Fragment-Based QSAR and Molecular Modeling Studies on a Series of Discodermolide Analogs as Microtubule-Stabilizing Anticancer Agents

Inhibition of microtubule function is an attractive rational approach to anticancer therapy. Although taxanes are the most prominent among the microtubule-stabilizers, their clinical toxicity, poor pharmacokinetic properties, and resistance have stimulated the search for new antitumor agents having the same mechanism of action. Discodermolide is an example of nontaxane natural product that has the same mechanism of action, demonstrating superior antitumor efficacy and therapeutic index. The extraordinary chemical and biological properties have qualified discodermolide as a lead structure for the design of novel anticancer agents with optimized therapeutic properties. In the present work, we have employed a specialized fragment-based method to develop robust quantitative structure - activity relationship models for a series of synthetic discodermolide analogs. The generated molecular recognition patterns were combined with three-dimensional molecular modeling studies as a fundamental step on the path to understanding the molecular basis of drug-receptor interactions within this important series of potent antitumoral agents.

A logic-based agent that plans for extended reachability goals

Planning to reach a goal is an essential capability for rational agents. In general, a goal specifies a condition to be achieved at the end of the plan execution. In this article, we introduce nondeterministic planning for extended reachability goals (i.e., goals that also specify a condition to be preserved during the plan execution). We show that, when this kind of goal is considered, the temporal logic CTL turns out to be inadequate to formalize plan synthesis and plan validation algorithms. This is mainly due to the fact that the CTL`s semantics cannot discern among the various actions that produce state transitions. To overcome this limitation, we propose a new temporal logic called alpha-CTL. Then, based on this new logic, we implement a planner capable of synthesizing reliable plans for extended reachability goals, as a side effect of model checking.

Modeling and illustrating requirement prioritization in public e-service development from a value-based perspective

A major problem in e-service development is the prioritization of the requirements of different stakeholders. The main stakeholders are governments and their citizens, all of whom have different and sometimes conflicting requirements. In this paper, the prioritization problem is addressed by combining a value-based approach with an illustration technique. This paper examines the following research question: How can multiple stakeholder requirements be illustrated from a value-based perspective in order to be prioritizable? We used an e-service development case taken from a Swedish municipality to elaborate on our approach. Our contributions are: 1) a model of the relevant domains for requirement prioritization for government, citizens, technology, finances and laws and regulations; and 2) a requirement fulfillment analysis tool (RFA) that consists of a requirement-goal-value matrix (RGV), and a calculation and illustration module (CIM). The model reduces cognitive load, helps developers to focus on value fulfillment in e-service development and supports them in the formulation of requirements. It also offers an input to public policy makers, should they aim to target values in the design of e-services.

A reputation-based trust model for agent societies

Trust and security issues are prevalent in agent societies, where agents are autonomously owned and operated in a networked environment. Nowadays, trust and reputation management is a promising approach to manage them. However, many reputation models su.ered from a major drawback – there is no mechanism to discourage agents from lying information when making a recommendation. Although some works do take into account of this issue, they usually do not penalize an agent for making poor referrals. Worse, some systems actually judge an agents referral reputation based on its service reputation. In situations where this is unacceptable, we need to have a mechanism where agents are not only discouraged from making poor referrals, but are also penalized when doing so. Towards this, we propose a reputation-based trust model that considers an agents referral reputation as a separate entity within the broader sense of an agents reputation. Our objective is not to replace any existing reputation mechanisms, but rather to complement and extend them.

Observer-based control of multi-agent systems under decentralized information structure

This paper addresses the problem of decentralized implementation of a global state feedback controller for multi-agent systems. The system is assumed to be under the constraint of a complete decentralized information structure. The decentralization of the control task is achieved through the construction of low-order decentralized functional observers with the purpose of generating the required corresponding control signal for each local control station. A design procedure is developed for obtaining an approximate solution to the design of the observers. Stability analysis is provided for the global system using the proposed observer-based approach. A numerical example is given to illustrate the design procedure and cases when the observers' order increases from the lowest value.

Observer-based robust finite-time cooperative consensus control for multi-agent networks

This paper studies the finite-time consensus tracking control for multi-agent networks. The time-varying control input and the velocity of the leader is unknown to any follower. Only the position of the leader is known to its neighbors. We first propose a new finite-time multiple-surface sliding mode observer to estimate the leader's velocity. It is seen that the estimation error of the observer can converge to zero in a finite time. Then, we prove that finite-time consensus tracking of multi-agent networks can be achieved on a new terminal sliding mode surface. Simulation results are presented to validate the analysis.

A state space based approach in non-linear hemodynamic response modeling with fMRI data

In this paper we use the modified and integrated version of the balloon model in the analysis of fMRI data. We propose a new state space model realization for this balloon model and represent it with the standard A,B,C and D matrices widely used in system theory. A second order Padé approximation with equal numerator and denominator degree is used for the time delay approximation in the modeling of the cerebral blood flow. The results obtained through numerical solutions showed that the new state space model realization is in close agreement to the actual modified and integrated version of the balloon model. This new system theoretic formulation is likely to open doors to a novel way of analyzing fMRI data with real time robust estimators. With further development and validation, the new model has the potential to devise a generalized measure to make a significant contribution to improve the diagnosis and treatment of clinical scenarios where the brain functioning get altered. Concepts from system theory can readily be used in the analysis of fMRI data and the subsequent synthesis of filters and estimators.

CARSA : A context-aware reasoning-based service agent model for AI planning of web service compostion

In order to achieve automatic and more intelligent service composition, dynamic description logic (DDL) is proposed and utilized as one emerging logic-level solution. However, reasoning optimization and utilization in such DDL-related solutions is still an open problem. In this paper, we propose the context-aware reasoning-based service agent model (CARSA) which exploits the relationships among different service consumers and providers, together with the corresponding optimization approach to strengthen the effectiveness of Web service composition. Through the model, two reasoning optimization methods are proposed based on the substitute relationship and the dependency relationship, respectively, so irrelevant actions can be filtered out of the reasoning space before the DDL reasoning process is carried out. The case study and experimental analysis demonstrates the capability of the proposed approach.

Adaptive data based neural network leader-follower control of multi-agent networks

In this paper, we propose a data based neural network leader-follower control for multi-agent networks where each agent is described by a class of high-order uncertain nonlinear systems with input perturbation. The control laws are developed using multiple-surface sliding control technique. In particular, novel set of sliding variables are proposed to guarantee leader-follower consensus on the sliding surfaces. Novel switching is proposed to overcome the unavailability of instantaneous control output from the neighbor. By utilizing RBF neural network and Fourier series to approximate the unknown functions, leader-follower consensus can be reached, under the condition that the dynamic equations of all agents are unknown. An O(n) data based algorithm is developed, using only the network’s measurable input/output data to generate the distributed virtual control laws. Simulation results demonstrate the effectiveness of the approach.

Software reliability growth models based on local polynomial modeling with kernel smoothing

Software reliability growth models (SRGMs) are extensively employed in software engineering to assess the reliability of software before their release for operational use. These models are usually parametric functions obtained by statistically fitting parametric curves, using Maximum Likelihood estimation or Least–squared method, to the plots of the cumulative number of failures observed N(t) against a period of systematic testing time t. Since the 1970s, a very large number of SRGMs have been proposed in the reliability and software engineering literature and these are often very complex, reflecting the involved testing regime that often took place during the software development process. In this paper we extend some of our previous work by adopting a nonparametric approach to SRGM modeling based on local polynomial modeling with kernel smoothing. These models require very few assumptions, thereby facilitating the estimation process and also rendering them more relevant under a wide variety of situations. Finally, we provide numerical examples where these models will be evaluated and compared.

Mobile agent tracking with single frequency continuous wave radar : a linear robust filtering based approach

3-alkylpyrrole to the fabric surface. Direct applications of a conductive paint to the textile surface eliminate the exposure of the substrate to damaging oxidizing agents which allow the coating of more sensitive and delicate substrates. All textiles produced are tested for abrasion resistance and conductivity. For alkyl polypyrrole coated fabrics, the optimum carbon chain lengths are between n=10 and n=14, which result in optimum values of conductivity and solubility. The darkness of the tone is inversely related to the surface resistivity of the resulting conductive fabric. Therefore, deep black coatings have low resistivity whereas light gray coatings on a white fabric surface have higher surface resistivity. Longer alkyl chains result in higher surface resistivity in fabrics. The conductive coating of poly(3-decanylpyrrole) on the textile surface has a better abrasion resistance compared to that of an unsubstituted polypyrrole coating.