北斗系统伪随机码的硬件仿真与演化设计

作为国家战略空间基础设施,北斗卫星导航系统(BeiDou Navigation Satellite System,BDS)可以提供民用的标准定位服务和军用的精确定位服务,对我国的国防和经济建设意义重大。为研究BDS信号的产生机理和导航服务技术,在介绍伪随机码基本原理及BDS的 CB1I 码和CB2I码产生方法的基础上,基于FPGA硬件对该码生成器进行了硬件仿真实现;通过定义11位寄存器用来描述11级移位寄存器各级的状态,以此为基础生成了m序列,并最终生成了CB1I 码和CB2I码;通过Modelsim软件进行了仿真实验,下载至FPGA进行了硬件实现实验,验证了该生成电路能准确得到目的CB1I 码和CB2I码。设计了基于Nios II 和虚拟可重构(Virtual reconfigurable circuits,VRC)阵列的演化电路来实现该电路的方法,以可编程逻辑器件实现码生成电路,有助于对空间中BDS码生成器的抗干扰能力和自修复能力的研究。     

改进的语言模型和循环神经网络优化新药设计

近年来，以深度学习为代表的机器学习已成为新药设计的有力工具。计算策略用于从没有先验关系的原子构建块生成新的分子结构。循环神经网络能够捕获大量已知生物活性化合物的组成，使用简化的分子输入行输入系统的化学结构字符串表示来预测新化合物的期望性质。通过使用在NPL中广泛使用的Word2Vec方法设计语言模型，探索SMILES序列分子底层特征之间的联系，并将其整合到LSTM网络中，结果表明，该模型对药物的初始设计有更好的优化效果。     

虚拟组合化学分子库的程序设计、实现与应用

介绍了一个组合化学基本工具程序：虚拟组合化学分子库生成程序(Virtual Combinatorial Library Enumerator，VCLE)。以Accelrys公司Accord开发包为基础用C／C 语言进行开发，支持微软公司Windows系统上和太阳微系统公司的Solaris操作系统。VCLE通过解析通式反应，以通式反应物为模板把实际反应物裁剪为取代基，再把取代基连接到通式产物对应的取代位置上，从而组合出以通式产物为骨架的大量分子结构。作为药物发现研究的方便工具，VCLE既可以运行于桌面系统也可以运行于服务器上。     

具有7-(8,0)型自同构的二元双偶极值码

把长度为56的具有7-(8,0)型自同构的二元双偶极值码看成二元域上的多项式,分解成一个收缩码和一个偶重量多项式的直和。利用已知的码长较短的编码构造出长度为56的具有7-(8,0)型自同构的二元双偶极值码,并给出可能的生成矩阵。由于该双偶极值码的最小距离为12,根据两个码等价的类型,对生成矩阵运行Matlab程序,证明了在等价情况下,当E1(σ)*的维数K=2时,不存在有7-(8,0)型自同构的二元双偶极值码;当E1(σ)*的维数K=4时,有7-(8,0)型自同构二元双偶极值码共75种。对长度为56到70的具有类似型自同构的双偶极值码进行相似讨论,得到了其生成矩阵和分类情况。至此,长度在50到70之间的二元双偶极值码的生成矩阵和分类情况得到完全解决。     

基于回溯树的Web服务自动组合

在服务规则库的基础上,介绍了回溯树与完备回溯树的概念,并证明了其重要性质.提出了基于回溯树的Web服务自动组合方法.该方法采用分步分治的思想进行服务的自动组合:1) 针对用户请求的输出对象生成完备回溯树;2) 在完备回溯树中选取最佳生成源(生成路径);3) 将生成路径合成为可执行的流程服务.与已有的基于图搜索的自动Web服务组合方法相比,该方法极大地减小了搜索空间,避免了循环搜索,能够满足单目标和多目标的用户请求.仿真实验结果表明,该方法能够在大规模的服务规则库中进行快速的服务组合,从而满足用户请求.     

有13-(4,m)型的二元自对偶码(m=2,4,6)

论述纠错码中的二元自对偶码,把码字看成二元域GF(2n)上的多项式,并分解因式。根据码长较短的二元自对偶码,构造出长度较长的二元自对偶码,并给出生成矩阵。运用2个码等价的类型,得到在等价下可能的码的分类情况,运行Matlab程序,证明具有13-(4,2)型自同构的二元自对偶码[54,27,10]只有8个等价的自对偶码。应用该方法,得到二元自对偶码[56,28,10]的生成矩阵。运行程序证明在等价情况下,存在16个有13-(4,4)型的自对偶码,而有13-(4,6)型的二元自对偶码[58,29,10]在等价下只有10种码。     

GPS伪随机码的软件和硬件仿真实现

目前四大全球卫星导航定位系统中,美国的GPS是发展最早也是应用面最广的系统,GPS提供民用的标准定位服务和军规的精确定位服务;为研究GPS卫星导航电文的产生机理和针对GPS的导航对抗技术,在详细介绍GPS伪随机码的基本原理和C/A码生成电路的基础上,通过MATLAB和FPGA分别对C/A码进行了软件和硬件仿真实现;基于MATLAB的软件仿真采用循环程序实现了m序列和C/A码,基于FPGA的硬件仿真首先构建一个D触发器元件,然后利用该元件通过并行指令实现m序列,最终生成C/A码;两种方法虽然采用不同的思路和技术,但是得到了一致的C/A码信号样式;伪随机码的产生是GPS实现扩频通信的重要环节,通过对GPS伪随机码的仿真实现,有助于对GPS卫星信号的捕获研究和针对GPS的欺骗式干扰研究。     

离散型细菌觅食算法求解TSP

旅行商问题(TSP)是组合优化问题的典型代表,针对TSP的求解提出一种离散型细菌觅食(DBFO)算法.该算法通过结合2-opt算法设计了一种适合处理离散型变量的趋化算子,将细菌觅食算法推广到了离散情形.同时,结合TSP的特点,在迁徙算子中引入基因库的思想来指导新个体的生成,提高了算法的搜索效率.通过对TSPLIB标准库中22个实例进行仿真实验.实验结果表明,该算法能够有效求解城市规模500以下的TSP,与混合蚁群算法和离散型萤火虫群算法相比,具有更好的全局收敛性和稳定性.     

基于OSG的虚拟化学实验平台的构建设计

为了突破虚拟化学实验平台在智能和可扩展方面的限制,基于开源软件OSG(OpenSceneCraph)的技术特点,设计了三维虚拟化学实验平台.给出了利用OSG实现虚拟实验平台的框架、实现过程和功能结构,特别提供了对虚拟实验操作结果的模糊评价功能.研究了化学反应的实验现象和过程,提出了化学建模,建立了化学实验模型库;提出了化学实验的智能识别机制,综合判别仪器组合、实验药品、反应条件和与之匹配的方程式,实现了智能识别实验类型和渲染实验结果.最后通过一个实例结表明了该实验平台的可行性,并将该平台与其它平台进行比较,表明了该平台操作的灵活性和设计的优越性,为化学实验学习提供了及时、有效的支持.     

面向分布式制造的虚拟控制端开发平台的设计与研究

在分析国内外几种有代表性的数控机床操作面板并对不同面板上各按钮间的功能逻辑关系进行总结归纳的基础上,通过对可定制虚拟控制端开发平台的各功能配置模块的构建,设计开发了一个包含多种类型控件的控件库和一个包含多个已实现的虚拟操作面板的面板库,进而基于控件技术,设计实现了该可定制虚拟控制端开发平台,用于分布式制造中任务调度的控制,并实现了该平台与分布式制造中任务调度执行端之间的网络通讯。最后以华中I型数控系统的远程操作与任务调度作为虚拟控制平台的应用实例。     

Designing targeted libraries with genetic algorithms

In combinatorial synthesis, molecules are assembled by linking chemically similar fragments. Because the number of available chemical fragments often greatly exceeds the number that can be used in one synthetic experiment, one needs a rational method for choosing a subset of desirable fragments. If a combinatorial library is to be targeted against a particular biological activity, virtual screening methods can be used to predict which molecules in a virtual library are most likely to be active. When the number of possible molecules in a virtual library is very large, genetic algorithms (GAs) or simulated annealing can be used to quickly find high-scoring molecules by sampling a small subset of the total combinatorial space. We previously demonstrated how a GA can be used to select a subset of fragments for a combinatorial library, and we used topology-based methods of scoring. Here we extend that earlier work in three ways. (1) We demonstrate use of the GA with 3D scoring methods developed in our laboratory. (2) We show that the approach of assembling libraries from fragments in high-scoring molecules is a reasonable one. (3) We compare results from a library-based GA to those from a molecule-based GA.     

Library design using BCUT chemistry-space descriptors and multiple four-point pharmacophore fingerprints: simultaneous optimization and structure-based diversity

New applications of fingerprints of multiple potential 4-point three-dimensional (3D) pharmacophores in combinatorial library design and virtual screening are presented. Preliminary results demonstrating the feasibility of a simulated annealing process for combinatorial reagent selection that concurrently optimizes product diversity in BCUT chemistry space and in terms of unique 4-point pharmacophores are discussed, and the advantage of using a customized chemistry-space derived for the library design is demonstrated. In addition, an extension to the multiple pharmacophore method for structure-based design that uses the shape of the target site as an additional constraint is presented. This development enables the docking process to be quantified in terms of the number and identities of the pharmacophoric hypotheses that can be matched by a compound or a library of compounds. The design of an example combinatorial library based on the Ugi condensation reaction and a serine protease active site is described.     

Designing focused libraries using MoSELECT

When designing a combinatorial library it is usually desirable to optimise multiple properties of the library simultaneously and often the properties are in competition with one another. For example, a library that is designed to be focused around a given target molecule should ideally have minimum cost and also contain molecules that are bioavailable. In this paper, we describe the program MoSELECT for multiobjective library design that is based on a multiobjective genetic algorithm (MOGA). MoSELECT searches the product-space of a virtual combinatorial library to generate a family of equivalent solutions where each solution represents a combinatorial subset of the virtual library optimised over multiple objectives. The family of solutions allows the relationships between the objectives to be explored and thus enables the library designer to make an informed choice on an appropriate compromise solution. Experiments are reported where MoSELECT has been applied to the design of various focused libraries.     

Hexahedral Mesh Generation by Successive Dual Cycle Elimination

We propose a new method for constructing all-hexahedral finite element meshes. The core of our method is to build up a compatible combinatorial cell complex of hexahedra for a solid body which is topologically a ball, and for which a quadrilateral surface mesh of a certain structure is prescribed. The step-wise creation of the hex complex is guided by the cycle structure of the combinatorial dual of the surface mesh. Our method transforms the graph of the surface mesh iteratively by changing the dual cycle structure until we get the surface mesh of a single hexahedron. Starting with a single hexahedron and reversing the order of the graph transformations, each transformation step can be interpreted as adding one or more hexahedra to the so far created hex complex. Given an arbitrary solid body, we first decompose it into simpler subdomains equivalent to topological balls by adding virtual 2-manifolds. Secondly, we determine a compatible quadrilateral surface mesh for all subdomains created. Then, in the main part we can use the core routine to build up a hex complex for each subdomain independently. The embedding and smoothing of the combinatorial mesh(es) finishes the mesh generation process. First results obtained for complex geometries are encouraging.     

Development and screening of a polyketide virtual library for drug leads against a motilide pharmacophore

A virtual library of macrocyclic polyketide molecules was generated and screened to identify novel, conformationally constrained potential motilin receptor agonists ("motilides"). A motilide pharmacophore model was generated from the potent 6,9-enol ether erythromycin and known derivatives from the literature. The pharmacophore for each molecular conformation was a point in a distance-volume space based on presentation of the putative binding moieties. Two methods, one fragment based method and the other reaction based, were explored for constructing the polyketide virtual library. First, a virtual library was assembled from monomeric fragments using the CHORTLES language. Second, the virtual library was assembled by the in silico application of all possible polyketide synthase enzyme reactions to generate the product library. Each library was converted to low-energy 3D conformations by distance geometry and standard minimization methods. The distance-volume metric was calculated for low-energy conformations of the members of the virtual polyketide library and screened against the enol ether pharmacophore. The goal was to identify novel macrocycles that satisfy the pharmacophore. We identified three conformationally constrained, novel polyketide series that have low-energy conformations satisfying the distance-volume constraints of the motilide pharmacophore.     

基于Qt的虚拟仪器设计与应用

以数据采集系统为例,介绍了使用跨平台图形用户界面库Qt及其扩展库配合自制硬件平台构建虚拟仪器的方法。相比于基于LabVIEW平台的虚拟仪器系统,基于Qt及其扩展库的虚拟仪器不仅具备同样良好的图形用户接口,还具有更好的移植性、扩展性和灵活性。     

Oriented substituent pharmacophore PRopErtY space (OSPPREYS): a substituent-based calculation that describes combinatorial library products better than the corresponding product-based calculation

Initial combinatorial library designs were based on 2D substituent properties. Subsequently, two important extensions were introduced to improve the approach: use of pharmacophores to introduce 3D information, and performing calculations on the enumerated library products rather than just on the substituents. Unfortunately, practical compromises due to the large number of possible products, the large number of conformations per product, and the explicit dependence on the scaffold limit the application of these extensions in five important ways: (1) to small virtual libraries, (2) to only 3- or 4-point pharmacophores, (3) to inadequate conformational sampling, (4) to simplistic diversity measures, and (5) to requiring a complete new calculation for every new library. The 3D oriented substituent pharmacophores have been developed to overcome these limitations. These add two additional points and corresponding distances to each substituent pharmacophore. This adds little additional computation beyond a normal 3D pharmacophore calculation on the substituents, but recaptures most of the orienting information lost in breaking up the enumerated products into fragments. Two main approximations are still implicitly required: the combinatorial conformer assumption and the template alignment assumption. In turn, however, they are designed to account not just for the 3- and 4-point pharmacophores, but for pharmacophores with up to 9 points in enumerated products with three sites of diversity. Perhaps more importantly, pharmacophore calculations are shown to be very sensitive to conformational sampling. The small number of substituents, plus the small number of rotatable bonds per substituent, permits very thorough conformational sampling. For a rigid scaffold with three diversity sites of 1,000 candidate substituents each, the number of molecules to analyze is reduced by a factor of 10(6), and the number of conformations per molecule is reduced by another 10(4). In addition, the modest number of pairwise substituent similarities permits the creation of a Euclidean property space by MDS. This allows for sophisticated experimental design methods that require coordinates, rather than just the counting of the number of set bits in a library union fingerprint. Finally, oriented substituent calculations are scaffold independent and transferable. They can be stored in a database and need not be repeated for every new library. Thus, there are some approximations in the correspondence between oriented substituent pharmacophore similarities and enumerated product pharmacophore similarities. However, these errors are minor compared to the five advantages that the new method enables: large virtual library sizes, thorough conformational sampling, accounting for 1- to 9-point pharmacophores, creation of a Euclidean property space, and a reusable database of precomputed substituent values.