基于重叠栅工艺的硅量子点阵列的制备与调控

利用半导体量子点阵列结构实现近邻耦合是规模化扩展自旋量子比特的主要方案之一.随着量子点数目的增加,量子点阵列器件的制作工艺及参数调控均愈加复杂.本文介绍了一种重叠栅工艺结构,利用多层相互重叠且具有不同功能的栅极定义量子点,制作出结构紧凑、调控性好的量子点阵列器件,解决了工艺扩展的难题.此外,本文发展了一套高效可靠的调控方法,按顺序逐个添加量子点并建立虚拟电极,实现了对量子点参数的独立控制,并且能够高效且独立地调控各量子点中的电子数目,克服了大规模量子点阵列中电压参数配置的困难.这些方法为未来实现大规模自旋比特阵列提供了一种标准化的方案.     

基于虚拟仪器的导弹质心定位系统设计与实现

针对传统导弹质心定位设备精度低,操作繁琐等弊端,从弹体质心定位原理出发,合理选取力矩计算参考点,建立质心定位模型;以基于PCI总线的内插式DAQ虚拟仪器测控平台为依托,突出“通用性、精确性、高效性”的设计理念,制定系统总体设计方案,围绕导弹质量测量与质心定位技术展开研究与工程实现;实际应用表明,本系统可拓展应用于多型导弹和大型圆柱形工件的称重与质心定位,满足导弹飞行控制研究和装配工艺要求。     

弯曲圆盘换能器与镜像虚源的互辐射作用

建立了弯曲圆盘换能器镜像虚源等效模型,利用脉动球源互作用原理对弯曲圆盘与其镜像虚源的互辐射作用进行理论分析,给出了互辐射阻抗及系统谐振频率的数学表达。提出了虚源互作用的低频换能器设计思想,将刚性反射板引入弯曲圆盘换能器临近辐射面的声场中,通过理论分析、有限元模拟和样机实验研究了低频换能器谐振频率与主要结构参数之间的关系。结果表明,弯曲圆盘与镜像虚源间的互辐射作用可以有效降低换能器的谐振频率,当反射板直径与弯曲圆盘辐射面直径相当时,谐振频率可降低至其自身谐振频率的50%以下;当反射板直径为弯曲圆盘辐射面直径2倍时,谐振频率可降低至37%。     

Simple laser vision sensor calibration for surface profiling applications

Due to the relatively large structures in the Oil and Gas industry, original equipment manufacturers (OEMs) have been implementing custom-designed laser vision sensor (LVS) surface profiling systems as part of quality control in their manufacturing processes. The rough manufacturing environment and the continuous movement and misalignment of these custom-designed tools adversely affect the accuracy of laser-based vision surface profiling applications. Accordingly, Oil and Gas businesses have been raising the demand from the OEMs to implement practical and robust LVS calibration techniques prior to running any visual inspections. This effort introduces an LVS calibration technique representing a simplified version of two known calibration techniques, which are commonly implemented to obtain a calibrated LVS system for surface profiling applications. Both calibration techniques are implemented virtually and experimentally to scan simulated and three-dimensional (3D) printed features of known profiles, respectively. Scanned data is transformed from the camera frame to points in the world coordinate system and compared with the input profiles to validate the introduced calibration technique capability against the more complex approach and preliminarily assess the measurement technique for weld profiling applications. Moreover, the sensitivity to stand-off distances is analyzed to illustrate the practicality of the presented technique.     

The (S−1,S) inventory model and its counterparts in queueing theory

We explore the relationship between the ($S?1,S$) inventory model and three well-known queueing models: the Erlang loss system, the machine-repair model and a two-node Jackson network. Exploiting this relationship allows us to obtain key performance measures of the ($S?1,S$) model, like the so-called virtual outdating time, the number of items on the shelf in steady state, the long-run rate of unsatisfied demands and the distribution of the empty shelf period.     

Message passing interface and multithreading hybrid for parallel molecular docking of large databases on petascale high performance computing machines

A mixed parallel scheme that combines message passing interface (MPI) and multithreading was implemented in the AutoDock Vina molecular docking program. The resulting program, named VinaLC, was tested on the petascale high performance computing (HPC) machines at Lawrence Livermore National Laboratory. To exploit the typical cluster‐type supercomputers, thousands of docking calculations were dispatched by the master process to run simultaneously on thousands of slave processes, where each docking calculation takes one slave process on one node, and within the node each docking calculation runs via multithreading on multiple CPU cores and shared memory. Input and output of the program and the data handling within the program were carefully designed to deal with large databases and ultimately achieve HPC on a large number of CPU cores. Parallel performance analysis of the VinaLC program shows that the code scales up to more than 15K CPUs with a very low overhead cost of 3.94%. One million flexible compound docking calculations took only 1.4 h to finish on about 15K CPUs. The docking accuracy of VinaLC has been validated against the DUD data set by the re‐docking of X‐ray ligands and an enrichment study, 64.4% of the top scoring poses have RMSD values under 2.0 Å. The program has been demonstrated to have good enrichment performance on 70% of the targets in the DUD data set. An analysis of the enrichment factors calculated at various percentages of the screening database indicates VinaLC has very good early recovery of actives. © 2013 Wiley Periodicals, Inc.     

Targeting tribbles homolog 3 (TRIB3) protein against type 2 diabetes for the identification of potential inhibitors by in silico screening

Tribbles homolog 3 (TRIB3) protein is inhibiting the insulin signaling by directly binding to the Akt/PKB leading to insulin resistance in the pancreas causing type 2 diabetes mellitus. Hence, TRIB3 protein is considered as a possible drug target for the new lead identification against type 2 diabetes. In the present study, the homology model of TRIB3 protein was generated to explore its biochemical function and molecular interactions in the new lead identification. The energy minimization of TRIB3 protein was carried out and evaluated by validation protocols for structure reliability. The druggable binding site of TRIB3 protein was identified for the virtual screening and molecular docking studies. The Asinex-fragments library of 22634 small molecules was docked at TRIB3 active site using the Glide module to identify new chemical entities. A total of 9 molecules were identified as final hits from virtual screening and their potency was ranked using Glide score, Glide energies, and residues interactions. The 6 prioritized lead molecules were further optimized using AutoDock, Prime MM/GBSA, and percentage of human oral absorption for the identification of potential leads. The molecules L2, L5, and L6 are identified as lead inhibitors and are showing consistent interactions with key residues Glu194 and Lys196 of TRIB3 protein. The identified potential leads were analyzed by ADME properties for their drug likeness and HergIC50 values are predicted for the prevention of preclinical failures. The present work sheds light on the identification of the best lead molecules against TRIB3 protein and offers a route to design as novel potential drug candidates for T2DM.     

ω-芋螺毒素的定量构效关系与虚拟筛选

ω-芋螺毒素属于海洋生物活性多肽,由24-31个氨基酸残基组成.特异性作用于电压敏感的钙离子通道(VGCCs),能够直接开发成药物或作为先导化合物进行新药开发.本文应用新型氨基酸残基结构描述符cscales和遗传偏最小二乘算法,对ω-芋螺毒素进行定量构效关系(QSAR)研究,并设计、构建了容量为2244个化合物的N-型和P/Q-型VGCC拮抗剂虚拟组合多肽库,然后分别采用QSAR模型预测和相似性搜索方法对组合多肽库进行了虚拟筛选.研究结果表明,建立的N-型和P/Q-型VGCC拮抗剂QSAR模型均具有较好的预测能力,交叉验证相关系数(CV-r2)均大于0.89.主成分分析和聚类分析结果表明,虚拟组合多肽库中化合物具有较好的结构多样性和差异性.通过虚拟筛选,得到了具有高预测活性的6个N-型和19个P/Q-型钙离子通道拮抗剂,为进一步的合成和活性评价奠定了理论基础.同时,本文建立的多肽QSAR预测模型和虚拟筛选策略,为其它多肽类化合物的定量构效关系研究和虚拟筛选提供了参考.     

Structure-based virtual screening of natural products as potential stearoyl-coenzyme a desaturase 1 (SCD1) inhibitors

Stearyl coenzyme A desaturase enzyme 1 (SCD1) is a key enzyme that catalyzes the conversion of saturated fatty acids (SFA) into monounsaturated fatty acids (MUFA) and plays a vital role in lipid metabolism of tumor cells. SCD1 is overexpressed in a variety of malignant tumors, and its related inhibitors showed significant anti-tumor activity in vitro and in vivo experiments, which is a new target for tumor therapy. The focus of this study is to identify novel SCD1 inhibitors from natural products through computer simulations. First, 176,602 compounds from natural product databases were virtually screened. By molecular dynamics (MD) simulations, the ligand-protein interactions of 5 compounds with high docking manifestation were analyzed accurately. Then, MM-GBSA and MM-PBMA methods were used to verify the results. Finally, ADMET prediction was performed for the 5 compounds. As a result, two natural products with potential inhibition towards SCD1 were identified, which had the excellent docking manifestation, binding mode within SCD1 pocket and stability during molecular dynamics simulation. This study provides a meaningful model for the development and optimization of new inhibitors and anti-tumor drugs targeting SCD1.     

Structure-based virtual screening of influenza virus RNA polymerase inhibitors from natural compounds: Molecular dynamics simulation and MM-GBSA calculation

The resistances of matrix protein 2 (M2) protein inhibitors and neuraminidase inhibitors for influenza virus have attracted much attention and there is an urgent need for new drug. The antiviral drugs that selectively act on RNA polymerase are less prone to resistance and possess fewer side effects on the patient. Therefore, there is increased interest in screening compounds that can inhibit influenza virus RNA polymerase. Three natural compounds were found by using molecular docking-based virtual screening, which could bind tightly within the polymerase acidic protein-polymerase basic protein 1 (PA-PB1) subunit of influenza virus polymerase. Firstly, their drug likeness properties were evaluated, which showed that the hepatotoxicity values of all the three compounds indicating they had less or no hepatotoxicity, and did not have the plasma protein biding (PPB) ability, the three compounds needed to be modified in some aspects, like bulky molecular size. The stability of the complexes of PA-hits was validated through molecular dynamics (MD) simulation, revealing compound 2 could form more stable complex with PA subunit. The torsional conformations of each rotatable bond of the ligands in PA subunit were also monitored, to investigate variation in the ligand properties during the simulation, compound 3 had fewer rotatable bonds, indicating that the molecule had stronger rigidity. The bar charts of protein–ligand contacts and contacts over the course of trajectory showed that four key residues (Glu623, Lys643, Asn703 and Trp706) of PA subunit that participated in hydrogen-bond, water bridge and hydrophobic interactions with the hit compounds. Finally, the binding free energy and contributed energies were calculated by using MM-GBSA method. Out of the three compounds, compound 1 showed the lowest total binding free energy. Among all the interactions, the contribution of the covalent binding and the van der Waals energy were more than other items, compound 1 formed more stable hydrogen bonds with the residues of PA subunit binding pocket. This study smoothed the path for the development of novel lead compounds with improved binding properties, high drug likeness, and low toxicity to humans for the treatment of influenza, which provided a good basis for further research on novel and effective influenza virus PA-PB1 interaction inhibitors.