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Author |
David Roche; Debora Gil; Jesus Giraldo |
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Title |
Mathematical modeling of G protein-coupled receptor function: What can we learn from empirical and mechanistic models? |
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Book Chapter |
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Year |
2014 |
Publication |
G Protein-Coupled Receptors – Modeling and Simulation Advances in Experimental Medicine and Biology |
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Volume |
796 |
Issue |
3 |
Pages |
159-181 |
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Keywords |
β-arrestin; biased agonism; curve fitting; empirical modeling; evolutionary algorithm; functional selectivity; G protein; GPCR; Hill coefficient; intrinsic efficacy; inverse agonism; mathematical modeling; mechanistic modeling; operational model; parameter optimization; receptor dimer; receptor oligomerization; receptor constitutive activity; signal transduction; two-state model |
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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. |
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Springer Netherlands |
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ISSN |
0065-2598 |
ISBN |
978-94-007-7422-3 |
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Notes |
IAM; 600.075 |
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Call Number |
IAM @ iam @ RGG2014 |
Serial |
2197 |
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Author |
David Roche |
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Title |
A Statistical Framework for Terminating Evolutionary Algorithms at their Steady State |
Type |
Book Whole |
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Year |
2015 |
Publication |
PhD Thesis, Universitat Autonoma de Barcelona-CVC |
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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. |
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Address |
July 2015 |
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Thesis |
Ph.D. thesis |
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Publisher |
Ediciones Graficas Rey |
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Editor |
Debora Gil;Jesus Giraldo |
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Notes |
IAM; 600.075 |
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no |
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Call Number |
Admin @ si @ Roc2015 |
Serial |
2686 |
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