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.     

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。     

Degradation analysis of the core components of metal plate proton exchange membrane fuel cell stack under dynamic load cycles

The durability of metal plate proton exchange membrane fuel cell (PEMFC) stack is still an important factor that hinders its large-scale commercial application. In this paper, we have conducted a 1000 h durability test on a 1 kW metal plate PEMFC stack, and explored the degradation of the core components. After 1000 h of dynamic load cycles, the voltage decay percentage of the stack under the current densities of 1000 mA cm^?2 is 5.67%. By analyzing the scanning electron microscopy (SEM) images, the surfaces of the metal plates are contaminated locally by organic matter precipitated from the membrane electrode assembly (MEA). The SEM images of the catalyst coated membrane (CCM) cross section indicate that the MEA has undergone severe degradation, including the agglomeration of the catalyst layer, and the thinning and perforation of the PEM. These are the main factors that cause the rapid increase in hydrogen crossover flow rate and performance decay of the PEMFC stack.     

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。     

“灰绿”协同措施对银川市合流制溢流污染的影响EI北大核心CSCD

针对合流制管网系统在雨天溢流污染严重,造成城市水体黑臭现象的问题,以银川市某高密度城区合流制管网系统为例,基于SWMM模型,在短历时设计降雨和长历时设计降雨两种条件下,模拟分析了合流制溢流(CSO)调蓄池、雨污管道混错接改造、绿化带海绵化改造等“灰绿”协同措施对CSO污染的影响。结果表明:CSO调蓄池、雨污管道混错接改造、绿化带海绵化改造及“灰绿”措施结合4种方案在短历时、长历时设计降雨条件下,随着降水量的增加,溢流水量及溢流污染物负荷均增加,溢流削减率均逐渐减小,其中“灰绿”措施结合方案对溢流污染的削减效果最为显著;重现期小于5 a时,溢流水量削减率与溢流污染物负荷削减率基本达到80%;降雨条件为中雨时,污染物负荷削减率基本达到75%;重现期为20 a时,溢流水量削减率及TSS、COD、TP、NH^(+)_(4)-N负荷削减率分别达到64%、70%、70%、70%、70%;降雨条件为大雨时,溢流水量削减率及TSS、COD、TP、NH^(+)_(4)-N负荷削减率分别达到28%、32%、26%、31%、33%。     

基于跨临界CO2热泵的茶叶生产能源系统负荷削减潜力

乡村产业中的化石能源设备逐渐被电能技术替代，引起了乡村负荷波动增大、部分时段产生集中高负荷的问题。为了解决以上问题，将低品位清洁能源应用至乡村的茶叶生产中，针对烘茶全过程的工艺要求提出了跨临界CO₂热泵烘茶技术；并以某茶叶生产乡村为对象，对其代表台区的全年日用电量及产茶日负荷进行了分析，得出采用CO₂热泵烘茶后其负荷得到大幅度削减，整体可降低至原负荷的39.6%~46.8%，峰值负荷与平时负荷的比值由原本的13.6降至5.4~6.2。跨临界CO₂热泵应用至农产品生产中可有效缓解乡村供电压力。     

Thermomechanical stability and inelastic energy dissipation as durability criteria for fuel cell gas diffusion media with pre-assembly effects

In this article, pre-assembly hot-press pressure and thermal expansion effects in gas-diffusion layers (GDLs) are addressed to explore the practicalities of the constitutive model reported in the companion article. A facile technique is proposed to include deformation history dependent residual strain effects. The model is implemented in the numerical environment and compared with widely followed conventional models such as isotropic and orthotropic material models. With the normal and accelerated thermal expansion effects no significant variation in stresses or strains is reported with the compressible GDL model in contrast to the conventional incompressible form of the GDL model. The present work identifies the critical differences with advanced and extended variants of the model along with conventional GDL material models in terms of planar stress/strain distribution and the membrane response. Finally, the model is simulated for micro-cyclic stress loads of varying amplitudes that imitate the real working conditions of fuel cell. The inelastic energy dissipation in GDLs is predicted using the proposed model, which is utilized further to distinguish the safe (elastic) and unsafe (inelastic shakedown) operating limits. The inelastic collapse of GDLs is shown to be a active function of high amplitude micro-cyclic load with high initial clamping load.     

Effect of heat treatment and zircon addition on the properties of low-cement castables based on recycled alumina grog

In this investigation, low-cement castables were prepared using 70% alumina grog aggregates obtained from crushed alumina brick waste. The aggregates were thermally treated at 1550 °C for 3 h. Four types of low-cement castables were prepared with various types of aggregates (alumina grog with or without thermal treatment) and fillers (with or without zircon addition), and they were evaluated in terms of their physical, thermal, and chemical properties. Microstructural analysis via scanning electron microscopy (SEM) was performed on the castables before and after slag attack. Compared to the other fabricated castables, the thermally treated alumina grog castables with zircon showed better physical properties, such as a higher bulk density, cold crushing strength, and modulus of rupture and a lower apparent porosity and water absorption. In addition, they had a higher positive linear thermal expansion, refractoriness under load, permanent linear change, and hot modulus of rupture. The results of the SEM with energy dispersive X-ray analysis of the prepared castables confirmed that the mullite and anorthite phases were predominant when zircon was not added and the zircon–mullite phase additionally appeared upon the incorporation of zircon. A quantitative elemental analysis via X-ray fluorescence spectroscopy was employed to determine the composition of the castables. X-ray diffraction analysis showed that the alumina grog castables had a high mullite and low anorthite content, and the thermally treated alumina grog had a high anorthite, low mullite, and high zircon content. The improvement in the mechanical and thermo-mechanical properties of the castables with thermally treated alumina grog and added zircon can be attributed to the formation of the zircon–mullite phase with a low mullite phase content.