Abstract: As any iterative technique, it is a necessary condition a stop criterion for terminating Evolutionary Algorithms (EA). In the case of optimization methods, the algorithm should stop at the time it has reached a steady state so it can not improve results anymore. Assessing the reliability of termination conditions for EAs is of prime importance. A wrong or weak stop criterion can negatively aect both the computational eort and the nal result.
In this Thesis, we introduce a statistical framework for assessing whether a termination condition is able to stop EA at its steady state. In one hand a numeric approximation to steady states to detect the point in which EA population has lost its diversity has been presented for EA termination. This approximation has been applied to dierent EA paradigms based on diversity and a selection of functions covering the properties most relevant for EA convergence. Experiments show that our condition works regardless of the search space dimension and function landscape and Dierential Evolution (DE) arises as the best paradigm. On the other hand, we use a regression model in order to determine the requirements ensuring that a measure derived from EA evolving population is related to the distance to the optimum in xspace.
Our theoretical framework is analyzed across several benchmark test functions
and two standard termination criteria based on function improvement in f-space and EA population x-space distribution for the DE paradigm. Results validate our statistical framework as a powerful tool for determining the capability of a measure for terminating EA and select the x-space distribution as the best-suited for accurately stopping DE in real-world applications.

Abstract: Empirical and mechanistic models differ in their approaches to the analysis of pharmacological effect. Whereas the parameters of the former are not physical constants those of the latter embody the nature, often complex, of biology. Empirical models are exclusively used for curve fitting, merely to characterize the shape of the E/[A] curves. Mechanistic models, on the contrary, enable the examination of mechanistic hypotheses by parameter simulation. Regretfully, the many parameters that mechanistic models may include can represent a great difficulty for curve fitting, representing, thus, a challenge for computational method development. In the present study some empirical and mechanistic models are shown and the connections, which may appear in a number of cases between them, are analyzed from the curves they yield. It may be concluded that systematic and careful curve shape analysis can be extremely useful for the understanding of receptor function, ligand classification and drug discovery, thus providing a common language for the communication between pharmacologists and medicinal chemists.

Abstract: Two-state and operational models of both agonism and allosterism are compared to identify and characterize common pharmacological parameters. To account for the receptor-dependent basal response, constitutive receptor activity is considered in the operational models. By arranging two-state models as the fraction of active receptors and operational models as the fractional response relative to the maximum effect of the system, a one-by-one correspondence between parameters is found. The comparative analysis allows a better understanding of complex allosteric interactions. In particular, the inclusion of constitutive receptor activity in the operational model of allosterism allows the characterization of modulators able to lower the basal response of the system; that is, allosteric modulators with negative intrinsic efficacy. Theoretical simulations and overall goodness of fit of the models to simulated data suggest that it is feasible to apply the models to experimental data and constitute one step forward in receptor theory formalism.

Abstract: The operational model of agonism has been widely used for the analysis of agonist action since its formulation in 1983. The model includes the Em parameter, which is defined as the maximum response of the system. The methods for Em estimation provide Em values not significantly higher than the maximum responses achieved by full agonists. However, it has been found that that some classes of compounds as, for instance, superagonists and positive allosteric modulators can increase the full agonist maximum response, implying upper limits for Em and thereby posing doubts on the validity of Em estimates. Because of the correlation between Em and operational efficacy, τ, wrong Em estimates will yield wrong τ estimates.
In this presentation, the operational model of agonism and various methods for the simulation of allosteric modulation will be analyzed. Alternatives for curve fitting will be presented and discussed.

Abstract: A main challenge in Evolutionary Algorithms (EAs) is determining a termination condition ensuring stabilization close to the optimum in real-world applications. Although for known test functions distribution-based quantities are good candidates (as far as suitable parameters are used), in real-world problems an open question still remains unsolved. How can we estimate an upper-bound for the termination condition value ensuring a given accuracy for the (unknown) EA solution?
We claim that the termination problem would be fully solved if we defined a quantity (depending only on the EA output) behaving like the solution accuracy. The open question would be, then, satisfactorily answered if we had a model relating both quantities, since accuracy could be predicted from the alternative quantity. We present a statistical inference framework addressing two topics: checking the correlation between the two quantities and defining a regression model for predicting (at a given confidence level) accuracy values from the EA output.