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.     

Thermal desorption and pyrolysis direct analysis in real time mass spectrometry of Nafion membrane

Perfluorosulfonic acid ionomer membranes have been widely used as proton conducting membranes in various electrochemical processes such as polymer electrolyte fuel cells and water electrolysis. While their thermal stability has been studied by thermogravimetry and analysis of low molecular weight products, their decomposition mechanism is little understood. In this study a newly developed methodology of thermal desorption and pyrolysis in combination with direct analysis in real time mass spectrometry is applied for Nafion membrane. An ambient ionization source and a high-resolution time-of-flight mass spectrometer enabled unambiguous assignment of gaseous products. Thermal decomposition is initiated by side chain detachment above 350°C, which leaves carbonyls on the main chain at the locations of the side chains. Perfluoroalkanes are released above 400°C by main chain scission and their further decomposition products dominate above 500 °C. DFT calculation of reaction energies and barrier heights of model compounds support proposed decomposition reactions.     

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。     

An integrated dimensionality reduction and surrogate optimization approach for plant-wide chemical process operation

With liquefied natural gas becoming increasingly prevalent as a flexible source of energy, the design and optimization of industrial refrigeration cycles becomes even more important. In this article, we propose an integrated surrogate modeling and optimization framework to model and optimize the complex CryoMan Cascade refrigeration cycle. Dimensionality reduction techniques are used to reduce the large number of process decision variables which are subsequently supplied to an array of Gaussian processes, modeling both the process objective as well as feasibility constraints. Through iterative resampling of the rigorous model, this data-driven surrogate is continually refined and subsequently optimized. This approach was not only able to improve on the results of directly optimizing the process flow sheet but also located the set of optimal operating conditions in only 2 h as opposed to the original 3 weeks, facilitating its use in the operational optimization and enhanced process design of large-scale industrial chemical systems.     

梯度铝蜂窝夹芯板的力学行为

梯度分层铝合金蜂窝板是一种有效的吸能结构,本工作在梯度铝蜂窝结构的基础上根据梯度率的概念,通过改变蜂窝芯层的胞壁长度,设计了4种质量相同、梯度率不同的铝蜂窝夹芯结构。通过准静态压缩实验,并结合非线性有限元模拟准静态及冲击态下梯度铝蜂窝夹芯结构的变形情况及其力学性能,分析对比了相同质量下梯度铝蜂窝夹芯结构在准静态下的变形模式以及冲击载荷下分层均质蜂窝结构和不同梯度率的分层梯度蜂窝结构的动态响应和能量吸收特性。结果表明:在准静态压缩过程中,铝蜂窝梯度夹芯板的变形具有明显的局部化特征,蜂窝芯的变形为低密度优先变形直至密实,层级之间的密实化应变差随芯层密度的增大而逐渐减小;在高速冲击下,梯度蜂窝板并非严格按照准静态过程中逐级变形直至密实,而是在锤头冲击惯性及芯层密度的相互作用下整体发生的线弹性变形、弹性屈曲、塑性坍塌及密实化;另外,在本工作所设计的梯度率中,当梯度率为γ₁=0.0276时,梯度蜂窝夹芯板的吸能性达到最好,相较于同等质量下的均质蜂窝夹芯板,能量吸收提高了10.63%。     

In Silico Investigation of Potential Applications of Gamma Carbonic Anhydrases as Catalysts of CO2 Biomineralization Processes: A Visit to the Thermophilic Bacteria Persephonella hydrogeniphila,Persephonella marina,Thermosulfidibacter takaii,and Thermus thermophilus

Carbonic anhydrases (CAs) have been identified as ideal catalysts for CO₂ sequestration. Here, we report the sequence and structural analyses as well as the molecular dynamics (MD) simulations of four γ-CAs from thermophilic bacteria. Three of these, Persephonella marina, Persephonella hydrogeniphila, and Thermosulfidibacter takaii originate from hydrothermal vents and one, Thermus thermophilus HB8, from hot springs. Protein sequences were retrieved and aligned with previously characterized γ-CAs, revealing differences in the catalytic pocket residues. Further analysis of the structures following homology modeling revealed a hydrophobic patch in the catalytic pocket, presumed important for CO₂ binding. Monitoring of proton shuttling residue His69 (P. marina γ-CA numbering) during MD simulations of P. hydrogeniphila and P. marina’s γ-CAs (γ-PhCA and γ-PmCA), showed a different behavior to that observed in the γ-CA of Escherichia coli, which periodically coordinates Zn²⁺. This work also involved the search for hotspot residues that contribute to interface stability. Some of these residues were further identified as key in protein communication via betweenness centrality metric of dynamic residue network analysis. T. takaii’s γ-CA showed marginally lower thermostability compared to the other three γ-CA proteins with an increase in conformations visited at high temperatures being observed. Hydrogen bond analysis revealed important interactions, some unique and others common in all γ-CAs, which contribute to interface formation and thermostability. The seemingly thermostable γ-CA from T. thermophilus strangely showed increased unsynchronized residue motions at 423 K. γ-PhCA and γ-PmCA were, however, preliminarily considered suitable as prospective thermostable CO₂ sequestration agents.     

Optimization of PEMFC system operating conditions based on neural network and PSO to achieve the best system performance

PEMFC system is a complex new clean power system. Based on MATLAB/Simulink, this paper develops a system-level dynamic model of PEMFC, including the gas supply system, hydrogen supply system, hydrothermal management system, and electric stack. The neural network fits the electric stack model to the simulation data. The effects of different operating conditions on the PEMFC stack power and system efficiency are analyzed. Combining the power of the reactor and the system efficiency to define the integrated performance index, the particle swarm optimization (PSO) algorithm is introduced to optimize the power density and system efficiency of the PEMFC with multiple objectives. The final optimal operating point increases the power density and system efficiency by 1.33% and 12.8%, respectively, which maximizes the output performance and reduces the parasitic power.     

Role of exchange coupling between the hard and soft magnetic phases on the absorption of microwaves by SrFe10Al2O19/Co0.6Zn0.4Fe2O4 nanocomposite

(1-x)SrFe₁₀Al₂O₁₉/(x)Co_0.6Zn_0.4Fe₂O₄-(SFAO/CZFO) hard/soft nanocomposite ferrite materials were synthesized by ‘one-pot’ self-propagating combustion route. The co-existence of the two magnetic phases were confirmed by XRD, FESEM, EDS and VSM. The prepared nanocomposite samples were also characterized by TGA/DSC, Raman spectroscopy and VNA. Exchange coupling between the hard and the soft magnetic grains was observed by determining the switching field distribution (SFD) curve. As a result of the competing effects of exchange interaction and dipolar interaction, magnetic parameters were observed to be sensitive to the incorporation of soft magnetic phase into the nanocomposite. Results showed that with the inclusion of soft magnetic phase, exchange coupling behaviour between the hard and the soft ferrite phases had significant influence on the microwave absorption capacity of the samples. Related electromagnetic parameters and impedance matching ratio of the nanocomposite system were discussed. A minimum reflection loss of ?42.9 dB with an absorber thickness of 2.5 mm was attained by the nanocomposite (90 wt%)SrFe₁₀Al₂O₁₉/(10 wt %)Co_0.6Zn_0.4Fe₂O₄ at a matching frequency of 11.45 GHz. This assured the candidacy of SrFe₁₀Al₂O₁₉/Co_0.6Zn_0.4Fe₂O₄ nanocomposite as a promising microwave absorption material in the X-band (8–12 GHz).     

Optimization of flow in additively manufactured porous columns with graded permeability

Chemical engineering systems often involve a functional porous medium, such as in catalyzed reactive flows, fluid purifiers, and chromatographic separations. Ideally, the flow rates throughout the porous medium are uniform, and all portions of the medium contribute efficiently to its function. The permeability is a property of a porous medium that depends on pore geometry and relates flow rate to pressure drop. Additive manufacturing techniques raise the possibilities that permeability can be arbitrarily specified in three dimensions, and that a broader range of permeabilities can be achieved than by traditional manufacturing methods. Using numerical optimization methods, we show that designs with spatially varying permeability can achieve greater flow uniformity than designs with uniform permeability. We consider geometries involving hemispherical regions that distribute flow, as in many glass chromatography columns. By several measures, significant improvements in flow uniformity can be obtained by modifying permeability only near the inlet and outlet.     

基于CFD⁃DEM的水下切粒装置水室内颗粒流动过程数值模拟

基于CFD?DEM耦合方法，研究了颗粒在水室内的流动状态，分析了不同刀盘转速、粒子水通入量和水室出口角度对造粒过程的影响，发现提高刀盘转速、增加粒子水通入量和水室出口倾斜一定的角度都有利于水室内颗粒的排出。进一步研究了颗粒与碎屑在水室内的流动，发现在水室出口处二者的流动基本呈现出一定的分离角度。