Astragalin identification in graviola pericarp indicates a possible participation in the anticancer activity of pericarp crude extracts: In vitro and in silico approaches

Graviola, soursop, or guanabana (Annona muricata L.), is an ethnomedical fruit consumed to alleviate headache, diarrhea, diabetes, and cancer. Pericarp is the inedible part of graviola least studied in comparison to seeds and leaves, even thought, it contains the highest concentration of graviola total polyphenols. Anticancer effect of graviola pericarp has been demonstrated in crude extracts attributing the effect to acetogenins, however, crude extracts contain several active molecules. Thus, the present work aimed to fractionate and purify an ethanolic crude extract from graviola pericarp. Purified graviola pericarp fraction (PGPF) was evaluated on cancerous and non-cancerous cell lines, and then was identified by NMR, TOF-MS, and HPLC. Finally, an in silico analysis was performed to predict targets cancer-related of the molecule detected. Our results revealed IC₅₀ values for cervix adenocarcinoma (HeLa), hepatocellular carcinoma (HepG2), triple-negative breast cancer (MDA-MB-231), and non-cancerous cell line (HaCaT) of 92.85 ± 1.23, 81.70 ± 1.09, 84.28 ± 1.08, and 170.2 ± 1.12 µg PGPF/mL, respectively. In vitro therapeutic indexes estimated as quantitative relationship between safety and efficacy of PGPF were 1.83, 2.08, and 2.02 for HeLa, HepG2, and MDA-MB-231, respectively. The NMR analysis revealed astragalin (kaempferol-3-O-glucoside) in PGPF, a flavonoid not reported in graviola pericarp until now. Astragalin identity was confirmed by TOF-MS and HPLC. In silico results support previous reports about astragalin modulating proteins such as Bcl-2, CDK2, CDK4, MAPK and RAF1. Also, results suggest that astragalin may interact with other cancer-related proteins not associated previously with astragalin. In conclusion, astragalin may be contributing to the anticancer effect observed in graviola pericarp extracts.     

离散异质多智能体系统的分组一致性控制

针对一类混合异质多智能体系统的分组一致性控制问题进行了研究。具体分析了由一阶智能体和二阶智能体组成的混合异质系统,研究其在离散情况下的分组一致性。基于两个合理的假设提出了线性控制协议,运用代数图论、稳定性理论和矩阵理论,分析协议作用下闭环系统的系统矩阵及动态特性,取得了系统渐近实现分组一致性的充分条件,该条件与系统拓扑结构、采样周期以及控制参数有关。结论同时适用于有向拓扑与无向拓扑,最后通过仿真实例对所得分析结果进行了验证。     

基于consensus滤波器的新型电压监测仪的设计

在进行深入分析consensus滤波器原理的基础上,提出了一种新的电压监测仪设计方法。首先将数模转换器在各个时刻测量的电压有效值看做一个小世界网络模型G中的一个节点。由于测量的电压信号容易被电网中的随机噪声所污染,通过consensus滤波器算法进行滤波,使得数模转换器测量的信号最终趋近于一个稳定的数值。仿真结果表明,该方法可以有效的还原被噪声污染的电压信号,而且即使在某一个时刻数模转换器出现故障失灵,所测量的数据也不受影响,仿真结果和实践应用表明了本文所提出方法的有效性和可行性。     

Further improvement of finite-time consensus protocols for detail-balanced networks

This paper presents a new class of protocols to solve finite-time consensus for multi-agent systems. The protocols are induced from the classical finite-time consensus algorithm by using the so-called protocol function. Sufficient conditions are established for networked agents to experience finite-time consensus under time-varying undirected and fixed directed topologies. Numerical simulations show that the proposed protocols can provide more flexibility to improve convergence rate.     

The group consensus based evidential reasoning approach for multiple attributive group decision analysis

Many multiple attribute decision analysis problems include both quantitative and qualitative attributes with various kinds of uncertainties such as ignorance, fuzziness, interval data, and interval belief degrees. An evidential reasoning (ER) approach developed in the 1990s and in recent years can be used to model these problems. In this paper, the ER approach is extended to group consensus (GC) situations for multiple attributive group decision analysis problems. In order to construct and check the GC, a compatibility measure between two belief structures is developed first. Considering two experts’ utilities, the compatibility between their assessments is naturally constructed using the compatibility measure. Based on the compatibility between two experts’ assessments, the GC at a specific level that may be the attribute level, the alternative level, or the global level, can be constructed and reached after the group analysis and discussion within specified times. Under the condition of GC, we conduct a study on the forming of group assessments for alternatives, the achievement of the aggregated utilities of assessment grades, and the properties and procedure of the extended ER approach. An engineering project management software selection problem is solved by the extended ER approach to demonstrate its detailed implementation process, and its validity and applicability.     

解决一类群决策问题的改进德尔菲法

专家综合评价属于委员会形式的群决策问题,提出了基于一致性分析的群决策机制和基于OWA算子的群决策机制,用来弥补常用机制的缺陷;介绍了判断群体意见分歧特征和定量判断标准;提出了基于一致性分析的改进德尔菲法,介绍了这种方法的思想、特点和应用步骤;分析了这类群决策的人员组成和工作程序图.     

A consensus line search algorithm for molecular potential energy functions

Force field based energy minimization of molecular structures is a central task in computational chemistry and biology. Solving this problem usually requires efficient local minimization techniques, i.e., iterative two‐step methods that search first for a descent direction and then try to estimate the step width. The second step, the so called line search, typically uses polynomial interpolation schemes to estimate the next trial step. However, dependent on local properties of the objective function alternative schemes may be more appropriate especially if the objective function shows singularities or exponential behavior. As the choice of the best interpolation scheme cannot be made a priori, we propose a new consensus line search approach that performs several different interpolation schemes at each step and then decides which one is the most reliable at the current position. Although a naive consensus approach would lead to severe performance impacts, our method does not require additional evaluations of the energy function, imposing only negligible computational overhead. Additionally, our method can be easily adapted to the local behavior of other objective functions by incorporating suitable interpolation schemes or omitting non‐fitting schemes. The performance of our consensus line search approach has been evaluated and compared to established standard line search algorithms by minimizing the structures of a large set of molecules using different force fields. The proposed algorithm shows better performance in almost all test cases, i.e., it reduces the number of iterations and function and gradient evaluations, leading to significantly reduced run times. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009     

Multiple ligand-binding modes in bacterial R67 dihydrofolate reductase

Summary R67 dihydrofolate reductase (DHFR), a bacterial plasmid-encoded enzyme associated with resistance to the drug trimethoprim, shows neither sequence nor structural homology with the chromosomal DHFR. It presents a highly symmetrical toroidal structure, where four identical monomers contribute to the unique central active-site pore. Two reactants (dihydrofolate, DHF), two cofactors (NADPH) or one of each (R67•DHF•NADPH) can be found simultaneously within the active site, the last one being the reactive ternary complex. As the positioning of the ligands has proven elusive to empirical determination, we addressed the problem from a theoretical perspective. Several potential structures of the ternary complex were generated using the docking programs AutoDock and FlexX. The variability among the final poses, many of which conformed to experimental data, prompted us to perform a comparative scoring analysis and molecular dynamics simulations to assess the stability of the complexes. Analysis of ligand–ligand and ligand–protein interactions along the 4 ns trajectories of eight different structures allowed us to identify important inter-ligand contacts and key protein residues. Our results, combined with published empirical data, clearly suggest that multipe binding modes of the ligands are possible within R67 DHFR. While the pterin ring of DHF and the nicotinamide ring of NADPH assume a stacked endo-conformation at the centre of the pore, probably assisted by V66, Q67 and I68, the tails of the molecules extend towards opposite ends of the cavity, adopting multiple configurations in a solvent rich-environment where hydrogen-bond interactions with K32 and Y69 may play important roles.     

Simple Majority Consensus in Networks with Unreliable Communication

In this work, we analyze the performance of a simple majority-rule protocol solving a fundamental coordination problem in distributed systems—binary majority consensus—in the presence of probabilistic message loss. Using probabilistic analysis for a large-scale, fully-connected, network of 2n agents, we prove that the Simple Majority Protocol (SMP) reaches consensus in only three communication rounds, with probability approaching 1 as n grows to infinity. Moreover, if the difference between the numbers of agents that hold different opinions grows at a rate of n, then the SMP with only two communication rounds attains consensus on the majority opinion of the network, and if this difference grows faster than n, then the SMP reaches consensus on the majority opinion of the network in a single round, with probability converging to 1 as exponentially fast as n→∞. We also provide some converse results, showing that these requirements are not only sufficient, but also necessary.     

On the mathematics of emergence

We describe a setting where convergence to consensus in a population of autonomous agents can be formally addressed and prove some general results establishing conditions under which such convergence occurs. Both continuous and discrete time are considered and a number of particular examples, notably the way in which a population of animals move together, are considered as particular instances of our setting. This article is based on the 1st Takagi Lectures that the second author delivered at Research Institute for Mathematical Sciences, Kyoto University on November 25 and 26, 2006. Steve Smale Partially supported by an NSF grant.