Establishment of a search library about benzylisoquinoline alkaloids based on selective separation on the binaphthyl column and standard analysis on C18 column

A search library about benzylisoquinoline alkaloids was established based on preparation of alkaloid fractions from Rhizoma coptidis, Cortex phellodendri, and Rhizoma corydalis. In this work, two alkaloid fractions from each herbal medicine were first prepared based on selective separation on the “click” binaphthyl column. And then these alkaloid fractions were analyzed on C18 column by liquid chromatography coupled with tandem mass spectrometry. Many structure‐related compounds were included in these alkaloids fractions, which led to easy separation and good MS response in further work. Therefore, a search library of 52 benzylisoquinoline alkaloids was established, which included eight aporphine, 19 tetrahydroprotoberberine, two protopine, two benzyltetrahydroisoquinoline, and 21 protoberberine alkaloids. The information of the search library contained compound names, structures, retention times, accurate masses, fragmentation pathways of benzylisoquionline alkaloids, and their sources from three herbal medicines. Using such a library, the alkaloids, especially those trace and unknown components in some herbal medicine could be accurately and quickly identified. In addition, the distribution of benzylisoquinoline alkaloids in the herbal medicines could be also summarized by searching the source samples in the library.     

Precise and global identification of phospholipid molecular species by an Orbitrap mass spectrometer and automated search engine Lipid Search

In the present research, we have established a new lipidomics approach for the comprehensive and precise identification of molecular species in a crude lipid mixture using a LTQ Orbitrap mass spectrometer (MS) and reverse-phase liquid chromatography (RPLC) combination with our newly developed lipid search engine “Lipid Search”. LTQ Orbitrap provides high mass accuracy MS spectra by Fourier-transform (FT) mass spectrometer mode and can perform rapid MSⁿ by ion trap (IT) mass spectrometer mode. In this study, the negative ion mode was selected to detect fragment ions from phospholipids, such as fatty acid anions, by MS2 or MS3. We selected the specific detection approach by neutral loss survey-dependent MS3, for the identification of molecular species of phosphatidylcholine, sphingomyelin and phosphatidylserine. Identification of molecular species was performed by using both the high mass accuracy of the mass spectrometric data obtained from FT mode and structural data obtained from fragments in IT mode. Some alkylacyl and alkenylacyl species have the same m/z value as molecular-related ions and fragment ions, thus, direct acid hydrolysis analysis was performed to identify alkylacyl and alkenylacyl species, and then the RPLC–LTQ Orbitrap method was applied. As a result, 290 species from mouse liver and 248 species from mouse brain were identified within six different classes of phospholipid, only those in manually detected and confirmed. Most of all manually detected mass peaks were also automatically detected by “Lipid Search”. Adding to differences in molecular species in different classes of phospholipids, many characteristic differences in molecular species were detected in mouse liver and brain. More variable number of saturated and monounsaturated fatty acid-containing molecular species were detected in mouse brain than liver.     

R基团搜索技术用于HIV-1逆转录酶抑制剂的分子设计

本文采用基于R基团搜索技术的Topomer CoMFA方法对41个人类免疫缺陷病毒(HIV-1)逆转录酶抑制剂进行了三维定量构效关系(3D-QSAR)分析。所得优化模型的拟合、交互验证及外部验证的复相关系数分别为0.995、0.859和0.945。采用Topomer Search技术对ZINC数据库进行R基团的虚拟筛选,得到R贡献高的基团,以活性最高的13号分子为模板进行过滤得到1个Ra基团和20个Rb基团。并以此设计得到20个新化合物分子,其中有19个化合物的预测活性值高于13号分子。研究结果表明,所建立的Topomer CoMFA模型具有良好的稳定性和预测能力,基于R基团的Topomer Search技术可以有效筛选并设计出新的HIV-1逆转录酶抑制剂,为抗艾滋病新药设计提供了理论依据。     

Frequency optimization in public transportation systems: Formulation and metaheuristic approach

We study the transit frequency optimization problem, which aims to determine the time interval between subsequent buses for a set of public transportation lines given by their itineraries, i.e., sequences of stops and street sections. The solution should satisfy a given origin–destination demand and a constraint on the available fleet of buses. We propose a new mixed integer linear programming (MILP) formulation for an already existing model, originally formulated as a nonlinear bilevel one. The proposed formulation is able to solve to optimality real small-sized instances of the problem using MILP techniques. For solving larger instances we propose a metaheuristic which accuracy is estimated by comparing against exact results (when possible). Both exact and approximated approaches are tested by using existing cases, including a real one related to a small-city which public transportation system comprises 13 lines. The magnitude of the improvement of that system obtained by applying the proposed methodologies, is comparable with the improvements reported in the literature, related to other real systems. Also, we investigate the applicability of the metaheuristic to a larger-sized real case, comprising more than 130 lines.     

A Combinatorial Approach to Piecewise Linear Time Series Analysis

Over recent years, several nonlinear time series models have been proposed in the literature. One model that has found a large number of successful applications is the threshold autoregressive model (TAR). The TAR model is a piecewise linear process whose central idea is to change the parameters of a linear autoregressive model according to the value of an observable variable, called the threshold variable. If this variable is a lagged value of the time series, the model is called a self-exciting threshold autoregressive (SETAR) model. In this article, we propose a heuristic to estimate a more general SETAR model, where the thresholds are multivariate. We formulate the task of finding multivariate thresholds as a combinatorial optimization problem. We develop an algorithm based on a greedy randomized adaptive search procedure (GRASP) to solve the problem. GRASP is an iterative randomized sampling technique that has been shown to quickly produce good quality solutions for a wide variety of optimization problems. The proposed model performs well on both simulated and real data.     

The Capacitated Team Orienteering Problem: A Bi-level Filter-and-Fan method

This paper focuses on vehicle routing problems with profits and addresses the so-called Capacitated Team Orienteering Problem. Given a set of customers with a priori known profits and demands, the objective is to find the subset of customers, for which the collected profit is maximized, and to determine the visiting sequence and assignment to vehicle routes assuming capacity and route duration restrictions. The proposed method adopts a hierarchical bi-level search framework that takes advantage of different search landscapes. At the upper level, the solution space is explored on the basis of the collected profit, using a Filter-and-Fan method and a combination of profit oriented neighborhoods, while at the lower level the routing of customers is optimized in terms of traveling distance via a Variable Neighborhood Descent method. Computational experiments on benchmark data sets illustrate the efficiency and effectiveness of the proposed approach. Compared to existing results, new upper bounds are produced with competitive computational times.     

The capture time of a graph

We consider the game of Cops and Robbers played on finite and countably infinite connected graphs. The length of games is considered on cop-win graphs, leading to a new parameter, the capture time of a graph. While the capture time of a cop-win graph on n vertices is bounded above by n−3, half the number of vertices is sufficient for a large class of graphs including chordal graphs. Examples are given of cop-win graphs which have unique corners and have capture time within a small additive constant of the number of vertices. We consider the ratio of the capture time to the number of vertices, and extend this notion of capture time density to infinite graphs. For the infinite random graph, the capture time density can be any real number in [0,1]. We also consider the capture time when more than one cop is required to win. While the capture time can be calculated by a polynomial algorithm if the number k of cops is fixed, it is NP-complete to decide whether k cops can capture the robber in no more than t moves for every fixed t.     

VRPTW的扰动恢复及其TABU SEARCH算法

本文对带时间窗的车辆路线安排扰动恢复问题进行了讨论,分析了各种可能的扰动:增加减少客户,时间窗、客户需求及路线可行性的扰动,构造了扰动模型.利用禁忌搜索算法对问题进行求解,同时通过对模型参数重新设置,得到了多个满足要求的不同的解,这样使解更具有实际可行性和有效性.     

一种带时间窗和车辆数目限制的车辆路线问题及其算法

本文提出了带时间窗和车辆数目限制的车辆路线问题的数学模型,针对该问题的特征构造了一种路线生成算法和禁忌搜索算法,并对Solomon提出的C1、R1、RC1类数据集给出了数值运算的结果,实验结果表明算法是有效的.     

基于混合算法的实时订货信息下的车辆调度优化

实时订货信息下的车辆调度是随机性车辆调度中货物需求量、需求点均不确定的情况下的车辆调度.针对该问题,本文构建了配送总成本最小的目标函数,提出了采用混合算法求解的思路.即以局部搜索法求得初始解,采用遗传算法优化初始解,并在送货时间更新后,利用禁忌搜索法求解速度快的特点改进调度方案,得到订货信息不断更新的条件下的车辆调度方案.通过实例分析,本方法既可解决电子商务条件下实时订货的车辆调度问题,也具有求解结果可靠、求解过程快速的特点.