用，新混凝土表面拉应力呈现“驼峰”分布。开裂后表面被划分为多个收缩区，收缩区边界受拉应力，内部受压应力；③界面的拉伸和剪切应力由两侧开始增加，并且随着界面剥离的增加不断内移。在界面内部未剥离区域内存在由界面附近骨料约束导致的局部压应力和剪切应力增大。