Combining Different Docking Engines and Consensus Strategies to Design and Validate Optimized Virtual Screening Protocols for the SARS-CoV-2 3CL Protease

The 3CL-Protease appears to be a very promising medicinal target to develop anti-SARS-CoV-2 agents. The availability of resolved structures allows structure-based computational approaches to be carried out even though the lack of known inhibitors prevents a proper validation of the performed simulations. The innovative idea of the study is to exploit known inhibitors of SARS-CoV 3CL-Pro as a training set to perform and validate multiple virtual screening campaigns. Docking simulations using four different programs (Fred, Glide, LiGen, and PLANTS) were performed investigating the role of both multiple binding modes (by binding space) and multiple isomers/states (by developing the corresponding isomeric space). The computed docking scores were used to develop consensus models, which allow an in-depth comparison of the resulting performances. On average, the reached performances revealed the different sensitivity to isomeric differences and multiple binding modes between the four docking engines. In detail, Glide and LiGen are the tools that best benefit from isomeric and binding space, respectively, while Fred is the most insensitive program. The obtained results emphasize the fruitful role of combining various docking tools to optimize the predictive performances. Taken together, the performed simulations allowed the rational development of highly performing virtual screening workflows, which could be further optimized by considering different 3CL-Pro structures and, more importantly, by including true SARS-CoV-2 3CL-Pro inhibitors (as learning set) when available.     

Structural and immunogenicity analysis of reconstructed ancestral and consensus P48/45 for cross-species anti malaria transmission-blocking vaccine

The development of the anti-malaria vaccine holds a promising future in malaria control. One of the anti-malaria vaccine strategies known as the transmission-blocking vaccine (TBV) is to inhibit the parasite transmission between humans and mosquitoes by targeting the parasite gametocyte. Previously, we found that P48/45 included in the 6-Cysteine protein family shared by Plasmodium sp. We also detected vaccine properties possessed by all human-infecting Plasmodium and could be used as a cross-species anti-malaria vaccine. In this study, we investigated the efficacy of P48/45 through the ancestral and consensus reconstruction approach. P48/45 phylogenetic and time tree analysis was done by RAXML and BEAST2. GRASP server and Ugene software were used to reconstruct ancestral and consensus sequences, respectively. The protein structural prediction was made by using a psipred and Rosetta program. Each protein characteristic of P48/45 was analyzed by assessing hydrophobicity and Post-Translational Modification sites. Meanwhile, the Epitope sequence for B-cell, T-cell, and HLA was determined using an immunoinformatics approach. Lastly, molecular docking simulation was done to determine native binding interactions of P48/45-P230. The result showed a distinct protein characteristic of ancestral and consensus sequences. The immunogenicity analysis revealed the number of epitopes in the ancestral sequence is greater than the consensus sequence. The study also found a conserved epitope located in the binding site and consists of specific Post-Translational Modification sites. Hence, our research provides detailed insight into ancestral and consensus P48/45 efficacy for the cross-species anti-malaria vaccine.     

基于评价信息随机化的群体评价方法与应用

针对群体评价中共识集结的相关问题,从仿真的视角讨论了评价信息随机化的群体共识聚合求解方法。首先,面向实数类型的评价信息,将精确性的数据给予一定的宽松性处理,进一步结合正态分布的3σ原则,利用随机模拟的方式集结出带有概率特征的可能性排序;其次,面向区间数类型的评价信息,整合出各子区间发生概率不同的区间数评价信息,在充分随机模拟的情况下,给出了带有优胜概率特征的可能性排序。最后,通过相应的算例进行求解分析,说明了该方法的可行性和有效性。基于群体共识视角,针对实数和区间数两种类型的评价信息,分别进行相应的随机化处理,并为进一步探索区间数的分布形式提供了一种新的研究思路。     

Consensus problems on networks with free protocol

In the real world, rule makers can only restrict, not completely control the behavior of the governed, while the governed can only choose their behavior patterns under these restrictions. In this paper, we design a new control protocol called free protocol to describe this situation. First, we calculate consensus probabilities based on the information of the interaction networks. Then, sufficient conditions are obtained for all agents converging to a same value with probability one. Finally, numerical simulation results are given to verify the above results.     

概率语言多属性群决策方法及其在新型智慧城市市民获得感评价中的应用

针对公众参与的语言信息多属性群决策问题，研究了考虑参与者满意度的概率语言多属性群决策方法。首先，根据参与者的语言评价信息确定并规范化概率语言决策矩阵。然后，对大群体进行共识分析，由最大化参与者群体的满意度构建线性规划模型，确定参与者群组的权重；构造正、负理想方案的评价向量，构建多目标规划模型，用拉格朗日乘子法求解属性权重；定义各方案的加权贴近度，并以此对方案进行排序和优选。最后，通过新型智慧城市市民获得感评价案例验证了模型的可行性和有效性。     

基于邻域贡献权值细化的圆心亚像素定位算法

针对传统的圆心算法过程复杂、定位精度受初始边缘提取效果影响较大等问题,提出了一种基于邻域贡献权值细化的圆心亚像素定位算法。首先引入邻域贡献权值系数,改进传统非极大值抑制法,细化边缘;然后在边缘点的梯度方向对灰度值进行高斯拟合,确定亚像素边缘位置;最后针对边缘突变点提出了基于随机抽样一致的最小二乘法来拟合圆心。实验结果表明,该算法具有较好的精度和稳定性,圆心的提取精度可以达到0.1个像素。     

Stability analysis of a class of uncertain switched systems on time scale using Lyapunov functions

This paper deals with the stability analysis of a class of uncertain switched systems on non-uniform time domains. The considered class consists of dynamical systems which commute between an uncertain continuous-time subsystem and an uncertain discrete-time subsystem during a certain period of time. The theory of dynamic equations on time scale is used to study the stability of these systems on non-uniform time domains formed by a union of disjoint intervals with variable length and variable gap. Using the concept of common Lyapunov function, sufficient conditions are derived to guarantee the asymptotic stability of this class of systems on time scale with bounded graininess function. The proposed scheme is used to study the leader–follower consensus problem under intermittent information transmissions.     

Dynamic output feedback consensus of continuous‐time networked multiagent systems

This article addresses the dynamic output feedback consensus problem of continuous‐time networked multiagent systems. Both a fixed topology and Markovian switching topologies are considered. The consensus algorithms are on the base of the output information of each agent's itself and its neighbors. Some sufficient conditions for consensus of multiagent systems are obtained in forms of bilinear matrix inequalities. The algorithm based on the homotopy continuation method is given to compute the feasible controller gains. Numerical simulations are given to show the effectiveness of the proposed results. © 2014 Wiley Periodicals, Inc. Complexity 20: 35–42, 2015     

An attribute weight based feedback model for multiple attributive group decision analysis problems with group consensus requirements in evidential reasoning context

In an evidential reasoning context, a group consensus (GC) based approach can model multiple attributive group decision analysis problems with GC requirements. The predefined GC is reached through several rounds of group analysis and discussion (GAD) in the approach. However, the GAD with no guidance may not be the most appropriate way to reach the predefined GC because several rounds of GAD will spend a lot of time of all experts and yet cannot help them to effectively emphasize on the assessments which primarily damage the GC. In this paper, an attribute weight based feedback model is constructed to effectively identify the assessments primarily damaging the GC and accelerate the GC convergence. Considering important attributes with the weights more than or at least equal to the mean of the weights of all attributes, the feedback model constructs identification rules to identify the assessments damaging the GC for the experts to renew. In addition, a suggestion rule is introduced to generate appropriate recommendations for the experts to renew their identified assessments. The identification rules are constructed at three levels including the attribute, alternative and global levels. The feedback model is used to solve an engineering project management software selection problem to demonstrate its detailed implementation process, its validity and applicability, and its advantages compared with the GC based approach.